MARCH+APRIL 2011

the 15th annual

HIV Drug Positively Aware

Guide

March+APRIL 2011

SIDE EFFECTS Help Paying for meds NEW HIV DRUGS IN Development The HIV Treatment & Health Journal of

Test Positive Aware Network

INDICATION: REYATAZ is a prescription medicine used in combination with other medicines to treat people who are infected with the human immunodeficiency virus (HIV). REYATAZ has been studied in a 48-week trial in patients who have taken anti-HIV medicines and a 96-week trial in patients who have never taken anti-HIV medicines.

REYATAZ does not cure HIV or lower your chance of passing HIV to others.

On REYATAZ,

IMPORTANT SAFETY INFORMATION: Do not take REYATAZ if you are taking the following medicines due to potential for serious, life-threatening side effects or death: Versed® (midazolam) when taken by mouth, Halcion® (triazolam), ergot medicines (dihydroergotamine, ergonovine, ergotamine, and methylergonovine such as Cafergot®, Migranal®, D.H.E. 45®, ergotrate maleate, Methergine®, and others), Propulsid® (cisapride), or Orap® (pimozide).

Do not take REYATAZ with the following medicines due to potential for serious side effects: Camptosar® (irinotecan), Crixivan® (indinavir), Mevacor® (lovastatin), Zocor® (simvastatin), Uroxatral® (alfuzosin), or Revatio® (sildenafil).

Do not take REYATAZ with the following medicines as they may lower the amount of REYATAZ in your blood, which may lead to increased HIV viral load and resistance to REYATAZ or other anti-HIV medicines: rifampin (also known as Rimactane®, Rifadin®, Rifater®, or Rifamate®), St. John’s wort (Hypericum perforatum)-containing products, or Viramune® (nevirapine).

Serevent Diskus® (salmeterol) and Advair® (salmeterol with fluticasone) are not recommended with REYATAZ. Do not take Vfend® (voriconazole) if you are taking REYATAZ and Norvir® (ritonavir).

The above lists of medicines are not complete. Taking REYATAZ with some other medicines may require your therapy to be monitored more closely or may require a change in dose or dose schedule of REYATAZ or the other medicine. Discuss with your healthcare provider all prescription and non-prescription medicines, vitamin and herbal supplements, or other health preparations you are taking or plan to take.

Tell your healthcare provider if you are pregnant, breast-feeding, planning to become pregnant or breast-feed, or if you have end-stage kidney disease managed with hemodialysis or severe liver dysfunction.

Tell your healthcare provider right away if you have any side effects, symptoms, or conditions, including the following: • Mild rash (redness and itching) without other symptoms sometimes occurs in patients taking REYATAZ, most often in the first few weeks after the medicine is started, and usually goes away within 2 weeks with no change in treatment.

• Severe rash has occurred in a small number of patients taking REYATAZ. This type of rash is associated with other symptoms that could be serious and potentially cause death. If you develop a rash with any of the following symptoms, stop using REYATAZ and call your healthcare provider right away: – Conjunctivitis (red or inflamed eyes, – Shortness of breath like “pink-eye”) – General ill-feeling or “flu-like” – Blisters symptoms – Mouth sores – Fever – Swelling of your face – Muscle or joint aches • Yellowing of the skin and/or eyes may occur due to increases in bilirubin levels in the blood (bilirubin is made by the liver).

• A change in the way your heart beats may occur. You may feel dizzy or lightheaded. These could be symptoms of a heart problem.

• Diabetes and high blood sugar may occur in patients taking protease inhibitor medicines like REYATAZ. Some patients may need changes in their diabetes medicine.

• If you have liver disease, including hepatitis B or C, it may get worse when you take anti-HIV medicines like REYATAZ. • Kidney stones have been reported in patients taking REYATAZ. Signs or symptoms of kidney stones include pain in your side, blood in your urine, and pain when you urinate.

• Some patients with hemophilia have increased bleeding problems with protease inhibitor medicines like REYATAZ. • Changes in body fat have been seen in some patients taking anti-HIV medicines.

The cause and long-term effects are not known at this time.

• Gallbladder disorders (including gallstones and gallbladder inflammation) have been reported in patients taking REYATAZ. Other common side effects of REYATAZ taken with other anti-HIV medicines include: nausea; headache; stomach pain; vomiting; diarrhea; depression; fever; dizziness; trouble sleeping; numbness, tingling, or burning of hands or feet; and muscle pain.

You should take REYATAZ once daily with food (a meal or snack). Swallow the capsules whole; do not open the capsules. You should take REYATAZ and your other anti-HIV medicines exactly as instructed by your healthcare provider.

Wedn esd Ma ry a y ’s birthd ay pa rty Thursda y 5:30 C h oi r e practic

Bu y new shoes for Latish a

Fight HIV your way.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Please see Important Patient Information about REYATAZ on the adjacent pages.

how you spend your time is up to you.

Individual results may vary.

Once-daily REYATAZ can help fight your HIV. REYATAZ, a protease inhibitor (PI), in HIV combination therapy: ◆ Can

help lower your viral load and raise your T-cell (CD4+ cell) count

Find out if you can save on REYATAZ. Call 1-888-281-8981 or visit ReyatazSavings.com for details.

◆ Has

a low chance of diarrhea (shown in clinical trials) - REYATAZ in combination therapy had a 1%-3% rate of moderate-to-severe diarrhea in adults

◆ Is

taken once a day with a snack or meal

Subject to terms and conditions. Restrictions apply.

REYATAZ is one of several treatment options your doctor may consider.

Do not take REYATAZ if you are allergic to REYATAZ or to any of its ingredients.

Ask your healthcare team about REYATAZ

www.REYATAZ.com

REYATAZ does not cure HIV and has not been shown to reduce the risk of passing HIV to others.

REYATAZ is a registered trademark of Bristol-Myers Squibb.

All other trademarks are the property of their respective owners and not of Bristol-Myers Squibb. © 2010 Bristol-Myers Squibb, Princeton, NJ 08543 U.S.A. 687US10AB06404 06/10

FDA-Approved Patient Labeling Patient Information

REYATAZÂŽ (RAY-ah-taz) (generic name = atazanavir sulfate) Capsules

ALERT: Find out about medicines that should NOT be taken with REYATAZ. Read the section “What important information should I know about taking REYATAZ with other medicines?�

Read the Patient Information that comes with REYATAZ before you start using it and each time you get a refill. There may be new information. This leaflet provides a summary about REYATAZ and does not include everything there is to know about your medicine. This information does not take the place of talking with your healthcare provider about your medical condition or treatment.

What is REYATAZ? REYATAZ is a prescription medicine used with other anti-HIV medicines to treat people who are infected with the human immunodeficiency virus (HIV). HIV is the virus that causes acquired immune deficiency syndrome (AIDS). REYATAZ is a type of anti-HIV medicine called a protease inhibitor. HIV infection destroys CD4+ (T) cells, which are important to the immune system. The immune system helps fight infection. After a large number of (T) cells are destroyed, AIDS develops.

REYATAZ helps to block HIV protease, an enzyme that is needed for the HIV virus to multiply. REYATAZ may lower the amount of HIV in your blood, help your body keep its supply of CD4+ (T) cells, and reduce the risk of death and illness associated with HIV. Does REYATAZ cure HIV or AIDS? REYATAZ does not cure HIV infection or AIDS. At present there is no cure for HIV infection. People taking REYATAZ may still get opportunistic infections or other conditions that happen with HIV infection. Opportunistic infections are infections that develop because the immune system is weak. Some of these conditions are pneumonia, herpes virus infections, and Mycobacterium avium complex (MAC) infections. It is very important that you see your healthcare provider regularly while taking REYATAZ. REYATAZ does not lower your chance of passing HIV to other people through sexual contact, sharing needles, or being exposed to your blood. For your health and the health of others, it is important to always practice safer sex by using a latex or polyurethane condom or other barrier to lower the chance of sexual contact with semen, vaginal secretions, or blood. Never use or share dirty needles.

Who should not take REYATAZ? Do not take REYATAZ if you: t are taking certain medicines. (See “What important information should I know about taking REYATAZ with other medicines?�) Serious life-threatening side effects or death may happen. Before you take REYATAZ, tell your healthcare provider about all medicines you are taking or planning to take.

These include other prescription and nonprescription medicines, vitamins, and herbal supplements. t are allergic to REYATAZ or to any of its ingredients. The active ingredient is atazanavir sulfate. See the end of this leaflet for a complete list of ingredients in REYATAZ. Tell your healthcare provider if you think you have had an allergic reaction to any of these ingredients.

What should I tell my healthcare provider before I take REYATAZ? Tell your healthcare provider: t If you are pregnant or planning to become pregnant. It is not known if REYATAZ can harm your unborn baby. Pregnant women have experienced serious side effects when taking REYATAZ with other HIV medicines called nucleoside analogues. You and your healthcare provider will need to decide if REYATAZ is right for you. If you use REYATAZ while you are pregnant, talk to your healthcare provider about the Antiretroviral Pregnancy Registry. t If you are breast-feeding. You should not breast-feed if you are HIV-positive because of the chance of passing HIV to your baby. Also, it is not known if REYATAZ can pass into your breast milk and if it can harm your baby. If you are a woman who has or will have a baby, talk with your healthcare provider about the best way to feed your baby. t If you have liver problems or are infected with the hepatitis B or C virus.

See “What are the possible side effects of REYATAZ?� t If you have end stage kidney disease managed with hemodialysis. t If you have diabetes. See “What are the possible side effects of REYATAZ?� t If you have hemophilia. See “What are the possible side effects of REYATAZ?� t About all the medicines you take including prescription and nonprescription medicines, vitamins, and herbal supplements. Keep a list of your medicines with you to show your healthcare provider. For more information, see “What important information should I know about taking REYATAZ with other medicines?� and “Who should not take REYATAZ?� Some medicines can cause serious side effects if taken with REYATAZ.

REYATAZÂŽ (atazanavir sulfate) How should I take REYATAZ? t Take REYATAZ once every day exactly as instructed by your healthcare provider. Your healthcare provider will prescribe the amount of REYATAZ that is right for you.

t 'PS BEVMUT XIP IBWF OFWFS UBLFO BOUJ )*7 NFEJDJOFT CFGPSF UIF EPTF is 300 mg once daily with 100 mg of NORVIRÂŽ (ritonavir) once daily taken with food. For adults who are unable to tolerate ritonavir, 400 mg (two 200-mg capsules) once daily (without NORVIRÂŽ) taken with food is recommended.

t 'PS BEVMUT XIP IBWF UBLFO BOUJ )*7 NFEJDJOFT JO UIF QBTU UIF VTVBM dose is 300 mg plus 100 mg of NORVIRÂŽ (ritonavir) once daily taken with food. t :PVS EPTF XJMM EFQFOE PO ZPVS MJWFS GVODUJPO BOE PO UIF PUIFS BOUJ )*7 medicines that you are taking. REYATAZ is always used with other anti-HIV medicines. If you are taking REYATAZ with SUSTIVAÂŽ (efavirenz) or with VIREADÂŽ (tenofovir disoproxil fumarate), you should also be taking NORVIRÂŽ (ritonavir). t Always take REYATAZ with food (a meal or snack) to help it work better.

Swallow the capsules whole. Do not open the capsules. Take REYATAZ at the same time each day. t If you are taking antacids or didanosine (VIDEXŽ or VIDEXŽ EC), take REYATAZ 2 hours before or 1 hour after these medicines. t If you are taking medicines for indigestion, heartburn, or ulcers such as AXIDŽ (nizatidine), PEPCID ACŽ (famotidine), TAGAMETŽ (cimetidine), ZANTACŽ (ranitidine), AcipHexŽ (rabeprazole), NEXIUMŽ (esomeprazole), PREVACIDŽ (lansoprazole), PRILOSECŽ (omeprazole), or PROTONIXŽ (pantoprazole), talk to your healthcare provider. t Do not change your dose or stop taking REYATAZ without first talking with your healthcare provider. It is important to stay under a healthcare provider’s care while taking REYATAZ. t When your supply of REYATAZ starts to run low, get more from your healthcare provider or pharmacy. It is important not to run out of REYATAZ. The amount of HIV in your blood may increase if the medicine is stopped for even a short time. t If you miss a dose of REYATAZ, take it as soon as possible and then take your next scheduled dose at its regular time. If, however, it is within 6 hours of your next dose, do not take the missed dose. Wait and take the next dose at the regular time. Do not double the next dose. It is important that you do not miss any doses of REYATAZ or your other anti-HIV medicines. t If you take more than the prescribed dose of REYATAZ, call your healthcare provider or poison control center right away.

Can children take REYATAZ? Dosing recommendations are available for children 6 years of age and older for REYATAZ Capsules. Dosing recommendations are not available for children from 3 months to less than 6 years of age. REYATAZ should not be used in babies under the age of 3 months.

What are the possible side effects of REYATAZ? The following list of side effects is not complete. Report any new or continuing symptoms to your healthcare provider. If you have questions about side effects, ask your healthcare provider. Your healthcare provider may be able to help you manage these side effects.

The following side effects have been reported with REYATAZ: t mild rash (redness and itching) without other symptoms sometimes occurs in patients taking REYATAZ, most often in the first few weeks after the medicine is started. Rashes usually go away within 2 weeks with no change in treatment. Tell your healthcare provider if rash occurs. t severe rash: In a small number of patients, a rash can develop that is associated with other symptoms which could be serious and potentially cause death.

If you develop a rash with any of the following symptoms stop using REYATAZ and call your healthcare provider right away:

t TIPSUOFTT PG CSFBUI

t HFOFSBM JMM GFFMJOH PS iGMV MJLFw TZNQUPNT

t GFWFS

t NVTDMF PS KPJOU BDIFT

t DPOKVODUJWJUJT SFE PS JOGMBNFE FZFT MJLF iQJOL FZFw

t CMJTUFST

t NPVUI TPSFT

t TXFMMJOH PG ZPVS GBDF t yellowing of the skin or eyes. These effects may be due to increases in bilirubin levels in the blood (bilirubin is made by the liver). Call your healthcare provider if your skin or the white part of your eyes turn yellow.

Although these effects may not be damaging to your liver, skin, or eyes, it is important to tell your healthcare provider promptly if they occur.

REYATAZŽ (atazanavir sulfate) a change in the way your heart beats (heart rhythm change). Call your healthcare provider right away if you get dizzy or lightheaded. These could be symptoms of a heart problem. t diabetes and high blood sugar (hyperglycemia) sometimes happen in patients taking protease inhibitor medicines like REYATAZ. Some patients had diabetes before taking protease inhibitors while others did not. Some patients may need changes in their diabetes medicine. t if you have liver disease including hepatitis B or C, your liver disease may get worse when you take anti-HIV medicines like REYATAZ. t kidney stones have been reported in patients taking REYATAZ. If you develop signs or symptoms of kidney stones (pain in your side, blood in your urine, pain when you urinate) tell your healthcare provider promptly. t some patients with hemophilia have increased bleeding problems with protease inhibitors like REYATAZ. t changes in body fat. These changes may include an increased amount of fat in the upper back and neck (“buffalo hump�), breast, and around the trunk. Loss of fat from the legs, arms, and face may also happen. The cause and long-term health effects of these conditions are not known at this time.

Other common side effects of REYATAZ taken with other anti-HIV medicines include nausea; headache; stomach pain; vomiting; diarrhea; depression; fever; dizziness; trouble sleeping; numbness, tingling, or burning of hands or feet; and muscle pain.

Gallbladder disorders (which may include gallstones and gallbladder inflammation) have been reported in patients taking REYATAZ. What important information should I know about taking REYATAZ with other medicines?

Do not take REYATAZ if you take the following medicines (not all brands may be listed; tell your healthcare provider about all the medicines you take).

REYATAZ may cause serious, life-threatening side effects or death when used with these medicines. t &SHPU NFEJDJOFT EJIZESPFSHPUBNJOF FSHPOPWJOF FSHPUBNJOF BOE methylergonovine such as CAFERGOTŽ, MIGRANALŽ, D.H.E. 45Ž, ergotrate maleate, METHERGINEŽ, and others (used for migraine headaches). t 03"1Ž (pimozide, used for Tourette’s disorder). t 13016-4*%Ž (cisapride, used for certain stomach problems). t 5SJB[PMBN BMTP LOPXO BT )"-$*0/Ž (used for insomnia). t .JEB[PMBN BMTP LOPXO BT 7&34&%Ž (used for sedation), when taken by mouth.

Do not take the following medicines with REYATAZ because of possible serious side effects: t $".1504"3ÂŽ (irinotecan, used for cancer). t $3*9*7"/ÂŽ JOEJOBWJS VTFE GPS )*7 JOGFDUJPO #PUI 3&:"5"; BOE $3*9*7"/ sometimes cause increased levels of bilirubin in the blood. t Cholesterol-lowering medicines MEVACORÂŽ (lovastatin) or ZOCORÂŽ (simvastatin). t 6309"53"-ÂŽ (alfuzosin, used to treat benign enlargement of the prostate). t 3&7"5*0ÂŽ (sildenafil, used to treat pulmonary arterial hypertension).

Do not take the following medicines with REYATAZ because they may lower the amount of REYATAZ in your blood. This may lead to an increased HIV viral load. Resistance to REYATAZ or cross-resistance to other HIV medicines may EFWFMPQ t 3JGBNQJO BMTP LOPXO BT 3*."$5"/&ÂŽ, RIFADINÂŽ, RIFATERÂŽ, or RIFAMATEÂŽ, used for tuberculosis). t 4U +PIO T XPSU (Hypericum perforatum), an herbal product sold as a dietary TVQQMFNFOU PS QSPEVDUT DPOUBJOJOH 4U +PIO T XPSU t 7*3".6/&ÂŽ (nevirapine, used for HIV infection).

The following medicines are not recommended with REYATAZ: t 4&3&7&/5 %*4,64ÂŽ (salmeterol) and ADVAIRÂŽ (salmeterol with fluticasone), used to treat asthma, emphysema/chronic obstructive pulmonary disease also known as COPD. Do not take the following medicine if you are taking REYATAZ and NORVIRÂŽ together: t 7'&/%ÂŽ (voriconazole).

The following medicines may require your healthcare provider to monitor your therapy more closely (for some medicines a change in the dose or dose schedule may be needed): t $*"-*4ÂŽ (tadalafil), LEVITRAÂŽ (vardenafil), or VIAGRAÂŽ (sildenafil), used to treat erectile dysfunction. REYATAZ may increase the chances of serious side effects that can happen with CIALIS, LEVITRA, or VIAGRA. Do not use CIALIS, LEVITRA, or VIAGRA while you are taking REYATAZ unless your healthcare provider tells you it is okay. t "%$*3$"ÂŽ (tadalafil) or TRACLEERÂŽ (bosentan), used to treat pulmonary arterial hypertension. t -*1*503ÂŽ (atorvastatin) or CRESTORÂŽ (rosuvastatin). There is an increased chance of serious side effects if you take REYATAZ with this cholesterollowering medicine. t

REYATAZÂŽ (atazanavir sulfate) t

FEJDJOFT GPS BCOPSNBM IFBSU SIZUIN $03%"30/&ÂŽ (amiodarone), lidocaine, . quinidine (also known as CARDIOQUINÂŽ 26*/*%&9ÂŽ, and others). t .:$0#65*/ÂŽ (rifabutin, an antibiotic used to treat tuberculosis). t #613&/&9ÂŽ 46#65&9ÂŽ 46#090/&ÂŽ, (buprenorphine or buprenorphine/ naloxone, used to treat pain and addiction to narcotic painkillers). t 7"4$03ÂŽ (bepridil, used for chest pain). t $06."%*/ÂŽ (warfarin). t 5SJDZDMJD BOUJEFQSFTTBOUT TVDI BT &-"7*-ÂŽ (amitriptyline), NORPRAMINÂŽ (desipramine), SINEQUANÂŽ (doxepin), SURMONTILÂŽ (trimipramine), TOFRANILÂŽ (imipramine), or VIVACTILÂŽ (protriptyline). t .FEJDJOFT UP QSFWFOU PSHBO USBOTQMBOU SFKFDUJPO 4"/%*..6/&ÂŽ or NEORALÂŽ (cyclosporin), RAPAMUNEÂŽ (sirolimus), or PROGRAFÂŽ (tacrolimus). t 5IF BOUJEFQSFTTBOU USB[PEPOF %&4:3&-ÂŽ and others). t 'MVUJDBTPOF QSPQJPOBUF '-0/"4&ÂŽ, FLOVENTÂŽ), given by nose or inhaled to treat allergic symptoms or asthma. Your doctor may choose not to keep you on fluticasone, especially if you are also taking NORVIRÂŽ. t $PMDIJDJOF $0-$3:4ÂŽ), used to prevent or treat gout or treat familial Mediterranean fever.

The following medicines may require a change in the dose or dose schedule of either REYATAZ or the other medicine: t */7*3"4&ÂŽ (saquinavir). t /037*3ÂŽ (ritonavir). t 4645*7"ÂŽ (efavirenz). t "OUBDJET PS CVGGFSFE NFEJDJOFT t 7*%&9ÂŽ (didanosine). t 7*3&"%ÂŽ (tenofovir disoproxil fumarate). t .:$0#65*/ÂŽ (rifabutin). t $BMDJVN DIBOOFM CMPDLFST TVDI BT $"3%*;&.ÂŽ or TIAZACÂŽ (diltiazem), COVERA-HSÂŽ or ISOPTIN SRÂŽ (verapamil) and others. t #*"9*/ÂŽ (clarithromycin). t .FEJDJOFT GPS JOEJHFTUJPO IFBSUCVSO PS VMDFST TVDI BT "9*%ÂŽ (nizatidine), PEPCID ACÂŽ (famotidine), TAGAMETÂŽ (cimetidine), or ZANTACÂŽ (ranitidine).

Talk to your healthcare provider about choosing an effective method of contraception. REYATAZ may affect the safety and effectiveness of hormonal contraceptives such as birth control pills or the contraceptive patch. Hormonal contraceptives do not prevent the spread of HIV to others.

Remember: 1.

Know all the medicines you take.

2.

Tell your healthcare provider about all the medicines you take.

3.

Do not start a new medicine without talking to your healthcare provider.

How should I store REYATAZ? t 4UPSF 3&:"5"; $BQTVMFT BU SPPN UFNQFSBUVSF ÂĄ UP ÂĄ ' ÂĄ UP ÂĄ $

Do not store this medicine in a damp place such as a bathroom medicine cabinet or near the kitchen sink. t ,FFQ ZPVS NFEJDJOF JO B UJHIUMZ DMPTFE DPOUBJOFS t ,FFQ BMM NFEJDJOFT PVU PG UIF SFBDI PG DIJMESFO BOE QFUT BU BMM UJNFT %P OPU keep medicine that is out of date or that you no longer need. Dispose of unused medicines through community take-back disposal programs when available or place REYATAZ in an unrecognizable, closed container in the household trash.

General information about REYATAZ This medicine was prescribed for your particular condition. Do not use REYATAZ for another condition. Do not give REYATAZ to other people, even if they have the same symptoms you have. It may harm them. Keep REYATAZ and all medicines out of the reach of children and pets.

This summary does not include everything there is to know about REYATAZ. Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Remember no written summary can replace careful discussion with your healthcare provider. If you would like more information, talk XJUI ZPVS IFBMUIDBSF QSPWJEFS PS ZPV DBO DBMM What are the ingredients in REYATAZ? Active Ingredient: atazanavir sulfate Inactive Ingredients: Crospovidone, lactose monohydrate (milk sugar), magnesium stearate, gelatin, FD&C Blue #2, and titanium dioxide.

7*%&9ÂŽ and REYATAZÂŽ are registered trademarks of Bristol-Myers Squibb Company. COUMADINÂŽ and SUSTIVAÂŽ are registered trademarks of Bristol-Myers Squibb Pharma Company. DESYRELÂŽ JT B SFHJTUFSFE USBEFNBSL PG .FBE +PIOTPO and Company. Other brands listed are the trademarks of their respective owners and are not trademarks of Bristol-Myers Squibb Company.

1SJODFUPO /+ 64" 1246226A7

F1-B0001B-04-10

Rev April 2010

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| M arch+ A pril 2011 P os i t i v e lyAwar e .com

INSIDE

MARCH+APRIL 2011 VO L U M E 2 3 N U M B ER 2

D e p a r t m e n ts

In Box

6 PA Reader poll

7 Editor’s Note The school of HIV.

8

Contributors

9 F e a tu r es

Getting help to pay for HIV meds

HIV co-pay and patient assistance programs can help cover the cost of meds.

67

T he d r u g g uide

the 15th annual

An introduction 13

Guide

Getting the most from this guide 19

HIV Drug

The 15th Annual HIV Drug Guide

A handbook to the 30 medications for treating HIV—including their cost, side effects, potential interactions—and what a doctor and an activist have to say about them.

21-50

T he t a b l es

Drug interactions

Coming into view

Do your HIV meds play well with other drugs?

74

Drug side effects

New HIV drugs on the horizon.

52

Possible side effects that can result from HIV meds.

INTRODUCING QR CODES: Beginning with this issue of Positively Aware, next to some URLs, you’ll find a QR (Quick Response) code. Using a QR code reader app, scan the code with your iPhone or other smart phone; you’ll be directed to the cited web page. The QR code above will take you to www.PositivelyAware.com

On the cover and this page: image by Chris Knight Model: Asher glaser

P o s i t i v e lyAwa r e . c o m

60

Rules of the game

Treatment guidelines from the U.S. Dept. of Health and Human Services.

76

2011 HIV Drug Pull-out chart Is sponsored by

for a list of Walgreens HIV specialty pharmacies, and other resources, Go to HIV.walgreens.com/chart

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In Box

“A breath of fresh air” I picked up Positively Aware (January/February 2011 issue) for the first time and I have to tell you, among all the HIV/AIDS magazines and newsletters, yours is a breath of fresh air.

I’m a 62-year-old gay white man who tested positive in 1987 but knew I had the virus years before— when all of my friends and partners started dying in the early 80s, it was the only logical conclusion.

But I’m still here. Today, I deal with both the side effects of the handful of medications I take each day and of getting older. Talk about a TKO! It’s good to know that finally, there’s a journal that gets it. Articles that I can

relate to. Information smartly presented in a clear, concise manner.

Thank you.

—Stan Stoj

Loving is knowing I am HIV-negative, but my partner is positive, and we are both bisexual and inmates in the same state prison. It hasn’t been easy for us—we have had to deal with namecalling, discrimination, and a lot of people talking behind our backs.

Myself being negative, I knew nothing about HIV before I met my partner. He has taught me a lot. It’s been difficult at times in our relationship because there

are things we have to be careful about like open cuts and bleeding. We’ve worked through it though, and it has made our relationship stronger.

It sometimes gets stressful for me because I want to make sure he gets his treatment every day and make sure he takes his pills. I try to keep his spirits up. Your magazine has helped me to understand how to deal with his mood swings and I’ve learned about the different medications and the ones soon to be available. I share this information with him and his nurse.

It hasn’t been an easy road, but with effort and love, we make it work. So just because one of us is negative and one positive, both bisexual and inmates, doesn’t mean a relationship can’t work.

Thank you for keeping us both informed— it gives us hope for the future.

—Darrell C.

Hope for Today, Strategies for Life!

HIVandYourHeart.org is a new website developed by the American Heart Association and the American Academy of HIV Medicine. We are dedicated to helping people living with HIV make life changes for

Please visit:

HIVandYourHeart.org

better heart health and overall wellness.

©2011, American Heart Association. 1/11DS4445

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M a r c h +A p r i l 2 0 1 1 P o s i t i v e lyAwa r e . c o m

Positivelyaware.com

It’s complicated I picked up a copy of PA (January/February 2011) at my pharmacist’s office today and when I read your opening note, I almost fell over. Our stories are so similar: I was living in San Jose and the week before I turned 30, I decided to get an HIV test. I honestly didn’t think I would test positive; not because I was so pure or a stranger to the occasional bath-house, but just because it seemed (in 1985) the people getting sick were people who were on the “extreme”, or so I thought.

I actually was the first person at this clinic to test positive. The woman giving me the results was so upset that she almost couldn’t tell me. There was no counseling or follow-up; she just handed me my slip and out I walked.

The rest of your editorial is so on-themoney. AIDS is so complicated. People see that I’m still alive and want to believe that it is a “manageable chronic illness”— like diabetes. What people don’t get is that it is not “just” a manageable illness. Like you, I’ve dealt with fat displacement, diabetes, had all the calcium leeched from my teeth and bones, etc. etc. etc. The people that are coming up behind us who think that “Well, by the time I get sick they will have a cure, or there will be better treatments” need to think again.

In fact, we are just beginning to understand the long-term destruction that nukes do to our bodies. These drugs are not benign in any way. Yes, we have streamlined some of the therapies, but like you said, I also am dealing with cholesterol and heart issues, high blood pressure, and other diseases that shouldn’t occur for another couple of decades.

I felt compelled to tell you how much your column struck home with me. I wish that every young person could be handed a copy of it before they make the decision that “it won’t be that big of a deal.”

—Doug Halloran

You are not alone I wanted to let you know just how much I enjoy your magazine. I tested positive in 2002 when my T-cells were at 50. I’m very P os i t i velyAware.co m

Last issue’s poll question:

much better now, with T-cells at 600-700 and I’ve been undetectable since 2003.

I’ve been in prison since 2005 and discovered your magazine in here. I find your magazine goes more in depth on lots of subjects than other publications.

I study HIV from any source I can get and I’m not so scared of HIV now. You give me hope for the future with the stories and great tales from all over the country. You show me that I am not alone.

I look forward to receiving your magazine to smile, inform, and make me cry, too—it’s all good. Thank you.

—Ronnie C.

Have you ever experienced any complications from HIV or HIV meds?

NO:

7%

HIV:

UNSURE:

27%

20%

MEDS: BOTH:

13%

33%

Wearing IT on your sleeve Your comments:

In reading “Status Symbols” by Sue Saltmarsh, I was struck by the comment, “Could we conclude from this experience that perhaps stigma and prejudice are more internal than external?”

After developing and presenting many trainings on stigma to providers of social services, medical facilities, and groups of those living with and affected by HIV/ AIDS, I can say that the statement is partly true. I find that there is as much internalizing of stigma among those living with and affected by HIV/AIDS as there is ignorance in the general population.

Once when I explained that I was buying things for an HIV support group, a woman asked me, “Oh HIV, doesn’t that cause them to lose their hair?”

It was an indication of the public’s ignorance about AIDS and demonstrated that we educators are not doing enough to educate our whole communities about what HIV/AIDS is. I want one of those t-shirts to wear maybe I can show them my full head of hair and dispel any other myths held about life with HIV. —Paolo Presta-Gunton Sue Saltmarsh responds: Thanks to Paolo and all the others who have written in asking where they can get one of the “HIV Positive” T-shirts featured in the article. Though not the same ones, HIV-related T-shirts are available at www. nightsweats.com and www.cafepress.com.

“Crixivan was the worst. Sludge buildup was super painful.”

“Meds seem to cause GI issues.”

this issue’s poll question:

When you think about or refer to the HIV drugs you take, prescribe, or discuss with someone, do you call them by their brand name or their generic/common name? cast your vote at

positivelyaware.com

Do the write thing

Positively Aware will treat all communications (letters, faxes, e-mail, etc.) as letters to the editor unless otherwise instructed. We reserve the right to edit for length, style, or clarity. Unless you tell us not to, we will use your name and city.

Positively aware

5537 N. Broadway St. Chicago, IL 60640 E-Mail: readersforum@tpan.com

Follow us on Facebook and Twitter M a r c h +Ap r i l 201 1 |

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Editor’s NOTE Jeff Berry

Have you ever bought something, such as a shelving unit or a piece of furniture from Ikea, brought it home, and then tried to assemble it without reading the instructions fully, thinking that you could figure it out by yourself? Or maybe you recently purchased a new appliance or electronic gadget, looked briefly at the thick manual that came with it, tossed it aside, and thought to yourself, “I know most of this already.”

Many times we need a manual, or a guide, to help us to do things correctly the first time, so that we don’t ruin it before we’ve even started using it. We may think we know what’s best, but often there are little tidbits of information that we didn’t realize, or we leave out a step in the process that is integral and key to its success.

It’s interesting that some of us wouldn’t think twice about being sure to read the user’s manual for our new computer or X-Box. But when it comes to the life-saving medications that we put into our body, we often don’t know how many milligrams we are taking, or even worse, the name of the drug itself.

All we know is that it’s two of the pink pills, one of the white pills, and one of the blue ones, once a day. And sometimes that’s okay, and we learn how to get by on a “need-to-know basis” with our meds and with our virus. Until one day we find ourselves in the emergency room and the physician or nurse is asking us what medications we are on so that they don’t give us another med that might cause a dangerous interaction—and we draw a complete blank.

When I first started taking HIV meds over 20 years ago, I subscribed to the “ignorance is bliss” school of thought in regards to HIV. The less I knew about what this insidious virus was doing to my body, the better. I never used to like to get all of 8

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those boring details from my doctor about viral replication, mutations, and resistance, and so on. My rationale was that I would just think the worst and visualize those awful things going on inside of me, causing more harm than good. What can I say, back then I was visualizing Louise Hay affirmations, not viral assembly and cleavage.

And then I started working at an HIV organization, and I had no choice but to learn. I needed to find out as much as I could about the virus, how it worked, and the medications used to treat it in order to be able to even carry on a simple conversation with my co-workers and not sound like a complete and total idiot. Soon clients, friends, and even total strangers began asking me for advice on what medication to take, who was a good HIV doc I could recommend, or how they could get housing or financial assistance.

Which brings us to this issue: the Positively Aware 15th Annual HIV Drug Guide. Here in your hands lies a powerful tool. It’s up to you to decide how you will ultimately choose to use it, and how much you need to know to get by. This is the seventh Drug Guide that I have produced as Editor, and every year even I learn something new when reading through it.

And anything that you might learn could one day help not only you, but perhaps a client, a patient, or even a friend.

The PA HIV Drug Guide is a huge undertaking, requiring many hours of intense work by a great number of individuals, sometimes late into the night and even on weekends. I’d like to thank the Publications team for their unwavering dedication and support, including Editorial Assistant Sue Saltmarsh for her keen attention to detail and keeping us all on schedule, Associate Editor Enid Vázquez for the herculean task of updating the guide, and Art Director Rick Guasco for the fantastic design and fresh look of this year’s edition; last minute hero Dr. Joel Gallant, pharmacists Michael Low and Swarup Mehta, and activist Jeff Taylor for contributing to this year’s guide; photographers Joshua Thorne and Chris Knight for your kick-ass imagery; Advertising Coordinator Jessie Mott who makes it all possible; Distribution Coordinator Billy Surber for getting it out there; web gurus Brad Mazzie and Mark Larson for making it look pretty and functional; and last but not least, proofreader Jason Lancaster for his eagle eye!

As you can see, there are a lot of people who have worked long and hard to get this thing right, get it to you in a timely fashion and in a format that’s easy to understand, and make it easy on the eyes. Now the decision is yours as to how much of it you will read, use, and share.

Let’s make 2011 the year in which we all decide to learn something new that we never knew before—to create that “a-ha” moment for ourselves—and to then use what we learn to help someone else who may just be entering the school of HIV. Take care of yourself, and each other.

M a r c h +A p r i l 2 0 1 1 P o s i t i v e lyAwa r e . c o m

PHOTO: Chris Knight

The school of Hiv

2011 HIV Drug guide

Joel Gallant, MD, MPH is Professor of Medicine and Epidemiology at the Johns Hopkins University School of Medicine’s Division of Infectious Diseases, and Associate Director of the Johns Hopkins AIDS Service, and author of the book, 100 Questions & Answers About HIV and AIDS. In the last year, Dr. Gallant has served on scientific advisory boards or acted as a paid consultant to BristolMyers Squibb, Gilead Sciences, Merck & Co., Tibotec Therapeutics, and ViiV Healthcare. He serves on Data Safety Monitoring Boards or Endpoint Review Committees for Gilead Sciences and Sangamo Biosciences. Johns Hopkins University has received research grants from Gilead Sciences for clinical trials being conducted

by Dr. Gallant.

P o s i t i v e lyAwa r e . c o m

Michael Low, PharmD grew up in a small rural town in Minnesota.

He earned his BA at Concordia College in Moorhead, and his PharmD at the University of Minnesota.

He is the Clinic Pharmacy Manager for the on-site Walgreens located across from The Doctors Uptown-Allina Clinic in Minneapolis. He specializes in HIV, hepatitis, MS, and oncology.

His aim is to use his talents and resources to empower each patient to improve their health and quality of life.

Swarup Mehta, PharmD, MBA, AAHIVE was born and raised in Naperville, Illinios. He earned his PharmD and MBA at Drake University in Des Moines, Iowa in 2002. After graduation, Swarup worked for Walgreens Pharmacy in many Chicagoland locations. He is currently the Clinic Pharmacy Manager for Walgreens at Northstar Medical in Chicago. There, he specializes in and counsels on HIV, hepatitis, and oncology. He is also an immunizer and offers a variety of vaccinations at his clinic. He has served on the TPAN board for four years and is the co-chair of the fundraising committee. Swarup received the 2009 Outstanding Health Care Advocate of the Year award from the AIDS Legal Council of Chicago.

Photo: Joshua Thorne

Photo: David Gray

Photo: Joshua Thorne

Photo courtesy of Michael Low

Photo Courtesy of Joel Gallant

Contributors

A survivor of AIDS and cancer for over 25 years, Jeff Taylor got his start in HIV research advocacy when he enrolled in the first AZT trials at the AIDS Clinical Trials Group back in the late 80’s. He went on to serve on their advisory board, and currently serves on the National Cancer Institute’s AIDS Malignancy Consortium, UCSD Antiviral Research Center, and on the DHHS Antiviral Guidelines Panel.

With fellow activists in the AIDS Treatment Activists Coalition Drug Development Committee, he works with pharmaceutical companies, the FDA, and academia to advocate for more research and better HIV treatments. At home in Palm Springs, he produces a monthly HIV treatment education program.

PA Associate Editor Enid Vázquez has worked on the HIV drug guide since its inception in 1997 (when her sister Sylvia appeared on the cover), and each year looks forward to writing up the latest news, good or bad.

She earned her B.A. in journalism from the University of Wisconsin, Madison, and has worked as an intern for The Chicago Reporter and a cub reporter for The Hartford Courant.

Her freelance work has appeared in publications around the country.

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• EPZICOM, in combination with other antiretroviral agents, is indicated for the treatment of HIV-1 infection in adults.

• EPZICOM is one of 3 medicines containing abacavir.

Before starting EPZICOM, your healthcare provider will review your medical history in order to avoid the use of abacavir if you have experienced an allergic reaction to abacavir in the past.

• In one study, more patients had a severe hypersensitivity reaction in the abacavir once-daily group than in the abacavir twice-daily group.

• EPZICOM should not be used as part of a triple-nucleoside regimen.

• EPZICOM does not cure HIV infection/AIDS or prevent passing HIV to others.

Important Safety Information EPZICOM contains abacavir, which is also contained in ZIAGEN® (abacavir sulfate) and TRIZIVIR® (abacavir sulfate, lamivudine, and zidovudine). Patients taking abacavir may have a serious allergic reaction (hypersensitivity reaction) that can cause death. Your risk of this allergic reaction is much higher if you have a gene variation called HLA-B*5701 than if you do not.

Your healthcare provider can determine with a blood test if you have this gene variation. If you get a symptom from 2 or more of the following groups while taking EPZICOM, call your doctor right away to determine if you should stop taking this medicine.

1. Fever 2. Rash 3. Nausea, vomiting, diarrhea, or abdominal (stomach area) pain 4. Generally ill feeling, extreme tiredness, or achiness 5. Shortness of breath, cough, or sore throat Carefully read the Warning Card that your pharmacist gives you and carry it with you at all times.

If you stop EPZICOM because of an allergic reaction, NEVER take EPZICOM or any other abacavir-containing medicine (ZIAGEN, TRIZIVIR) again. If you take EPZICOM or any other abacavir-containing medicine again after you have had an allergic reaction, WITHIN HOURS you may get life-threatening symptoms that may include very low blood pressure or death.

I’ve got the fight in me.

If you stop EPZICOM for any other reason, even for a few days, and you are not allergic to EPZICOM, talk with your healthcare provider before taking it again. Taking EPZICOM again can cause a serious allergic or life-threatening reaction, even if you never had an allergic reaction to it before. If your healthcare provider tells you that you can take EPZICOM again, start taking it when you are around medical help or people who can call a healthcare provider if you need one.

A buildup of lactic acid in the blood and an enlarged liver, including fatal cases, have been reported.

Do not take EPZICOM if your liver does not function normally.

Some patients infected with both hepatitis B virus (HBV) and HIV have worsening of hepatitis after stopping lamivudine (a component of EPZICOM). Discuss any change in treatment with your healthcare provider. If you have both HBV and HIV and stop treatment with EPZICOM, you should be closely monitored by your healthcare provider for at least several months.

Worsening of liver disease (sometimes resulting in death) has occurred in patients infected with both HIV and hepatitis C virus who are taking anti-HIV medicines and are also being treated for hepatitis C with interferon with or without ribavirin. If you are taking EPZICOM as well as interferon with or without ribavirin and you experience side effects, be sure to tell your healthcare provider.

When you start taking HIV medicines, your immune system may get stronger and could begin to fight infections that have been hidden in your body, such as pneumonia, herpes virus, or tuberculosis. If you have new symptoms after starting your HIV medicines, be sure to tell your healthcare provider.

Changes in body fat may occur in some patients taking antiretroviral therapy. These changes may include an increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the trunk. Loss of fat from the legs, arms, and face may also occur. The cause and long-term health effects of these conditions are not known at this time.

Some HIV medicines, including those containing abacavir (ZIAGEN, EPZICOM, and TRIZIVIR), may increase your risk of heart attack. If you have heart problems, smoke, or suffer from diseases that increase your risk of heart disease, such as high blood pressure, high cholesterol, or diabetes, tell your healthcare provider.

The most common side effects seen with the drugs in EPZICOM dosed once daily were allergic reaction, trouble sleeping, depression, headache, tiredness, dizziness, nausea, diarrhea, rash, fever, stomach pain, abnormal dreams, and anxiety. Most of the side effects do not cause people to stop taking EPZICOM. By prescription only.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please see additional important information about EPZICOM, including boxed warnings, on the adjacent pages.

Save on your medication!

Ask your doctor about the Patient Savings Card or visit www.mysupportcard.com to learn how to save on your out-of-pocket expenses.

Subject to eligibility. Restrictions apply.

“EVEN WITH HIV,

I NEVER STOP FIGHTING.” “When I was first diagnosed with HIV, I didn’t know what each day would bring or how the virus would affect my body over time. But at some point, I realized I had to take control. So I worked on my body. My mind. And my attitude. Since then, I’ve dedicated my life to fighting HIV with everything in me.

My meds help a lot. About a year ago, my doctor told me about EPZICOM. In combination with other medications, it’s been shown to help keep HIV from making more copies of itself and infecting healthy cells. 68% of patients taking a regimen with EPZICOM had their viral load become undetectable in less than one year. Plus, patients saw a 93% increase in their T-cell counts.* So I started taking it as part of my combination therapy.

Turns out that was a good thing. My viral load is undetectable.

And me? I just keep fighting on.” † †

Not an actual patient testimonial. Based on collection of real patient experiences. Individual results may vary.

* HEAT study of 688 patients defines undetectable as a viral load less than 50 copies/mL. Baseline median T-cell count for patients receiving EPZICOM was 214 cells/mm3 and at 48 weeks, patients saw a median increase of 201 cells/mm3 in their T-cell count.

Ask your healthcare provider if EPZICOM is right for you.

Learn more at www.EpzicomForYou.com

EPZICOM® (abacavir sulfate and lamivudine) Tablets MEDICATION GUIDE EPZICOM® (ep′ zih com) Tablets Generic name: abacavir (uH-BACK-ah-veer) sulfate and lamivudine (la-MIV-yoo-deen) Read the Medication Guide that comes with EPZICOM before you start taking it and each time you get a refill because there may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment. Be sure to carry your EPZICOM Warning Card with you at all times.

What is the most important information I should know about EPZICOM? • Serious Allergic Reaction to Abacavir. EPZICOM contains abacavir (also contained in ZIAGEN® and TRIZIVIR®). Patients taking EPZICOM may have a serious allergic reaction (hypersensitivity reaction) that can cause death. Your risk of this allergic reaction is much higher if you have a gene variation called HLA-B*5701 than if you do not. Your doctor can determine with a blood test if you have this gene variation. If you get a symptom from 2 or more of the following groups while taking EPZICOM, call your doctor right away to determine if you should stop taking this medicine.

Group 1 Group 2 Group 3 Group 4 Group 5

Symptom(s) Fever Rash Nausea, vomiting, diarrhea, abdominal (stomach area) pain Generally ill feeling, extreme tiredness, or achiness Shortness of breath, cough, sore throat

A list of these symptoms is on the Warning Card your pharmacist gives you. Carry this Warning Card with you.

If you stop EPZICOM because of an allergic reaction, NEVER take EPZICOM (abacavir sulfate and lamivudine) or any other abacavir-containing medicine (ZIAGEN and TRIZIVIR) again. If you take EPZICOM or any other abacavir-containing medicine again after you have had an allergic reaction, WITHIN HOURS you may get life-threatening symptoms that may include very low blood pressure or death.

If you stop EPZICOM for any other reason, even for a few days, and you are not allergic to EPZICOM, talk with your doctor before taking it again. Taking EPZICOM again can cause a serious allergic or life-threatening reaction, even if you never had an allergic reaction to it before. If your doctor tells you that you can take EPZICOM again, start taking it when you are around medical help or people who can call a doctor if you need one.

• Lactic Acidosis. Some human immunodeficiency virus (HIV) medicines, including EPZICOM, can cause a rare but serious condition called lactic acidosis with liver enlargement (hepatomegaly).

Nausea and tiredness that don’t get better may be symptoms of lactic acidosis. In some cases this condition can cause death. Women, overweight people, and people who have taken HIV medicines like EPZICOM for a long time have a higher chance of getting lactic acidosis and liver enlargement. Lactic acidosis is a medical emergency and must be treated in the hospital.

• Worsening of hepatitis B virus (HBV) infection. Patients with HBV infection, who take EPZICOM and then stop it, may get “flare-ups” of their hepatitis. “Flare-up” is when the disease suddenly returns in a worse way than before. If you have HBV infection, your doctor should closely monitor your liver function for several months after stopping EPZICOM. You may need to take anti-HBV medicines.

• Use with interferon- and ribavirin-based regimens. Worsening of liver disease (sometimes resulting in death) has occurred in patients infected with both HIV and hepatitis C virus who are taking anti-HIV medicines and are also being treated for hepatitis C with interferon with or without ribavirin. If you are taking EPZICOM as well as interferon with or without ribavirin and you experience side effects, be sure to tell your doctor.

EPZICOM can have other serious side effects. Be sure to read the section below entitled “What are the possible side effects of EPZICOM?” What is EPZICOM? EPZICOM is a prescription medicine used to treat HIV infection. EPZICOM includes 2 medicines: abacavir (ZIAGEN) and lamivudine or 3TC (EPIVIR®). See the end of this Medication Guide for a complete list of ingredients in EPZICOM. Both of these medicines are called nucleoside analogue reverse transcriptase inhibitors (NRTIs). When used together, they help lower the amount of HIV in your blood. This helps to keep your immune system as healthy as possible so that it can help fight infection.

Different combinations of medicines are used to treat HIV infection. You and your doctor should discuss which combination of medicines is best for you.

• EPZICOM does not cure HIV infection or AIDS. We do not know if EPZICOM will help you live longer or have fewer of the medical problems that people get with HIV or AIDS. It is very important that you see your doctor regularly while you are taking EPZICOM. • EPZICOM does not lower the risk of passing HIV to other people through sexual contact, sharing needles, or being exposed to your blood. For your health and the health of others, it is important to always practice safe sex by using a latex or polyurethane condom or other barrier method to lower the chance of sexual contact with semen, vaginal secretions, or blood. Never use or share dirty needles.

Who should not take EPZICOM? Do not take EPZICOM if you: • have ever had a serious allergic reaction (a hypersensitivity reaction) to EPZICOM or any other medicine that has abacavir as one of its ingredients (TRIZIVIR and ZIAGEN). See the end of this Medication Guide for a complete list of ingredients in EPZICOM. • have a liver that does not function properly.

• are less than 18 years of age.

Before starting EPZICOM tell your doctor about all of your medical conditions, including if you: • have been tested and know whether or not you have a particular gene variation called HLA-B*5701.

• are pregnant or planning to become pregnant. We do not know if EPZICOM will harm your unborn child.

You and your doctor will need to decide if EPZICOM is right for you. If you use EPZICOM while you are pregnant, talk to your doctor about how you can be on the Antiviral Pregnancy Registry for EPZICOM. • are breastfeeding. Some of the ingredients in EPZICOM can be passed to your baby in your breast milk. It is not known if they could harm your baby. Also, mothers with HIV should not breastfeed because HIV can be passed to the baby in the breast milk.

• have liver problems including hepatitis B virus infection.

• have kidney problems.

• have heart problems, smoke, or suffer from diseases that increase your risk of heart disease such as high blood pressure, high cholesterol, or diabetes.

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take any of the following medicines*: • methadone • HIVID® (zalcitabine, ddC) • EPIVIR or EPIVIR-HBV® (lamivudine, 3TC), ZIAGEN (abacavir sulfate), COMBIVIR® (lamivudine and zidovudine), or TRIZIVIR (abacavir sulfate, lamivudine, and zidovudine).

How should I take EPZICOM? • Take EPZICOM by mouth exactly as your doctor prescribes it. The usual dose is 1 tablet once a day. Do not skip doses.

• You can take EPZICOM with or without food.

• If you miss a dose of EPZICOM, take the missed dose right away. Then, take the next dose at the usual time.

• Do not let your EPZICOM run out.

• Starting EPZICOM again can cause a serious allergic or life-threatening reaction, even if you never had an allergic reaction to it before. If you run out of EPZICOM even for a few days, you must ask your doctor if you can start EPZICOM again. If your doctor tells you that you can take EPZICOM again, start taking it when you are around medical help or people who can call a doctor if you need one.

• If you stop your anti-HIV drugs, even for a short time, the amount of virus in your blood may increase and the virus may become harder to treat.

• If you take too much EPZICOM, call your doctor or poison control center right away.

What should I avoid while taking EPZICOM? • Do not take EPIVIR (lamivudine, 3TC), COMBIVIR (lamivudine and zidovudine), ZIAGEN (abacavir sulfate), or TRIZIVIR (abacavir sulfate, lamivudine, and zidovudine) while taking EPZICOM. Some of these medicines are already in EPZICOM. • Do not take zalcitabine (HIVID, ddC) while taking EPZICOM. Avoid doing things that can spread HIV infection, as EPZICOM does not stop you from passing the HIV infection to others.

• Do not share needles or other injection equipment.

• Do not share personal items that can have blood or body fluids on them, like toothbrushes and razor blades.

• Do not have any kind of sex without protection. Always practice safe sex by using a latex or polyurethane condom or other barrier method to lower the chance of sexual contact with semen, vaginal secretions, or blood.

• Do not breastfeed. EPZICOM can be passed to babies in breast milk and could harm the baby. Also, mothers with HIV should not breastfeed because HIV can be passed to the baby in the breast milk.

What are the possible side effects of EPZICOM? EPZICOM can cause the following serious side effects: • Serious allergic reaction that can cause death. (See “What is the most important information I should know about EPZICOM?” at the beginning of this Medication Guide.)

• Lactic acidosis with liver enlargement (hepatomegaly) that can cause death. (See “What is the most important information I should know about EPZICOM?” at the beginning of this Medication Guide.)

• Worsening of HBV infection. (See “What is the most important information I should know about EPZICOM?” at the beginning of this Medication Guide.)

• Changes in immune system. When you start taking HIV medicines, your immune system may get stronger and could begin to fight infections that have been hidden in your body, such as pneumonia, herpes virus, or tuberculosis. If you have new symptoms after starting your HIV medicines, be sure to tell your doctor.

• Changes in body fat. These changes have happened in patients taking antiretroviral medicines like EPZICOM. The changes may include an increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the back, chest, and stomach area. Loss of fat from the legs, arms, and face may also happen. The cause and long-term health effects of these conditions are not known.

Some HIV medicines including EPZICOM may increase your risk of heart attack. If you have heart problems, smoke, or suffer from diseases that increase your risk of heart disease such as high blood pressure, high cholesterol, or diabetes, tell your doctor.

The most common side effects with EPZICOM are trouble sleeping, depression, headache, tiredness, dizziness, nausea, diarrhea, rash, fever, stomach pain, abnormal dreams, and anxiety. Most of these side effects did not cause people to stop taking EPZICOM. This list of side effects is not complete. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store EPZICOM? • Store EPZICOM at room temperature between 59º to 86ºF (15º to 30ºC).

• Keep EPZICOM and all medicines out of the reach of children.

General information for safe and effective use of EPZICOM Medicines are sometimes prescribed for conditions that are not mentioned in Medication Guides. Do not use EPZICOM for a condition for which it was not prescribed. Do not give EPZICOM to other people, even if they have the same symptoms that you have. It may harm them.

This Medication Guide summarizes the most important information about EPZICOM. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for the information that is written for healthcare professionals or call 1-888-825-5249.

What are the ingredients in EPZICOM? Active ingredients: abacavir sulfate and lamivudine Inactive ingredients: Each film-coated EPZICOM Tablet contains the inactive ingredients magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The tablets are coated with a film (OPADRY® orange YS-1-13065-A) that is made of FD&C Yellow No. 6, hypromellose, polyethylene glycol 400, polysorbate 80, and titanium dioxide.

COMBIVIR, EPIVIR, EPZICOM, TRIZIVIR, and ZIAGEN are registered trademarks of GlaxoSmithKline. *The brands listed are trademarks of their respective owners and are not trademarks of GlaxoSmithKline. The makers of these brands are not affiliated with and do not endorse GlaxoSmithKline or its products.

This Medication Guide has been approved by the US Food and Drug Administration.

Lamivudine is manufactured under agreement from Shire Pharmaceuticals Group plc, Basingstoke, UK ©2009, GlaxoSmithKline. All rights reserved.

March 2009 EPZ:2MG ©2010 ViiV Healthcare Group of Companies All rights reserved.

Printed in USA.

ECM521R0

June 2010

2011 HIV Drug guide Introduction

A proper Introduction

Photo: Joshua Thorne

by Joel Gallant, MD, MPH

All antiretroviral drugs work in essentially the same way—by preventing the virus from replicating. They’re classified based on the stage of the HIV life cycle they target. Most antiretroviral regimens include drugs from at least two of the six classes, because attacking the virus with drugs that work in different ways helps prevent resistance.

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Nucleoside Analog Reverse Transcriptase Inhibitors (NRTIs) or “Nukes” Nucleoside analogs (“nukes” or NRTIs) prevent reverse transcriptase, a viral enzyme, from turning the virus’s RNA into DNA. NRTIs mimic the normal building blocks of DNA, but when they join the

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2011 HIV Drug guide Introduction

growing DNA chain, they keep the process from being completed. The nukes have been around since Retrovir (zidovudine or AZT) was approved in the mid-1980s, and they’ve been components of just about every drug regimen ever since. Although we sometimes refer to the two NRTIs used in most regimens as the “backbone,” they tend to be weaker than the drugs they’re combined with, serving mainly to prevent resistance. Some of the earliest nukes— Zerit (d4T), Retrovir, and Videx (ddI)—are no longer widely used because of toxicity.

The four safer and better tolerated drugs are Viread (tenofovir), Emtriva (emtricitabine or FTC), Ziagen (abacavir), and Epivir (lamivudine or 3TC). Viread and Emtriva are combined together in the form of either Truvada or Atripla, which also contains Sustiva. Ziagen and Epivir are combined together in the form of Epzicom. These drugs are a big improvement over their older cousins, though Viread sometimes causes kidney problems, and Ziagen may increase the risk of heart attacks, especially in people with other cardiac risk factors.

Current guidelines recommend Truvada

as the preferred nuke backbone, with Epzicom as an alternative. So-called “nukesparing regimens” are being studied; they usually consist of a protease inhibitor plus either an NNRTI or an integrase inhibitor.

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) or “Non-Nukes” The NNRTIs, or “non-nukes,” block the activity of reverse transcriptase so it can’t make DNA. NNRTIs are most often used in first-line therapy. Sustiva (efavirenz, also a part of Atripla), is the preferred NNRTI, and Viramune (nevirapine) is an alternative.

Intelence (etravirine) is used for people who have resistance to the other NNRTIs. NNRTIs are well tolerated over the long term, but side effects can occur, usually during the first few weeks, including nervous system side effects with Sustiva, liver toxicity with Viramune, and rash with both.

Resistance to NNRTIs can occur easily and quickly if the viral load isn’t suppressed or if treatment is interrupted. The big event for 2011 is likely to be the approval of rilpivirine, a new NNRTI, as well as a single

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pill combination of rilpivirine with the components of Truvada. Rilpivirine will be used for initial therapy. It has fewer side effects than Sustiva/Atripla, but may be somewhat less potent, especially in people with high viral loads.

Protease Inhibitors (PIs) The PIs block protease, an enzyme used

by HIV to cleave large proteins into smaller proteins, which are then used to assemble new viral particles. It was the combination of NRTIs plus PIs that revolutionized HIV treatment, allowing us to completely and durably suppress viral replication.

Although they saved countless lives, the early PIs were hard to take, requiring lots of pills frequently, and having many side effects and long-term toxicities. That’s changed, partly because newer PIs were developed, and partly because of boosting: all recommended PIs are taken with a low dose of Norvir (ritonavir), which boosts drug levels and simplifies dosing. The two preferred PIs for initial therapy, Prezista (darunavir) and Reyataz (atazanavir), are once-daily drugs with few side effects and

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2011 HIV Drug guide Introduction

little toxicity. Still, they can cause diarrhea or elevatated lipid levels. Reyataz sometimes causes jaundice, and Prezista can cause an allergic rash. It’s not easy to develop resistance to boosted PIs, which make them good choices for people who are likely to miss doses or interrupt therapy. Non-Norvir boosters are being developed; the one furthest along is cobicistat.

Integrase Inhibitors Integrase inhibitors block the insertion of HIV DNA into human DNA. There is one approved integrase inhibitor, Isentress (raltegravir), which is now a preferred drug for initial therapy. It’s very well tolerated, but has to be taken twice a day. Two more are in advanced stages of development.

Elvitegravir, a once-daily drug, will be available in a “quad” pill that also contains the booster cobicistat and the Truvada components. S/GSK1349572 (“572”) is another once-daily integrase inhibitor now in clinical trials. There’s a lot of crossresistance among these three drugs, so it’s not clear that you can use another if you develop resistance to one.

CCR5 Antagonists CCR5 inhibitors are a type of entry inhibitor; they block entry of the virus into the CD4 cell by interfering with its binding to the CCR5 co-receptor. Selzentry (maraviroc) is approved for both treatmentexperienced patients and for initial therapy.

However, Selzentry is not a preferred agent for first-line treatment, in part because you can’t use it without first doing a tropism test to make sure you have purely “R5 virus”: virus that gets into the cell using the CCR5 co-receptor. If you have any virus that uses CXCR4, Selzentry won’t work.

Fusion Inhibitors The final step of viral entry involves fusion of the envelope of the virus with the membrane of the CD4 cell, a step blocked

by Fuzeon (enfuvirtide or T-20). Fuzeon requires subcutaneous injections twice a day, and because we now have so many easier options, it’s rarely used. However, it’s still a useful option for people with extensive drug resistance. e P o s i t i v e lyAwa r e . c o m

find your HIV drug in the guide Nucleoside reverse transcriptase inhibitors also called nucleoside analogs, NRTIs, or nukes Combivir | combination of Epivir and Retrovir

page 21

Emtriva | generic name: emtricitabine, FTC

22

Epivir | generic name: lamivudine, 3TC

23

Epzicom | combination of Epivir and Ziagen

24

Retrovir | generic name: zidovudine, AZT, or ZDV

25

Trizivir | combination of Epivir, Retrovir, and Ziagen

26

Truvada | combination of Emtriva and Viread

27

Videx & Videx EC | generic name: didanosine, or ddI

28

Viread | generic name: tenofovir disoproxil fumarate, or TDF

29

Zerit | generic name: stavudine, or d4T

30

Ziagen | generic name: abacavir, or ABC

31

Non-nucleoside reverse transcRiptase inhibitors also called non-nucleosides, NNRTIs, or non-nukes Intelence | generic name: etravirine, ETR

32

Rescriptor | generic name: delavirdine, or DLV

33

rilpivirine

34

Sustiva | generic name: efavirenz, or EFV

35

Viramune | generic name: nevirapine, or NVP

36

Fixed dose regimens Atripla | combination of Sustiva and Truvada

37

rilpivirine/Truvada combination

38

Protease inhibitors (PIs) Aptivus | generic name: tipranavir, or TPV

39

Crixivan | generic name: indinavir, or IDV

40

Invirase | generic name: saquinavir, or SQV

41

Kaletra | generic name: lopinavir/ritonavir, or LPV/r

42

Lexiva | generic name: fosamprenavir, or FPV

43

Norvir | generic name: ritonavir, or RTV

44

Prezista | generic name: darunavir, or DRV

45

Reyataz | generic name: atazanavir, or ATV

46

Viracept | generic name: nelfinavir, or NFV

47

Entry inhibitors Fuzeon | generic name: enfuvirtide, T-20, or ENF

48

Selzentry | generic name: maraviroc, or MVC

49

Integrase inhibitor Isentress | generic name: raltegravir, or RAL

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INDICATIONS ISENTRESS is an anti-HIV medicine used for the treatment of HIV. ISENTRESS must be used with other anti-HIV medicines, which may increase the likelihood of response to treatment.

The safety and effectiveness of ISENTRESS in children has not been studied.

It is important that you remain under your doctor’s care.

ISENTRESS will NOT cure HIV infection or reduce your chance of passing HIV to others through sexual contact, sharing needles, or being exposed to your blood.

IMPORTANT RISK INFORMATION A condition called Immune Reconstitution Syndrome can happen in some patients with advanced HIV infection (AIDS) when anti-HIV treatment is started. Signs and symptoms of inflammation from opportunistic infections may occur as the medicines work to treat the HIV infection and strengthen the immune system.

Call your doctor right away if you notice any signs or symptoms of an infection after starting ISENTRESS. Contact your doctor immediately if you experience unexplained muscle pain, tenderness, or weakness while taking ISENTRESS. This is because on rare occasions muscle problems can be serious and can lead to kidney damage.

When ISENTRESS has been given with other anti-HIV drugs, side effects included nausea, headache, tiredness, weakness, trouble sleeping, stomach pain, dizziness, depression, and suicidal thoughts and actions.

Rash occurred more often in patients taking ISENTRESS and darunavir together than with either drug separately, but was generally mild.

You are special, unique, and different from anyone else.

And so is your path to managing HIV. When you’re ready to start HIV therapy, talk to your doctor about a medication that may fit your needs and lifestyle.

In clinical studies lasting 96 weeks, patients being treated with HIV medication for the first time who took ISENTRESS plus Truvada: Had a low rate of side effects — The most common side effect of moderate to severe intensity (that interfered with or kept patients from performing daily activities) was trouble sleeping — This side effect occurred more often in patients taking ISENTRESS plus Truvada (4%) versus Sustiva plus Truvada (3%) Experienced less effect on LDL cholesterol (“bad” cholesterol) — Cholesterol increased an average of 7 mg/dL with ISENTRESS plus Truvada versus 21 mg/dL with Sustiva plus Truvada

Ask your doctor about ISeNTReSS. Not sure where to start? Visit isentress.com/questions People taking ISENTRESS may still develop infections, including opportunistic infections or other conditions that occur with HIV infection.

Tell your doctor about all of your medical conditions, including if you have any allergies, are pregnant or plan to become pregnant, or are breast-feeding or plan to breast-feed. ISENTRESS is not recommended for use during pregnancy. Women with HIV should not breast-feed because their babies could be infected with HIV through their breast milk.

Tell your doctor about all the medicines you take, including prescription medicines like rifampin (a medicine used to treat infections such as tuberculosis), non-prescription medicines, vitamins, and herbal supplements.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

For more information about ISENTRESS, please read the Patient Information on the following page.

Need help paying for ISENTRESS? Call 1-866-350-9232

Copyright © 2011 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. All rights reserved.

21052250(50)(110)-03/11-ISN-CON Sustiva is a registered trademark of Bristol-Myers Squibb Truvada is a registered trademark of Gilead Sciences, Inc.

T:7 in

Patient Information ISENTRESS ® (eye sen tris) (raltegravir) Tablets If you fail to take ISENTRESS the way you should, here’s what to do: • If you miss a dose, take it as soon as you remember. If you do not remember until it is time for your next dose, skip the missed dose and go back to your regular schedule. Do NOT take two tablets of ISENTRESS at the same time. In other words, do NOT take a double dose.

• If you take too much ISENTRESS, call your doctor or local Poison Control Center.

Be sure to keep a supply of your anti-HIV medicines.

• When your ISENTRESS supply starts to run low, get more from your doctor or pharmacy.

• Do not wait until your medicine runs out to get more.

What are the possible side effects of ISENTRESS? When ISENTRESS has been given with other anti-HIV drugs, side effects included: • nausea • headache • tiredness • weakness • trouble sleeping • stomach pain • dizziness • depression • suicidal thoughts and actions Other side effects include rash, severe skin reactions, feeling anxious, paranoia, low blood platelet count.

A condition called Immune Reconstitution Syndrome can happen in some patients with advanced HIV infection (AIDS) when combination antiretroviral treatment is started. Signs and symptoms of inflammation from opportunistic infections that a person has or had may occur as the medicines work to treat the HIV infection and help to strengthen the immune system. Call your doctor right away if you notice any signs or symptoms of an infection after starting ISENTRESS with other anti-HIV medicines.

Contact your doctor promptly if you experience unexplained muscle pain, tenderness, or weakness while taking ISENTRESS. This is because on rare occasions, muscle problems can be serious and can lead to kidney damage.

Rash occurred more often in patients taking ISENTRESS and darunavir together than with either drug separately, but was generally mild.

Tell your doctor if you have any side effects that bother you.

These are not all the side effects of ISENTRESS. For more information, ask your doctor or pharmacist.

How should I store ISENTRESS? • Store ISENTRESS at room temperature (68 to 77°F).

• Keep ISENTRESS and all medicines out of the reach of children.

General information about the use of ISENTRESS Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets.

• Do not use ISENTRESS for a condition for which it was not prescribed.

• Do not give ISENTRESS to other people, even if they have the same symptoms you have. It may harm them.

This leaflet gives you the most important information about ISENTRESS. • If you would like to know more, talk with your doctor.

• You can ask your doctor or pharmacist for additional information about ISENTRESS that is written for health professionals.

• For more information go to www.ISENTRESS.com or call 1-800-622-4477.

What are the ingredients in ISENTRESS? Active ingredient: Each film-coated tablet contains 400 mg of raltegravir.

Inactive ingredients: Microcrystalline cellulose, lactose monohydrate, calcium phosphate dibasic anhydrous, hypromellose 2208, poloxamer 407 (contains 0.01% butylated hydroxytoluene as antioxidant), sodium stearyl fumarate, magnesium stearate. In addition, the film coating contains the following inactive ingredients: polyvinyl alcohol, titanium dioxide, polyethylene glycol 3350, talc, red iron oxide and black iron oxide.

IMPORTANT: Take ISENTRESS exactly as your doctor prescribed and at the right times of day because if you don’t: • The amount of virus (HIV) in your blood may increase if the medicine is stopped for even a short period of time.

• The virus may develop resistance to ISENTRESS and become harder to treat.

• Your medicines may stop working to fight HIV. • The activity of ISENTRESS may be reduced (due to resistance).

Distributed by: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. Whitehouse Station, NJ 08889, USA

Registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. Copyright © 2011 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. All rights reserved.

Revised June 2010 9795110 U.S. Patent Nos. US 7,169,780 21052250(50)(110)-03/11-ISN-CON

1

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Read the patient information that comes with ISENTRESS1 before you start taking it and each time you get a refill. There may be new information. This leaflet is a summary of the information for patients. Your doctor or pharmacist can give you additional information. This leaflet does not take the place of talking with your doctor about your medical condition or your treatment.

What is ISENTRESS? • ISENTRESS is an anti-HIV (antiretroviral) medicine used for the treatment of HIV. The term HIV stands for Human Immunodeficiency Virus. It is the virus that causes AIDS (Acquired Immune Deficiency Syndrome). ISENTRESS is used along with other anti-HIV medicines. ISENTRESS will NOT cure HIV infection.

• People taking ISENTRESS may still develop infections, including opportunistic infections or other conditions that happen with HIV infection.

• Stay under the care of your doctor during treatment with ISENTRESS. • The safety and effectiveness of ISENTRESS in children has not been studied.

ISENTRESS must be used with other anti-HIV medicines.

How does ISENTRESS work?

• ISENTRESS blocks an enzyme which the virus (HIV) needs in order to make more virus. The enzyme that ISENTRESS blocks is called HIV integrase.

• When used with other anti-HIV medicines, ISENTRESS may do two things: 1. Reduce the amount of HIV in your blood. This is called your “viral load”.

2. Increase the number of white blood cells called CD4 (T) cells.

• ISENTRESS may not have these effects in all patients.

Does ISENTRESS lower the chance of passing HIV to other people?

No. ISENTRESS does not reduce the chance of passing HIV to others through sexual contact, sharing needles, or being exposed to your blood.

• Continue to practice safer sex.

• Use latex or polyurethane condoms or other barrier methods to lower the chance of sexual contact with any body fluids. This includes semen from a man, vaginal secretions from a woman, or blood.

• Never re-use or share needles.

Ask your doctor if you have any questions about safer sex or how to prevent passing HIV to other people.

What should I tell my doctor before and during treatment with ISENTRESS? Tell your doctor about all of your medical conditions. Include any of the following that applies to you: • You have any allergies.

• You are pregnant or plan to become pregnant.

- ISENTRESS is not recommended for use during pregnancy.

ISENTRESS has not been studied in pregnant women. If you take

ISENTRESS while you are pregnant, talk to your doctor about how

you can be included in the Antiretroviral Pregnancy Registry.

• You are breast-feeding or plan to breast-feed.

- It is recommended that HIV-infected women should not breast-feed their infants. This is because their babies could be infected with HIV through their breast milk.

- Talk with your doctor about the best way to feed your baby.

Tell your doctor about all the medicines you take. Include the following: • prescription medicines, including rifampin (a medicine used to treat some infections such as tuberculosis) • non-prescription medicines • vitamins • herbal supplements Know the medicines you take.

• Keep a list of your medicines. Show the list to your doctor and pharmacist when you get a new medicine.

How should I take ISENTRESS? Take ISENTRESS exactly as your doctor has prescribed. The recommended dose is as follows: • Take only one 400-mg tablet at a time.

• Take it twice a day.

• Take it by mouth.

• Take it with or without food.

Do not change your dose or stop taking ISENTRESS or your other anti-HIV medicines without first talking with your doctor.

2011 HIV Drug guide Introduction

A guide to

USING this guide

By Jeff Berry

As with any reference tool, you often need a legend or guide in order to decipher what exactly everything means, where to look for it, and how to best find it. Hopefully, the following tips will help you to get all of the information you need, when you need it.

Drugs included in the Positively Aware HIV Drug Guide are only those which are FDA approved and currently on the market, available through an expanded access program (EAP), or expected to receive FDA approval in the coming year.

Drugs are color-coded by class and are listed alphabetically within each class by brand name. The brand name is listed first, and typically begins with a capital letter.

The generic name, or scientific designation (in lower case), along with more common names and abbreviations, is listed in parentheses. Example: Retrovir (zidovudine, AZT, or ZDV). Retrovir is the brand name, zidovudine is the generic name or scientific designation, AZT is the common name, and ZDV is the abbreviation.

A fixed dose combination (FDC) is a formulation that combines two or more

charts make it easier to identify some of the more common side effects and interactions associated with each drug.

Always refer to the individual drug pages, manufacturer’s package insert, or talk to your physician or pharmacist for more information.

drugs into one tablet or capsule, such

Our special pull-out drug chart allows

as Combivir (lamivudine/zidovudine).

A fixed dose regimen (FDR) combines two or more drugs from different drug classes and is a complete regimen in one pill, such as Atripla (efavirenz/tenofovir/ emtricitabine). Atripla is the only fixed dose regimen currently available, with approval of another FDR, rilpivirine/ tenofovir/emtricitabine, expected sometime during 2011.

you to easily pinpoint dosing information and food and liquid requirements for each medication. Check with your health care provider, or refer to the drug page or package insert for more information.

The Average Wholesale Price (AWP) is an industry standard that pharmacies and other buyers use to negotiate the amount they pay for drugs. The AWP is included on the drug page as a way to compare drug prices. It is not necessarily what you would pay out-of-pocket if you do not have drug coverage.

In 2009, Pfizer and GlaxoSmithKline merged their HIV divisions together to form ViiV Healthcare, so all drugs formerly listed as manufactured by Pfizer or GSK are now listed as made by ViiV. For more information on the co-pay and/or patient assistance programs available for ViiV drugs, visit www.viivhealthcareforyou.com.

For a complete list of drug co-pay and patient assistance programs for all HIV drugs, see “It’s in the Cards” on page 67.

The side effect and drug interaction

Get the latest treatment guidelines online. The U.S. Department of Health and Human Services (DHHS) periodically updates its HIV treatment guidelines. See page 76 for an abbreviated list of recommended regimens. The entire document is available online as a downloadable PDF, and includes comprehensive and detailed guidelines including treatment strategies, explanation of lab tests, when and what to start, use in special populations, co-infection, and much more. Visit www.aidsinfo.nih.gov, or you can scan the QR code at left using a QR scanner app on your iPhone or other smart phone.

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2011 HIV Drug guide Combivir brand name:

Combivir

zidovudine (AZT) and lamivudine (3TC) Nucleoside analog reverse transcriptase inhibitor

(nucleoside analog, NRTI, or nuke)—fixed dose combination manufacturer: ViiV Healthcare | www.viivhealthcare.com, (877) 844-8872 common name: class:

Standard dose: One tablet (150 mg Epivir/lamivudine/3TC, 300 mg Retrovir/zidovudine/ AZT), twice a day (12 hours apart), with or without food, with no dietary restrictions. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.

AWP: $992.98 / month

Potential side effects and toxicity Also see Epivir (lamivudine, 3TC), page 23; and Retrovir (zidovudine, AZT), page 25, for details. Fatigue, myopathy (muscle damage), and flare-up of hepatitis B upon stopping (due to the withdrawal of Epivir, which is contained in Combivir). The zidovudine (AZT) in Combivir has been associated with alteration of various cells in the blood through bone marrow suppression, resulting in anemia (low red blood cell counts) and/or neutropenia (low white blood cell counts), particularly during the first three months of therapy in people with advanced HIV. Zidovudine is also associated with lipoatrophy (fat loss of the arms, legs, face, and/or buttocks—sometimes called “AZT butt”). The lipoatrophy could be irreversible or fat could take a long time to rebuild. Rare but potentially serious toxicity with all NRTIs: enlarged, fatty liver (hepatomegaly with steatosis) and lactic acidosis (accumulation of lactate in the blood and abnormal acid-base balance). Lactic acidosis may cause persistent fatigue, abdominal pain or distension, nausea/ vomiting, difficulty breathing or shortness of breath, and enlarged liver.

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Potential drug interactions Also see the drugs contained in Combivir, Epivir and Retrovir, for more information. Do not take Combivir with Atripla, Emtriva, Epivir, Epivir-HBV, Epzicom, Retrovir (zidovudine), Trizivir, Truvada or Zerit (stavudine), since all or part of these medications are already in Combivir or have equivalent medications.

More infoRmation Combivir is the combination of Epivir (lamivudine, 3TC), page 23; and Retrovir (zidovudine, AZT), page 25 in one pill; see the pages of those individual drugs for more information.

May be taken with food to decrease potential nausea associated with AZT. One head-tohead study against Truvada (Emtriva and Viread) found greater toxicity with Combivir, due to anemia (see Retrovir, page 25). Thanks to extensive data, Combivir is preferred to Truvada for pregnant women who are taking therapy for the first time, according to U.S. HIV treatment guidelines from the Department of Health and Human Services (DHHS). See package insert for more complete information on potential side effects and interactions.

Doctor’s COMMENTS In the early years of the HAART era, Combivir was the most commonly used nucleoside “backbone” in what was often referred to as the “cocktail.” However, it’s taken twice a day and has the disadvantages of AZT toxicity (see Retrovir, page 25). As a result, it’s been largely replaced by the safer, once-daily coformulations, Truvada and Epzicom. Epzicom is better tolerated and safer than Combivir, and Truvada was shown to be more effective and less toxic. When it’s necessary to use AZT, it makes sense to use it in the form of Combivir, since there are resistance advantages to combining 3TC with AZT (see Epivir, page 23). —Joel Gallant, MD, MPH ACTIVIST’S COMMENTS The first of the fixed dose combinations that now dominate the market, Combivir suffers from the anemia, fatigue, dizziness, and fat wasting caused by its AZT component. Oncea-day combos have largely supplanted it, but its long history and efficacy still make it a widely prescribed combo—especially useful for those needing a drug with good central nervous system (CNS) penetration and for women who are pregnant or trying to conceive. —Jeff Taylor

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2011 HIV Drug guide Emtriva brand name:

Emtriva

emtricitabine or FTC Nucleoside analog reverse transcriptase inhibitor

(nucleoside analog, NRTI, or nuke) manufacturer: Gilead Sciences, Inc. | www.gilead.com, (800) GILEAD5 (445–3235) common name: class:

Standard dose: One 200 mg capsule once a day, with or without food, with no dietary restrictions. The dosing needs to be adjusted for people who have decreased kidney function.

It is also available as an oral solution; for children 0-3 months the dose is 3 mg per 2.2 lbs. and children 3 months–17 years, 6 mg per 2.2 lbs. up to a maximum of 240 mg. For children weighing more than 73 pounds who can swallow an intact capsule, one 200 mg capsule once daily. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.

AWP: $467.45 / month for 200 mg capsules; $110.38 for 170 ml solution (10 mg/ml)

Potential side effects and toxicity Very tolerable. Side effects (rarely seen) may include headache, diarrhea, nausea, and rash. Flare-up of HBV (hepatitis B) in people co-infected with HIV/HBV has occurred when Emtriva was discontinued (see More Information). Skin discoloration (darkening of the skin on the palms and the soles of the feet) can occur, but is generally mild and without other symptoms. Rare but potentially serious toxicity with all NRTIs: enlarged, fatty liver (hepatomegaly with steatosis) and lactic acidosis (accumulation of lactate in the blood and abnormal acid-base balance). Lactic acidosis may cause persistent fatigue, abdominal pain or distension, nausea/vomiting, difficulty breathing or shortness of breath, and enlarged liver.

Potential drug interactions No significant drug interactions. Do not take Emtriva with Atripla, Combivir, Epivir, EpivirHBV, Epzicom, Trizivir, or Truvada, since they contain Emtriva or medication equivalent to Emtriva.

More information Emtriva (FTC) is similar to Epivir (3TC).

However, unlike Epivir, Emtriva remains in blood cells in excess of the 24-hour dosing interval. Emtriva is known to be effective against chronic hepatitis B, but is not indicated for its treatment; stopping the medicine

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could thus stop the suppression of the hep B virus. Patients co-infected with HIV/HBV who stop taking Emtriva should be closely monitored by their physician. They should also use the Truvada formulation as their NRTI backbone to increase activity and avoid HBV resistance. Emtriva is available as a combination tablet with Viread (tenofovir DF), which is called Truvada. Truvada is the only NRTI combination on the preferred list of the U.S. HIV treatment guidelines for the NRTI component of an HIV regimen. Drug resistance that the virus develops against Emtriva, the M184V mutation, makes the virus less fit to replicate.

It also slightly improves the antiviral activity of Retrovir (zidovudine) and Viread, and for that reason, some doctors keep Emtriva onboard in combination with those drugs after M184V resistance develops. In 2006, Emtriva was combined with Sustiva (efavirenz) and Viread (tenofovir) in one pill, which is known as Atripla. Atripla is used quite often as first-line treatment due to ease of taking one pill once a day. Emtriva oral solution should be kept in the refrigerator. If kept at room temperature, the oral solution should be used within three months. See package insert for more complete information on potential side effects and interactions.

Doctor’s COMMENTS Few people take Emtriva itself; it’s almost always combined with tenofovir in the form of

Truvada, or with tenofovir and efavirenz in the form of Atripla. The characteristics of FTC are similar to those of 3TC: it has the same resistance profile and is also safe and extremely well tolerated. The main difference between the two drugs is that FTC tends to be combined with tenofovir (see Truvada, page 27), while 3TC is usually taken in combination with AZT (see Combivir, page 21), abacavir (see Epzicom, page 24), or both (see Trizivir, page 26). Aside from the convenience of the coformulations, there may be other reasons why these combinations make sense. Both tenofovir and FTC have similar half-lives, which are longer than those of other nucleoside analogs.

This means they hang around longer in the blood and in CD4 cells. Combining two drugs with similar half-lives may help to prevent resistance if doses are missed or treatment is interrupted. Indeed, we seem to see less tenofovir resistance when tenofovir is combined with FTC than when it’s combined with 3TC, a consideration that may become relevant when 3TC becomes available in generic form.

—Joel Gallant, MD, MPH ACTIVIST’S COMMENTS Gilead’s once-daily version of 3TC, they’ve conveniently combined it with Viread in Truvada, and with Viread and Sustiva in Atripla. It causes the same resistance mutation as 3TC that can make your virus more sensitive to AZT or Viread. It can also be useful for salvage patients with lots of drug resistance because it can make their virus “less fit” and help lower their viral load even when they’re resistant to it. Because of its activity against hepatitis B, patients should check before using this drug alone or in any of the fixed dose combinations containing Emtriva to prevent HBV cross resistance to both Emtriva and Epivir. —Jeff Taylor

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2011 HIV Drug guide Epivir brand name:

Epivir

lamivudine or 3TC Nucleoside analog reverse transcriptase inhibitor

(nucleoside analog, NRTI, or nuke) manufacturer: ViiV Healthcare | www.viivhealthcare.com, (877) 844-8872 common name: class:

Standard dose: One 300 mg tablet once a day (or one 150 mg tablet twice daily), with or without food, with no dietary restrictions. Dose is lowered for people with kidney impairment.

Dose for children 3 months to 16 years of age is 4 mg per 2.2 pounds twice daily to a maximum of 150 mg twice daily. A strawberry/banana-flavored liquid (10 mg/1 mL) is available. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.

AWP: $457.97 / month for 300 mg tablets, $122.14 / month for 240 ml solution (10 mg/ml)

Potential side effects and toxicity Very tolerable. Side effects (though rarely seen) may include headache, nausea, vomiting, diarrhea, fever, fatigue, hair loss, insomnia, malaise (general ill feeling), nasal symptoms, cough, peripheral neuropathy, low white blood cells, and anemia. Rare but potentially serious toxicity with all NRTIs: enlarged, fatty liver (hepatomegaly with steatosis) and lactic acidosis (accumulation of lactate in the blood and abnormal acid-base balance). Lactic acidosis may cause persistent fatigue, abdominal pain or distension, nausea/ vomiting, difficulty breathing or shortness of breath, and enlarged liver.

Potential drug interactions No significant drug interactions. Do not take Epivir with Atripla, Combivir, Emtriva, EpivirHBV, Epzicom, Trizivir, or Truvada, since they contain Epivir or medication equivalent to Epivir.

More infoRMATION One benefit is that the drug resistance the virus develops against Epivir, the M184V mutation, makes the virus less fit to replicate and has even been shown to keep T-cells from dropping during a treatment interruption as much

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as they would have otherwise. The mutation also slightly improves the antiviral activity of Retrovir (zidovudine) and Viread, and for that reason, some doctors keep Epivir onboard in combination with those drugs after M184V resistance develops. Epivir is also approved for the treatment of hepatitis B virus (HBV), under the brand name Epivir-HBV, which has a lower dose than Epivir for HIV. Patients co-infected with HIV and HBV who also need to take HIV medications, need to treat both HBV and HIV. Epivir and Viread both work against HBV and HIV and should be used together as the NRTI backbone to increase activity and avoid HBV resistance. Make sure you are taking Epivir at HIV doses—always ask your doctor or pharmacist. Worsening of hepatitis B (HBV) in people co-infected with HIV/HBV has occurred when Epivir was discontinued. These patients should be closely monitored by their physician. Epivir is also available in three combination products: Combivir (Epivir and Retrovir [zidovudine]), taken one tablet twice a day; Epzicom (Epivir and Ziagen), taken one tablet once daily; and Trizivir (Epivir, Retrovir, and Ziagen), taken one tablet twice a day. See package insert for more complete information on potential side effects and interactions.

Doctor’s COMMENTS In the early ‘90s the approval of 3TC was a big shot in the arm to the tired nucleoside class.

Adding it to other nucleoside analogs after they’d stopped working seemed to revive them for awhile, and if you started 3TC and AZT together, resistance was delayed. We later learned that the 3TC mutation, M184V, could delay the emergence of thymidine analog mutations (TAMs, the mutations you got from taking AZT or d4T). M184V could also partially reverse the resistance caused by TAMs. During the early years of the HAART era, 3TC became a component of virtually every antiretroviral regimen, and even today, most people taking either AZT or abacavir are also taking 3TC using a co-formulation (see Combivir, page 21; Epzicom, page 24; and Trizivir, page 26). 3TC is extremely well tolerated and very safe with long-term use.

Resistance to 3TC occurs quickly if the viral load isn’t completely suppressed, and while there are some resistance advantages to having an M184V mutation, it’s still better not to have it, allowing 3TC to retain its full antiviral activity. —Joel Gallant, MD, MPH ACTIVIST’S COMMENTS The father of Emtriva (FTC), ViiV’s Epivir is a convenient drug that they used in their early fixed dose combos like Combivir (AZT and 3TC), Epzicom (Ziagen and 3TC), and Trizivir (AZT, Ziagen, and 3TC). It has the same potential advantages as FTC in salvage regimens, and the same caveats for those with hepatitis B. —Jeff Taylor

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2011 HIV Drug guide Epzicom brand name:

Epzicom

abacavir sulfate and lamivudine Nucleoside analog reverse transcriptase inhibitor

(nucleoside analog, NRTI, or nuke)—fixed dose combination manufacturer: ViiV Healthcare | www.viivhealthcare.com, (877) 844-8872 common name: class:

Standard dose: One tablet (600 mg Ziagen/abacavir sulfate/ABC and 300 mg Epivir/ lamivudine/3TC), once a day, with or without food, with no dietary restrictions. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.

AWP: $1,073.35 / month

Potential side effects and toxicity The most common side effects of Epzicom are the same as the drugs it contains—see Epivir (page 23) and Ziagen (page 31). Of note is the hypersensitivity reaction (HSR, an allergic-like reaction) warning on Ziagen (abacavir); see Ziagen. A simple and inexpensive blood test for HLA-B*5701 (a genetic marker) can identify people at high risk for this reaction and virtually eliminate HSR. About 90% of HSR occurs within the first six weeks of treatment.

Symptoms of HSR usually worsen, very slowly, with every dose. If treatment is stopped because of this serious reaction, you can never take products containing abacavir, such as Epzicom, Trizivir, or Ziagen, again (called “re-challenging”). Rechallenging could cause a rare life-threatening reaction. (This does not apply to missed doses when there’s no HSR, but watch for symptoms if you’ve stopped the drug for at least a few days). Symptoms usually, but not always, include some combination of sudden fever; muscle ache; malaise (general ill feeling); severe nausea, vomiting, diarrhea, or abdominal pain; severe tiredness; respiratory symptoms (cough, difficulty breathing, and sore throat); and possible rash. Symptoms are listed on the patient information sheet and warning card that you receive each time you fill your prescription. You should keep the warning card with you. Hypersensitivity might be confused with flu during flu season, but remember that HSR worsens with every dose. Check with your doctor if you have any side effects after taking this medicine—don’t just stop! Some observational studies seemed to indicate that Ziagen may increase the risk of cardiovascular events, including heart attacks, in people with greater risk factors (such as smoking, diabetes, high blood pressure, and drug use), and that the risk is reversible upon discontinuation. Studies looking into this possible association had mixed results. The

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available data regarding cardiovascular risk with Ziagen remain inconclusive.

Potential drug interactions See the drugs contained in Epzicom, Epivir and Ziagen, for more information. Do not take Epzicom with Atripla, Combivir, Emtriva, Epivir, Epivir-HBV, rilpivirine/Truvada, Trizivir, Truvada, or Ziagen, since all or part of these medications are already in Epzicom or have equivalent medications.

More information Epzicom is the combination of Epivir (lamivudine) and Ziagen (abacavir sulfate) in one tablet, so see the pages for those drugs.

Currently, U.S. HIV treatment guidelines recommend Truvada over Epzicom as the preferred backbone for the NRTI component of an HIV drug combination. Epzicom is listed as an alternative NRTI backbone. Study ACTG 5202 reported that for those people who started treatment with more than 100,000 viral load, Epzicom was “significantly less effective at controlling HIV” in the regimens tested. Moreover, time to a serious adverse event was sooner in the people taking Epzicom. A smaller but newer study (ASSERT) also found less likelihood of reaching undetectable viral load with Epzicom compared to Truvada (all with Sustiva) in people starting HIV treatment for the first time. These efficacy and safety findings were not confirmed in a manufacturer-sponsored study, HEAT, another large study comparing Epzicom and Truvada. Still, in HIV therapy, there is always use for an alternative choice of drugs. The DHHS guidelines state, “Pending additional data, [Epzicom] should be used with caution in individuals who have plasma HIV RNA [viral load] greater than 100,000 copies/mL, as well as in persons at higher risk for cardiovascular disease. However, Epzicom remains

a good alternative dual-NRTI option for some treatment-naïve patients.” Remember, too, that Truvada has its own side effect and drug interaction issues, although it’s famed for its tolerability. The HLA-B*5701 test should never be used to diagnose HSR. Do not use a skin patch test to confirm HSR. Regardless of the results, it is important to monitor the potential for this reaction. If HSR is suspected or cannot be ruled out, products containing Ziagen should be discontinued. The incidence of HSR was the same between Epzicom once-daily and Ziagen twice-daily (8% vs. 9%), but the incidence of severe reactions was higher with Epzicom (5% vs. 2%). Remember that the HSR cited may have been suspected, not definitely diagnosed. See package insert for more complete information on potential side effects and interactions.

Doctor’s COMMENTS Epzicom is the safe, well-tolerated, oncedaily co-formulation of abacavir and 3TC. It’s generally viewed as the best alternative to Truvada when tenofovir can’t be used (usually for reasons having to do with the kidneys).

The issues of abacavir hypersensitivity (see Ziagen) apply to Epzicom as well, so an HLA B*5701 test should always be ordered before taking this drug. Epzicom appears to be somewhat less effective than Truvada in people with viral loads above 100,000. For reasons discussed elsewhere (see Ziagen, page 31), we also tend to avoid Epzicom in people who are at high risk of having coronary heart disease.

—Joel Gallant, MD, MPH ACTIVIST’S COMMENTS A combination of Ziagen and Epivir, it was a convenient once-a-day improvement over Combivir. Like with Ziagen, those starting Epzicom should take a test to rule out susceptibility to the hypersensitivity reaction. A more recent concern is the possibility of increased risk of heart disease. The jury is still out, but cautious doctors and patients with other cardiovascular risk factors are avoiding the drug until more data is available. —Jeff Taylor

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2011 HIV Drug guide Retrovir brand name:

Retrovir

zidovudine or AZT Nucleoside analog reverse transcriptase inhibitor

(nucleoside analog, NRTI, or nuke) manufacturer: ViiV Healthcare | www.viivhealthcare.com, (877) 844-8872 common name: class:

Standard dose: One 300 mg tablet twice a day (12 hours apart); two 100 mg capsules three times a day (8 hours apart) also available; with or without food, with no dietary restrictions. Clear, strawberry-flavored liquid available for infants four weeks of age and up; dose is weight-based. Take missed dose as soon as possible, unless it is almost time for your next dose.

Do not double up on your next dose. Generic is available.

AWP: $535.12 (generic $365.09) / month for 300 mg tablets, $71.34 (generic $56.42) for 240 ml of 10 mg/ml syrup

Potential side effects and toxicity May include headache, fever, chills, muscle soreness, fatigue, nausea, and fingernail discoloration. Zidovudine (AZT) has been associated with alteration of various cells in the blood through bone marrow suppression, resulting in anemia (low red blood cell counts) and/or neutropenia (low white blood cell counts), particularly during the first three months of therapy in people with advanced HIV. Potential exists for severe anemia requiring blood transfusion, erythropoietin injections, or hospitalization when used on its own or in combination with hydroxyurea.

Zidovudine/AZT is associated with lipoatrophy (fat loss of the arms, legs, face, and/ or buttocks— sometimes called “AZT butt”).

The lipoatrophy could be irreversible or fat could take a long time to rebuild. Rare but potentially serious toxicity with all NRTIs: enlarged fatty liver (hepatomegaly with steatosis) and lactic acidosis (accumulation of lactate in the blood and abnormal acid-base balance). Lactic acidosis may cause persistent fatigue, abdominal pain or distension, nausea/ vomiting, difficulty breathing or shortness of breath, and enlarged liver.

Potential drug interactions Do not take with Combivir or Trizivir, since AZT is already in these medications. Biaxin and rifampin (under various brand names) may decrease AZT blood levels. Benemid (probenecid), Dilantin (phenytoin), and Depakote (valproic acid) may increase blood levels and zidovudine clearance of AZT, but no dosing adjustments are recommended. AZT

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and Zerit should not be used together due to evidence that one limits the other’s effectiveness. Also, bone marrow suppression should be monitored with use of Cytovene (ganciclovir), Valcyte, amphotericin B, pentamidine, dapsone, flucytosine, sulfadiazine, interferonalpha, ribavirin (Rebetol), and with cancer treatments such as hydroxyurea and doxorubicin. Ribavirin may decrease the efficacy of AZT and increase the risk of lactic acidosis.

Avoid this combination if possible. Procrit or Epogen warning: if hemoglobin target is above manufacturer’s recommendation (12 g/ dL), the risk for serious and life-threatening cardiovascular complications significantly increases. For AZT patients, measure hemoglobin once a week after starting the anemia drugs until hemoglobin has stabilized. Notify health care provider if experiencing pain and/ or swelling in the legs, worsening in shortness of breath, increases in blood pressure, dizziness, or loss of consciousness, extreme tiredness, or blood clots in hemodialysis vascular access ports. Methadone can increase AZT levels. Monitor for adverse effects.

More information The not-so-good news for people adding AZT—the fatigue and the potential anemia.

You can start taking erythropoietin (Procrit or Epogen) for some anemias, but that’s adding an expensive weekly injectable. Some doctors would prefer switching out the zidovudine for another drug. Taking with food may minimize upset stomach. Zidovudine crosses the bloodbrain barrier to a useful degree, which may be beneficial for patients at risk for neurological

damage (such as dementia) from HIV. Thanks to extensive data, zidovudine is a preferred drug for pregnant women who are taking therapy for the first time, according to U.S. HIV treatment guidelines. See package insert for more complete information on potential side effects and interactions.

Doctor’s COMMENTS Retrovir (AZT) was the first drug approved for the treatment of HIV, and while its benefits were modest and temporary, it did make a difference for many people. It enjoyed two revivals, first with the approval of Combivir (AZT plus 3TC) and later with the approval of Trizivir (AZT plus 3TC plus abacavir). However, the use of AZT in any form has declined with the approval of safer, more convenient, and more effective alternatives. AZT must be taken twice a day and can cause anemia, nausea, fatigue, and lipoatrophy. In fact, while AZT may not cause lipoatrophy as often or as quickly as Zerit (d4T) does, there’s some evidence that lipoatrophy caused by AZT may be less reversible. Because of its long history of safety in pregnancy, AZT remains a preferred nucleoside for pregnant women, though there is growing comfort with the use of other agents.

—Joel Gallant, MD, MPH ACTIVIST’S COMMENTS The drug that started it all, AZT was despised and feared even as it became the first drug to save lives. The anemia that killed some patients on the early high doses, and the fatigue, dizziness, and lipoatrophy (remember AZT butt?) have largely made this drug a relic of history. That said, it remains a very effective antiviral that some patients continue to tolerate well and it has excellent brain penetration that makes it useful for those with neurocognitive problems. Its long history of safety in pregnancy also makes it an option for women who are pregnant or hoping to conceive.

—Jeff Taylor

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2011 HIV Drug guide Trizivir brand name:

Trizivir

abacavir sulfate, zidovudine, and lamivudine Nucleoside analog reverse transcriptase inhibitor

(nucleoside analog, NRTI, or nuke)—fixed dose combination manufacturer: ViiV Healthcare | www.viivhealthcare.com, (877) 844-8872 common name: class:

Standard dose: One tablet (300 mg Ziagen/abacavir/ABC, 150 mg Epivir/lamivudine/3TC, and 300 mg Retrovir/zidovudine/AZT), twice a day, with or without food, with no dietary restrictions. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.

AWP: $1,608.36 / month

Potential side effects and toxicity The most common side effects of Trizivir are the same as those of the drugs it contains— see Epivir (page 23), Retrovir (page 25), and Ziagen (page 31). Of note is the hypersensitivity reaction (HSR, an allergic-like reaction) warning on abacavir; see Ziagen. A simple and inexpensive blood test for HLA-B*5701 (a genetic marker) can identify people at high risk for this reaction and virtually eliminate HSR. The HLA-B*5701 test should never be used to diagnose HSR. Do not use a skin patch test to confirm HSR. Regardless of the results, it is important to monitor the potential for this reaction. If HSR is suspected or cannot be ruled out, products containing abacavir should be discontinued. If treatment is stopped because of this serious reaction, you can never take products containing abacavir, such as Epzicom, Trizivir, or Ziagen, again (called “re-challenging”). Rechallenging can cause a rare life-threatening reaction. (This does not apply to missed doses when there’s no HSR, but watch for symptoms if you’ve stopped the drug for at least a few days). Symptoms worsen, very slowly, with every dose. Symptoms usually, but not always, include some combination of sudden fever; muscle ache; severe nausea, vomiting, diarrhea, or abdominal pain; severe tiredness; respiratory symptoms (cough, difficulty breathing, and sore throat); and possibly rash. Symptoms are listed on the patient information sheet and warning card that you receive each time you fill your prescription. You should keep the warning card with you. Hypersensitivity might be confused with flu during flu season, but remember that HSR worsens with every dose. Check with your doctor if you have any side effects after taking this medicine—don’t just stop!

See Ziagen (page 31) and More Information below. Some observational studies seemed to indicate that abacavir may increase the risk of cardiovascular events, including heart attacks,

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in people with greater risk factors (such as smoking, diabetes, high blood pressure, and drug use); the risk is reversible upon discontinuation. Studies examining this possible association are inconclusive. One explanation for the unexpected link was that people with kidney problems were put on Ziagen to avoid medications containing Viread, which have potential for kidney toxicity. These individuals already have a strong risk for cardiovascular disease. Other side effects associated with Trizivir may include headache, nausea, upset stomach, and fatigue. May be taken with food to decrease potential nausea associated with AZT. The AZT in Trizivir has been associated with alteration of various cells in the blood through bone marrow suppression, resulting in anemia (low red blood cell counts) and/or neutropenia (low white blood cell counts), particularly during the first three months of therapy in people with advanced HIV. Zidovudine is also associated with lipoatrophy (fat loss in the arms, legs, face, and/or buttocks—sometimes called “AZT butt”). The lipoatrophy could be irreversible or fat could take a long time to rebuild.

Potential drug interactions See the drugs contained in Trizivir—AZT (page 25), Epivir (page 24), and Ziagen (page 31), for details. Do not take Trizivir with Atripla, Emtriva, Epivir, Epivir-HBV, Epzicom, Retrovir (AZT), rilpivirine/Truvada, Truvada, or Ziagen; all or part of these medications are already in Trizivir or have equivalent medications. If you’re taking any of the following medications, consult your doctor or pharmacist before starting Trizivir: Zerit (stavudine), ribavirin, interferon, rifampin, probenecid, methadone, Cytovene (ganciclovir), Valcyte (valganciclovir), Biaxin (clarithromycin), Daraprim (pyrimethamine), flucytosine, Fungizone (amphotericin B), doxorubicin, and hydroxyurea.

More information See the drugs contained in Trizivir—Epivir, Retrovir (zidovudine, AZT), and Ziagen.

Trizivir is the only triple combination NRTI that has been studied in a randomized, controlled study, which has shown it to be inferior to the standard treatment of two NRTIs plus Sustiva.

U.S. treatment guidelines recommend that Trizivir should only be used if other options are not available due to toxicities or drug interactions associated with other HIV regimens. See package insert for more complete information on potential side effects and interactions.

Doctor’s COMMENTS In the early years of the HAART era, when people were suffering on effective but complex and toxic regimens like Combivir plus Crixivan, Trizivir appeared like a breath of fresh air. Just one pill twice a day, with no need to watch the clock or time your meals, and no kidney stones, diabetes, dry skin, cracked lips, or ingrown toenails to worry about. Sure, some people developed abacavir hypersensitivity reactions (see Ziagen, page 31), and many had the usual AZT side effects (see Retrovir, page 25). But compared to what we had before, it seemed almost too good to be true. Well, it was. This “triple-nuke” regimen was shown to be less effective than a regimen containing Sustiva, both at high and low viral loads, and its use declined rapidly after that. Today, if you had some reason to be taking AZT, 3TC, and abacavir, it would make sense to take them in the form of Trizivir. But taking Trizivir alone is no longer recommended.

—Joel Gallant, MD, MPH ACTIVIST’S COMMENTS A mash-up of all of GSK’s (now ViiV’s) nukes: AZT, 3TC and Ziagen, Trizivir’s promise as a convenient single pill regimen was sadly unfulfilled. Subsequent studies showed Trizivir to be inferior to the two class/three drug combos that are now standard of care. It also combined the anemia, fatigue, and possible fat loss from AZT, with the danger of a hypersensitivity reaction and possible cardiovascular risk from Ziagen. But it did pave the way for combos like Atripla that have revolutionized HIV treatment. —Jeff Taylor

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2011 HIV Drug guide Truvada brand name:

Truvada

emtricitabine and tenofovir DF Nucleoside/nucleotide analog reverse transcriptase inhibitor

(nucleoside/nucleotide analog, NRTI, or nuke)—fixed dose combination manufacturer: Gilead Sciences, Inc. | www.gilead.com, (800) GILEAD5 (445–3235) common name: class:

Standard dose: One tablet (300 mg Viread and 200 mg Emtriva) once a day, with or without food, with no dietary restrictions. Dosing frequency needs to be adjusted for people with decreased kidney function. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.

AWP: $1,195.15 / month

Potential side effects and toxicity See the drugs contained in Truvada—Viread (page 29) and Emtriva (page 22). Overall, fairly well tolerated, however, individuals may experience nausea, fatigue, headache, dizziness, diarrhea, depression, insomnia, abnormal dreams, rash, vomiting, abdominal distension/pain, and gas. Skin discoloration may also occur. The Viread in Truvada is associated with decreases in bone mineral density (BMD). BMD monitoring should be considered in people who have a history of pathologic bone fracture or are at risk for osteopenia or osteoporosis.

Potential drug interactions See the drugs contained in Truvada—Viread (page 29) and Emtriva (page 22). Do not take with Atripla, Combivir, Emtriva, Epivir, EpivirHBV, Epzicom, rilpivirine/Truvada, Trizivir, Truvada, or Viread, since all or part of these medications are already in Truvada or have equivalent medications. The levels of Videx EC and Videx (didanosine, ddI) are increased by 44–60% when taken at the same time as Viread, which is in Truvada. Therefore, a dose reduction to 250 mg for Videx EC is recommended for people who weigh more than 132 pounds and 200 mg for those who weigh less than this. Higher Videx (ddI) concentrations could increase the risk of ddI-associated adverse events, including neuropathy. See More Information. Viread decreases the concentration levels of Reyataz. In addition, Reyataz and Kaletra increase Viread concentrations. The reason for these interactions is unknown. The FDA suggests that patients taking Reyataz and Truvada should be monitored for Truvada-associated adverse events.

When taken with Truvada, it is recommended that Reyataz 300 mg is taken with Norvir

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100 mg (all as a single daily dose with food).

Reyataz without Norvir should not be taken with Truvada.

More information Truvada is two medicines in one pill, so see the pages for those medications, Emtriva (page 22) and Viread (page 29). Currently, U.S. DHHS HIV treatment guidelines recommend Truvada over Epzicom as the only preferred medication for the NRTI component of an HIV regimen. Study ACTG 5202 reported that while both medications reduced viral load, for those people who started treatment with a viral load of more than 100,000, Epzicom was “significantly less effective at controlling HIV” in the regimens tested. Moreover, time to a serious adverse event was sooner in the people taking Epzicom. Remember, however, that Truvada has its own side effect and drug interaction issues, although it’s famed for its tolerability. Kidney function must be monitored before and during treatment with Truvada and it may not be a good option for patients with underlying kidney problems. After years of being used off-label (not an FDA approved use) for HIV prevention, one of the biggest HIV news reports last year was from the international iPrEx study, showing Truvada reduced rates of HIV infection in men who have sex with men (MSM) and transgender women born men who have sex with men, with a success rate between 44 and 73% (depending on adherence). Research continues in the quest for answers to several important questions, such as the development of drug resistance. Truvada combines with Sustiva to form Atripla, a very popular HIV regimen.

There’s another triple regimen in one pill in the works. Gilead entered into an agreement to combine Truvada with the experimental

rilpivirine from Tibotec Therapeutics, maker of Prezista and Intelence (see rilpivirine/Truvada, page 38). Truvada is also in advanced Phase 3 study in a quadruple formula with two of Gilead’s experimental drugs: elvitegravir, an integrase inhibitor (same class as Isentress) and the drug booster cobicistat (GS-9350).

Although the effect of supplementation with calcium and vitamin D has not been studied, such supplementation may be beneficial for all patients, according to the FDA. See package insert for more information on potential side effects and interactions.

Doctor’s COMMENTS Truvada is now the preferred nucleoside backbone for initial regimens according to DHHS and IAS-USA guidelines, based on studies showing that it’s more effective and safer than Combivir, and more effective at high viral loads than Epzicom. When combined with Sustiva, it can be used in the form of Atripla, currently the only approved single-pill regimen, but other co-formulated pills containing tenofovir and FTC are being developed.

People taking Truvada need to be monitored for kidney toxicity (see Viread, page 29), and those who already have kidney disease may need to take Truvada less frequently than once a day, or better yet, avoid it altogether.

The bone issues seen with tenofovir (see Viread, page 29) also apply to Truvada.

—Joel Gallant, MD, MPH ACTIVIST’S COMMENTS This combination of Gilead’s Viread and Emtriva is the most widely used combination today—thanks to its proven efficacy and durability, and relatively few side effects. It doesn’t hurt that combining two drugs extends the patent life in addition to providing dosing convenience. Its only downside is that there are no comparable alternatives for those who need to avoid the possibility of kidney toxicity and possible bone loss from the Viread component. —Jeff Taylor

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2011 HIV Drug guide Videx and Videx EC brand name:

Videx and Videx EC

didanosine or ddI Nucleoside analog reverse transcriptase inhibitor

(nucleoside analog, NRTI, or nuke) manufacturer: Bristol-Myers Squibb | www.bms.com, (800) 321-1335 common name: class:

Standard dose: One 400 mg enteric-coated (Videx EC), delayed-release capsule once a day, with adjustments for weight, kidney impairment, and when combined with Viread, Truvada, or Atripla. (Also available in 125 mg, 200 mg, and 250 mg capsules.) Videx is also available as a buffered powder for oral solution. Take Videx and Videx EC strictly on an empty stomach (unless taking with Viread), one hour before or two hours after food or drink, except water.

Approved for children weighing at least 44 pounds. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose. Generic Videx EC is available.

AWP: $442.42 / month for Videx 400 mg capsules (generic Virex EC $368.72 / month)

Potential side effects and toxicity Peripheral neuropathy (tingling, burning, numbness or pain in the hands or feet) may go away once Videx is stopped, but can be painful and permanently debilitating if not treated in time. It occurs more frequently when Videx is used with Zerit. Upset stomach, diarrhea, headache, and, more rarely, pancreatitis (inflammation of the pancreas) have also been reported. Pancreatitis can be life-threatening and may cause pain in the stomach and back, along with nausea, vomiting, and blood in the urine. Risks for pancreatitis include higher than recommended doses of NRTIs, advanced HIV, and alcohol use. Stop all HIV medications and see a health care provider right away. Recent post-marketing surveillance has reported cases of non-cirrhotic portal hypertension (increased blood pressure in the vessels that connect to and from the liver) associated with the use of Videx EC. Symptoms (elevated liver enzymes, enlarged spleen, blood in vomit, and fluid collection in abdomen) may begin months to years after starting Videx EC. Routine doctor visits and lab tests will assist in early detection and prompt discontinuation of Videx EC. Other possible toxicities include eye changes and optic neuritis. Have periodic eye exams by someone who is aware you are HIV-positive. Increased uric acid levels (indicating a number of disorders, including kidney damage and metabolic diseases), and insomnia are other potential side effects. Rare but potentially serious toxicity with all NRTIs: enlarged fatty liver (hepatomegaly with steatosis) and lactic acidosis (accumulation of lactate in the blood and abnormal acid-base balance). Lactic acidosis may cause persistent fatigue, abdominal pain or distension, nausea/ vomiting, difficulty breathing or shortness of

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breath, and enlarged liver. People with a history of peripheral neuropathy, pancreatitis, or heavy alcohol use should avoid Videx. Body fat redistribution/accumulation has also been reported with Videx.

Potential drug interactions Should not be taken with Viread, if possible.

However, if co-administration is necessary, use Viread with caution and close monitoring, since Videx levels are increased with Viread (a drug also found in Truvada and Atripla). Dose adjust Videx or Videx EC when taking Viread, Truvada, or Atripla to avoid Videx-related toxicity, including neuropathy. The combined use of Videx and Retrovir (zidovudine, AZT), Zerit (stavudine, d4T), or hydroxyurea may increase risk of peripheral neuropathy. Either Videx or Videx EC taken with Zerit increases the risk of facial wasting and/or lactic acidosis.

Combining Videx with Zerit, hydroxyurea, alcohol, ganciclovir, valganciclovir, or intravenous (not inhaled) pentamidine may increase risk of pancreatitis. Do not take with ribavirin or allopurinol. Also, ganciclovir substantially increases Videx levels, and is generally recommended not to be taken together. If there is no alternative to ganciclovir, use it with caution and monitor for Videx toxicity. Videx oral solution should be taken on an empty stomach one hour before or two hours after protease inhibitors, Tagamet (cimetidine), ketoconazole, itraconazole, and dapsone, and one hour apart from Rescriptor, while Videx EC can be taken with them, but still on an empty stomach. With Viread, it may be taken with a light snack (low-fat, 373 calories).

Methadone decreases Videx powder concentrations significantly and should not be used together, but if necessary, the Videx EC formulation should be used.

More information Study indicates Videx EC compared to Zerit may have lower risk of peripheral neuropathy, but the rate found in clinical trials is still 12-34%. Swallow the capsules whole. The capsules eliminate the bad taste and texture of the tablets and the enteric coating reduces diarrhea. If you have reduced kidney function, you may require a lower dose. Notify your doctor right away if peripheral neuropathy is suspected. See package insert for more complete information on potential side effects and interactions.

Doctor’s COMMENTS Videx (ddI), approved in 1991, was our second antiretroviral drug. People often used it after AZT stopped working. Later, it was added to AZT in our primitive attempts at early combination therapy. It was a complicated drug to take, requiring twice-daily dosing on an empty stomach, and sometimes involving the use of powder formulations or the mixing of crushed tablets with antacids to improve tolerability. The new EC (enteric coated) formulation eliminates those problems, but this is no longer a drug with much of a purpose.

Its resistance patterns overlap with the better tolerated tenofovir and abacavir, and it causes neuropathy, pancreatitis, and probably lipoatrophy. More recently, questions have been raised about whether ddI might cause noncirrhotic portal hypertension, an uncommon but serious and potentially fatal liver condition that doesn’t get better after you stop taking the drug. —Joel Gallant, MD, MPH ACTIVIST’S COMMENTS Originally hailed as an improvement over AZT, when used alone, Videx proved just as ineffective. Even in combination with other drugs, the problematic dosing on an empty stomach, the crippling neuropathy, pancreatitis, and lactic acidosis combined to make this drug an alsoran. The fact that it’s rarely used anymore can work in its favor—making it a useful add-on drug to salvage regimens for patients who’ve exhausted all other options. —Jeff Taylor

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2011 HIV Drug guide Viread brand name:

Viread

tenofovir disoproxil fumarate (DF) Nucleotide analog reverse transcriptase inhibitor

(nucleotide analog, NtRTI, or nuke) manufacturer: Gilead Sciences, Inc. | www.viread.com, (800) GILEAD5 (445–3235) common name: class:

Standard dose: One 300 mg tablet once a day, with or without food, with no dietary restrictions. Dosing frequency needs to be adjusted for people with decreased kidney function.

Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.

AWP: $832.49 / month

Potential side effects and toxicity Overall, fairly well tolerated; however, diarrhea, nausea, vomiting, and gas are the most common side effects of Viread. Decreases in bone mineral density (BMD) have been observed with the use of Viread in HIV-positive people. BMD monitoring should be considered in people who have a history of pathologic bone fracture or are at risk for osteopenia or osteoporosis. Creatinine clearance (CrCl) should be assessed before initiating treatment with Viread. CrCl and serum phosphorus should be monitored in patients at risk. Less common side effects of Viread, occurring with undetermined incidence, include kidney toxicities and low blood phosphate. Rare but potentially serious toxicity with all NRTIs: enlarged, fatty liver (hepatomegaly with steatosis) and lactic acidosis (accumulation of lactate in the blood and abnormal acid-base balance). Lactic acidosis may cause persistent fatigue, abdominal pain or distension, nausea/ vomiting, difficulty breathing or shortness of breath, and enlarged liver. The effect of Viread on children and individuals with severe liver impairment was not studied during drug development. However, since Viread is not metabolized by the liver (and appears to have less toxicity in the liver than the majority of the NRTIs), it is believed the impact on individuals with liver disease should be minimal.

Potential drug interactions Do not take with Truvada or Atripla, since Viread is in these medications. Videx levels are increased with Viread; therefore, use with caution and monitor closely when taking Viread, Truvada, or Atripla with Videx or Videx EC to avoid Videx-related toxicity, including neuropathy. See More Information. Viread decreases the concentration levels of Reyataz. In addition, both Reyataz and Kaletra increase Viread concentrations. Higher Viread concentrations could increase the risk of Viread-associated adverse events, including kidney disorders.

Patients taking Reyataz and Viread should

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be monitored for Viread-associated adverse events. When taken with Viread, it is recommended that Reyataz 300 mg is given with Norvir 100 mg (all as a single daily dose with food). Unboosted Reyataz (without Norvir) should not be taken with Viread. No dosage adjustment is needed when used with Kaletra.

You should not take Viread with Hepsera, a hepatitis B treatment.

More information Viread combined with Emtriva (also available as Truvada) is considered the preferred NRTI combination by U.S. HIV treatment guidelines.

Viread is also combined with Emtriva and Sustiva (NNRTI) to make up Atripla, the first single-tablet HIV regimen. The body clears most of Viread through the kidneys and dosing adjustment is recommended for those with impaired kidney function. Serious kidney problems have been rare and most have been in those with pre-existing kidney disease or taking kidney-toxic drugs. However, the characteristics of kidney toxicity are still being defined. The manufacturer recommends that individuals with impaired kidney function be monitored closely, especially people with advanced HIV disease, even in those who did not start out with kidney disease. There have been reports of individuals who experienced severe kidney disorder, including some taking Kaletra with Viread. Since Kaletra increases blood levels of Viread, it may increase the likelihood of Viread side effects. Like Epivir and Emtriva, Viread has activity against hepatitis B, which may flare up when Viread is discontinued. Patients co-infected with HIV/HBV should use Epivir or Emtriva with Viread as their NRTI backbone to increase activity and avoid HBV resistance. These patients should be closely monitored by their physician. Viread may have prolonged activity against hepatitis B even when resistant to Epivir. Viread was approved last year for use in adolescents ages 12 to 18 who weigh more than 77 pounds, making it easier for Viread

and Truvada to be used in HIV prevention studies with this population. The FDA noted, “Although the effect of supplementation with calcium and vitamin D was not studied, such supplementation may be beneficial for all patients [taking Viread].” See package insert for more complete information on potential side effects and interactions.

Doctor’s COMMENTS Because of its safety and effectiveness, the combination of tenofovir and FTC, in the form of Truvada, or, when combined with efavirenz as Atripla, has become the preferred nucleoside combination in both the DHHS and IAS-USA guidelines. In most cases, an initial antiretroviral regimen should include tenofovir unless there’s a good reason to use something else. Tenofovir’s main flaw is kidney toxicity: it can reduce kidney function, and can also cause wasting of phosphate in the urine, leading to bone problems. However, these are toxicities that can be detected using simple and standard lab tests, and they’re uncommon, especially in people taking tenofovir with efavirenz as part of an initial regimen. Kidney toxicity may be somewhat more common when tenofovir is combined with protease inhibitors, but these are still widely used, recommended regimens. The other concern is bone: It’s now clear that there’s a mild and transient loss of bone density whenever you start anti retroviral therapy, but the loss of bone may be somewhat more pronounced in people taking tenofovir. —Joel Gallant, MD, MPH ACTIVIST’S COMMENTS Its convenient once-daily dosing and relatively few side effects have made Viread the preferred backbone of most regimens.

Since this is a drug that people can be on for decades, both patients and their doctors should be vigilant about possible loss of bone mineral density (osteopenia/osteoporosis) and kidney problems and other meds that can worsen those problems. And like Epivir and Emtriva, Viread has activity against hepatitis B, so those with hep B should check with their doctors when constructing a regimen with this drug to avoid the possibility of developing resistance to HBV drugs. —Jeff Taylor

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2011 HIV Drug guide Zerit brand name:

Zerit

stavudine or d4T Nucleoside analog reverse transcriptase inhibitor

(nucleoside analog, NRTI, or nuke) manufacturer: Bristol-Myers Squibb | www.bms.com, (800) 321-1335 common name: class:

Standard dose: One 40 mg capsule twice a day for people weighing 132 pounds or more, or one 30 mg capsule twice a day for people weighing less; with or without food, with no dietary restrictions. Zerit is also available in 15 mg, 20 mg, 30 mg and 40 mg capsules and a powder for oral solution; check for food restrictions. Dose reduction needed in people with kidney problems. Generic available. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.

AWP: $474.41 (generic $411.16) / month for 40 mg capsules

Potential side effects and toxicity Peripheral neuropathy (tingling, burning, numbness or pain in the hands or feet) may go away once Zerit is stopped, but can be painful and permanently debilitating if not treated in time. Caregivers of young children should be instructed regarding noticing and reporting peripheral neuropathy. Additive lipoatrophy (facial wasting) and mitochondrial toxicities can occur when combined with Videx. Adverse reactions and serious laboratory abnormalities in children were similar in type and frequency to those seen in adults.

Other side effects may include headache, chills/fever, malaise (general ill feeling), insomnia, anxiety, depression, rash, upset stomach (nausea and vomiting), diarrhea, and abdominal pain. Rare but potentially serious toxicity with all NRTIs: enlarged, fatty liver (hepatomegaly with steatosis) and lactic acidosis (accumulation of lactate in the blood and abnormal acid-base balance). Lactic acidosis may cause persistent fatigue, abdominal pain or distension, nausea/vomiting, difficulty breathing or shortness of breath, and enlarged liver. Pancreatitis (inflammation of the pancreas) can be life-threatening and may cause pain in the stomach and back, along with nausea, vomiting, and blood in the urine.

Risks for pancreatitis include higher than recommended doses of NRTIs, advanced HIV, and alcohol use. Stop all HIV medications and see a health care provider right away. Your

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physician will check for pancreatitis by doing blood tests. People with a history of peripheral neuropathy, pancreatitis, or heavy alcohol use should avoid Zerit. Lipoatrophy, fat loss in the face and limbs (arms and legs) and, to a lesser degree, lipohypertrophy (such as “buffalo hump” and increased abdominal fat) has been associated with Zerit. Zerit and Retrovir (zidovudine, AZT) are the HIV drugs most implicated by studies as causing lipoatrophy.

Zerit also seems to be implicated in blood lipid (fat) increases, particularly triglycerides.

Potential drug interactions When used in combination with Zerit, drugs such as Fungizone (amphotericin B), Foscavir (foscarnet), dapsone, and Videx/Videx EC may increase the risk of developing peripheral neuropathy. Cytovene (ganciclovir), valganciclovir (Valcyte), intravenous Pentam (pentamidine), and Videx (ddI) may increase the risk of pancreatitis. Should be used with caution by people with pre-existing bone marrow suppression, kidney problems, or peripheral neuropathy. Retrovir (zidovudine, AZT) and Zerit should not be used together due to evidence that one limits the other’s effectiveness. Because of additive neurotoxicity, if possible, Zerit should not be combined with Videx.

toxicity and the availability of newer medications. Contact your health care provider right away if peripheral neuropathy is suspected, but do not stop taking medication unless directed to do so by your health care provider. Studies show that Zerit crosses the blood-brain barrier to a useful degree, which may be beneficial for patients at risk for neurological damage (such as dementia) from HIV. Zerit is associated with facial wasting, peripheral neuropathy, and pancreatitis, and many leading HIV advocates are adamant that it should be avoided because of these serious, and relatively common, toxicities. See package insert for more complete information on potential side effects and interactions.

Doctor’s COMMENTS There aren’t any good reasons to use this toxic drug anymore. Even resource-limited countries, where it has been used widely because of its low cost, are trying to move away from d4T. It can cause neuropathy, lipoatrophy, lactic acidosis, and hepatic steatosis (fatty infiltration of the liver). The originally approved dose (40 mg twice a day) was clearly too high, but while d4T might be safer at lower doses, why bother? —Joel Gallant, MD, MPH ACTIVIST’S COMMENTS Once considered an improvement over AZT, painful neuropathy and lipoatrophy (fat loss in the face, limbs, and buttocks) has made this drug a thing of the past in the developed world. Because it’s no longer profitable here, its low cost makes it a backbone of many regimens in the rest of the world—condemning HIVers to suffer the pain and disfigurement all over again when better, but more expensive, alternatives are available. —Jeff Taylor

More information Zerit is rarely used in the U.S., due to its

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2011 HIV Drug guide Ziagen brand name:

Ziagen

abacavir sulfate Nucleoside analog reverse transcriptase inhibitor

(nucleoside analog, NRTI, or nuke) manufacturer: ViiV Healthcare | www.viivhealthcare.com, (877) 844-8872 common name: class:

Standard dose: Two 300 mg tablets once a day (or one 300 mg tablet twice a day), with or without food, with no dietary restrictions; scored tablets available for children. A strawberry/ banana flavored liquid is available (20 mg/ml). Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose. Dose does not need to be adjusted for people with kidney impairment.

AWP: $615.38 / month, $161.78 for 240 ml solution (20 mg/ml)

Potential side effects and toxicity Approximately 5-8% of people who took abacavir experienced hypersensitivity reaction (HSR, an allergic-like reaction). A simple and inexpensive blood test for HLA-B*5701 (a genetic marker) can now identify patients at high risk for this reaction and virtually eliminate HSR. If treatment is stopped because of this serious reaction, you can never take Ziagen or any other product containing abacavir, such as Epzicom or Trizivir again (called “re-challenging”). Rechallenging can cause a rare life-threatening reaction. (This does not apply to missed doses when there’s no HSR, but watch for symptoms if you’ve stopped the drug for at least a few days). About 90% of HSR occurs within the first six weeks of treatment. Symptoms of HSR usually worsen, very slowly, with every dose. People who think they are experiencing HSR must be evaluated by an experienced HIV provider right away before they stop taking abacavir. Symptoms resolve quickly (24–48 hours) after permanent discontinuation. Symptoms usually, but not always, include some combination of sudden fever; muscle ache; malaise (general ill feeling); severe nausea, vomiting, diarrhea, or abdominal pain; severe tiredness; respiratory symptoms (cough, difficulty breathing, and sore throat); and possible rash. Symptoms are listed on the patient information sheet and warning card that you receive each time you fill your prescription. You should keep the warning card with you. HSR might be confused with flu during flu season, but remember that HSR worsens with every dose. Check with your doctor if you have any side effects after taking this medicine—don’t just stop!

See More Information. More common side effects may include nausea, vomiting, diarrhea, fatigue, headache, fever, rash, trouble sleeping, unusual dreams, and anorexia (loss

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of appetite). Some observational studies seemed to indicate that abacavir may increase the risk of cardiovascular events, including heart attacks, in people with greater risk factors (such as smoking, diabetes, high blood pressure, and drug use), and that the risk is reversible upon discontinuation. Studies looking into this possible association had mixed results. One explanation for the unexpected link was a finding that people with kidney problems were put on Ziagen in order to avoid medications containing Viread, which have the potential for kidney toxicity. These individuals already have a strong risk for cardiovascular disease. The available data regarding cardiovascular risk with abacavir remain inconclusive. Rare but potentially serious toxicity with all NRTIs: enlarged, fatty liver (hepatomegaly with steatosis) and lactic acidosis (accumulation of lactate in the blood and abnormal acid-base balance). Lactic acidosis may cause persistent fatigue, abdominal pain or distension, nausea/vomiting, difficulty breathing or shortness of breath, and enlarged liver.

Potential drug interactions Do not take with Epzicom or Trizivir, since Ziagen is already in these medications.

Excessive alcohol increases Ziagen levels and may increase side effects.

More information The manufacturer recommends that people with symptoms of acute respiratory disease consider HSR even if another diagnosis such as pneumonia, bronchitis, or flu is possible.

Do not use a skin patch test to confirm HSR. Dose adjustment is needed in people with mild liver disease. Avoid Ziagen in people with moderate/severe liver disease. See package insert for more complete information on potential side effects and interactions.

Doctor’s COMMENTS Ziagen is a well tolerated drug that is typically combined with 3TC (see Epzicom, page 24), or less commonly with 3TC and AZT (see Trizivir, page 26). While it has few side effects, it can cause a potentially dangerous hypersensitivity reaction (abacavir HSR) in some people.

Fortunately, we now have a blood test, HLA B*5701, that accurately predicts who will develop this reaction and who won’t. The test should always be ordered before starting abacavir, and people with a positive test should never take abacavir in any of its forms (Ziagen, Epzicom, or Trizivir). There is controversial evidence linking abacavir with an increased risk of heart attack. This evidence comes from several large observational studies, but the association hasn’t been seen in several other large studies, and no one knows what the mechanism of the association would be. Experts disagree on whether abacavir increases cardiac risk or not, but most agree that until we know for sure, it’s best to avoid the drug in people with coronary heart disease or multiple risk factors for heart disease.

The comparison of Ziagen and Viread for initial therapy is discussed under Epzicom and Truvada. —Joel Gallant, MD, MPH ACTIVIST’S COMMENTS Once a popular once-daily drug, Ziagen has had a couple of setbacks. A potentially fatal hypersensitivity reaction (usually starting as a severe rash) can now be avoided by a genetic test to rule out people predisposed to it. The second was the finding of several large trials that those on Ziagen had an increased risk of cardiovascular events. Further studies yielded conflicting results, so it’s still unclear whether, or to what degree, Ziagen might cause cardiovascular disease. Consequently, cautious doctors and patients with other risk factors for heart disease (those who smoke, have high blood pressure or a family history of heart disease, etc.) have been avoiding it until further research can answer the question.

—Jeff Taylor

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2011 HIV Drug guide Intelence brand name:

Intelence

etravirine Non-nucleoside reverse transcriptase inhibitor

(non-nucleoside, NNRTI, or non-nuke) manufacturer: Tibotec Therapeutics | (877) REACH-TT (732-2488), www.intelence-info.com common name: class:

Standard dose: One 200 mg tablet, or two 100 mg tablets, twice daily, with food. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.

AWP: $919.78 / month

Potential side effects and toxicity Intelence is generally tolerable. The most common side effects include nausea, rash, and peripheral neuropathy. Drug label warns of hypersensitivity (allergic-like) reactions, which sometimes occur with hepatic (liver) failure, and fatality due to Stevens-Johnson Syndrome, erythema multiforme, and toxic epidermal necrolysis (TEN), all skin disorders.

These are very rare side effects. The FDA advised, “Discontinue Intelence immediately if signs or symptoms of severe skin reactions or hypersensitivity reactions develop (including, but not limited to, severe rash or rash accompanied by fever, malaise [general ill feeling], fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema [swelling], hepatitis, and eosinophilia [increased levels of the white blood cell eosinophil, a sign of an allergic reaction]).” In addition, levels of liver enzymes called transaminases should be monitored. Rash is associated with all of the current non-nukes.

Potential drug interactions Do not take Intelence with Plavix, Biaxin (clarithromycin), Dilantin (phenytoin), phenobarbital, rifampin, St. John’s wort, or Tegretol (carbamazepine). Intelence should not be used with unboosted (without Norvir) PIs (Intelence may cause a significant alteration in the levels of the PI), or with Sustiva, Viramune, Rescriptor, or full-dose (600 mg twice daily) Norvir (Intelence levels are lowered with each of these). Should also not be taken with Aptivus/Norvir (Intelence level is lowered 76% with Aptivus), Reyataz/Norvir, or Lexiva/Norvir. Intelence has been studied and can be used without dose adjustment with the boosted protease inhibitors Prezista/Norvir and Invirase/Norvir. Since Kaletra increases Intelence blood levels, use together with caution. Intelence may be taken without dose adjustment with Isentress and the experimental integrase inhibitor elvitegravir (when it becomes available), but Selzentry does require dose adjustment to 600 mg twice a day with Intelence when used without a boosted PI, or 150 mg twice a day if taken with both Intelence and Prezista 600 mg twice a day. In people who’ve failed therapy with other NNRTIs, Intelence should not be taken

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only with NRTIs (including Viread). Use with caution when combined with antifungals (fluconazole and voriconazole). Monitor the effectiveness of Coumadin (warfarin) and adjust dose if needed. Do not take Intelence with Mycobutin if you’re on a Norvir-boosted PI. If you’re not, Mycobutin dose should be 300 mg once daily. No interaction was found between Intelence and the acid suppressants ranitidine (Zantac and others) or Prilosec (omeprazole).

Intelence can be safely combined with methadone. Intelence can also be safely combined with Viagra, Cialis, and Levitra, though a higher dose of these drugs may be needed to achieve the same clinical effect.

More information Intelence is a very important addition to the NNRTI class. The older NNRTIs can develop resistance quickly, and with only one mutation in the virus. In fact, an estimated 7% of newly infected individuals in the U.S. are infected with an NNRTI-resistant virus. The secondgeneration NNRTI Intelence was developed to have a higher genetic barrier to drug resistance. It is not approved for people taking HIV therapy for the first time, although that use is being explored. It has shown significant viral load reduction in people with drug resistance to Sustiva or Viramune, although it may work better in Sustiva failures (where the HIV mutation K103N is more likely present, and which does not affect Intelence activity). Intelence showed evidence of tremendous potency, a nearly 2 log drop in viral load (99% reduction in circulating virus) in a 7-day monotherapy study with people taking HIV meds for the first time. Benefits in this group, however, have not been established. Tibotec has also developed another NNRTI, rilpivirine (TMC 278), for treatment-naïve people (first time on HIV therapy), which may have pharmacologic advantages over Intelence (see rilpivirine, page 34). The company reached an agreement with Gilead, maker of Emtriva and Viread, to combine rilpivirine with those two drugs into a regimen in one pill. See rilpivirine/Truvada, page 38. Some physicians are prescribing Intelence once daily to increase adherence. Some patients complain of hardto-swallow large chalky pills. Those unable to swallow the tablets can stir them in a glass

of water until there’s a milky appearance and drink the solution. Rinse the glass with water a few more times and swallow the rinse each time to make sure you get the full dose. The new 200 mg tablets that became available early this year are dissolvable, and decrease pill burden. See package insert for more complete information on potential side effects and interactions.

Doctor’s COMMENTS Intelence is the newest of the NNRTIs, and it is a true “second-generation” agent, in that it often works after Viramune or Sustiva have failed. There are some exceptions: People who continued to take NNRTIs (especially Viramune) long after their virus had developed NNRTI resistance may have cross-resistance to Intelence. But Intelence will be active for the majority, and fortunately, it’s a safe and well tolerated drug, which has recently been made simpler by the approval of a 200 mg tablet, which is taken twice a day. Intelence tablets can be a little chalky, and people who aren’t good at quickly swallowing pills sometimes complain that the tablets start to dissolve before they’ve been swallowed. One way of dealing with this is to dissolve the tablets in water, and then drink the water with your other pills. Once-daily dosing is probably possible because of the long half-life of the drug, but it hasn’t been studied or approved for once-daily dosing. It also hasn’t been studied or approved for initial therapy, though it could be an option for some people who were infected with NNRTI-resistant virus. Intelence is usually combined with a boosted protease inhibitor, but can’t be given with all of them because of drug interactions. It’s been best studied in combination with Prezista/Norvir.

—Joel Gallant, MD, MPH ACTIVIST’S COMMENTS Newest of the non-nukes, Intelence is effective against typical non-nuke resistance. It saved many lives when it was released at the same time as Isentress and Prezista—allowing many salvage patients to finally have two or three new drugs to construct an effective regimen.

It’s taken twice daily with food, and because it can lower drug levels of PIs, they need to be boosted with Norvir. The only major side effect is a possible rash. It may never replace Sustiva, but it doesn’t have Sustiva’s sleep and lipid problems, and has been a lifesaving drug for many patients who had run out of options.

—Jeff Taylor

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2011 HIV Drug guide Rescriptor brand name:

Rescriptor

delavirdine Non-nucleoside reverse transcriptase inhibitor

(non-nucleoside, NNRTI, or non-nuke) manufacturer: ViiV Healthcare | www.viivhealthcare.com, (877) 844-8872 common name: class:

Standard dose: Two 200 mg tablets or four 100 mg tablets three times a day (every 8 hours). Only the 100 mg tablets can be dissolved in liquid; however, avoid grapefruit juice. Take with or without food, but again, avoid grapefruit juice. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.

AWP: $350.57 / month for 200 mg tablets

Potential side effects and toxicity Most common side effects include headache, nausea, vomiting, diarrhea, fatigue, elevated liver enzymes, and itchy skin or rash. A serious side effect of the NNRTI class is rash, which can be life threatening. Most rashes occur one-three weeks after starting Rescriptor. If you experience blistering, mouth lesions, conjunctivitis (redness or inflammation of the eye, which if untreated may result in permanent vision loss), swelling, muscle or joint aches, fever, or malaise (general ill feeling), you should stop the medication, and seek medical attention right away. Body fat accumulation or redistribution may occur.

Potential drug interactions You should not take Rescriptor with oral Versed (midazolam), Halcion (triazolam), Xanax (alprazolam), Orap (pimozide), ergot alkaloids used for migraine headaches (such as Wigraine, Methergine, and Cafergot) in any form, or the herb St. John’s wort. Do not use Zocor, Vytorin, or Mevacor cholesterol (lipid) lowering meds; suggested alternatives are Lipitor (atorva-statin) and Lescol (fluvastatin). Liver enzymes should be checked regularly if you are on these cholesterol meds, as they can increase risk for liver toxicity with Rescriptor. Certain amphetamines and antiarrhythmic drugs should not be used with Rescriptor, therefore, inform your health care provider if you have a history of heart or blood pressure problems. Dose adjustment may be needed when taken with Biaxin (clarithromycin). Rescriptor should be used

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with caution with Procardia or Adalat (nifedipine), Norvasc (amlodipine), Plendil (felodipine), Coumadin (warfarin), and quinidine.

Use caution with anti-convulsants: Tegretol (carbamazepine), phenobarbital, and Dilantin (phenytoin). Mycobutin (rifabutin) and Rifadin (rifampin), used to treat tuberculosis, are drugs that decrease Rescriptor levels.

Rescriptor is not recommended with either rifampin or Mycobutin. Rescriptor increases levels of protease inhibitors Crixivan, Lexiva, Invirase, Kaletra, Norvir, and Viracept, as well as immunosuppressants, birth control pills (ethinyl estradiol), and methadone, so caution is advised if using together. Cialis, Levitra, and sildanafil (Viagra) levels are increased

by Rescriptor; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Also, increased levels of trazodone can occur with Rescriptor and therefore should be used with caution.

Increased levels of the inhaled and nasal sprays that contain fluticasone, a steroid for asthma or allergies (found in Advair, Flonase, and Flovent) can occur with Rescriptor and therefore should be used with caution or an alternative should be considered.

More information Very rarely used. Research demonstrates that smaller doses of Rescriptor increase blood levels of some protease inhibitors, making it unique among the NNRTIs. Some people who cannot tolerate Norvir (ritonavir) are successfully using Rescriptor instead to boost their protease inhibitor. Studies of this use,

however, have not been published. Antacids (like Tagamet, Zantac, Prilosec, and Tums) and gastric achlorhydria (low stomach acid) decrease absorption of Rescriptor, so take at least one hour apart from these drugs and take with acidic beverages such as orange or cranberry juice to increase stomach acidity. See package insert for more complete information on potential side effects and interactions.

Doctor’s COMMENTS It’s the rare patient who takes Rescriptor anymore, not that it was ever a widely used drug.

It may be less potent than other NNRTIs, was never extensively studied, and has to be taken three times a day. It was sometimes used in patients with unusual NNRTI mutations that caused resistance to Viramune and Sustiva but not to Rescriptor, but most of those patients are now taking Intelence. As with any NNRTI, Rescriptor can cause rash. It has drug interactions that are different from those of other NNRTIs: It increases levels of protease inhibitors rather than decreasing them. It was once suggested as an alternative PI booster for that reason, but no one was excited about taking a booster three times a day.

—Joel Gallant, MD, MPH ACTIVIST’S COMMENTS A heavy pill burden three times a day, combined with GI problems, fatigue, a host of drug interactions, and the typical non-nuke rash kept Rescriptor from ever being used much.

However, some studies have shown that it can increase PI levels like Norvir does—making it a potentially useful drug for people who can’t tolerate Norvir but need a booster. (At least for another year, assuming Gilead’s Norviralternative cobicistat gets approved.)

—Jeff Taylor

Ma r c h +A p r i l 2 0 1 1 | 3 3

2011 HIV Drug guide rilpivirine (TMC 278)

rilpivirine (TMC 278)

(brand name not yet established)

unavailable at press time Non-nucleoside reverse transcriptase inhibitor

(non-nucleoside, NNRTI, or non-nuke) manufacturer: Tibotec Therapeutics | (877) REACH-TT (732-2488),

www.tibotectherapeutics.com common name: class:

Standard dose: 25 mg once daily with food has been selected in the Phase 3 trials. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.

AWP: pricing unavailable at press time

Potential side effects and toxicity When looking at pooled data of the two Phase 3 studies (ECHO and THRIVE), rilpivirine had significant tolerability advantages when compared to Sustiva (efavirenz). There were lower rates of discontinuation due to side effects.

The most common side effects of rilpivirine and Sustiva compared in these studies were central nervous system symptoms (17% vs.

38%), psychiatric symptoms (15% vs. 23%), dizziness (8% vs. 26%), abnormal dreams or nightmares (8% vs. 13%), skin rash (3% vs.

14%), and lab abnormalities (11% vs. 18%).

Rilpivirine also has a favorable lipid profile when compared to Sustiva. There were minimal increases in LDL (“bad” cholesterol), total cholesterol, and triglycerides. Available data are limited due to experimental drug status.

Potential drug interactions Can decrease levels of methadone; however, no dosage adjustments are necessary. Careful monitoring is recommended to avoid methadone withdrawal symptoms. Again, available data is limited due to experimental drug status.

More information Expected to be approved by the FDA in May, 2011, either as a stand-alone medication or in a fixed dose regimen with Truvada (one pill, once-a-day regimen—see rilpivirine/Truvada, page 38) as well. On July 23, 2010, Tibotec Ther apeutics filed a NDA (new drug application) for rilpivirine to the U.S. FDA based on 48-week data from two Phase 3, double blind, randomized studies called ECHO and THRIVE. The main objective of these studies is to show safety and efficacy in treatment-naïve (first

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time on treatment) adults. Pooled data from the two studies showed that 1,368 adults were randomized 1:1 into two arms, a rilpivirine arm and a Sustiva arm. Both studies mostly used Truvada as the backbone (100% in ECHO and 60% in THRIVE), but the backbone made no impact in response. The data shows that rilpivirine is non-inferior (a term used in scientific research that means the drug is no worse nor better than those it’s compared to) to Sustiva in efficacy—84% vs. 82% of patients achieved viral load of less than 50 copies/ml (undetectable) and CD4 count increases of 190 vs. 172 when comparing rilpivirine and Sustiva arms, respectively. Although individuals were less likely to stop treatment due to side effects, their HIV was more likely to develop drug resistance mutations when compared to Sustiva. A new NRTI resistance mutation was developed by 68% vs. 32% and 63% vs. 54% developed a new NNRTI resistance mutation.

Pooled data from the two studies showed 9% virologic failure in the rilpivirine arm when compared to 4.8% in the Sustiva arm. This can be explained by looking at an individual’s baseline viral load and their adherence to medication. With the combination of high viral load and poor adherence, individuals in the study were three times more likely to experience virological failure with rilpivirine when compared to Sustiva. The 25 mg rilpivirine dose was selected because the 75 mg and 150 mg doses studied were associated with a risk of abnormal heart rhythm (prolonged QT interval). Perhaps a 50 mg dose would have been more successful at avoiding the development of drug resistance, including crossresistance to other medications in this drug

class, without increasing toxicity. The greater potential for cross-resistance compared to Sustiva puts rilpivirine at a disadvantage for first-time treatment with an NNRTI, since people may be less likely to switch to another NNRTI if their HIV develops NNRTI resistance mutations with rilpivirine. See package insert, once approved, for complete information on potential side effects and drug interactions.

Doctor’s COMMENTS Rilpivirine is an investigational NNRTI that will be approved this spring if all goes well at the FDA. Although it has activity against NNRTIresistant virus, it will be approved only for initial therapy. The combination of rilpivirine plus two NRTIs was shown to be better tolerated than Atripla in two large clinical trials. Overall results were similar, but Atripla looked better in people with high viral loads, and there was more virologic failure and resistance in subjects taking rilpivirine. In addition, rilpivirine resistance caused cross-resistance to Intelence, which wasn’t the case with Atripla.

Rilpivirine will have clear advantages over Sustiva in terms of side effects, but it may not be the complete replacement we were hoping for. Rilpivirine must be taken with a meal and should not be taken with drugs that reduce stomach acid. —Joel Gallant, MD, MPH ACTIVIST’S COMMENTS Expected to be approved in 2011 for people starting meds for the first time, this non-nuke has proven to be comparable to Sustiva, without the mind-warping side effects. The downside is that it may not be as effective as Sustiva in those with higher viral loads (over 100,000). In addition to not making you crazy, it also doesn’t raise cholesterol and triglycerides like Sustiva can. It’s a small pill, so look to see it used in fixed dose combos with other drugs like Truvada. —Jeff Taylor

M a r c h +A p r i l 2 0 1 1 P o s i t i v e lyAwa r e . c o m

2011 HIV Drug guide Sustiva brand name:

Sustiva

efavirenz Non-nucleoside reverse transcriptase inhibitor

(non-nucleoside, NNRTI, or non-nuke) manufacturer: Bristol-Myers Squibb | www.sustiva.com; (800) 321-1335 common name: class:

Standard dose: One 600 mg tablet, once a day, typically at bedtime; on an empty stomach or with a light, low-fat snack. Also available in smaller 50 mg and 200 mg capsules. Approved for children 3 years and older. Strawberry/mint flavored solution available for children under expanded access program. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.

AWP: $663.00 / month for 600 mg tablets

Potential side effects and toxicity Central nervous system (CNS) or psychiatric symptoms (dizziness, headache, memory loss, somnolence, hypnotic trance, confusion, insomnia, hallucinations, vivid or abnormal dreams or nightmares, depression, euphoria or mania, and agitation). These symptoms typically diminish within four weeks. Other side effects may include rash, nausea, vomiting, diarrhea, fever, and increased liver enzymes.

These symptoms occur early and generally resolve within two to four weeks. A serious side effect of the NNRTI class is rash, which can be life-threatening. Rash is more common, and more severe, in children, as are low levels of some blood cells. May raise levels of triglycerides, and both “good” and “bad” cholesterol. May lead to false positive tests for use of marijuana. Women taking Sustiva should not become pregnant or breast-feed because of the risk of birth defects. Increases in liver enzymes in people with hepatitis B and/or C can occur and should be monitored. Use with caution in people with mild liver impairment; not recommended for people with moderate or severe liver impairment.

Sustiva concentrations, so maintain 600 mg once-daily dose and monitor. Rifabutin levels are decreased, so daily dose of rifabutin should be increased by 50%. When taken with anticonvulsants Dilantin, phenobarbital, or Tegretol, periodic monitoring of blood levels of anticonvulsants and Sustiva should be performed or alternative anti-seizure medications should be considered. Can affect birth control pill levels, so a second barrier contraceptive method is advised. Sustiva can lower the concentrations of Sporanox, Noxafil, immunosuppressants (including transplant drugs), Zoloft, Lipitor, pravastatin, simvastatin, and diltiazem.

Dose adjustment may be needed. The maintenance dose of Vfend should be increased to 400 mg every 12 hours and the Sustiva dose should be decreased to 300 mg once daily using the capsule formulation. Drug levels of bupropion and sertraline are lowered; titrate dose based on clinical response. Sustiva can decrease levels of buprenorphine. No dose adjustment is recommended, but monitor for withdrawal symptoms. Sustiva can decrease the effects of Malarone; consider alternative drug.

Potential drug interactions Do not take with Atripla, since Sustiva is already in Atripla. Do not take with Intelence, Rescriptor, rilpivirine, or Viramune. Do not take the following medications with Sustiva: midazolam, triazolam, ergot medications (Wigraine, Methergine, and Cafergot), St. John’s wort, Gingko biloba, pimozide, bepridil, or Biaxin. May affect Coumadin therapy.

Sustiva decreases methadone levels; dosing adjustment may be necessary to avoid withdrawal symptoms. Increase Kaletra to three tablets twice daily with food (recommended) when taken with Sustiva in treatment-experienced people. Kaletra cannot be taken once daily with Sustiva. Monitor liver enzymes closely if Sustiva and Norvir are used together due to potential risk of liver damage. Reyataz dose should be higher and also boosted with Norvir (Reyataz 400 mg/Norvir 100 mg once daily) when taken with Sustiva, but treatment– experienced people should not take this combination at all. With once-daily Lexiva, boost with 300 mg Norvir. Rifampin decreases

More information According to current U.S. guidelines, when choosing an NNRTI-based regimen, Sustiva is the preferred drug. Avoid driving or operating heavy machinery for a few hours after dose. Some people adjust to Sustiva by taking Ativan or Ambien to sleep for the first few weeks. However, either may make you even more groggy the next morning. If you can’t sleep (which more commonly develops later), ask about switching the timing of your dose little by little until you’re taking it in the daytime. It is usually recommended that you continue your other HIV medications for several days after stopping Sustiva to avoid developing resistance. Sustiva remains a class D drug and should not be used in women planning pregnancy or started in pregnant women during the first trimester. According to one meta-anyalysis, if women get pregnant while on Sustiva or Atripla, however, the concern for birth defects is minimal. See package insert for more complete information on potential side effects and interactions.

P o s i t i v e lyAwa r e . c o m

Doctor’s COMMENTS Nine years after its approval in 2002, Sustiva (as well as Atripla, the combination of Sustiva, Viread, and Emtriva) has still never been beaten in clinical trials, and remains a preferred drug in all treatment guidelines. Besides its excellent potency, it also has a very long halflife, which makes it forgiving of missed or delayed doses (not that you would ever miss or delay a dose!), and excellent long-term safety. Its flaws, however, include “neuropsychiatric” side effects, (dizziness, vivid dreams or nightmares, difficulty concentrating, and mood changes) and allergic rashes, also common during the first few weeks, though they generally go away without having to stop the drug. Sustiva can cause birth defects; pregnant women should avoid it during the first trimester. Once you’re been on Sustiva for three to four weeks, it’s usually smooth sailing, though it can raise lipid levels. Some people may have persistent neurologic side effects, including depression. When starting Sustiva or Atripla, take it in the evening on an empty stomach (at least two hours after dinner) to minimize side effects. You may be dizzy. Start it on a weekend, or some evening when you have nothing important to do for the next few mornings. In most cases, things get better with each dose, so stick with it, though if you don’t feel like your normal self after a month on Sustiva or Atripla, it’s time for a change. It’s easy to become resistant to Sustiva, so don’t stop this drug unless you’re replacing it with something else. —Joel Gallant, MD, MPH ACTIVIST’S COMMENTS Convenient once-daily dosing of Sustiva is counterbalanced by the side effects that range from vivid dreams to screaming nightmares and walking zombie status. For most people, these effects diminish after the first few weeks, but for some, they never go away.

Add a host of drug interactions, worsening of cholesterol, triglycerides, and liver enzymes, possible osteoporosis, and the need to avoid a heavy or fatty meal to prevent making the side effects even worse, and it’s not so convenient any more. Its long half-life can be a problem if you need to stop your meds for any reason— make sure you talk to your doctor about stopping the Sustiva before your other meds and perhaps switch to another med to “cover the tail” while you still have low levels of Sustiva in your blood. And for women of childbearing age—this drug can cause birth defects, so if you have any plans to get pregnant, don’t take it. —Jeff Taylor

Ma r c h +A p r i l 2 0 1 1 | 3 5

2011 HIV Drug guide Viramune brand name:

Viramune

nevirapine Non-nucleoside reverse transcriptase inhibitor

(non-nucleoside, NNRTI, or non-nuke) manufacturer: Boehringer-Ingelheim | www.viramune.com, (800) 274–8651 common name: class:

Standard dose: One 200 mg tablet daily for two weeks, then full dose of one 200 mg tablet twice daily, with or without food, with no dietary restrictions. Frequently prescribed as two 200 mg tablets once a day, although once-daily dosing is not FDA approved. Dose for children 15 days or older is 150 mg/m2 once daily for 14 days, then 150 mg/m2 twice daily thereafter, not to exceed 400 mg. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose. For dialysis patients, an additional dose of 200 mg is required after each dialysis. A 50 mg/5 ml oral suspension is also available.

AWP: $614.24 / month, $133.02 for 240 ml solution (50 mg/5 ml)

Potential side effects and toxicity Most common side effects include headache, nausea, vomiting, fever, and rash. 14-day lead-in dosing reduces the risk of rash. Severe rash, including Stevens-Johnson syndrome, while rare, can be life-threatening; notify your health care provider immediately. Seek medical attention right away if you experience blistering, mouth sores, conjunctivitis (redness or inflammation of the eye, or pink eye, which if untreated may result in permanent vision loss), swelling, muscle or joint aches, fever, or malaise (general ill feeling). Do not increase dose if rash develops during dose escalation or if you develop any rash accompanied by the above listed conditions. Once-daily lead-in dose should not exceed 28 days. An alternative drug should be considered at this time.

An increase in liver enzyme levels has been observed and in rare instances, hepatitis has developed. In such cases, it may be necessary to stop taking Viramune until liver function returns to normal. Permanently discontinue it if abnormalities return. Rarely, severe and life-threatening liver damage, including fatal cases, has occurred. Women with CD4 counts greater than 250 T-cells, including pregnant women, and men with more than 400 T-cells have a higher risk of serious liver damage, with women being at greater risk. The package insert says Viramune should not be started in these groups unless the benefit outweighs the risk. The highest risk period is within the first six weeks of treatment, but patients should be monitored closely for the first 18 weeks.

Potential drug interactions Do not take with Intelence, Rescriptor, Reyataz, rilpivirine, Sustiva, or St. John’s wort.

Rifampin should not be used with Viramune; Mycobutin is the recommended alternative for tuberculosis treatment. Use with caution with midazolam, triazolam, cisapride, fluconazole, or ergot medications used for migraine headaches (Wigraine, Methergine, and Cafergot), Cordarone, lidocaine or disopyramide, carbamazepine, ethosuxomide, or clonazepam, calcium channel blockers (Procardia and others), immunosuppressants, Coumadin. Do not use 3 6 | Ma r c h +A p r i l

2 0 1 1

with Biaxin or Nizoral. Viramune decreases methadone levels; dose adjustment may be necessary to avoid withdrawal symptoms.

Can reduce levels of protease inhibitors; dose adjustment may be needed if they are taken together. Kaletra should be increased to three tablets twice a day in treatment-experienced.

Use caution with anti-convulsants: Dilantin, phenobarbital, and Tegretol. Effectiveness of birth control pills may be decreased; consider the use of alternative or additional contraception. During the first six weeks of therapy, prednisone should be avoided; it can cause increased severity and incidence of rash.

More information An extended release formula that can be taken once a day is in the works, but many providers already prescribe once-daily dosing with the current formulation. Monitor liver function tests and signs of rash during first six months. Do not ignore yellowing of your eyes or skin, as this may be a sign of a severe liver effect. A recent study found no correlation between CD4 count and risk of liver toxicity with nevirapine among women in Zambia, Thailand, and Kenya. Studies show that Viramune crosses the blood-brain barrier to a useful degree, which may be beneficial for patients at risk for neurological damage (such as dementia) from HIV. If at any time of treatment you stop Viramune for more than seven days, you will need to start at the lower dose for two weeks and then increase back up to twice-daily dosing. Viramune should not be used for PEP (post-exposure prophylaxis). Be careful when stopping Viramune, so that you avoid rapid development of HIV resistance to it—check with your doctor or pharmacist first.

It is usually recommended that you continue your other HIV medications for several days after stopping Viramune. Viramune has also been shown to have a positive impact on triglycerides and cholesterol levels. When taken around the time of labor, Viramune has demonstrated effectiveness in preventing the transmission of HIV from mother to child, but there was an increase in HIV drug resistance when taken alone. The use of at least one other

HIV drug helped to cut down the incidence of resistance, and women have been shown to experience effectiveness with the drug six months after giving birth. Viramune was updated from Pregnancy Class C to Class B in 2007, meaning that it was found to be even safer. Single- or two-dose Viramune may be used for babies born to HIV-positive mothers.

Mothers should not breastfeed their infants while taking Viramune. See package insert for more complete information on potential side effects and interactions.

Doctor’s COMMENTS Viramune (nevirapine) is a component of the vast majority of first-line regimens worldwide, in part because of the low cost of generic nevirapine. It has not been as popular in the United States, however, in part because of the stronger clinical data with Sustiva, but also because of its greater early toxicity. It’s listed as an alternative NNRTI in the DHHS and IAS-USA guidelines. Viramune can cause skin rashes and liver toxicity during the first few weeks, which can be severe and even life-threatening. The risk is greatest when it’s started in people with high CD4 counts: above 250 in women and above 400 in men).

Below those CD4 thresholds, the risk is low, and the long-term safety is excellent, with less lipid elevation than with Sustiva. Viramune should be started at half-dose (200 mg once daily) and increased to the full dose (200 mg twice daily) after two weeks only if there is no rash or liver enzyme elevation. Compared to Sustiva, resistance to Viramune is somewhat more likely to cause cross-resistance to Intelence. —Joel Gallant, MD, MPH ACTIVIST’S COMMENTS Originally a twice-daily drug, by press time, the FDA is expected to have approved the new once-daily XR (extended release) formula that may help it regain some market share back from Sustiva. When starting, it will still need a 14-day lead-in period, and the same “black box” warnings about serious skin rash and liver damage in women with over 250 T-cells and men with over 400 T-cells still apply. However, recent studies have shown that people undetectable on another regimen can safely switch to Viramune, regardless of CD4 count. That, and its metabolically friendly profile (i.e., better cholesterol and triglyceride levels), make it a useful option for those who can’t tolerate the crazies from Sustiva or Atripla. The same caveats as for Sustiva about stopping the drug apply with Viramune as well. —Jeff Taylor P o s i t i v e lyAwa r e . c o m

2011 HIV Drug guide Atripla brand name:

Atripla

efavirenz, emtricitabine, and tenofovir disoproxil fumarate Nucleoside/nucleotide analog reverse transcriptase inhibitor (nucleoside/nucleotide analog, NRTI, or nuke) and non-nucleoside reverse transcriptase inhibitor (non-nucleoside, NNRTI, or non-nuke)—fixed dose regimen manufacturers: Bristol-Myers Squibb | www.bms.com, (800) 321–1335, and

Gilead Sciences | www.gilead.com, (800) GILEAD5 (445–3235), www.atripla.com common name: class:

Standard dose: One tablet (Sustiva [600 mg] and Truvada [200 mg Emtriva and 300 mg Viread]), once a day, preferrably at bedtime, on an empty stomach or with a light, low-fat snack.

Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.

AWP: $1,858.15 / month

Potential side effects and toxicity See the drugs contained in Atripla—Sustiva (page 35), Emtriva (page 22), and Viread (page 29). Atripla is well tolerated in most, but not all, individuals. Use with caution in individuals with depression or other psychiatric issues. Diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash. Women taking Atripla should not become pregnant or breast-feed because of the risk of birth defects. Dose cannot be adjusted for people with kidney problems. Immune Reconstitution Inflammatory Syndrome (IRIS) may occur as the immune system regains strength; signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is initiated. Report symptoms of illness, such as shingles and TB, to a health care provider.

Potential drug interactions See the drugs contained in Atripla: Sustiva (page 35), Emtriva (page 22), and Viread (page 29). Do not take Atripla with Combivir, Emtriva, Epivir, Epivir-HBV, Epzicom, rilpivirine/Truvada, Sustiva, Trizivir, Truvada, or Viread, since these medications are already in Atripla or have equivalent medications.

More information Atripla is the first complete HIV treatment regimen in one pill, taken once daily. It’s a first in HIV. It is on the current list of preferred regimens for treatment-naïve patients in the U.S. DHHS HIV treatment guidelines (see Sustiva,

P o s i t i v e lyAwa r e . c o m

page 35). Atripla is one of the most commonly prescribed medications for those taking HIV medicine for the first time due to the ease of taking one pill, once a day. Another benefit: the single tablet cuts the number of insurance co-pays. Despite that, a new three-in-one HIV regimen coming down the pike (see rilpivirine/Truvada, page 38) will make Atripla’s difficulties harder to overlook; there is also a quad tablet being studied (see “Coming into View,” page 74). Most treatment-experienced people (those who’ve already been on HIV therapy) may not be able to use Atripla due to their having developed drug resistance (when medications may no longer work against the virus). Drug resistance most commonly occurs when people don’t take their HIV medicine as prescribed, but you may also be infected with a drug-resistant virus against which some of the medications in Atripla will not work. Because it is one dose once a day, it is important not to miss a dose. Be careful when stopping Atripla, so that you avoid the rapid development of HIV resistance to it—check with your doctor or pharmacist first. Remember, Atripla is a combination of three drugs, so see the pages for its components: Sustiva, Emtriva, and Viread.

Sustiva cannot be taken during pregnancy, and use of Viread must be monitored in people with underlying kidney problems. In this combination product, the Viread dose cannot be adjusted. Therefore, Atripla should not be used in people with severe kidney problems. The Sustiva in Atripla can cause a false positive for marijuana on certain drug tests. A

more specific confirmatory test can be done.

Atripla should not be used in patients under 18 years of age. Gilead and BMS are forever to be commended for collaborating to bring Atripla to market. See package insert for more complete information on potential side effects and interactions.

Doctor’s COMMENTS Atripla is the first and only single-tablet, oncedaily regimen, although there are others in development. It’s a preferred regimen in all treatment guidelines based on its outstanding efficacy, safety, tolerability and convenience.

The main disadvantages include the potential for kidney toxicity with tenofovir (see Viread, page 29) and the early side effects of efavirenz (see Sustiva, page 35). While Atripla is by far the most convenient regimen for initial therapy, it’s not a good choice for people who aren’t fully committed to staying on therapy without interruption. The long half-lives of the three drugs mean that an occasional missed dose or two won’t matter, but interrupting therapy altogether can cause drug resistance, especially to efavirenz.

—Joel Gallant, MD, MPH ACTIVIST’S COMMENTS The drug that started the current one pill/ once-a-day craze, Atripla still remains the sum of its parts. The Sustiva component especially can cause sleep disturbances, lipid and bone density problems, and taking it with a high fat meal can make these side effects worse.

Fortunately, it’s paved the way for other onepill/once-a-day combos in the pipeline, so patients will soon have other options with the same convenience and a single co-pay.

—Jeff Taylor

Ma r c h +A p r i l 2 0 1 1 | 3 7

2011 HIV Drug guide rilpivirine (TMC 278), emtricitabine, and tenofovir dF

rilpivirine (TMC 278)/Truvada (combination brand name not yet established)

rilpivirine (TMC 278), emtricitabine, and tenofovir DF Nucleoside/nucleotide analog reverse transcriptase inhibitor (nucleoside/nucleotide analog, NRTI, or nuke) and non-nucleoside reverse transcriptase inhibitor (non-nucleoside, NNRTI, or non-nuke)—fixed dose regimen manufacturers: Tibotec Therapeutics | (877) REACH-TT (732-2488),

www.tibotectherapeutics.com; and

Gilead Sciences | www.gilead.com, (800) GILEAD5 (445-3235) common name: class:

Standard dose: One tablet (rilpivirine [25 mg] and Truvada [200 mg Emtriva and 300 mg Viread] once daily has been selected in the Phase 3 trials. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose. Dose cannot be adjusted for people with kidney problems.

AWP: pricing unavailable at press time Manufacturers: Tibotec Therapeutics, (877) REACH-TT (732-2488)

www.tibotectherapeutics.com; and Gilead Sciences, www.gilead.com,

(800) GILEAD5 (445-3235)

Potential side effects and toxicity See the drugs rilpivirine (page 34) and Truvada (page 27). Available data are limited due to experimental drug status.

Potential drug interactions See the drugs rilpivirine (page 34) and Truvada (page 27). Do not take this drug with Atripla, Combivir, Emtriva, Epivir, EpivirHBV, Epzicom, rilpivirine, Trizivir, Truvada, or Viread, since these medications are already in this fixed dose pill or have equivalent medications. Again, available data is limited due to its experimental drug status.

More information Expected to be approved by the FDA in 2011.

On November 23, 2010, Gilead Sciences submitted an NDA (new drug application) to the U.S. FDA. As of press time, this medication

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has not yet been approved. If approved, this will be the second once-daily, single tablet, complete regimen on the market (see Atripla, page 37). The pill will be smaller in size than Atripla. The NDA is supported by a bioequivalence study showing the single tablet formulation containing rilpivirine, emtricitabine, and tenofovir disoproxil DF achieved the same drug levels in the blood as if these drugs were taken simultaneously as individual pills. Both Truvada and rilpivirine also have long halflives (time it takes a drug in the body to be reduced by half), making them a great pairing.

See package insert, once approved, for more complete information on potential side effects and drug interactions.

Doctor’s COMMENTS It was hoped that this combination, the second single-tablet, once-daily regimen, would

be approved this spring along with rilpivirine, but the FDA has asked for some additional data before they’ll approve the combination pill, which may delay approval for a short time.

The advantages and disadvantages of this regimen vs. Atripla are discussed elsewhere (see rilpivirine, page 34), and a head-to-head comparison of the two regimens is in progress (the original rilpivirine studies didn’t use the single-tablet regimen). While it’s possible that this won’t achieve Atripla status in the guidelines, its better tolerability will be a big plus. It may turn out to be a good choice for people with low baseline viral loads or those who have trouble tolerating Atripla, Sustiva, or boosted PIs. —Joel Gallant, MD, MPH ACTIVIST’S COMMENTS Dubbed “B-tripla”, this one pill/once-a-day pairing of rilpivirine with Truvada will offer the convenience of Atripla without the crazies or high lipids. The same caveats about not starting this drug in people with high viral loads (more than 100,000) apply as with rilpivirine by itself. But this drug should prove to be an attractive option for those starting meds, without the downside of the Sustiva in Atripla.

It’s in the pipeline for FDA approval—expect to see it on pharmacy shelves sometime in 2011. —Jeff Taylor

M a r c h +A p r i l 2 0 1 1 P o s i t i v e lyAwa r e . c o m

2011 HIV Drug guide Aptivus brand name:

Aptivus

tipranavir Protease inhibitor (PI) manufacturer: Boehringer-Ingelheim | www.aptivus.com, (800) 542–6257 common name: class:

Standard dose: Two 250 mg capsules with two 100 mg capsules of Norvir, both twice daily. Must be taken with Norvir. Oral solution available; both formulas available for children ages 2 years and older and adults. Take with food when using Norvir tablets; no food restrictions with Norvir capsules, but preferably taken with food to improve Norvir tolerability. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.

AWP: $1,259.57 / month; $419.84 for 95 ml bottle of solution

Potential side effects and toxicity Aptivus contains sulfa, so use cautiously in patients with sulfa allergies. Mostly gastrointestinal-related: mild diarrhea, nausea, vomiting, abdominal pain, and fatigue. Other side effects may include headache, fever, dry mouth, and dizziness. Rash, including sensitivity to the sun, has occurred (most commonly among children) with Aptivus. Women taking birth control pills may be at higher risk for rash. If a severe rash occurs, Aptivus should be discontinued. Stop using Aptivus if rash appears with joint pain or stiffness, throat tightness, generalized itching, muscle aches, fever, redness, blisters, or peeling of the skin, and call your medical provider right away. Caution should be used in people with mild liver impairment, and it should not be taken by people with moderate to severe hepatitis, since Aptivus concentrations may be increased. Be sure to know your hepatitis status if you are about to or are taking this drug! Use with caution by people who may be at risk of increased bleeding from trauma, surgery, or other medical conditions, or who are taking medications known to increase the risk of bleeding such as anti-platelet drugs, anticoagulants, or supplemental high doses of vitamin E. As seen with other protease inhibitors (except unboosted Reyataz), there can be increased levels of cholesterol and triglycerides which may be associated with an increased risk of heart disease. Other possible side effects are lipodystrophy (body fat changes), onset of new cases or worsening of diabetes (see your doctor promptly), and increased bleeding in hemophiliacs. Immune Reconstitution Inflammatory Syndrome (IRIS) may occur as the immune system regains strength; signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is initiated.

Report symptoms of illness, such as shingles and TB, to a health care provider.

Potential drug interactions Aptivus/Norvir interacts with many other drugs, so tell your health care provider of the medications you are taking. Aptivus lowers Intelence levels, and they should not be combined. Do not take with alfuzosin, Revatio, Tambocor, Rythmol, Cordarone (amiodarone), quinidine, oral Versed (midazolam), Halcion (triazolam), pimozide (Orap), P o s i t i v e lyAwa r e . c o m

cisapride, ergot alkaloids (such as Cafergot, Wigraine, Methergine, and D.H.E. 45), or the herb Saint John’s wort. Do not use Advicor, Altoprev, Livalo, Mevacor (lovastatin), Simcor, Vytorin, or Zocor (simvastatin) for the treatment of high lipids. Lipid-lowering alternatives are Crestor, Lescol, Lipitor, and Pravacol (pravastatin), but should be used with caution. Increased levels of the inhaled and nasal sprays with fluticasone (found in Advair, Flonase, Flovent), can occur with Aptivus/ Norvir and therefore should be used with caution. Aptivus can lower blood levels of Ziagen, Videx, and Retrovir (zidovudine, AZT). Take Videx and Aptivus two hours apart. Aptivus should not be taken with other protease inhibitors because it greatly lowers their blood levels. Trough concentration (lowest level) of Aptivus is increased 45% with Fuzeon, but dose adjustments are not recommended.

Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Effectiveness of birth control pills may be decreased; consider the use of alternative or additional contraception. Methadone doses may need to be increased. Blood levels of Aptivus decrease 40% with Suboxone, but dose adjustments are not recommended, and the effectiveness of Suboxone is not affected.

Trazodone concentrations may increase; a lower dose of trazodone is recommended.

Calcium channel blockers should be used with caution and monitored for side effects.

Monitoring may be required when taking Coumadin. Carbamazepine, Dilantin (phenytoin), or phenobarbital may decrease Aptivus levels, so alternate seizure medications should be used and monitoring of Aptivus drug levels is recommended. Caution should be used with valproic acid, which may be less effective due to decreased concentrations when used with Aptivus. Use caution when taking itraconazole or fluconazole. Rifampin should not be used; Mycobutin is the recommended alternative for the treatment of TB. It requires a reduced dose and frequency. Use with caution with bosentan, salmeterol, immunosuppressants (including transplant drugs), and colchicine; use lower dose of colchicine.

Norvir and Aptivus capsules contain alcohol (but should not be enough to trigger relapse),

so be cautious with Antabuse or Flagyl. Oral solution contains vitamin E; do not take additional vitamin E beyond that found in a standard multivitamin. Antacids can decrease levels of Aptivus. Aptivus should be taken two hours before or one hour after antacids.

Aptivus decreases Prilosec (omeprazole) concentrations and Prilosec dose may need to be increased. Buprenorphine can lower Aptivus levels; consider monitoring Aptivus levels.

More information Due to its resistance profile and drug interactions, Aptivus is not as popular as other PIs. It is only for treatment-experienced patients.

Take with food to minimize stomach problems.

It does less well for people with combinations of certain protease-related mutations.

Although Aptivus has to be taken with Norvir, it actually lowers the blood levels of Norvir, so you may not see as many of the GI side effects. Refrigerate capsules before opening, though Aptivus can be stored at room temperature (up to 77˚F), but must be used within 60 days. See package insert for details.

Doctor’s COMMENTS Aptivus is a “second-generation” PI, meaning that it’s often active against PI-resistant virus. However, it is not widely used, mainly because of the availability of Prezista, which is safer, better tolerated, and is active against a wider range of PI-resistant virus. Aptivus causes more lipid elevation and liver toxicity than other PIs, possibly because it requires a higher boosting dose of Norvir (200 mg twice a day). However, there are some situations in which Aptivus is a better choice than Prezista. People who developed resistance to Agenerase (amprenavir) or Lexiva (fos-amprenavir), for example, may have Prezista crossresistance but will still respond to Aptivus. For that reason, it’s always important to make the choice of a second-line PI based on resistance testing. —Joel Gallant, MD, MPH ACTIVIST’S COMMENTS Though it has saved many lives, this is now a drug for patients without other protease inhibitor options. It’s two pills with twice the normal boosting dose of Norvir—twice a day.

That pill burden, and the resulting GI problems like diarrhea, bloating, and gas, along with the host of drug interactions for patients who are likely to already be on many other drugs, make this a tough drug to balance in an already loaded salvage cocktail. Not a drug for the faint of heart, or those with other options. —Jeff Taylor

Ma r c h +A p r i l 2 0 1 1 | 3 9

2011 HIV Drug guide Crixivan brand name:

Crixivan

indinavir sulfate Protease inhibitor (PI) manufacturer: Merck and Co. | www.merck.com, (800) 850–3430 common name: class:

Standard dose: Rarely used by itself (two 400 mg capsules every eight hours with no food or a low-fat snack). Almost always boosted with Norvir, both twice daily: 400 mg Crixivan + 400 mg Norvir; 800 mg + 100 mg; or 800 mg + 200 mg (all doses taken with food and with plenty of water to avoid kidney sludge or stones). Avoid grapefruit juice and vitamin C (more than one gram a day), which decrease Crixivan blood levels. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose. Also available in 100 mg, 200 mg, and 333 mg capsules.

AWP: $548.12 / month for 400 mg, 180 capsules

Potential side effects and toxicity Headache, fatigue or weakness, malaise (general ill feeling), nausea, diarrhea, stomach pain, loss of appetite, yellowing of skin/eyes, changed skin color, dry mouth/sore throat, taste changes, painful urination, indigestion, joint pain, hives, and liver toxicity. Itchy/dry skin, ingrown toe nails, and hair loss are unique to Crixivan. Kidney stones, which may lead to more serious problems, can also occur—if pain develops in the middle to lower stomach or the back, or if there is blood in the urine, call your health care provider immediately. An increase in bilirubin (a test of liver function) has been reported, but it is not associated with liver problems. It may sometimes cause yellowing of the skin or eyes. As seen with other protease inhibitors (except unboosted Reyataz), there can be increased levels of cholesterol and triglycerides which may be associated with an increased risk of heart disease. Other possible side effects are lipodystrophy (body fat changes, including thinning of the face, arms, and legs, with or without fat accumulation in the stomach, breasts, and upper back), onset of new cases or worsening of diabetes (see your doctor promptly) and increased bleeding in hemophiliacs. Immune Reconstitution Inflammatory Syndrome (IRIS) may occur as the immune system regains strength; signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is initiated. Report symptoms of illness, such as shingles and TB, to a health care provider.

Potential drug interactions Do not take with alfuzosin, Revatio, Tambocor

4 0 | Ma r c h +A p r i l

2 0 1 1

(flecainide), Rythmol (propafenone), Cordarone (amiodarone), oral versed (midazolam), triazolam, rifampin, pimozide, ergot derivatives (such as Cafergot, Wigraine, Methergine, and D.H.E. 45), garlic supplements, or the herb St. John’s wort. Do not use Advicor, Altoprev, Livalo, Mevacor (lovastatin), Simcor, Vytorin, or Zocor (simvastatin) for the treatment of high lipids. Lipid-lowering alternatives are Crestor, Lescol, Lipitor, and Pravacol (pravastatin), but should be used with caution. Not recommended in combination with Reyataz. Reduce Crixivan to 600 mg every eight hours when taken with Rescriptor, itraconazole (200 mg twice a day), or ketoconazole (200 mg once a day). The dose of Mycobutin should be reduced to 150 mg daily or 300 mg three times a week and Crixivan dose increased to 1,000 mg every eight hours or use Norvir-boosted dose when taken together. Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Effectiveness of birth control pills may be decreased; consider the use of alternative or additional contraception.

Additional monitoring may be required when taking Coumadin (warfarin) or calcium channel blockers (such as Norvasc, Procardia, and others). Use caution with anti-convulsants: Tegretol (carbamazepine), phenobarbital, and Dilantin (phenytoin). Crixivan may decrease levels of methadone, but withdrawal rarely occurs. Methadone doses may need to be increased. Also, increased levels of trazodone can occur with Crixivan. Increased levels of the inhaled and nasal sprays with fluticasone, a steroid for asthma or allergies (found in

Advair, Flonase, and Flovent) can occur with Crixivan and therefore should be used with caution. Use with caution with bosentan, salmeterol, immunosuppressants (including transplant drugs), and colchicine; use lower dose of colchicine.

More information Drink at least 48 oz. of fluids daily, preferably water or clear liquids (soda pop doesn’t count!) to decrease the chances of kidney stones. Don’t forget to drink more water in summer or with increased sweating. Large amounts of coffee or alcohol can increase risk of stones due to increased dehydration.

Stones may continue after stopping Crixivan.

Store in original container and keep dry. See package insert for more complete information on potential side effects and interactions.

Doctor’s COMMENTS Crixivan deserves our undying gratitude for having saved many lives in the late ’90s, but it’s now a drug of purely historical importance. Side effects included kidney stones or kidney failure, diabetes, lipid changes, dry skin, chapped lips, ingrown toenails, and possibly body-shape changes (the dreaded “Crix belly,” for example). When taken without Norvir boosting, its dosing schedule was unforgiving and complex; when boosted by Norvir, it just became more toxic. Avoid it.

—Joel Gallant, MD, MPH ACTIVIST’S COMMENTS A drug that saved many lives when first introduced, its three-times-a-day on an empty stomach dosing schedule, and painful kidney stones if you didn’t drink enough water (and sometimes even if you did) made this a tough drug to tolerate. Norvir boosting has made it more convenient to take twice a day with or without food, but the kidney stones are still a danger—as is lipodystrophy (remember Crix belly?). Fortunately, there are better PI options these days. —Jeff Taylor

P o s i t i v e lyAwa r e . c o m

2011 HIV Drug guide Invirase brand name:

Invirase

saquinavir Protease inhibitor (PI) manufacturer: Genentech | www.genentech.com, (800) 626-3553 common name: class:

Standard dose: Two 500 mg film-coated tablets with 100 mg Norvir two times a day with food, or within two hours of a meal. Must be taken with Norvir. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.

AWP: $1,057.13 / month for 500 mg tablets

starting HIV therapy due to the new warning on heart activity (see Potential Side Effects, page 62). Must be taken with food. See package insert for more complete information on potential side effects and interactions.

(amiodarone), oral Versed (midazolam), Halcion (triazolam), Orap (pimozide), Lanoxin (digoxin), ergot derivatives (such as Cafergot, D.H.E. 45, Methergine, and Wigraine), quindine, trazodone, Tykosyn (dofetilide), lidocaine (systemic), garlic supplements, or the herb St. John’s wort. Colchicine levels may be increased and dose reduction is necessary. Do not use Advicor, Altoprev, Livalo, Mevacor (lovastatin), Simcor, Vytorin, or Zocor (simvastatin) for the treatment of high lipids. Lipid-lowering alternatives are Crestor, Lescol, Lipitor, and Pravacol (pravastatin), but should be used with caution. Data show that when rifampin is taken with Invirase/Norvir, there is significant liver toxicity in 40% of patients. The combination should be avoided.

Methadone doses may need to be increased.

Invirase increases levels of fluticasone (active component of Advair, Flonase, and Flovent); use with caution. Use calcium channel blockers with caution. Monitor digoxin levels; digoxin dose may need to be decreased. Use caution with anti-convulsants Tegretol (carbamazepine), phenobarbital, and Dilantin (phenytoin).

Invirase may increase dapsone levels. Invirase may alter Coumadin levels; additional monitoring may be required. Do not take with birth control pills as Invirase reduces the level of the hormone ethinyl estradiol. Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Use with caution with bosentan, salmeterol, and immunosuppressants (including transplant drugs).

Doctor’s COMMENTS Saquinavir has a long and confusing history. In the form of Invirase, it was the first approved PI, but it had limited appeal because of poor absorption and low drug levels. Then came Fortovase, which was better absorbed but had more gastrointestinal side effects. The combination of Fortovase plus Norvir (initially using high doses of both drugs) was highly effective but not easy to take. Since the boosting effect of Norvir eliminated the absorption concerns with Invirase, Fortovase was eventually retired and Invirase made a small come-back, combined with lower, better tolerated doses of Norvir. In fact, it would still be a reasonable combination if it weren’t for the availability of once-daily boosted PIs (Prezista and Reyataz) that use half the daily dose of Norvir. The FDA also issued a recent warning about potentially serious EKG changes with Invirase. Saquinavir will be the first PI to go generic, though it seems unlikely that this will increase its use much, at least in the United States.

—Joel Gallant, MD, MPH

Potential side effects and toxicity Most common are diarrhea, abdominal discomfort, vomiting, and nausea. New warning added to the drug label last year states that Invirase/Norvir may change the electrical activity of the heart, which may lead to abnormal heart rhythms called prolonged QT or PR intervals. People with underlying heart conditions, or who have heart rate or heart rhythm problems, are at greater risk. Symptoms may include lightheadedness and fainting.

A medication guide is now required with a prescription. As seen with other protease inhibitors (except unboosted Reyataz), there can be increased levels of cholesterol and triglycerides which may be associated with an increased risk of heart disease. Other possible side effects are lipodystrophy (body fat changes, including thinning of the face, arms, and legs, with or without fat accumulation in the stomach, breasts, and upper back), onset of new cases or worsening of diabetes (see your doctor promptly) and increased bleeding in hemophiliacs. Immune Reconstitution Inflammatory Syndrome (IRIS) may occur as the immune system regains strength; signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is initiated. Report symptoms of illness, such as shingles and TB, to a health care provider.

Potential drug interactions Viramune, Sustiva, and Mycobutin (rifabutin) decrease Invirase levels. Not recommended to be used with Aptivus/Norvir or Prezista.

Should be used with caution and may require dose adjustment with Reyataz. Rescriptor, Crixivan, Norvir, Viracept, and Kaletra all significantly increase Invirase’s concentrations.

No dosage change when taken with Kaletra.

Do not take with alfuzosin, Revatio, Tambocor (flecainide), Rythmol (propafenone), Biaxin (clarithromycin), dexamethasone, Cordarone

P o s i t i v e lyAwa r e . c o m

More information Invirase has efficacy similar to Kaletra with less hyperlipidemia (elevated cholesterol and triglycerides). Invirase/Norvir was downgraded from “alternative choice” to the list of “regimens that are acceptable but should be used with caution” in the U.S. DHHS HIV treatment guidelines for what to take when

ACTIVIST’S COMMENTS A drug with many names and many lives— as one of the first PIs, it required many pills taken twice a day with a high fat meal, and it still had uneven absorption. A new version dubbed Fortovase came in a gel cap with better absorption, but also caused more GI problems like gas and diarrhea, and it quickly fell out of favor as better-tolerated PIs were introduced. Then it was discovered that with Norvir boosting you could just take two of the old pills twice a day (still with food) but with far fewer side effects. It’s still one of the better tolerated twice-daily PIs, and it may get yet another life when it goes generic and payers require patients to sacrifice the convenience of once-daily dosing to save money.

—Jeff Taylor

Ma r c h +A p r i l 2 0 1 1 | 41

2011 HIV Drug guide Kaletra brand name:

Kaletra

lopinavir/ritonavir, or LPV/r Protease inhibitor (PI) manufacturer: Abbott Laboratories | www.kaletra.com, (800) 222–6885 common name: class:

Standard dose: Two 200/50 mg tablets twice a day or four 200/50 mg tablets once daily for people with less than 3 lopinavir resistance-related mutations, as shown on a resistance test (no once-daily dose if taken with Sustiva or Viramune, or anticonvulsants). Three tablets twice a day may be considered for treatment-experienced people or those taking it with Sustiva or Viramune. Half-strength film-coated tablet available. Tablets should be swallowed whole, not chewed, broken, or crushed. Can be taken with or without food, with no dietary restrictions, but preferably taken with food to lessen side effects; liquid formula available. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on next dose.

AWP: $841.90 / month for tablets, $420.95 for 160 ml solution (400 mg/5 ml lopinavir and 100 mg/5ml ritonavir)

Potential side effects and toxicity Diarrhea is the most common and can be very severe. Rash, nausea, vomiting, stomach pain, headache, muscle weakness, and elevated liver enzymes, (a sign of liver damage—this may be more common in people with hepatitis B or C).

As seen with other protease inhibitors (except unboosted Reyataz), there can be increased levels of cholesterol and triglycerides which may be associated with an increased risk of heart disease. Other possible side effects are lipodystrophy (body fat changes, including thinning of the face, arms, and legs, with or without fat accumulation in the stomach, breasts, and upper back), onset of new cases or worsening of diabetes (see your doctor promptly) and increased bleeding in hemophiliacs. Immune Reconstitution Inflammatory Syndrome (IRIS) may occur as the immune system regains strength; signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is initiated.

Report symptoms of illness, such as shingles and TB, to a health care provider.

Potential drug interactions Do not take with alfuzosin, Revatio, Tambocor, Rythmol, Cordarone, oral Versed (midazolam), Halcion, Uroxatral, rifampin, pimozide, ergot derivatives (such as Cafergot, Wigraine, Methergine, and D.H.E. 45), garlic supplements, or the herb St. John’s wort. Do not use Advicor, Altoprev, Livalo, Mevacor, Simcor, Vytorin, or Zocor for the treatment of high lipids. Lipid-lowering alternatives are Crestor, Lescol, Lipitor, and Pravacol, but should be used with caution. Oral solution contains alcohol, so do not use with Antabuse or Flagyl. Use calcium channel blockers (such as Norvasc, Procardia, and others) with caution. Dosage of methadone may need to be increased when taken with Kaletra. Current guidelines state the Kaletra dose should total 500 mg lopinavir and 125 mg ritonavir twice daily when used with Sustiva or Viramune.

Because of high pill burden, physicians usually prescibe three tablets twice a day with food of the 200/50 mg dose when using with 42

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Sustiva or Viramune. Not recommended to be taken with Lexiva. Kaletra may lower levels of Retrovir (zidovudine, AZT) and Ziagen. Videx and Kaletra can be taken together, but without food. If Kaletra is taken with food, Videx should be taken an hour before or two hours after Kaletra. Mycobutin dosage should be reduced to 150 mg every other day (or 150 mg three times per week) when used with Kaletra.

Effectiveness of birth control pills may be decreased; consider the use of alternative or additional contraception. Mepron levels may be reduced with Kaletra. Avoid Sporanox or Nizoral doses greater than 200 mg per day with Kaletra. Decreases Vfend levels. People with kidney impairment may require lower Biaxin doses with Kaletra. Blood levels of immunosuppressants should be monitored, because their blood levels may increase when taken with Kaletra. Kaletra may alter Coumadin levels; additional monitoring may be required. Steroids, especially Decadron, may decrease levels of Kaletra. Kaletra increases levels of fluticasone (active component of Advair, Flonase, and Flovent) and trazodone. Use caution with anti-convulsants: Tegretol, phenobarbital, and Dilantin, as they may lower blood levels of Kaletra. Drug levels of bupropion are lowered; titrate dose based on clinical response. Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Use with caution with bosentan, salmeterol, immunosuppressants (including transplant drugs), and colchicine; use lower dose of colchicine. Kaletra can decrease the effects of Malarone; consider alternative drug for malaria prophylaxis.

More information In December 2009, Kaletra, like Lexiva, was downgraded from “preferred” to “alternative” therapy for treatment-naïve people in the U.S. HIV treatment guidelines. For people doing well on Kaletra, this should not be an issue.

Kaletra is preferred, however, for pregnant women with twice-daily dosing only. Oncedaily dosing cannot be taken by people with

more than three Kaletra-related HIV mutations. According to the guidelines, the need for 200 mg a day of Norvir (contained in Kaletra) and the higher rate of gastrointestinal side effects compared with boosted PIs using 100 mg Norvir make Kaletra an alternative for treatment-naïve people. Four tablets once daily can increase side effects, especially diarrhea. Taking with food and anti-diarrheal medicine helps lessen diarrhea. A few studies have shown an increased risk in heart attacks, not explained by cholesterol increases.

Kaletra should not be taken only once a day by children under 18. See package insert for more complete information on potential side effects and interactions.

Doctor’s COMMENTS Kaletra transformed our use of HAART, ushering in the widespread use of ritonavirboosted PIs, not just for treatment-experienced patients, but for anyone using a PI. The advantages of boosting include less frequent dosing and a big barrier to resistance, especially if you have no PI resistance to start with.

Kaletra was far easier and better tolerated than drugs like Crixivan, and more effective than Viracept, which was in common use at the time of its approval. It became the goldstandard PI and maintained that title for many years. However, Kaletra use has declined in the last few years, and it’s now considered a preferred PI only for pregnant women. It’s increasingly being replaced by Norvir-boosted Prezista and Reyataz, which can be taken with just 100 mg per day of Norvir compared to 200 mg in a daily dose of Kaletra. These drugs cause less diarrhea and lipid elevation than Kaletra. Kaletra still has the advantage of being the only co-formulated PI, meaning that you don’t have to take Norvir as a separate tablet. This can reduce co-pays, and it also makes it impossible to take the PI without the ritonavir needed to achieve adequate drug levels. —Joel Gallant, MD, MPH ACTIVIST’S COMMENTS No longer a preferred regimen in the treatment guidelines, Kaletra has the GI and lipid problems of many older PIs, as well as a host of drug interactions. Recent studies have shown it not to be as durable as Prezista, so it is losing ground to that and the more lipid-friendly Reyataz. All this despite Abbott’s efforts to combine it with their new non-refrigerated Norvir for convenience, and their shameful refusal to make that same non-refrigerated Norvir available to be combined with competing PIs for years in a desperate attempt to preserve market share. —Jeff Taylor

M a r c h +A p r i l 2 0 1 1 P o s i t i v e lyAwa r e . c o m

2011 HIV Drug guide Lexiva brand name:

Lexiva

fosamprenavir calcium Protease inhibitor (PI) manufacturer: ViiV Healthcare | www.viivhealthcare.com, (877) 844-8872 common name: class:

Standard dose: For people on a PI for the first time: two 700 mg tablets with either one 100 mg or two 100 mg Norvir, both once daily; or two 700 mg tablets (without Norvir), twice daily; or one 700 mg tablet with 100 mg Norvir, twice daily. For PI-experienced patients, one 700 mg tablet of Lexiva with 100 mg Norvir, twice daily. A grape/bubblegum/peppermintflavored oral suspension is also available. Can be taken with or without food, with no dietary restrictions, at any dose. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.

AWP: $869.44 / month for 60 tablets; $133.20 for 225 ml oral suspension (50 mg/ml)

Potential side effects and toxicity Because Lexiva contains sulfa, it should be used with caution in patients with allergies to sulfa drugs. The most common moderate to severe side effects may include nausea, rash, diarrhea, headache, vomiting, fatigue, and abdominal pain. Rash occurred in about 19% of patients, but severe rashes were uncommon.

If you experience a rash, notify your doctor.

For mild or moderate rashes, your doctor may choose to continue Lexiva, with close monitoring. Patients with hepatitis B or C should be monitored closely for the possibility of elevated liver enzyme levels. Dose adjustment is recommended for people with liver impairment. Side effects and laboratory abnormalities were similar when Lexiva was taken once or twice daily, with or without Norvir. As seen with other protease inhibitors (except unboosted Reyataz), there can be increased levels of cholesterol and triglycerides which may be associated with an increased risk of heart disease. A drug label change last year states that people should have cholesterol and triglyceride levels checked before going on Lexiva and monitored thereafter. Other possible side effects are lipodystrophy (body fat changes, including thinning of the face, arms, and legs, with or without fat accumulation in the stomach, breasts, and upper back), onset of new cases or worsening of diabetes (see your doctor promptly) and increased bleeding in hemophiliacs. Immune Reconstitution Inflammatory Syndrome (IRIS) may occur as the immune system regains strength; signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is initiated. Report symptoms of illness, such as shingles and TB, to a health care provider.

derivatives (such as Cafergot, Wigraine, Methergine, and D.H.E. 45), or the herb St. John’s wort. Do not use Advicor, Altoprev, Livalo, Mevacor (lovastatin), Simcor, Vytorin, or Zocor (simvastatin) for the treatment of high lipids. Lipid-lowering alternatives are Crestor, Lescol, Lipitor, and Pravacol (pravastatin), but should be used with caution.

Calcium channel blockers (such as Norvasc, Procardia, and others) should be used with caution and careful monitoring. Lexiva should be taken two hours before H2 blockers (Zantac, Pepsid, and others). Lexiva can lower methadone concentrations. A dose adjustment of Mycobutin (rifabutin) will be needed when used in combination with Lexiva.

Steroids, such as Decadron, may decrease levels of Lexiva. Increased levels of the inhaled and nasal sprays with fluticasone, a steroid for asthma or allergies (found in Advair, Flonase, and Flovent) can occur with Lexiva and therefore should be used with caution. Trazodone concentrations may increase; a lower dose of trazodone is recommended. Use caution with Paxil; drug levels of Paxil are lowered; titrate dose based on clinical response. Use caution with anti-convulsants Tegretol (carbamazepine), phenobarbital, and Dilantin (phenytoin).

Lexiva may alter Coumadin levels; additional monitoring may be required. Effectiveness of birth control pills may be decreased; consider the use of alternative or additional contraception methods. Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Use with caution with Biaxin (clarithromycin), bosentan, salmeterol, immunosuppressants (including transplant drugs), and colchicine; use lower dose of colchicine.

Potential drug interactions Not recommended to be taken with Kaletra.

When taken with Sustiva, boost a once-daily dose of Lexiva with 300 mg of Norvir. Do not take with alfuzosin, Revatio, Tambocor, Rythmol, oral Versed (midazolam), Halcion (triazolam), rifampin, Orap (pimozide), ergot

More information As with Kaletra, U.S. HIV treatment guidelines dropped Lexiva/Norvir as “preferred” for first-time therapy and listed it as an alternative. According to the guidelines, the change was made because regimens consisting of once-daily dosing and no more than 100 mg of

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Norvir are now favored. It can be taken once daily in treatment-naïve patients. The lower dose of Norvir may cause less of an increase in cholesterol and triglycerides, but there is limited clinical data with this dose. Studies have demonstrated that protease inhibitorexperienced patients should take Lexiva 700 mg with Norvir 100 mg, both twice daily.

The once-daily dosing is not recommended for treatment-experienced patients for whom a PI therapy has previously failed. It is important to take Lexiva exactly as your doctor instructs, and not to change dosing without discussing it with your doctor. An analysis from a French cohort showed Lexiva was associated with an increased risk of heart attacks, heart disease, and stroke. A liquid formula of Lexiva is available. See package insert for more complete information on potential side effects and interactions.

Doctor’s COMMENTS Before there was Lexiva, there was Agenerase (amprenavir), which came in enormous, suppository-sized capsules taken at large, stomach-filling doses. The approval of Lexiva, a “pro-drug” of Agenerase, was a big improvement, and it had the most versatility of any PI. It could be taken with or without food, with or without Norvir boosting, and once or twice a day. However, a comparison of twice-daily Norvir-boosted Lexiva showed no advantages over Kaletra in terms of effectiveness, safety or tolerability, and Kaletra had the advantage of co-formulation. Later, a once-daily regimen of two tablets (1400 mg) of Lexiva with 100 mg of Norvir was approved for people who hadn’t taken PIs before, but there weren’t any clear advantages of this combination over boosted Reyataz or Prezista, which had been more extensively studied. As a result, this worthy PI hasn’t been widely used. While it’s one of the few PIs that doesn’t have to be boosted, the use of unboosted Lexiva can lead to Prezista cross-resistance, and therefore should be avoided. —Joel Gallant, MD, MPH ACTIVIST’S COMMENTS Originally released as Agenerase, the newer Lexiva offers the option of once-daily dosing with Norvir, or without Norvir twice daily. But like many older PIs, it causes GI problems, raises lipids, and can cause body shape changes.

It also contains sulfa, so it can cause allergic reactions in the same way that Bactrim can.

These problems have caused it to be replaced by newer PIs like Prezista and Reyataz.

—Jeff Taylor

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2011 HIV Drug guide Norvir brand name:

Norvir

ritonavir Protease inhibitor (PI) manufacturer: Abbott Laboratories | www.norvir.com, (800) 222–6885 common name: class:

Standard dose: Almost never used at its approved dose (a lead-in dosing, then six 100 mg tablets twice daily). Norvir is primarily used as a boosting agent for other PIs, at smaller doses of 100 to 400 mg, either once or twice a day with a meal. See drug label of the other PI. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose. Approved for children ages one month and older. Liquid formula available, but tastes unbelievably horrific.

AWP: $308.60 / for 30 tablets; $1,728.24 for 240 ml oral solution (80 mg/ml)

Potential side effects and toxicity Most common side effects include weakness, stomach pain, upset stomach (nausea, diarrhea, and vomiting), tingling/numbness around the mouth, hands or feet, loss of appetite, taste disturbance, weight loss, headache, dizziness, pancreatitis, and alcohol intolerance. Other potential side effects are liver problems, such as an increase in liver enzymes (AST, ALT, and GGT), hepatitis, or jaundice (yellowing of skin), and increased muscle enzyme (CPK) and uric acid. People with hepatitis B or C may be at increased risk. There can be increased levels of cholesterol and triglycerides which may be associated with an increased risk of heart disease. Other possible side effects are lipodystrophy (body fat changes, including thinning of the face, arms, and legs, with or without fat accumulation in the stomach, breasts, and upper back), onset of new cases or worsening of diabetes (see your doctor promptly) and increased bleeding in hemophiliacs. Immune Reconstitution Inflammatory Syndrome (IRIS) may occur as the immune system regains strength; signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is initiated. Report symptoms of illness, such as shingles and TB, to a health care provider.

Potential drug interactions Norvir interacts with many other drugs. See the package insert for the most complete list.

Tell your provider of all drugs you are taking, prescribed or non-prescribed. Do not take with alfuzosin, Revatio, Tambocor, Rythmol, Cordarone, oral Versed, Halcion, Uroxatral, Rifadin (rifampin—reduces Norvir levels by 35%), Orap, ergot derivatives (such as Cafergot, Wigraine, Methergine, and D.H.E. 45), Vfend (voriconazole), garlic supplements, or the herb St. John’s wort. Do not use Advicor, Altoprev, Livalo, Mevacor, Simcor, Vytorin, or Zocor for the treatment of high lipids. Lipid-lowering alternatives are Crestor, Lescol, Lipitor, and Pravacol, but should be used with caution.

Norvir increases levels of fluticasone (active component of Advair, Flonase, and Flovent).

Trazodone concentrations may increase; a lower dose of trazodone is recommended.

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Norvir and Aptivus may decrease levels of methadone, but withdrawal rarely occurs.

Methadone doses may need to be increased.

Use caution with anti-convulsants Tegretol (carbamazepine), phenobarbital, and Dilantin (phenytoin). Use calcium channel blockers (such as Norvasc, Procardia, and others) with caution.

Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Effectiveness of birth control pills may be decreased; consider the use of alternative or additional contraception. Levels of the street drug Ecstasy are greatly increased by Norvir, and at least one death has been attributed to the combination. GHB is also dangerous with Norvir. Tobacco and alcohol may lower blood levels of Norvir. Increases up to 80% have been seen in Biaxin (clarithromycin) levels. Use with caution with bosentan, salmeterol, immunosuppressants (including transplant drugs), and colchicine; use lower dose of colchicine.

More information Norvir is now available in a tablet formulation that does not require refrigeration. Although the tablet is not bioequivalent to the capsule, no dosage adjustment is needed. Blood concentration is higher with the tablets when taken with food (as required), and may cause more side effects. The real strength of Norvir is in combination with other PIs (used as a boosting agent), allowing for a lower dose of both (decreased pill burden) and, in many cases, a decrease in the frequency of doses.

Abbott Laboratories increased the price of Norvir 400% in 2003 and has been in the doghouse with both medical providers and advocates since. A promising alternative to Norvir boosting called cobicistat (GS 9350) is in research. In one study, similar efficacy, safety, and tolerability were seen with cobicistat compared to Norvir-boosted Reyataz, with Truvada backbone. However, this medication may cause kidney impairment. More research is underway. Stomach side effects are reduced by taking Norvir with high fat foods (such as peanut butter or avocado)— however, be careful, because some other HIV medicines should not be taken with high fat foods. You can mix liquid solution in ice cream,

milk (especially chocolate), or pudding to hide the taste. Label says mix one hour before taking. Blood concentration increases in people with liver impairment. See package insert for more complete information on potential side effects and interactions.

Doctor’s COMMENTS Norvir enjoyed very brief use as a PI in its own right, but the people who took it at its full, virtually intolerable dose of 600 mg twice a day didn’t enjoy it at all. The dose was then reduced to 400 mg twice a day in combination with Invirase. That regimen was mainly popular because it wasn’t Crixivan and it wasn’t full dose Norvir, but it was still tough to take. No one takes Norvir at those doses now. It’s used only because of its interactions with the other PIs, at “booster” doses of 100200 mg per day, which prolong their half-lives, decrease dosing frequency, and reduce the risk of drug resistance. All PIs except Viracept can be boosted by Norvir, and the only PIs that can be given unboosted are Viracept and Reyataz. Of those, I would never prescribe an unboosted PI other than Reyataz, and I do that only for my patients whom I refer to as “ritonophobes,” people who, perhaps because of a Pavlovian response to memories of highdose Norvir, get nauseated just by looking at the bottle. Norvir now comes in a heat-stable tablet, so it no longer requires refrigeration.

Some drug companies are looking at alternative booster agents, which they hope will have the same boosting effect on PIs and other agents, but with advantages in terms of cost, tolerability, or the ability to co-formulate.

—Joel Gallant, MD, MPH ACTIVIST’S COMMENTS A drug that set new lows in pharmaceutical greed when Abbott quadrupled its price back in 2003, and new highs in side effects with diarrhea, cramps, gas, increased cholesterol and lipids, and fat gain (remember “protease paunch”?), Norvir remains a necessary evil because of its unique ability to boost the level of protease inhibitors (and also other drugs like Viagra, but that’s another subject).

It remains to be seen whether Gilead’s yetto-be-approved booster cobicistat will be substantially better in terms of side effects than Norvir. In the meantime, patients who want the convenience of a once-a-day protease inhibitor, or need its boosting strength to overcome resistance, will have to continue to tough out the side effects and avoid or exercise caution with the long list of drugs with which it can interact. —Jeff Taylor

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2011 HIV Drug guide Prezista brand name:

Prezista

darunavir Protease inhibitor (PI) manufacturer: Tibotec Therapeutics | www.prezista.com, (877) REACH-TT (732-2488) common name: class:

Standard dose: 800 mg (two 400 mg tablets) with 100 mg Norvir once daily with food for first-time therapy and treatment-experienced adults without Prezista-related HIV resistance, or 600 mg (one 600 mg tablet) with 100 mg Norvir twice daily with food for treatment-experienced adults with at least one Prezista-related HIV drug resistance mutation. 75 mg and 150 mg tablets available for children over six, dose based on weight. Take missed dose as soon as possible, but not if more than 12 hours late on the once-daily dose (or six hours late on the twicedaily dose). Do not double up on your next dose; take the next dose on schedule.

AWP: $1,156.21 / month

Potential side effects and toxicity Prezista contains sulfa, and should be used cautiously by people with sulfa allergies.

Prezista may cause mild to moderate rash, but the most common side effects may include diarrhea, nausea, headache, and abdominal pain. Laboratory testing for liver function should be done before starting therapy and patients should be monitored. Increased monitoring should be considered for people with underlying chronic hepatitis, cirrhosis, or elevated levels of AST/ALT (lab measures of liver function), especially during the first several months of therapy. No dose adjustment is necessary for those with mild to moderate liver disease, but Prezista/Norvir is not recommended for people with severe liver impairment. Severe rash, while very rare, can be life-threatening. Seek medical attention immediately. You may need to stop all medications. As seen with other protease inhibitors (except unboosted Reyataz), there can be increased levels of cholesterol and triglycerides. Increased cholesterol and triglycerides may be associated with an increased risk of heart disease. Other possible side effects are lipodystrophy (body fat changes, including thinning of the face, arms, and legs, with or without fat accumulation in the stomach, breasts, and upper back), onset of new cases or worsening of diabetes (see your doctor promptly) and increased bleeding in hemophiliacs. Immune Reconstitution Inflammatory Syndrome (IRIS) may occur as the immune system regains strength; signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is initiated. Report symptoms of illness, such as shingles and TB, to a health care provider.

Potential drug interactions Do not take with alfuzosin, Revatio, oral Versed (midazolam), triazolam (Halcion), ergot derivatives (D.H.E. 45, Migranal, Cafergot, Ergomar, ergonovine, methylergonovine), the herb St.

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John’s wort, cisapride, pimozide (Orap), and rifampin. Prezista may decrease levels of phenytoin (Dilantin), phenobarbital, and Tegretol; blood levels should be monitored. A reduced dose of rifabutin is recommended. Do not use Advicor, Altoprev, Livalo, Mevacor, Simcor, Vytorin, or Zocor for the treatment of high lipids. Lipid-lowering alternatives are Crestor, Lescol, Lipitor, and Pravacol (pravastatin), but should be used with caution. The antifungal drugs such as itraconazole and ketoconazole may increase levels of Prezista, and Prezista may increase theirs, so caution must be exercised when used together (maximum dose is 200 mg a day for the antifungals). Blood levels of voriconazole (Vfend) may decrease.

Voriconazole should not be administered unless benefit/risk justifies its use. Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Prezista may increase levels of calcium channel blockers, such as Norvasc and others, and clinical monitoring is recommended.

A lower dose of trazodone and disipramine is recommended. Monitoring may be required when using Coumadin (warfarin). Increased levels of the inhaled and nasal sprays with fluticasone (found in Advair, Flonase, and Flovent) can occur and therefore alternatives should be considered, particularly for long-term use. Effectiveness of birth control pills may be decreased; consider the use of alternative or additional methods of contraception. No dosing adjustment required with Subutex or Suboxone, but monitoring is recommended. Use with caution with bosentan, salmeterol, immunosuppressants (including transplant drugs), and colchicine; use lower dose of colchicine.

More information Prezista is one of two recommended PIs for initial therapy in treatment-naïve people in the U.S. DHHS HIV guidelines. FDA approval in late

2010 allows once-daily dosing for treatmentexperienced adults who do not have Prezistarelated drug mutations in their HIV, and both show it to be as effective as twice-daily dosing. This will also hopefully help adherence and decrease side effects. See package insert.

In one major study, Prezista showed success even in people who missed doses; while it’s not ideal to skip doses, its “forgiveness” profile helped make it popular. Tibotec received community kudos for not pricing Prezista higher than other new PIs. See package insert for more complete information on potential side effects and interactions.

Doctor’s COMMENTS Prezista started out as the best of the “secondgeneration” PIs, showing excellent activity in most people with PI-resistant virus. Then, it was shown to be more effective and more “resistant to resistance” than Kaletra in people who had taken PIs before but whose virus was susceptible to both drugs. A later study found that a once-daily dose of Prezista/Norvir had a number of advantages over Kaletra for firstline therapy, including less diarrhea, less lipid elevation, and better activity at higher viral loads. The latest development has been the approval of the once-daily dose for treatmentexperienced patients who have no Prezista mutations. In short, you could say it’s the “PI for all seasons.” The main downside of Prezista is that it’s more likely than other PIs to cause an allergic rash, and, unlike the rash with Sustiva, a rash when you’re on Prezista usually requires a switch to a different drug. Prezista must always be taken with Norvir, and with food.

—Joel Gallant, MD, MPH ACTIVIST’S COMMENTS Appropriate for either treatment-naïve or experienced patients, Prezista (along with Reyataz) has largely replaced Kaletra. It has fewer side effects than the older drugs—especially salvage drugs like Aptivus, and has been shown to be durable and well tolerated. It still needs to be taken with food, and has many of the drug interactions common to other PIs. Tibotec earned a gold star from the community when they introduced this drug by breaking the usual industry practice of pricing all new drugs higher than past drugs—helping keep costs down for patients and payers.

—Jeff Taylor

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2011 HIV Drug guide Reyataz brand name:

Reyataz

atazanavir sulfate Protease inhibitor (PI) manufacturer: Bristol-Myers Squibb | www.reyataz.com, (800) 321–1335 common name: class:

Standard dose: One 300 mg capsule plus 100 mg Norvir, once daily (this dose must be used if taking Viread or Truvada, or if pregnant), or two 200 mg capsules (without Norvir), once daily for treatment-naïve adults; take with food. Also available in 100 mg and 150 mg capsules.

Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.

AWP: $1,120.31 / month for 300 mg capsules; $1,130.99 / month for 200 mg capsules

Potential side effects and toxicity Dizziness and lightheadedness. Elevated levels of unconjugated bilirubin may cause jaundice (yellowing of the skin or eyes). Though this is not evidence of liver damage, some choose to change meds due to unsightliness.

Report jaundice to your medical provider right away. Other side effects may include rash, kidney stones, and elevated liver function enzymes, a sign of liver damage; more common in people with hepatitis B or C. Reyataz should not be taken by treatmentexperienced patients on hemodialysis due to end stage renal disease. Reyataz is the only PI not associated with increased lipid levels, which are associated with increased risk of heart disease, but higher lipid levels may be seen if Reyataz is boosted with Norvir. Other possible side effects are lipodystrophy, onset of new cases or worsening of diabetes (see your doctor promptly), and increased bleeding in hemophiliacs. Immune Reconstitution Inflammatory Syndrome (IRIS) may occur as the immune system regains strength; signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is initiated. Report symptoms of illness, such as shingles and TB, to a health care provider.

Potential drug interactions Treatment-experienced people cannot take Reyataz with proton pump inhibitors (PPIs— medicine for acid reflux). Treatment-naïve people can take a PPI in a dose comparable to Prilosec OTC 12 hours before Reyataz/Norvir.

H2-receptor antagonists like Pepcid may be taken (no more than 20 mg twice a day if treatment-experienced or 40 mg twice a day if treatment-naïve, or equivalent doses) at the same time as Reyataz/Norvir (before the antacid has started to work) or at least 10 hours later. If taking with Viread or Truvada and an H2-receptor antagonist, you must take the 400 mg Reyataz/100 mg Norvir dose. When taking Reyataz without Norvir, dose can be taken at least two hours before and at least 10 hours after Pepcid, Zantac, or Axid. Reyataz should be taken two hours before or one hour after antacids (Rolaids, Tums, etc.). Do not take with alfuzosin, Revatio, rifampin, Camptosar, oral Versed, Halcion, ergot derivatives, 4 6 | Ma r c h +A p r i l

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pimozide, Crixivan, or St. John’s wort. Do not use Advicor, Altoprev, Livalo, Mevacor, Simcor, Vytorin, or Zocor for the treatment of high lipids. Lipid-lowering alternatives are Crestor, Lescol, Lipitor, and Pravacol, but should be used with caution. Must be taken two hours apart from Videx, due to Videx’s buffer, and must be taken two hours before or one hour after Videx EC (unless taking Videx EC with Viread). Treatment-naïve people should take 400 mg Reyataz/Norvir (100 mg) when taking with Sustiva, but treatment-experienced people should not use Reyataz with Sustiva.

Viread decreases the concentration levels of Reyataz and Reyataz increases Viread concentrations, which could increase adverse events, including kidney disorders. Those taking Reyataz and Viread should be monitored for Viread-associated adverse events. Use the heart medications bepridil, Cordarone, quinidine, and lidocaine cautiously.

Monitoring may be required when used with Coumadin. Increased levels of the inhaled and nasal sprays with fluticasone (found in Advair, Flonase, and Flovent) can occur and should be used with caution. Effectiveness of birth control pills may be decreased; consider the use of alternative or additional contraception. Oral contraception should contain no more than 30 mcg of ethinyl estradiol if taking Reyataz without Norvir and at least 30 mcg if taken with Norvir. Use caution when using itraconazole or ketoconazole. Vfend is not recommended. Reducing dose and frequency of rifabutin to 150 mg every other day or three times a week is recommended. Use caution with Tegretol, phenobarbital, and Dilantin.

Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Calcium channel blockers should be monitored. A lower dose of trazodone is recommended. Use with caution with bosentan, salmeterol, immunosuppressants, and colchicine; use lower dose of colchicine. Boost Reyataz with Norvir when taking buprenorphine. Monitor before sedation. Reyataz can decrease the effects of Malarone; consider alternative drug for malaria prophylaxis.

More information Norvir-boosted Reyataz is one of two

protease inhibitors recommended by the U.S. HIV treatment guidelines for treatment naïve people. People who started out with unboosted Reyataz continued to do as well as those on boosted Reyataz, but many folks are still concerned about data showing that unboosted use is associated with a higher risk of treatment failure. Reyataz must be boosted if taken with Truvada, but can be unboosted with Epzicom. See package insert for more complete information on potential side effects and interactions.

Doctor’s COMMENTS The first of the “kindler, gentler PIs,” Reyataz was first thought to be less potent than Kaletra, but for initial therapy, it was as effective as Kaletra with less diarrhea and lipid elevations in a large clinical trial. It also has the most convenient dosing of any PI (see Standard Dose section). Reyataz is also the only PI I would consider prescribing without boosting, because resistance to Reyataz doesn’t cause cross-resistance to other PIs. Because of an interaction with tenofovir, Reyataz must be boosted when combined with Viread or Truvada, and if combined with Sustiva or Atripla, an even higher dose of Reyataz should be used (400 mg plus 100 mg Norvir). Reyataz needs an acidic environment for absorption; it can’t be taken with most proton pump inhibitors, and strict dosing separation is required with other stomach acid reducers, such as H2 blockers and antacids.

It’s probably better to just avoid Reyataz if you’re taking medications for reflux or ulcers.

Reyataz also increases the indirect bilirubin, which for most is a harmless lab abnormality, but for others, can result in yellowing of the eyes and/or skin. These side effects are harmless but unattractive, and most people who develop them elect to change drugs.

—Joel Gallant, MD, MPH ACTIVIST’S COMMENTS The first once-a-day PI, it can also be taken without a Norvir booster. It lacks the GI and increased cholesterol and triglycerides that plague most PIs. One downside to this heartfriendly drug is that it can raise levels of the liver enzyme bilirubin—which isn’t toxic but can cause unsightly yellowing of the eyes and even the skin. Another drawback is that it can’t be taken with proton pump inhibitors for acid reflux, and some other antacids can’t be taken at the same time. Despite this, the lack of usual PI side effects mean that,boosted with Norvir, it’s one of the most popular regimens when combined with Truvada.

—Jeff Taylor P o s i t i v e lyAwa r e . c o m

2011 HIV Drug guide Viracept brand name:

Viracept

nelfinavir Protease inhibitor (PI) manufacturer: ViiV Healthcare | www.viivhealthcare.com, (877) 844-8872 common name: class:

Standard dose: 1,250 mg taken as either two 625 mg tablets or five 250 mg tablets twice daily with food. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose. Viracept Oral Powder also available for children and individuals unable to swallow tablets.

AWP: $844.02 / month for 250 and 625 mg tablets

Potential side effects and toxicity Most common include diarrhea, stomach discomfort, nausea, gas, weakness, and rash.

People with phenylketonuria should be aware that the powder contains phenylalanine. As seen with other protease inhibitors (except unboosted Reyataz), there can be increased levels of cholesterol and triglycerides which may be associated with an increased risk of heart disease. Other possible side effects seen with protease inhibitors are lipodystrophy (body fat changes, including thinning of the face, arms, and legs, with or without fat accumulation in the stomach, breasts, and upper back), onset of new cases or worsening of diabetes (see your doctor promptly), and increased bleeding in hemophiliacs. Immune Reconstitution Inflammatory Syndrome (IRIS) may occur as the immune system regains strength; signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is initiated. Report symptoms of illness, such as shingles and TB, to a health care provider.

Potential drug interactions Viracept increases levels of Invirase and Crixivan (see Crixivan for potential drug interactions, page 40), so dose adjustments may be needed. Do not take with alfuzosin, Revatio, oral Versed (midazolam), Cordarone (amiodarone), Halcion (triazolam), Rifadin (rifampin), Prilosec OTC (omeprazole), ergot derivatives (such as Cafergot, D.H.E. 45, Methergine, Wigraine), garlic supplements, or the herb St. John’s wort. Do not use Advicor, Altoprev, Livalo, Mevacor (lovastatin), Simcor, Vytorin, or Zocor (simvastatin) for the treatment of high lipids. Lipid-lowering alternatives are Crestor, Lescol, Lipitor, and Pravacol (pravastatin), but should be used with caution.

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Viracept may decrease methadone levels but withdrawal rarely occurs; methadone doses may need to be increased. Use calcium channel blockers with caution. Blood levels of Viracept are reduced by rifampin and may be reduced by phenobarbital, phenytoin, and carbamazepine (Tegretol and others), so it is important to inform your doctor if you are taking any of these medications. Mycobutin (rifabutin) dose must be decreased when used with Viracept. Prescriber may need to adjust doses of any of these drugs accordingly.

Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Increased levels of inhaled and nasal sprays with fluticasone, a steroid for asthma or allergies (found in Advair, Flonase, and Flovent), can occur and therefore should be used with caution. Effectiveness of birth control pills may be decreased; consider the use of alternative or additional methods of contraception. Also, increased levels of trazodone can occur and this combination should be used with caution. A lower dose of trazodone is recommended. Use with caution with bosentan, salmeterol, immunosuppressants (including transplant drugs), and colchicine; use lower dose of colchicine.

More information This is the only protease inhibitor that is never used with Norvir. Do not leave the pharmacy without anti-diarrhea meds such as Immodium, or Tums or other calcium products. Taking a 500 mg calcium supplement with doses hugely decreases diarrhea. Also try Solgar oat bran tablets, psyllium husk fiber bars, and pancreatic enzymes (all with meals). As an extra precaution, take a change of clothes with you everyday for the first several weeks—stick it

out, most often, symptoms improve after two or three weeks. The oral powder tastes horrible and requires a large amount for mixing into food. People using Viracept can crush adult tablets or dissolve tablets in a small amount of water. Mixing Viracept with acidic food or juice (e.g. orange/apple juice or apple sauce) is not recommended, due to resulting bitter taste. To get the full benefit of Viracept by increasing its level in the body, it must be taken with a meal. See package insert for more complete information on potential side effects and interactions.

Doctor’s COMMENTS Viracept was once a popular alternative to more toxic or inconvenient PIs like Crixivan or Invirase/Norvir. However, there was a price to be paid for the greater convenience and relative tolerability (I say “relative” because it still caused a lot of diarrhea). It was less effective than other PIs, a fact that became clear in a head-to-head comparison with Kaletra. This may have been due in part to variable absorption and drug levels. And while its initial claim to fame was that Viracept mutations didn’t cause resistance to other PIs, that wasn’t always the case, and people on Kaletra didn’t develop mutations anyway. Viracept, the only “unboostable” PI, gradually fell out of favor, and is no longer recommended or widely used. —Joel Gallant, MD, MPH ACTIVIST’S COMMENTS A protease inhibitor dinosaur, Viracept was famous for its “Blue Velcro” pills that stuck in your throat, and once they got to your stomach caused explosive blue diarrhea. A new coating corrected the Velcro problem, but the twice-daily dosing and high pill burden contributed to making this PI an also-ran. Luckily for patients, it was a good drug to fail, as most could still get to undetectable if they switched to another boosted PI. However, it may still be a useful drug for women trying to conceive, as it is one of the alternative drugs recommended for prevention of mother-to-child transmission. —Jeff Taylor

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2011 HIV Drug guide Fuzeon brand name:

Fuzeon

enfuvirtide Fusion inhibitor (a type of entry inhibitor) manufacturer: Genentech | www.genentech.com, www.fuzeon.com,

(877) 4–FUZEON (438–9366) common name: class:

Standard dose: One subcutaneous (under the skin) injection of 90 mg (1 ml) twice daily (every 12 hours) into the upper arm, thigh, or abdomen. Can be taken with or without food, with no dietary restrictions. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.

AWP: $3,154.10 / month for 90 mg kit

Potential side effects and toxicity The most common are Injection Site Reactions (ISRs), which occur in virtually all patients. The severity of reaction is variable, and for most is mild to moderate. Symptoms could include itching, swelling, redness, pain or tenderness, and hardened skin or bumps. Bumps termed “nodules” seem to occur more frequently and severely in areas of high muscle mass (most notably the center of the stomach— the abs—and the thighs). They will hurt with movement. Other side effects may include diarrhea, nausea, and fatigue. Hypersensitivity (allergic-like) reactions are possible. In studies, pneumonia happened more often in the patients on Fuzeon. It is unclear if this was related to the use of Fuzeon, so report cough, fever, or trouble breathing to your health care provider immediately. Immune Reconstitution Inflammatory Syndrome (IRIS) may occur as the immune system regains strength; signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is initiated. Report symptoms of illness, such as shingles and TB, to a medical provider.

Potential drug interactions To date, none that are clinically significant have been found.

More information With other powerful, newer drugs on the market, the twice-daily injectable Fuzeon has truly become a medicine of last resort. Fuzeon is intended for treatment-experienced patients.

Store kit at room temperature. Preparing and

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injecting the Fuzeon can be complicated, so ask your health care provider how to do it. First, the drug needs to be dissolved with sterile water (provided in the kit), which may take up to 45 minutes. Never shake the vial with the Fuzeon, it will foam. Instead, roll it gently in your hands.

To save time, you can prepare the two daily doses at the same time. You should store your second dose in the refrigerator, but it must be used within 24 hours (allow it to warm to room temperature before using). Before injecting, it is important to make sure that the Fuzeon powder is completely dissolved. To minimize injection site reactions, inject where you can pinch an inch (upper arm, stomach, or thigh). If not, then be sure to use half the length of the needle. Inject slowly and apply a gentle massage after injection. Try using vibrating devices after injections. Follow proper hygiene instructions to avoid infection. ISR may worsen when injection is repeated in the same spot or given deeper than intended, for example, into the muscle. Always rotate injection sites frequently.

Never inject into moles, scars, bruises, nodules, or the navel. Switching to smaller needles, like insulin syringes, may also help with ISRs. Fuzeon can be taken at the same time as other anti-HIV drugs. Fuzeon is the only anti-HIV compound on the market called a fusion inhibitor. Fusion inhibitors block fusion of HIV with a cell before the virus enters the cell and begins its replication process. Fusion inhibitors are a type of entry inhibitor (see Selzentry). See package insert for more complete information on potential side effects and interactions.

Doctor’s COMMENTS Fuzeon inhibits fusion of the virus with the CD4 cell membrane, the final stage in the entry process. It was our first true “salvage drug,” a drug to be used in people with highly resistant virus. In fact, the original TORO trials not only led to the approval of Fuzeon, but ushered in the era of salvage therapy and set the standard for clinical trial design that would later lead to the approval of drugs like Prezista, Isentress, Selzentry, and Intelence.

However, Fuzeon, never a big seller, is now rarely used. For most people, even those with the most highly resistant virus, there are easier, less expensive options that don’t require twice-daily subcutaneous injections that leave long-lasting painful bumps on the skin (injection site reactions, or ISRs). But I wouldn’t dismiss Fuzeon altogether. We may be in a “honeymoon period” with respect to salvage therapy, when almost everyone can keep their viral load undetectable with a combination of other drugs. But the pipeline of drugs for treatment-experienced patients isn’t exactly gushing right now, and if we begin to see a lot of resistance to the newer drugs, especially Isentress, we may be forced to pull Fuzeon off the shelves again. —Joel Gallant, MD, MPH ACTIVIST’S COMMENTS Like its name suggests, it’s the first and only fusion inhibitor—so as the only drug in its class, there is no pre-existing resistance for those in desperate need of a new drug.

The twice-daily injections with often painful and lingering injection site reactions mean that, despite its unique activity and efficacy, it remains a drug of last resort for those who’ve run out of options. Even when added to a failing regimen it can help maintain T-cells—buying patients time until new drugs become available to construct a new regimen.

—Jeff Taylor

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2011 HIV Drug guide Selzentry brand name:

Selzentry

maraviroc CCR5 antagonist (a type of entry inhibitor) manufacturer: ViiV Healthcare | www.viivhealthcare.com, (877) 844-8872 common name: class:

Standard dose: Available in 150 mg and 300 mg tablets. Can be taken with or without food, with no dietary restrictions. The recommended dose varies, depending on other medications the patient is taking: 150 mg twice daily if taken with a protease inhibitor (except for Aptivus) and Rescriptor; 300 mg twice daily if taken with Aptivus, Viramune, Fuzeon, and all of the NRTIs; 600 mg twice daily if taken with Sustiva, Intelence, rifampin, and some anti-convulsant medications such as phenobarbital, phenytoin, and carbamazepine. Default to Selzentry 150 mg twice daily when combined with a CYP3A inhibitor dose (the PI group) if using medications from multiple classes (such as a PI with a NNRTI). Dose change may be required in kidney disease. Concurrent use of Selzentry and other medications that can either inhibit or induce liver metabolism will affect the dose of Selzentry. Your doctor or pharmacist can determine which medications will affect Selzentry.

AWP: $1,101.42 / month for 150 mg or 300 mg tablets

Potential side effects and toxicity Most common include cough, fever, cold, rash, muscle and joint pain, stomach pain, and dizziness. Other potential side effects may include liver toxicity; an allergic reaction may happen before the liver problems. It is recommended Selzentry be stopped and your doctor contacted right away if you develop a rash, yellowing of your eyes or skin, and/or dark urine, vomiting, and upper stomach pain. Other rare side effects may include low blood pressure when standing up that could lead to dizziness or fainting. New warning added to the drug label last year—should not be used in people with severe renal impairment or end-stage renal disease who are taking potent CYP3A inhibitors or inducers (check with your provider). Immune Reconstitution Inflammatory Syndrome (IRIS) may occur as the immune system regains strength; signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is initiated. Report symptoms of illness, such as shingles and TB, to a health care provider.

While no increased risk of infections or cancer was seen in clinical trials, Selzentry affects other immune system cells and could possibly increase the risk of infections and cancer.

Potential drug interactions Not recommended with rifampin or St. John’s wort. Dose adjustment needed for Biaxin, Dilantin (phenytoin), Tegretol (carbamazepine), phenobarbital, HIV NNRTIs and PIs, Mycobutin, Sporanox (itraconazole), Nizoral (ketoconazole), Vfend, oral contraceptives, and oral Versed (midazolam). See standard dosing section for interactions with other antiHIV medications.

More information Maraviroc is the first oral entry inhibitor available on the market. Originally indicated for treatment-experienced patients infected only

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with CCR5-tropic virus, it is now also FDAapproved for people starting HIV therapy for the first time. Complex dosing, the need for an expensive tropism test, and competition from newer drugs have dimmed some of the initial enthusiasm for this drug. Viral tropism refers to the types of HIV that a person can have: CCR5-tropic (R5) virus and CXCR4-tropic (X4) virus. (Tropism is pronounced with a long “o,” as in “okay.”) HIV attaches to the CD4 receptor on the surface of some human T-cells (hence, CD4+ T-cells), and then it latches on to one of the two co-receptors on the surface of the cells, CCR5 (R5) or CXCR4 (X4), thus gaining entry. As the name “CCR5 inhibitor” suggests, Selzentry inhibits (blocks) CCR5, shutting down this point of entry for the virus.

(The co-receptor inhibitors are also called “antagonists,” as in “CCR5 antagonist.”) X4 virus is associated with advanced HIV disease.

HIV infection may involve viruses that infect only CCR5 cells, only CXCR4, both of these types of cells (dual tropic), or a mix (mixed tropic). Most people are infected with CCR5 virus, and then over time more CXCR4 and mixed viruses accumulate. In results from various studies, Pfizer did not find that blocking R5 with maraviroc caused virus to shift to X4 or show a negative effect on disease progression or CD4 count in so-called “dual tropic” people (their virus can use either R5 or X4).

In 2007, the company reported that a switch to X4—or dual-tropic virus—was transient and reversible when people went off maraviroc. In studies with treatment-experienced people, a large number of patients were excluded because they did not have exclusive CCR5tropic virus, limiting the number of patients who could truly benefit from this drug. A sub-analysis reported that Selzentry seems to have minimal impact on lipid levels. Selzentry has been studied in treatment-naïve patients (first time on therapy) in the MERIT clinical trial. Although the initial analysis suggested

that Selzentry was unable to match Sustiva at viral loads less than 50 copies, a re-analysis of the data using the enhanced Trofile test (Trofile ES) showed the regimens to be comparable (59% for Selzentry vs. 63% for Sustiva in less than 50 copies at 96 weeks). The follow-up results of 96-week data led to its FDA approval for this population. Other CCR5 inhibitors are in the works. See package insert for more complete information on potential side effects and interactions.

Doctor’s COMMENTS Selzentry is an entry inhibitor that acts at an earlier stage of the entry process than Fuzeon: It blocks the binding of the virus to the CCR5 co-receptor on the CD4 cell surface. Since some people have virus that can get into the cell using CXCR4, another co-receptor, Selzentry won’t work against that kind of virus.

As a result, it’s necessary to test the “tropism” of the virus before using Selzentry. Only those with purely “R5-tropic” virus should use the drug. The need for this test has been the main obstacle to widespread use of Selzentry, which is an effective, safe and well tolerated agent. The test currently in use in the United States, the Trofile assay, is expensive and time-consuming. Outside of the U.S., cheaper genotypic tests are being used. These may turn out to be good alternatives to Trofile, but we need more data on how well they measure tropism and predict success with Selzentry before they can be recommended. Selzentry has now been approved by the FDA for initial therapy, and people are more likely to have R5-tropic virus at early stages, before they’ve been treated. However, Selzentry is not yet being widely used for that purpose, and for initial therapy, it’s categorized as “acceptable” or “alternative” in the DHHS and IAS-USA guidelines, respectively.

—Joel Gallant, MD, MPH ACTIVIST’S COMMENTS For those most in need of a new class of drug, the CCR5 antagonist Selzentry has proven to be a disappointment. It only works in those whose HIV virus has CCR5 receptors, who are not the sickest and who don’t need new drugs the most. Add to that the expensive tropism test required to see if one has the CCR5-tropic virus Selzentry is effective against, complicated interactions with other HIV drugs, and it becomes a difficult drug to use. But its unique mode of activity and few side effects mean that more research is needed to see how best to use this new class of drug. —Jeff Taylor

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2011 HIV Drug guide Isentress brand name:

Isentress

raltegravir Integrase inhibitor (integrase strand transfer inhibitor or INSTI) manufacturer: Merck and Co. | www.isentress.com, (800) 622–4477 common name: class:

Standard dose: One 400 mg film-coated tablet twice a day, with or without food, with no dietary restrictions. Take missed dose as soon as possible, unless it is almost time for your next dose. Do not double up on your next dose.

AWP: $1,121.93 / month

Potential side effects and toxicity Very tolerable, but most common are diarrhea, nausea, headache, and fever. Less common are abdominal pain, vomiting, fatigue, weakness, dizziness, and lipodystrophy.

Other observations with unclear relationship to Isentress include cancer (new and recurrent, though most patients had other risk factors for cancer), low white blood cell count (neutropenia), low platelets, and elevated liver enzyme levels. May cause elevated levels of a muscle enzyme (creatine kinase) on blood tests. Contact your health care provider if you experience unexplained muscle pain, tenderness, or weakness. May cause hypersensitivity (allergic reaction), anemia, neutropenia, and gastritis. Increases in ALT, AST, and total bilirubin, all signs of liver toxicity, seen in around 8% of people taking Isentress. Increases were more likely in people also infected with hepatitis B or C. Immune Reconstitution Inflammatory Syndrome (IRIS) may occur as the immune system regains strength; signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is initiated. Report symptoms of illness, such as shingles and TB, to a health care provider.

Potential drug interactions Aptivus/Norvir can decrease the concentrations of Isentress, but no clinically significant interaction was observed from the clinical studies in patients receiving both drugs. Dose adjustment is not required. Reyataz and Reyataz/Norvir increase blood levels of Isentress, but no dose adjustment is recommended. Use caution with rifampin, which reduces plasma concentrations of Isentress; increase dose of Isentress to 800 mg twice a day. Prilosec (omeprazole) can increase concentrations of Isentress, but no dose adjustment is recommended. There is no interaction with methadone.

More infoRmation U.S. HIV guidelines list Isentress along with a Truvada backbone as a preferred regimen for people taking HIV therapy for the first time.

Isentress, the first drug in a new class called integrase inhibitors, continues to shine bright.

Isentress is exciting for several reasons. Two years ago, Isentress did something no other

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HIV drug ever did: it dropped viral load to undetectable in more than a whopping 90% of treatment-experienced people, out to one full year. Undetectable viral load is more difficult to achieve in this population than in people on HIV therapy for the first time. The results were exciting, but from a small study. Isentress was taken with Prezista and Intelence, a novel, nuke-sparing combination. The data is in accord with the advocate view that advanced patients are having dramatic results and almost no side effects. Many people on long-time therapy became undetectable for the first time. The 96-week data show that Isentress continues to be effective with almost no side effects. The guidelines note drawbacks: twice-a-day dosing and a lower barrier to drug resistance than seen with boosted PIs. Greater tolerability, however, may help overcome those issues. Also, it’s only one tablet per dose, and does not have to be taken with the dreaded Norvir, the way PIs are. In fact, the SPIRAL study wanted to look at what would happen to patients with sustained virologic suppression on boosted protease inhibitors when switched to Isentress. The study of 273 people had 139 switch to Isentress and 134 to stay on their current Norvir-boosted protease inhibitor. It turns out that Isentress was non-inferior (a good thing) in terms of efficacy and resulted in a better lipid profile (lower cholesterol and triglycerides) after 48 weeks. The latest guidelines point out that two other studies showed increased risk of failure when switching from boosted PIs to Isentress in people with undetectable viral loads, and state that perhaps SPIRAL was successful because people had had undetectable viral loads for a longer time. The guidelines state that switching people from a boosted PI to Isentress should be done with caution, and avoided altogether in people who have HIV resistance to NRTI drugs unless they have fully active medications (to which their HIV is not resistant) to use. Moreover, the guidelines state that before prescribing Isentress, providers may want to order a resistance test that can measure INSTI resistance (standard tests cannot).

The community was hopeful when a oncedaily vs. twice-daily Isentress in people on HIV therapy for the first time was in advanced

(Phase 3) study. This would help adherence and make this an even more popular first line treatment. Unfortunately, the study was stopped short when once-daily Isentress was seen as inferior to twice daily. 83% of people taking once-daily Isentress reached undectable levels of HIV virus compared to 89% in the twice-daily arm. This was too much of a difference to continue the study. A deeper analysis shows that individuals with higher viral loads (greater than 100,000 copies/ml) were more prone to fail on the once-daily regimen (only 74% reached undetectable levels vs. 84% in the twice-daily arm). See package insert for more complete information on potential side effects and interactions.

Doctor’s COMMENTS Isentress made a stunning entrance when it was first approved for use in treatmentexperienced patients. Perhaps more than any other drug, it revolutionized so-called “salvage therapy.” In combination with other new or second-generation agents, it made it possible for just about anyone willing to swallow pills to have an undetectable viral load. The fact that it was virtually free of side effects or significant toxicity didn’t hurt, either. The combination of Isentress and Truvada was subsequently shown to be as effective as Atripla for initial therapy, but with fewer side effects and lipid elevations.

Isentress/Truvada is now a preferred regimen for initial therapy in the guidelines, though it is the only one that requires twice-daily dosing. Hopes that it could be dosed once a day were dashed by a recent clinical trial that clearly showed better results with twice-daily dosing, especially in people with high baseline viral loads. This combination also has no clear advantage over Atripla from a resistance standpoint: integrase mutations can occur quickly when viral suppression isn’t maintained, and Isentress resistance is likely to result in crossresistance to other integrase inhibitors in development. —Joel Gallant, MD, MPH ACTIVIST’S COMMENTS A lifesaver for many when it was the first integrase inhibitor introduced at about the same time as Prezista and Intelence, Isentress continues to be a versatile drug for both treatment-experienced and naïve patients. Hopes that it could be a once-a-day pill were dashed when study results showed that once-daily dosing was not as effective as twice-daily.

Still, it remains a very effective and well tolerated drug, with as yet no challengers in its class. —Jeff Taylor

P o s i t i v e lyAwa r e . c o m

500 T-CELLS

OR LESS. IT’S TIME

TO TAKE ACTION. 250

425 500

750

Talk with your doctor and consider all the factors about starting treatment.

HIV treatment is now recommended for everyone with a T-cell count of 500 or less and should be considered when T-cells are higher than 500, according to the DHHS* and the IAS-USA†. Starting treatment early may help protect your immune system and vital organs. Today’s medicines may have fewer, more manageable side effects. They may help you live a longer, healthier life. Receive helpful information about living with HIV that you should know. Call toll free 1-888-447-1728, or visit TREATHIVNOW.COM. *DHHS = Department of Health and Human Services †IAS-USA = International Aids Society USA. © 2011 Gilead Sciences, Inc. All rights reserved. UN7544 02/11

2011 HIV Drug guide Drug interactions

Do your meds play well with others?

A guide to HIV drug interactions

by Swarup Mehta, PharmD and Enid Vázquez

For details, read the drug’s page in the Drug Guide, or refer to the manufacturer’s package insert for a full comprehensive list of potential drug interactions.

Also, make your pharmacist and health care providers aware of any drug that you add. Some interactions are more serious

than others; some drugs may only require a dose adjustment, while others may either render the drug completely ineffective, or worse, lead to a potentially fatal reaction.

Discuss any changes, however minor, with your health care providers, including your pharmacist, since small reactions

may become serious. Look up your drugs with “Check my meds” at www.aidsmeds. com/cmm, which lists the effect of food as well as interactions for medications. The University of Liverpool also has an interactive database that allows you to look up antiretroviral drug interactions and has PDF charts of interactions between antiretrovirals and other drugs. Remember, brand names are usually capitalized, while generic names are not. Go to www.hiv-druginteractions.org.

Nucleoside reverse transcRiptase inhibitors also called nucleoside analogs, NRTIs, or nukes Potential drug class interactions

None.

Combivir (Retrovir and Epivir)

See Epivir and Retrovir (zidovudine). Do not take Atripla, Emtriva, Epivir, Epivir-HBV, Epzicom, Retrovir (zidovudine), rilpivirine/Truvada, Trizivir, or Truvada, since all or part of these medications are already in Combivir or have equivalent medications.

Emtriva (emtricitabine, or FTC)

No significant drug interactions. Do not take Emtriva with Atripla, Combivir, Epivir, Epivir-HBV, Epzicom, rilpivirine/Truvada, Trizivir, or Truvada, since they contain Emtriva or medication equivalent to Emtriva.

Epivir (lamivudine, or 3TC)

No significant drug interactions. Do not take Atripla, Combivir, Emtriva, Epivir-HBV, Epzicom, Trizivir, or Truvada, while taking Epivir, since they contain Epivir or medication equivalent to it.

Epzicom (Epivir and Ziagen)

See Epivir and Ziagen. Do not take Atripla, Combivir, Emtriva, Epivir, Epivir-HBV, rilpivirine/Truvada Trizivir, or Truvada, while taking Epzicom, since all or part of these medications are already in Epzicom or have equivalent medications.

Retrovir (zidovudine, or AZT)

Do not take with Combivir or Trizivir, since zidovudine is already in these medications.

Amphotericin B, Benemid, Biaxin, dapsone, Depakote, doxorubicin, flucytosine, ganciclovir, hydroxyurea, interferon-alpha, methadone, pentamidine, phenytoin (Dilantin), ribavirin, rifampin, sulfadiazine, Valcyte, and Zerit.

Trizivir (Epivir, Retrovir, and Ziagen)

See Epivir, Retrovir, and Ziagen. Do not take Atripla, Emtriva, Epivir, Epivir-HBV, Epzicom, Ziagen, Retrovir (zidovudine), or Truvada while taking Trizivir, since all or part of these medications are already in Trizivir or have equivalent medications.

Truvada (Viread and Emtriva)

See Emtriva and Viread. Do not take with Atripla, Combivir, Emtriva, Epivir, Epivir-HBV, Epzicom, rilpivirine/Truvada Trizivir, or Viread, since all or part of these medications are already in Truvada or have equivalent medications.

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2011 HIV Drug guide Drug Interactions

Videx & Videx EC (didanosine, or ddI)

Alcohol, allopurinol, cimetidine, dapsone, ganciclovir, HIV protease inhibitors, hydroxyurea, itraconazole, ketoconazole, methadone, pentamidine, Rescriptor, Retrovir (zidovudine), ribavirin, valganciclovir, Viread, and Zerit.

Viread (tenofovir)

Do not take with Atripla, rilpivirine/Truvadam or Truvada since Viread is in these medications. Hepsera, Kaletra, Norvir, Reyataz, Videx and Videx-EC.

Zerit (stavudine, or d4T)

Amphotericin B, dapsone, foscarnet, ganciclovir, pentamidine, Valcyte, Videx and Videx-EC, and Retrovir (zidovudine).

Ziagen (abacavir sulfate)

Do not take with Epzicom or Trizivir, since Ziagen is already in these medications.

Alcohol and methadone.

Non-nucleoside reverse transcriptase inhibitors also called non-nucleosides, NNRTIs, or non-nukes Potential drug class interactions

Anti-convulsants; HIV protease inhibitors; methadone.

Intelence (etravirine, or ETR)

Aptivus/Norvir, Atripla, Biaxin, Cialis, Coumadin (warfarin), diazepam, Dilantin (phenytoin), fluconazole, Kaletra, Lexiva/Norvir, Mycobutin, Levitra, Norvir, phenobarbital, Plavix, Rescriptor, Reyataz/Norvir, rifampin, rilpivirine, Selzentry, St. John’s wort, Sustiva, Tegretol (carbamazepine), Viagra, Viramune, voriconazole, and unboosted (without Norvir) PIs.

Rescriptor (delavirdine, or DLV)

Agenerase, amlodipine, certain amphetamines and antiarrhythmic drugs, Atripla, Biaxin, birth control pills, Cialis, cisapride, Coumadin (warfarin), Crixivan, dapsone, Dilantin (phenytoin), ergot alkaloids (Cafergot, D.H.E. 45, Methergine, Wigraine), felodipine, fluticasone (Advair, Flonase, Flovent), immunosuppressants, Intelence, Invirase, Kaletra, Levitra, Lexiva, methadone, lovastatin, midazolam, Mycobutin, nifedipine, Norvir, phenobarbital, pimozide, Propulsid, quinidine, Reyataz, rifampin, rilpivirine, simvastatin, St. John’s wort, Sustiva, Tegretol (carbamazepine), trazodone, triazolam, Viagra, Viracept, Viramune, Vytorin, and Xanax (alprazolam).

rilpivirine (TMC-278)

Methadone. Atripla, Intelence, Rescriptor, Sustiva, and Viramune. Available data is limited due to its experimental drug status at press time.

Sustiva (efavirenz, or EFV)

Do not take with Atripla, since Sustiva is already in Atripla. Bepridil, Biaxin, birth control pills, buprenorphine, bupropion, Coumadin (warfarin), Crixivan, Dilantin (phenytoin), diltiazem, ergot alkaloids (Cafergot, D.H.E. 45, Methergine, Wigraine), Gingko biloba, immunosuppressants, Intelence, Invirase, itraconazole, Kaletra, Lexiva, Lipitor, Malarone, methadone, midazolam, Mycobutin, Norvir, Noxafil (posaconazole), pimozide, pravastatin, Rescriptor, Reyataz, rifampin, rilpivirine, phenobarbital, pravastatin, sertraline, simvastatin, St. John’s wort, Tegretol (carbamazepine), triazolam, Vfend, Viramune, and Zoloft .

Viramune (nevirapine)

Atripla, Biaxin, birth control pills, calcium channel blockers (Adalat, Norvasc, Procardia, and others), cisapride, clonazepam, Cordarone, Coumadin (warfarin), Crixivan, Dilantin (phenytoin), disopyramide, ergot alkaloids (Cafergot, D.H.E. 45, Methergine, Wigraine), ethosuxomide, flucanozole, immunosuppressants, Intelence, Invirase, Kaletra, ketoconazole, Lexiva, lidocaine, methadone, midazolam, Mycobutin, Norvir, phenobarbital, prednisone, Rescriptor, Reyataz, rifampin, rilpivirine, St. John’s wort, Sustiva, Tegretol (carbamazepine), and triazolam.

Fixed dose regimens Atripla (Sustiva/Truvada)

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See Sustiva and Truvada (Emtriva/Viread). Do not take Combivir, Emtriva, Epivir, Epivir-HBV, Epzicom, rilpivirine/Truvada , Sustiva, Trizivir, Truvada, or Viread while taking Atripla, since all or part of these medications are already in Atripla or have equivalent medications.

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2011 HIV Drug guide Drug Interactions

Fixed dose regimens rilpivirine/Truvada

See rilpivirine and Truvada. Do not take Atrilpa, Combivir, Emtriva, Epivir, Epivir-HBV, Epzicom, rilpivirine, Sustiva, Trizivir, Truvada, or Viread while taking rilpivirine/Truvada, since all or part of these medications are already in ril pivirine/Truvada or have equivalent medications. Available data is limited due to its experimental drug status at press time.

Protease inhibitors (PIs) Potential drug class interactions

Cardiac medications, cholesterol medications, dexamethasone, erectile dysfunction drugs, ergot derivatives (vasoconstrictors), migraine medications, sedatives, tuberculosis drugs.

Aptivus (tipranavir, or TPV) (must be taken with Norvir)

There are many interactions—see the package insert for the most complete list and tell your health care professional about all the medications you are taking. Advicor, alfuzosin, Altoprev, antacids, birth control pills, bosentan, buprenorphine, bupropion, calcium channel blockers (Adalat, Norvasc, Procardia, and others), Cialis, colchicine, Coumadin (warfarin), Crestor, ergot alkaloids (Cafergot, D.H.E. 45, Methergine, Wigraine), disulfirum (Antabuse), Flagyl, fluconazole, fluticasone (Advair, Flonase, Flovent), Fuzeon, other HIV protease inhibitors, immunosuppressants, itraconazole, ketoconazole, Lescol, Levitra, Lipitor, Livalo, lovastatin, methadone, midazolam (oral), Mycobutin, Paxil, phenobarbital, phenytoin (Dilantin and others), pimozide, pravastatin, Prilosec (omeprazole), quinidine, Revatio, rifabutin, rifampin, Rythmol, salmeterol, simvastatin, St. John’s wort, Suboxone, Tambocor, Tegretol (carbamazepine), trazodone, triazolam, valproic acid, Viagra, vitamin E, Videx, Vytorin, Ziagen, Retrovir (zidovudine), and Zoloft.

Crixivan (indinavir sulfate, or IDV)

Advicor, alfuzosin, Altoprev, birth control pills, bosentan, calcium channel blockers (Adalat, Norvasc, Procardia, and others), Cialis, coffee or alcohol (and other diuretics), colchicine, Cordarone, Coumadin (warfarin), Dilantin (phenytoin), ergot alkaloids (Cafergot, D.H.E. 45, Livalo, Methergine, Wigraine), fluticasone (Advair, Flonase, Flovent), garlic supplements, grapefruit juice, itraconazole, immunosuppressants, ketoconazole, Lescol, Levitra, Lipitor, lovastatin, methadone, midazolam, Mycobutin, phenobarbitol, pimozide, pravastatin, Rescriptor, Revatio, Reyataz, rifampin, Rythmol, salmeterol, simvastatin, St. John’s wort, Sustiva, Tambocor, Tegretol (carbamazepine), trazodone, triazolam, Viagra, Viramune, vitamin C, and Vytorin.

Invirase (saquinavir, or SQV)) (must be taken with Norvir)

Advicor, alfuzosin, Altoprev, Aptivus/Norvir, Biaxin, birth control pills, bosentan, Cialis, colchicine, Cordarone, Coumadin (warfarin), Crestor, Crixivan, digoxin, ergot alkaloids (Cafergot, D.H.E. 45, Livalo, Methergine, Wigraine), dapsone, dexamethasone, fluticasone (Advair, Flonase, Flovent), garlic supplements, Kaletra, Lanoxin, Lescol, Levitra, Lipitor, lovastatin, methadone, midazolam (oral), Mycobutin, Nizoral, Norvir, pimozide, pravastatin, quindine, rifampin, Rescriptor, Revatio, Reyataz, rifampin, Rythmol, salmeterol, simvastatin, St. John’s wort, Sporanox, Sustiva, Tambocor, trazodone, triazolam, Viagra, Viracept, Viramune, and Vytorin.

Kaletra (lopinavir/ritonavir, or LPV/r)

Advicor, alfuzosin, Altoprev, anti-convulsants, Biaxin, birth control pills, bosentan, bupropion, certain calcium channel blockers, Cialis, colchicine, Cordarone, Coumadin (warfarin), digoxin, Dilantin (phenytoin), ergot alkaloids (Cafergot, D.H.E. 45, Methergine, Wigraine), Flagyl, fluticasone (Advair, Flonase, Flovent), garlic supplements, immunosuppressants, itraconazole, Lescol, Levitra, Lexiva, Lipitor, Livalo, lovastatin, Mepron, methadone, midazolam (oral), Mycobutin, nifedipine, pimozide, phenobarbital, pravastatin, rifampin, Retrovir, Revatio, Rythmol, salmeterol, simvastatin, St. John’s wort, steroids (especially Decadron), Sustiva, Tegretol (carbamazepine), trazodone, triazolam, Uroxatral, Viagra, Videx, Viracept, Viramune, Vytorin, and Ziagen.

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2011 HIV Drug guide Drug Interactions

Lexiva (fosamprenavir calcium, or FPV)

Advicor, alfuzosin, Altoprev, birth control pills, bosentan, calcium channel blockers, Cialis, colchicine, Coumadin (warfarin), Crestor, disulfirum (Antabuse), ergot alkaloids (Cafergot, D.H.E. 45, Methergine, Wigraine), Flagyl, fluticasone (Advair, Flonase, Flovent), Kaletra, Lipitor, Lescol, Levitra, Livalo, lovastatin, Paxil, pimozide, pravastatin, Rescriptor, Revatio, Rythmol, methadone, midazolam (oral), Mycobutin, rifampin, salmeterol, simvastatin, St. John’s wort, steroids (especially Decadron), Sustiva, Tambocor, trazodone, triazolam, Viagra, and Vytorin.

Norvir (ritonavir. or RTV)

See the manufacturer package insert for the most complete list. Advicor, alcohol, alfuzosin, Altoprev, Biaxin, birth control pills, bosentan, Cialis, colchicine, Cordarone, Dilantin (phenytoin), disulfiram (Antabuse), Ecstasy, ergot alkaloids (Cafergot, D.H.E. 45, Methergine, Wigraine), Flagyl, fluticasone (Advair, Flonase, Flovent), garlic supplements, GHB, immunosuppressants, Lescol, Levitra, Lipitor, lovastatin, midazolam (oral), methadone, phenobarbital, pimozide, pravastatin, rifampin, Revatio, Rythmol, salmeterol, simvastatin, St. John’s wort, Tambocor, Tegretol (carbamazepine), tobacco, trazodone, triazolam, Uroxatral, Viagra, and Vytorin.

Prezista (darunavir, or DRV) (must be taken with Norvir)

Advicor, alfuzosin, Altoprev, Biaxin, birth control pills, bosentan, calcium channel blockers (Norvasc, Procardia, and others), Cialis, cisapride, colchicine, Coumadin (warfarin), Crestor, desimpramine, Dilantin (phenytoin), ergot alkaloids (Cafergot, D.H.E. 45, Ergomar, ergonovine, methylergonovine, Migranal), fluticasone (Advair, Flonase, and Flovent), immunosuppressants, Invirase, itraconazole, Kaletra, ketoconazole, Levitra, Lipitor, Livalo, lovastatin, methadone, Mevacor, midazolam (oral), nifedipine, Paxil, pimozide, phenobarbital, pravastatin, Revatio, rifabutin, rifampin, salmeterol, Simcor, simvastatin, St. John’s wort, Suboxone, Subutex, Tegretol (carbamazepine), trazodone, triazolam, Vfend, Viagra, Vytorin, and Zoloft.

Reyataz (atazanavir sulfate, or ATV)

Advicor, alfuzosin, Altoprev, antacids (including Axid, Rolaids, Tums, Mylanta, Pepcid, and Zantac), bepridil, birth control pills, bosentan, buprenorphine, calcium channel blockers (Adalat, Norvasc, Procardia, and others), Cialis, colchicine, Coumadin (warfarin), Cordarone, Crixivan, Camptosar, Dilantin (phenytoin), ergot alkaloids (Cafergot, D.H.E. 45, Methergine, Wigraine), fluticasone (Advair, Flonase, Flovent), garlic supplements, immunosuppressants, itraconazole, ketoconazole, Lescol, Levitra, lidocaine, Lipitor, Livalo, lovastatin, midazolam (oral), Mylanta, pimozide, pravastatin, proton-pump inhibitors (Aciphex, Nexium, Prevacid, Prilosec OTC), quinidine, Revatio, rifabutin, rifampin, salmeterol, simvastatin, St. John’s wort, Sustiva, triazolam, trazodone, Vfend, Viagra, Videx and Videx-EC, Viread, and Vytorin.

Viracept (nelfinavir, or NFV)

Advicor, alfuzosin, Altoprev, birth control pills, bosentan, Cialis, colchicine, Cordarone, Crixivan, ergot alkaloids (Cafergot, D.H.E. 45, Methergine, Wigraine), fluticasone (Advair, Flonase, Flovent), garlic supplements, immunosuppressants, Invirase, Lescol, Levitra, Lipitor, Livalo, lovastatin, methadone, midazolam (oral), Mycobutin, phenobarbital, phenytoin (Dilantin and others), pravastatin, Prilosec OTC, Revatio, rifampin, salmeterol, simvastatin, St. John’s wort, Tegretol (carbamazepine), triazolam, trazodone, Viagra, and Vytorin.

Entry inhibitors Fuzeon (enfuvirtide, or T-20)

None found to be clinically significant.

Selzentry (maraviroc, or MVC)

Biaxin, Coumadin (warfarin), Intelence, Invirase, itraconazole, Kaletra, ketoconazole, midazolam (oral), Mycobutin, Norvir, Reyataz, rifampin, St. John’s wort, Sustiva, Tegretol (carbamazepine), Vfend, and Viramune.

Integrase inhibitor Isentress (raltegravir, or RAV)

P o s i t i v e lyAwa r e . c o m

Aptivus/Norvir, Prilosec (omeprazole), Reyataz, Reyataz/Norvir, and rifampin.

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PREZISTA IMPORTANT SAFETY INFORMATION AND INDICATION Talk to your healthcare ABOUT PREZISTA professional about the PREZISTA® (darunavir) is a signs and symptoms of liver prescription medicine. It is one problems. These may include treatment option in the class of yellowing of your skin or whites HIV (human immunodeficiency of your eyes, dark (tea-colored) virus) medicines known as urine, pale-colored stools protease inhibitors. (bowel movements), nausea, vomiting, loss of appetite, PREZISTA is always taken with or pain, aching or sensitivity on and at the same time as ritonavir (Norvir®), in combination with other your right side below your ribs.

HIV medicines for the treatment of • Skin rashes have been HIV infection in adults. PREZISTA reported in patients taking should also be taken with food.

PREZISTA. In a small number of patients, PREZISTA has • The use of other medicines active been reported to cause against HIV in combination with a severe or life-threatening PREZISTA/ritonavir (Norvir®) may rash. Contact your healthcare increase your ability to fight HIV. professional immediately if Your healthcare professional will you develop a rash. work with you to find the right combination of HIV medicines Can PREZISTA be taken with • It is important that you remain other medications? under the care of your healthcare professional during treatment with Taking PREZISTA with certain PREZISTA medicines could cause serious and/or life-threatening side PREZISTA does not cure HIV effects or may result in loss of infection or AIDS, and does not its effectiveness. Do not take prevent passing HIV to others.

PREZISTA if you are taking the following medicines: alfuzosin Please read Important Safety (Uroxatral®), dihydroergotamine Information below, and talk to (D.H.E.45®, Migranal®), your healthcare professional ergonovine, ergotamine (Wigraine®, to learn if PREZISTA is right Ergostat®, Cafergot®, Ergomar®), for you. methylergonovine, cisapride (Propulsid®), pimozide (Orap®), IMPORTANT SAFETY oral midazolam, triazolam (Halcion®), INFORMATION rifampin (Rifadin®, Rifater®, Rifamate®), sildenafil (Revatio®) What is the most important when used to treat pulmonary information I should know arterial hypertension, indinavir about PREZISTA? (Crixivan®), lopinavir/ritonavir (Kaletra®), saquinavir (Invirase®), • PREZISTA, together with lovastatin (Mevacor®, Altoprev®, Norvir®, has been observed Advicor®), pravastatin (Pravachol®), in a small number of simvastatin (Zocor®, Simcor®, patients to cause liver problems which may be life- Vytorin®), salmeterol (Serevent®), or threatening. Your healthcare products containing St. John’s wort professional should do • Before taking PREZISTA, tell your blood tests prior to starting healthcare professional if you combination treatment are taking sildenafil (Viagra®), including PREZISTA. If you vardenafil (Levitra®), tadalafil have chronic hepatitis B or (Cialis®, Adcirca®), atorvastatin C infection, your healthcare ® ), atorvastatin/amlodipine (Lipitor professional should check (Caduet®), rosuvastatin (Crestor®), your blood tests more or colchicine (Colcrys®). This often because you have is not a complete list of an increased chance of medicines. Be sure to tell developing liver problems

your healthcare professional about all the medicines you are taking or plan to take, including prescription and nonprescription medicines, vitamins, and herbal supplements • Tell your healthcare professional if you are taking estrogen-based contraceptives (birth control).

PREZISTA might reduce the effectiveness of estrogen-based contraceptives. You must take additional precautions for birth control, such as condoms What should I tell my doctor before I take PREZISTA? • Before taking PREZISTA, tell your healthcare professional if you have any medical conditions, including allergy to sulfa medicines, diabetes, liver problems (including hepatitis B or C), or hemophilia • Tell your healthcare professional if you are pregnant or planning to become pregnant, or are breastfeeding - The effects of PREZISTA on pregnant women or their unborn babies are not known. You and your healthcare professional will need to decide if taking PREZISTA is right for you - Do not breastfeed if you are taking PREZISTA. You should not breastfeed if you have HIV because of the chance of passing HIV to your baby What are the possible side effects of PREZISTA? • High blood sugar, diabetes or worsening of diabetes, and increased bleeding in people with hemophilia have been reported in patients taking protease inhibitor medicines, including PREZISTA • Changes in body fat have been seen in some patients taking HIV medicines, including PREZISTA. The cause and long-term health effects of these conditions are not known at this time • As with other protease inhibitors, taking PREZISTA may strengthen

the body’s immune response, enabling it to begin to fight infections that have been hidden. Patients may experience signs and symptoms of inflammation that can include swelling, tenderness, or redness • The most common side effects related to taking PREZISTA include diarrhea, nausea, rash, headache, stomach pain, and vomiting. Other important severe side effects such as inflammation of the liver or pancreas and increased blood fat levels have been reported.

• This is not a complete list of all possible side effects. If you experience these or other side effects, talk to your healthcare professional. Do not stop taking PREZISTA or any other medicines without first talking to your healthcare professional You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please refer to the ritonavir (Norvir®) Product Information (PI and PPI) for additional information on precautionary measures.

For adults taking HIV meds for the first time and for many adults who have taken HIV meds in the past: PREZISTA 800 mg (two 400-mg tablets) must be taken at the same time with 100 mg Norvir® once daily every day.

PREZISTA must be taken with food.

For some adults who have taken HIV meds in the past: PREZISTA 600 mg/Norvir® 100 mg must be taken twice daily at the same time every day with food.

Your healthcare professional can determine which dose is right for you.

Please see Important Patient Information on the next page for more information, or visit www.PREZISTA.com.

If you or someone you know needs help paying for medicine, call 1-888-4PPA-NOW (1-888-4772669) or go to www.pparx.org.

ONCE DAILY

www.PREZISTA.com Distributed by: Tibotec Therapeutics/Division of Centocor Ortho Biotech Products, L.P., Titusville, NJ 08560

©2011 Tibotec Therapeutics

01/11

28PRZDTC10035A

NEW

ONCEDAILY PREZISTA

NEWLY EXPANDED ONCE-DAILY DOSING FOR PREZISTA For adults who have not taken HIV medications before and NOW for many adults who have taken HIV medications in the past Once-daily PREZISTA 800 mg (two 400-mg tablets) must be taken with Norvir速 100 mg and food at the same time every day, as part of combination HIV therapy.

Talk to your doctor about your HIV treatment options and ask if once-daily PREZISTA is right for you.

Please read Important Safety Information on adjacent page.

ONCE DAILY

www.PREZISTA.com Registered trademarks are the property of their respective owners.

IMPORTANT PATIENT INFORMATION PREZISTA (pre-ZIS-ta) Darunavir ALERT: Find out about medicines that should Not be taken with PREZISTA. Please also read the section “Who should not take PREZISTA?”.

Read this Patient Information before you start taking PREZISTA and each time you get a refill. There may be new information.This information does not take the place of talking to your doctor or healthcare provider about your medical condition or your treatment.

What is the most important information I should know about PREZISTA? PREZISTA, together with NORVIR® (ritonavir), has been observed in a small number of patients to cause liver problems which may be life-threatening.

Your healthcare provider should do blood tests prior to initiating combination treatment including PREZISTA. If you have chronic hepatitis B or C infection, your healthcare provider should check your blood tests more often because you have an increased chance of developing liver problems. Talk to your healthcare provider about the signs and symptoms of liver problems. These may include yellowing of your skin or whites of your eyes, dark (tea colored) urine, pale colored stools (bowel movements), nausea, vomiting, loss of appetite, or pain, aching or sensitivity on your right side below your ribs.

In a small number of patients, PREZISTA has been reported to cause a severe or life-threatening rash. Contact your healthcare provider immediately if you develop a rash.

Please also read the section “What are the possible side effects of PREZISTA?” What is PREZISTA? PREZISTA is a prescription anti-HIV medicine used with other anti-HIV medicines used to treat adults. PREZISTA is a type of anti-HIV medicine called a protease (PRO-tee-ase) inhibitor. PREZISTA is used with ritonavir and other anti-HIV medicines to treat people with human immunodeficiency virus (HIV-1) infection. HIV is the virus that causes AIDS (Acquired Immune Deficiency Syndrome).

How does PREZISTA work?

PREZISTA blocks HIV protease, an enzyme which is needed for HIV to multiply. When used with other anti-HIV medicines, PREZISTA can help to reduce the amount of HIV in your blood (called “viral load”) and increase your CD4 (T) cell count. HIV infection destroys CD4 (T) cells, which are important to the immune system. The immune system helps fight infection. Reducing the amount of HIV and increasing the CD4 (T) cell count may improve your immune system and, thus, reduce the risk of death or infections that can happen when your immune system is weak (opportunistic infections).

PREZISTA is always taken with and at the same time as ritonavir (NORVIR®), in combination with other anti-HIV medicines. PREZISTA should also be taken with food.

Does PREZISTA cure HIV or AIDS? PREZISTA does not cure HIV infection or AIDS. At present, there is no cure for HIV infection. People taking PREZISTA may still develop infections or other conditions associated with HIV infection. Some of these conditions are pneumonia, herpes virus infection, and Mycobacterium avium complex (MAC) infections. Because of this, it is very important for you to remain under the care of a healthcare provider. Although PREZISTA is not a cure for HIV or AIDS, PREZISTA can help reduce your risks of getting illnesses associated with HIV infection (AIDS and opportunistic infection) and eventually dying from these conditions.

Does PREZISTA reduce the risk of passing HIV to others?

PREZISTA does not reduce the risk of passing HIV to others through sexual contact, sharing needles, or being exposed to your blood. For your health and the health of others, it is important to always practice safer sex by using a latex or polyurethane condom or other barrier method to lower the chance of sexual contact with any body fluids such as semen, vaginal secretions, or blood. Never re-use or share needles.

Ask your healthcare provider if you have any questions on how to prevent passing HIV to other people.

What should I tell my doctor before I take PREZISTA? PREZISTA may not be right for you. Before taking PREZISTA, tell your doctor or healthcare provider if you: • are allergic to sulfa medicines.

• h ave diabetes. Anti-HIV medicines, such as PREZISTA, might increase sugar levels in the blood.

• have liver problems, including hepatitis B and/or C. • have hemophilia. Anti-HIV medicines, such as PREZISTA, might increase the risk of bleeding.

• are pregnant or planning to become pregnant. The effects of PREZISTA on pregnant women or their unborn babies are not known. You and your healthcare provider will need to decide if taking PREZISTA is right for you. If you take PREZISTA while you are pregnant, talk to your healthcare provider about how you can be included in the Antiretroviral Pregnancy Registry.

• are breastfeeding. Do not breastfeed if you are taking PREZISTA. You should not breastfeed if you have HIV because of the chance of passing HIV to your baby. Talk with your healthcare provider about the best way to feed your baby. The Centers for Disease Control and Prevention (CDC) recommends that HIV-infected mothers not breastfeed to avoid the risk of passing HIV infection to your baby.

Who should not take PREZISTA?** Together with your healthcare provider, you need to decide whether taking PREZISTA is right for you.

Do not take PREZISTA if you: • are allergic to darunavir or any of the other ingredients in PREZISTA • are allergic to ritonavir (NORVIR®) • take any of the following types of medicines because you could experience serious side effects: – alfuzosin (Uroxatral®) – dihydroergotamine (D.H.E. 45®, Migranal®), ergonovine, ergotamine (Cafergot®, Ergomar®), methylergonovine – cisapride – pimozide (Orap®) – oral midazolam, triazolam (Halcion®) – St. John’s wort (Hypericum perforatum) – lovastatin (Mevacor®, Altoprev®, Advicor®), simvastatin (Zocor®, Simcor®, Vytorin®) – rifampin (Rifadin®, Rifater®, Rifamate®, Rimactane®) – sildenafil (Revatio®) when used to treat pulmonary arterial hypertension Can PREZISTA be taken with other medications?** Tell your healthcare provider about all the medicines you take including prescription and nonprescription medicines, vitamins, and herbal supplements. PREZISTA and many other medicines can interact. Sometimes serious side effects will happen if PREZISTA is taken with certain other medicines (see “Who should not take PREZISTA?”).

Tell your healthcare provider if you are taking estrogen-based contraceptives (birth control). PREZISTA might reduce the effectiveness of estrogen-based contraceptives. You must take additional precautions for birth control such as a condom.

Tell your healthcare provider if you take other anti-HIV medicines.

PREZISTA can be combined with some other anti-HIV medicines while other combinations are not recommended.

Tell your healthcare provider if you are taking any of the following medicines: – bepridil, lidocaine, quinidine, amiodarone (Cordarone®), digoxin (Lanoxin®), flecainide (Tambocor®), propafenone (Rythmol®) – warfarin (Coumadin®) – carbamazepine (Tegretol®, Carbatrol®), phenobarbital, phenytoin (Dilantin®, Phenytek®) – trazodone (Desyrel®), desipramine (Norpramin®) – colchicine (Colcrys®) – clarithromycin (Biaxin®) – ketoconazole (Nizoral®), itraconazole (Sporanox®), voriconazole (Vfend®) – rifabutin (Mycobutin®), – metoprolol (Lopressor®, Toprol-XL®), timolol (Betimol®, Combigan®, Istalol®, Cosopt®, Timoptic®) – midazolam administered by injection – felodipine (Plendil®), nifedipine (Adalat®), nicardipine (Cardene®)

IMPORTANT PATIENT INFORMATION – dexamethasone, fluticasone (Advair Diskus®, Cutivate®, Flonase®, Flovent Diskus®) – bosentan (Tracleer®) – atorvastatin (Lipitor®), pravastatin (Pravachol®), rosuvastatin (Crestor®) – cyclosporine (Sandimmune®, Neoral®), tacrolimus (Prograf®), sirolimus (Rapamune®) – salmeterol (Serevent®) – Methadone, buprenorphine, buprenorphine/naloxone – risperidone (Risperdal®, Risperdal® Consta®, Risperdal® M-TAB®), thioridazine – sildenafil (Viagra®), vardenafil (Levitra®), tadalafil (Cialis®) – tadalafil (Adcirca®) – paroxetine (Paxil®), sertraline (Zoloft®) Tell your healthcare provider if you are taking any medicines that you obtained without a prescription.

This is not a complete list of medicines that you should tell your healthcare provider that you are taking. Know and keep track of all the medicines you take and have a list of them with you. Show this list to all of your healthcare providers and pharmacists any time you get a new medicine. Both your healthcare provider and your pharmacist can tell you if you can take these other medicines with PREZISTA. Do not start any new medicines while you are taking PREZISTA without first talking with your healthcare provider or pharmacist. You can ask your healthcare provider or pharmacist for a list of medicines that can interact with PREZISTA. How should I take PREZISTA? Take PREZISTA tablets every day exactly as prescribed by your healthcare provider. You must take ritonavir (NORVIR®) at the same time as PREZISTA. • Do not change your dose of PREZISTA or stop treatment without talking to your healthcare provider first.

• Take PREZISTA and ritonavir (NORVIR®) with food.

• Swallow PREZISTA tablets whole with a drink.

What should I do if I miss a dose?

People who take PREZISTA one time a day: • If you miss a dose of PREZISTA or ritonavir (NORVIR®) by more than 12 hours, wait and then take the next dose of PREZISTA and ritonavir (NORVIR®) at your regularly scheduled time. If you miss a dose of PREZISTA or ritonavir (NORVIR®) by less than 12 hours, take your missed dose of PREZISTA and ritonavir (NORVIR®) right away. Then take your next dose of PREZISTA and ritonavir (NORVIR®) at your regularly scheduled time.

People who take PREZISTA two times a day • If you miss a dose of PREZISTA or ritonavir (NORVIR®) by more than 6 hours, wait and then take the next dose of PREZISTA and ritonavir (NORVIR®) at your regularly scheduled time.

• If you miss a dose of PREZISTA or ritonavir (NORVIR®) by less than 6 hours, take your missed dose of PREZISTA and ritonavir (NORVIR®) right away.

Then take your next dose of PREZISTA and ritonavir (NORVIR®) at your regularly scheduled time.

If a dose of PREZISTA or ritonavir (NORVIR®) is skipped, do not double the next dose. Do not take more or less than your prescribed dose of PREZISTA or ritonavir (NORVIR®) at any one time.

What are the possible side effects of PREZISTA? PREZISTA can cause side effects. The following is not a complete list of side effects reported with PREZISTA when taken either alone or with other antiHIV medicines. Do not rely on this leaflet alone for information about side effects. Your healthcare provider can discuss with you a more complete list of side effects.

PREZISTA, together with NORVIR® (ritonavir), has been observed in a small number of patients to cause liver problems which may be life-threatening.

Your healthcare provider should do blood tests prior to initiating combination treatment including PREZISTA. If you have chronic hepatitis B or C infection, your healthcare provider should check your blood tests more often because you have an increased chance of developing liver problems.

Talk to your healthcare provider about the signs and symptoms of liver problems. These may include yellowing of your skin or whites of your eyes, dark (tea colored) urine, pale colored stools (bowel movements), nausea,

vomiting, loss of appetite, or pain, aching or sensitivity on your right side below your ribs.

Rash has been reported in 10.3% of patients receiving PREZISTA. In a small number of patients, PREZISTA has been reported to cause a severe or life-threatening rash. Contact your healthcare provider immediately if you develop a rash.

Other relevant severe side effects were inflammation of the liver or pancreas, increased blood fat levels, diabetes, and changes in body fat.

The most common side effects include diarrhea, nausea, rash, headache, abdominal pain and vomiting.

Other side effects of PREZISTA include the following: • high blood sugar (hyperglycemia) and diabetes. This can happen in patients taking PREZISTA or other protease inhibitor medicines. Some patients have diabetes before starting treatment with PREZISTA which gets worse. Some patients get diabetes during treatment with PREZISTA. Some patients will need changes in their diabetes medicine. Some patients may need new diabetes medicine.

• increased bleeding in patients with hemophilia.

• changes in body fat. These changes can happen in patients taking anti-HIV medicines, including PREZISTA. The changes may include an increased amount of fat in the upper back and neck, breast, and around the back, chest, and stomach area. Loss of fat from the legs, arms, and face may also happen. The exact cause and long-term health effects of these conditions are not known.

• immune reconstitution syndrome. In some patients with advanced HIV infection (AIDS) and a history of opportunistic infection, signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment, including PREZISTA, is started.

Tell your healthcare provider promptly about these or any other unusual symptoms. If the condition persists or worsens, seek medical attention.

This medication is prescribed for your particular condition. Do not use it for any other condition or give it to anybody else. Keep PREZISTA and all of your medicines out of the reach of children. If you suspect that more than the prescribed dose of this medicine has been taken, contact your local poison control center or emergency room immediately.

This is a brief summary of information about PREZISTA for adult patients with HIV. If you have any questions or concerns about either PREZISTA or HIV, talk to your healthcare provider.

For additional information, you may also call Tibotec Therapeutics at 1-877-REACH-TT or 1-877-732-2488. ** The brands listed are the registered trademarks of their respective owners and are not trademarks of Tibotec Pharmaceuticals

Manufactured for Tibotec, Inc. by: JOLLC, Gurabo, Puerto Rico Distributed by: Tibotec Therapeutics, Division of Centocor Ortho Biotech Products, L.P., Raritan NJ 08869 NORVIR® is a registered trademark of its respective owner.

PREZISTA® is a registered trademark of Tibotec Pharmaceuticals © Tibotec, Inc. 2006

Revised: December 2010

10101712P

2011 HIV Drug guide Side Effects

(unintended) con A guide to side effects that can result from HIV medications Updated by Swarup Mehta, PharmD and Enid Vázquez

Read the drug’s page in the Drug Guide for details, or refer to the manufacturer’s package insert for a comprehensive list of potential drug side effects. Remember that side effects may or may not occur. Some are more common than others, and individuals react differently to the same drug. A drug

regimen cannot be chosen solely on the basis of minimal potential for side effects. Discuss any changes, however minor, with your health care providers, including your pharmacist, since small reactions may become serious. There may also be management techniques for the side effect.

Nucleoside reverse transcRiptase inhibitors also called nucleoside analogs, NRTIs, or nukes Potential drug class side effects

Enlarged, fatty liver and lactic acidosis.

Combivir (Retrovir and Epivir)

See Epivir and Retrovir.

Emtriva (emtricitabine, or FTC)

A very tolerable drug, but side effects may include headache, diarrhea, nausea and rash.

Darkening of the skin on the palms and the soles of the feet has also been reported.

Epivir (lamivudine, or 3TC)

A very tolerable drug, but side effects may include headache, nausea, vomiting, diarrhea, fever, fatigue, hair loss, insomnia, malaise, nasal symptoms, cough, peripheral neuropathy, low white blood cell count, and anemia.

Epzicom (Epivir and Ziagen)

See Epivir and Ziagen.

Retrovir (zidovudine, or AZT)

Headaches, fever, chills, muscle soreness and/or damage, fatigue, nausea, lipodystrophy, fingernail discoloration, anemia (low red blood cell count), and neutropenia (low white blood cell count).

Trizivir (Epivir, Retrovir, and Ziagen)

See Epivir, Retrovir, and Ziagen.

Truvada (Viread and Emtriva)

See Viread and Emtriva. Abdominal distension/pain.

Videx & Videx EC (didanosine, or ddI)

Peripheral neuropathy, upset stomach, diarrhea, headache, pancreatitis (inflammation of the pancreas), eye changes and optic neuritis, increased uric acid levels, insomnia, and body fat redistribution.

Viread (tenofovir DF)

Overall fairly well tolerated; however, side effects may include nausea, diarrhea, vomiting, flatulence (gas), bone changes, kidney toxicities, decreased bone mineral density, and low blood phosphate.

Zerit (stavudine, or d4T)

Peripheral neuropathy, facial wasting, mitochondrial toxicities (a variety of symptoms caused by cell damage), lipodystrophy, pancreatitis (inflammation of the pancreas), headache, chills/fever, malaise, insomnia, anxiety, depression, rash, upset stomach, diarrhea, abdominal pain, and blood lipid increases.

Ziagen (abacavir sulfate, or ABC)

Hypersensitivity reaction, nausea, vomiting, diarrhea, fatigue, headache, fever, rash, and loss of appetite.

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2011 HIV Drug guide Side Effects

Image: Joshua Thorne

nsequenceS

Non-nucleoside reverse transcriptase inhibitors also called non-nucleosides, NNRTIs, or non-nukes Potential drug class side effects

Rash.

Intelence (etravirine, or ETR)

Rash, diarrhea, nausea, nasopharyngitis (symptoms like a common cold), headache, hypersensitivity, and increased liver enzyme levels.

Rescriptor (delavirdine, or DLV)

Headache, nausea, vomiting, diarrhea, fatigue, increased liver enzyme levels, itchy skin or rash, and body fat accumulation or redistribution.

rilpivirine (TMC-278)

Central nervous system (CNS) and psychiatric symptoms, skin rash, and lab abnormalities.

Available data is limited due to its experimental drug status at press time.

Sustiva (efavirenz, or EFV)

Central nervous system (CNS) and psychiatric symptoms. Rash, nausea, vomiting, diarrhea, fever, insomnia, and increases in triglycerides, bad cholesterol (LDL), good cholesterol (HDL), and liver enzymes. False positive tests for marijuana. Birth defects.

Viramune (nevirapine, or NVP)

Headache, nausea, vomiting, fever, rash, Stevens-Johnson syndrome, increased liver enzyme levels, liver damage, and drug-induced hepatitis.

Fixed dose regimens Atripla (Sustiva/Truvada)

See Sustiva and Truvada (Emtriva and Viread). Atripla dose cannot be adjusted for people with kidney problems. Nausea, diarrhea, rash, and Immune Reconstitution Inflammatory Syndrome (IRIS).

rilpivirine/Truvada

See rilpivirine and Truvada. Available data is limited due to its experimental drug status at press time.

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2011 HIV Drug guide Side Effects

Protease inhibitors (PIs) Potential drug class side effects

Increased levels of cholesterol and triglycerides (except unboosted Reyataz), lipodystrophy, onset of new cases or worsening of diabetes, Immune Reconstitution Inflammatory Syndrome (IRIS), and increased bleeding in hemophiliacs.

Aptivus (tipranavir, or TPV) (must be taken with Norvir)

Mild diarrhea, nausea, vomiting, and abdominal pain. Headaches, fever, fatigue, dry mouth, rash (including sensitivity to sun), dizziness, liver toxicity, and bleeding in the brain. Aptivus has a sulfa component; use with caution in patients with allergies to sulfa drugs.

Also see Norvir.

Crixivan (indinavir sulfate, or IDV)

Headache, fatigue or weakness, malaise, nausea, diarrhea, stomach pains, loss of appetite, yellowing of skin/eyes, changed skin color, dry mouth/sore throat, taste changes, painful urination, indigestion, joint pain, hives, liver toxicity, kidney stones, increased bilirubin, itchy/dry skin, ingrown toenails, and hair loss.

Invirase (saquinavir, or SQV) (must be taken with Norvir)

Diarrhea, abdominal discomfort, vomiting, and nausea. Also see Norvir.

Kaletra (lopinavir/ritonavir, or LPV/r)

Rash, diarrhea, nausea, vomiting, stomach pain, headache, muscle weakness, increased cholesterol and triglycerides, and increased liver enzyme levels. Also see Norvir.

Lexiva (fosamprenavir calcium, or FPV)

Nausea, rash, diarrhea, headache, vomiting, fatigue, and abdominal pain. Lexiva has a sulfa component; use with caution in patients with allergies to sulfa drugs.

Norvir (ritonavir, or RTV)

Weakness, stomach pain, upset stomach, tingling/numbness around the mouth, hands or feet, loss of appetite, taste disturbance, weight loss, headache, dizziness, pancreatitis, alcohol intolerance, liver problems, increased muscle enzyme levels, and uric acid.

Prezista (darunavir, or DRV) (must be taken with Norvir)

Rash, diarrhea, nausea, headache, abdominal pain, and increased liver enzyme levels.

Prezista contains a sulfa component and should be used cautiously in patients with sulfa allergies. Also see Norvir.

Reyataz (atazanavir sulfate, or ATV)

Dizziness, lightheadedness, rash, kidney stones, and elevated liver function test results, including elevated levels of unconjugated bilirubin.

Viracept (nelfinavir, or NFV)

Diarrhea, stomach discomfort, nausea, gas, weakness, and rash.

Entry inhibitors Fuzeon (enfuvirtide, or T-20)

Injection site reactions (ISRs), Immune Reconstitution Inflammatory Syndrome (IRIS), pneumonia, diarrhea, nausea, and fatigue. Hypersensitivity reactions are possible.

Selzentry (maraviroc, or MVC)

Cough, fever, cold, rash, muscle and joint pain, stomach pain, dizziness, liver toxicity, allergic reaction, low blood pressure, and possible increased risk of infections and cancer.

Integrase inhibitor Isentress (raltegravir, or RAL)

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A very tolerable drug, but side effects may include diarrhea, nausea, vomiting, headache, fever, abdominal pain, fatigue, weakness, dizziness, lipodystrophy, increased levels of liver enzymes and creatine kinase, allergic reaction, and Immune Reconstitution Inflammatory Syndrome (IRIS).

M a r c h +A p r i l 2 0 1 1 P o s i t i v e lyAwa r e . c o m

Day 1 Of my next treatment regimen: KALETRA once a day with my other HIV medicines.

Ask your doctor if KALETRA once daily is right for you.

KALETRA once daily should not be given to children. KALETRA once daily should not be taken with efavirenz (Atripla® and Sustiva®), nevirapine (Viramune®), amprenavir (Agenerase®), nelfinavir (Viracept®), carbamazepine (Tegretol® and Epitol®), phenobarbital (Luminal®), or phenytoin (Dilantin®). There may be a greater chance of getting diarrhea with the once daily regimen compared with the twice daily regimen.

Use KALETRA® is a prescription anti-HIV-1 medicine called a protease inhibitor that contains lopinavir and ritonavir. KALETRA is used with other anti-HIV-1 medicines to increase the chance of treatment response in people with human immunodeficiency virus (HIV-1) infection. It is not known if KALETRA is safe and effective in children under 14 days old.

KALETRA does not cure HIV-1 infection or AIDS and does not stop you from passing HIV-1 to others. You may still get opportunistic infections or other conditions that happen with HIV-1.

KALETRA Safety Considerations Do not take KALETRA® if you are allergic to any of its ingredients, including lopinavir or ritonavir. Do not take KALETRA with certain medicines, as they can cause serious problems, death, or make KALETRA less effective against HIV. Some patients taking KALETRA can develop inflammation of the pancreas and liver problems, which can cause death. Patients may develop changes in heart rhythm, large increases in triglycerides and cholesterol, diabetes, high blood sugar, changes in body fat, and/or increased bleeding in people with hemophilia. Some patients may develop signs and symptoms of serious infections they already have after starting anti-HIV medicines.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088 (1-800-332-1088).

If you cannot afford your medication, contact: www.pparx.org or call the toll-free number (1-888-4PPA-NOW) or (1-888-477-2669) for assistance.

For additional information about KALETRA, call 1-866-KALETRA (1-866-525-3872) or visit KALETRA.com.

Please see Brief Summary on adjacent pages.

Model is for illustrative purposes only. ©2010 Abbott Laboratories Abbott Park, IL 60064 039-403018 July 2010 Printed in U.S.A.

KALETRA® (kuh-LEE-tra) (lopinavir/ritonavir) Tablets KALETRA® (kuh-LEE-tra) (lopinavir/ritonavir) Oral Solution Patient Information What is the most important information I should know about KALETRA? KALETRA may cause serious side effects, including: • Interactions with other medicines.

It is important to know the medicines that should not be taken with KALETRA. Read the section “What should I tell my doctor before taking KALETRA?” • Changes in your heart rhythm and the electrical activity of your heart. These changes may be seen on an EKG (electrocardiogram) and can lead to serious heart problems. Your risk for these problems may be higher if you: ° already have a history of abnormal heart rhythm or other types of heart disease. ° take other medicines that can affect your heart rhythm while you take KALETRA. Tell your doctor right away if you have any of these symptoms while taking KALETRA: • dizziness • lightheadedness • fainting • sensation of abnormal heartbeats See the section below “What are the possible side effects of KALETRA?” for more information about serious side effects.

CONSUMER BRIEF SUMMARY CONSULT PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION

Read the Medication Guide that comes with KALETRA before you start taking it and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or treatment.

You and your doctor should talk about your treatment with KALETRA before you start taking it and at regular check-ups. You should stay under your doctor’s care when taking KALETRA.

Who should not take KALETRA? • Do not take KALETRA if you are taking certain medicines. For more information about medicines you should not take with KALETRA, please see “Can I take other medicines with KALETRA?” and consult with your doctor about all other medicines you take.

• Do not take KALETRA if you have an allergy to KALETRA or any of its ingredients, including ritonavir and lopinavir.

What should I tell my doctor before taking KALETRA?

KALETRA may not be right for you.

Tell your doctor about all your medical conditions, including if you: • have any heart problems, including if you have a condition called Congenital Long QT Syndrome.

• have liver problems, including Hepatitis B or Hepatitis C. • have diabetes.

• have hemophilia. People who take KALETRA may have increased bleeding.

• have low potassium in your blood.

• are pregnant or plan to become pregnant. It is not known if KALETRA will harm your unborn baby. Birth control pills or patches may not work as well while you take KALETRA. To prevent pregnancy while taking KALETRA, women who take birth control pills or use estrogen patch for birth control should either use a different type of birth What is KALETRA? control or an extra form of birth control.

Talk to your doctor about how to prevent KALETRA is a prescription anti-HIV pregnancy while taking KALETRA. medicine that contains two medicines: lopinavir and ritonavir. KALETRA is called • take KALETRA during pregnancy, talk with your doctor about how you can a protease inhibitor that is used with other take part in an antiretroviral pregnancy anti-HIV-1 medicines to treat people with registry. The purpose of the pregnancy human immunodeficiency virus (HIV-1) registry is to follow the health of you infection. HIV-1 is the virus that causes and your baby.

AIDS (Acquired Immune Deficiency • are breast-feeding. Do not breast-feed if Syndrome). you are taking KALETRA. You should not It is not known if KALETRA is safe and breast-feed if you have HIV-1. If you are effective in children under 14 days old.

a woman who has or will have a baby while taking KALETRA, talk with your doctor about the best way to feed your baby. If your baby does not already have HIV-1, there is a chance that HIV-1 can be passed to your baby through your breast milk.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Many medicines interact with KALETRA. Do not start taking a new medicine without telling your doctor or pharmacist. Your doctor can tell you if it is safe to take KALETRA with other medicines. Your doctor may need to change the dose of other medicines while you take KALETRA.

Medicines you should not take with KALETRA. Serious problems or death can happen if you take these medicines with KALETRA: • ergot containing medicines, including: ° ergotamine tartrate (Cafergot®, Migergot, Ergomar, Ergostat, Medihaler Ergotamine, Wigraine, Wigrettes) mesylate ° dihydroergotamine (D.H.E. 45®, Embolex, Migranal®) ° ergonovine, ergonovine and methylergonovine (Ergotrate, Methergine), ergotamine and methylergonovine ° Ergotrate Maleate, methylergonovine maleate (Methergine) • triazolam (Halcion®), midazolam hydrochloride oral syrup • pimozide (Orap®) • the cholesterol lowering medicines lovastatin (Mevacor®) or simvastatin (Zocor®) • sildenafil (Revatio®) only when used for the treatment of pulmonary arterial hypertension. (See “Medicines that may need changes” and “What are the

possible side effects of Kaletra?” for information about the use of sildenafil for erectile problems.)

• alfuzosin (Uroxatral®) Medicines that you should not take with KALETRA since they may make KALETRA not work as well: • the herbal supplement St. John’s Wort (hypericum perforatum) • rifampin (Rimactane®, Rifadin®, Rifater®, or Rifamate®) Medicines that may need changes: • birth control pills that contain estrogen (“the pill”) or the birth control (contraceptive) patches • certain anticancer medicines, such as nilotinib (Tasigna®) and dasatinib (Sprycel®) • certain cholesterol lowering medicines, such as atorvastatin (Lipitor®) or rosuvastatin (Crestor®) • certain other antiretroviral medicines, such as efavirenz (Atripla® and Sustiva®), nevirapine (Viramune®), amprenavir (Agenerase®) and nelfinavir (Viracept®) • anti-seizure medicines, such as phenytoin (Dilantin®) carbamazepine, (Tegretol®), phenobarbital • medicines for erectile problems, such as sildenafil (Viagra®), tadalafil (Cialis®), or vardenafil (Levitra®) • medicines for tuberculosis (TB), such as rifabutin (Mycobutin®) • inhaled steroid medicines, such as fluticasone propionate (Flonase®) • inhaled medicines such as salmeterol (Serevent®) or salmeterol in combination with fluticasone propionate (Advair®). Your doctor may need to change to a different medicine • medicines for gout, such as colchicine (Colcrys®) • medicines to treat pulmonary arterial hypertension (PAH), such as bosentan (Tracleer®) or tadalafil (Adcirca®) • pain medicines, such as fentanyl (Duragesic®, IonsysTM, Fentora®) and methadone If you are not sure if you are taking a medicine above, ask your doctor.

• KALETRA tablets can be taken with or without food.

• If you are taking both Videx® (didanosine) and KALETRA: ° didanosine can be taken at the same time as KALETRA tablets, without food. ° take didanosine either one hour before or two hours after taking KALETRA oral solution.

• Do not miss a dose of KALETRA. This could make the virus harder to treat. If you forget to take KALETRA, take the missed dose right away. If it is almost time for your next dose, do not take the missed dose. Instead, follow your regular dosing schedule by taking your next dose at its regular time. Do not take more than one dose of KALETRA at one time.

• If you take more than the prescribed dose of KALETRA, call your local poison control center or emergency room right away.

• Take KALETRA oral solution with food to help it work better.

• If KALETRA is being used for your child, tell your doctor if your child’s weight changes.

• KALETRA should not be given one time each day in children. When giving KALETRA to your child, give KALETRA exactly as prescribed.

• KALETRA oral solution contains a large amount of alcohol. ° If a young child drinks more than the recommended dose, it could make them sick from too much alcohol.

Contact your local poison control center or emergency room right away. ° Talk with your doctor if you take or plan to take metronidazole or disulfiram. You can have severe nausea and vomiting if you take these medicines with KALETRA. • When your KALETRA supply starts to run low, get more from your doctor or pharmacy. It is important not to run out of KALETRA. The amount of HIV-1 virus in your blood may increase if the medicine is stopped for even a short time. The virus may become resistant to KALETRA and become harder to treat.

How should I take KALETRA? • KALETRA can be taken with acid • Take KALETRA every day exactly as reducing agents used for heartburn or prescribed by your doctor. reflux such as omeprazole (Prilosec®) • It is very important to set up a dosing and ranitidine (Zantac® ) with no dose schedule and follow it every day. adjustment.

• Do not change your treatment or stop • KALETRA should not be administered treatment without first talking with your once daily in combination with doctor. carbamazepine (Tegretol® and Epitol®), • Swallow KALETRA tablets whole. Do phenobarbital (Luminal®), or phenytoin not chew, break, or crush KALETRA (Dilantin®). tablets.

Avoid doing things that can spread HIV infection. KALETRA does not stop you from passing HIV infection to others. Do not share needles, other injection equipment or personal items that can have blood or body fluids on them, like toothbrushes and razor blades. Always practice safer sex by using a latex or polyurethane condom to lower the chance of sexual contact with semen, vaginal secretions, or blood.

What are the possible side effects of KALETRA? KALETRA can cause serious side effects.

• See “What is the most important information I should know about KALETRA?” • Liver problems. Liver problems, including death, can happen in people who take KALETRA. Blood tests in people who take KALETRA may show possible liver problems. People with liver disease such as Hepatitis B and Hepatitis C who take KALETRA may have worsening liver disease. Tell your healthcare provider right away if you have any of these signs and symptoms of liver problems: ° loss of appetite ° yellow skin and whites of eyes (jaundice) ° dark-colored urine ° pale colored stools, itchy skin ° stomach area (abdominal) pain.

• Inflammation of the pancreas (pancreatitis). Some people who take KALETRA get inflammation of the pancreas which may be serious and cause death. You have a higher chance of getting pancreatitis if you have had it before. Tell your doctor if you have nausea, vomiting, or abdominal pain while taking KALETRA. These may be signs of pancreatitis.

• Increases in certain fat (triglycerides and cholesterol) levels in your blood. Large increases of triglycerides and cholesterol can be seen in blood test results of some people who take KALETRA. The longterm chance of getting complications such as heart attacks or stroke due to increases in triglycerides and cholesterol caused by protease inhibitors is not known at this time.

• Diabetes and high blood sugar (hyperglycemia). Some people who take protease inhibitors including KALETRA get new or more serious diabetes, or high blood sugar. Tell your doctor if you notice an increase in thirst or urinate often while taking KALETRA.

• Changes in body fat. Changes in body fat in some people who take antiretroviral therapy. These changes may include increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the trunk.

Loss of fat from the legs, arms and face may also happen. The cause and long-term health effects of these conditions are not known at this time.

• Increased bleeding for hemophiliacs. Some people with hemophilia have increased bleeding with protease inhibitors including KALETRA. • Increased risk of certain problems when you take medicines used for the treatment of erectile problems such as sildenafil (Viagra®), tadalafil (Cialis®), or vardenafil (Levitra®) with KALETRA: ° low blood pressure. If you get dizzy or faint, you need to lie down.

Tell your doctor if you feel dizzy, or have fainting spells. ° vision changes. Tell your doctor right away if you have vision changes. penis erection lasting more ° than 4 hours. If you are a male and have an erection that lasts longer than 4 hours, get medical help right away to avoid permanent damage to your penis. Your doctor can explain these symptoms to you.

• Allergic reactions. Skin rashes, some of them severe, can occur in people who take KALETRA. Tell your healthcare provider if you had a rash when you took another medicine for your HIV infection or if you notice any skin rash when you take KALETRA. Common side effects of KALETRA include:

How should I store KALETRA?

polyethylene glycol 400, hydroxypropyl cellulose, talc, colloidal silicon dioxide, KALETRA tablets: polyethylene glycol 3350, yellow ferric • Store KALETRA tablets at room oxide 172, and polysorbate 80. temperature, between 59°F to 86°F KALETRA 100 mg lopinavir and (15°C to 30°C).

• Do not keep KALETRA tablets out of the 25 mg ritonavir tablets: copovidone, sorbitan monolaurate, colloidal silicon container it comes in for longer than dioxide, and sodium stearyl fumarate. The 2 weeks, especially in areas where film coating contains: polyvinyl alcohol, there is a lot of humidity. Keep the titanium dioxide, talc, polytheylene glycol container closed tightly.

3350, and yellow ferric oxide E172.

KALETRA oral solution: KALETRA oral solution: acesulfame • Store KALETRA oral solution in a refrigerator, between 36°F to 46°F (2°C potassium, alcohol, artificial cotton candy flavor, citric acid, glycerin, high to 8°C). KALETRA oral solution that is kept refrigerated may be used until the fructose corn syrup, Magnasweet-110 flavor, menthol, natural and artificial expiration date printed on the label. vanilla flavor, peppermint oil, polyoxyl • KALETRA oral solution that is stored at 40 hydrogenated castor oil, povidone, room temperature (less than 77°F or 25°C) should be used within 2 months. propylene glycol, saccharin sodium, sodium chloride, sodium citrate, and • Keep KALETRA away from high heat. water.

Throw away any medicine that is out of KALETRA oral solution contains date or that you no longer need.

42.4% alcohol (v/v). “See How Keep KALETRA and all medicines out should I take KALETRA?”. of the reach of children.

KALETRA Tablets, 200 mg lopinavir/50 mg General information about ritonavir Manufactured by Abbott Pharmaceuticals KALETRA PR Ltd., Barceloneta, PR 00617 KALETRA does not cure HIV-1 or AIDS. for Abbott Laboratories, North Chicago, IL The long-term effects of KALETRA are not 60064, U.S.A. known at this time. People taking KALETRA KALETRA Tablets, 100 mg lopinavir/25 mg may still get opportunistic infections or ritonavir and KALETRA Oral Solution other conditions that happen with HIV-1 Abbott Laboratories, North Chicago, IL infection. Some of these conditions are 60064, U.S.A. pneumonia, herpes virus infections, and 2010, ALL RIGHTS RESERVED Mycobacterium avium complex (MAC) infections. * The brands listed are trademarks of their Medicines are sometimes prescribed respective owners and are not trademarks for purposes other than those listed in a of Abbott Laboratories. The makers of Medication Guide. Do not use KALETRA for these brands are not affiliated with and a condition for which it was not prescribed. do not endorse Abbott Laboratories or its Do not give KALETRA to other people, even products. if they have the same condition you have.

It may harm them.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

• diarrhea This Medication Guide summarizes • nausea the most important information about Ref: 03-A387-R8 • stomach area (abdominal) pain KALETRA. If you would like more • feeling weak Revised: June, 2010 information, talk with your doctor. You • vomiting 036-395112 MASTER can ask your pharmacist or doctor for • headache information about KALETRA that is • upset stomach written for health professionals. For more These are not all of the possible side information about KALETRA call 1-800effects of KALETRA. For more information, 633-9110 or go to www.KALETRA.com.

039-403018 ask your doctor or pharmacist. Tell your doctor about any side effect that bothers What are the ingredients in KALETRA? you or that does not go away.

Active ingredient: lopinavir and ritonavir Call your doctor for medical advice about Inactive ingredients: side effects. You may report side effects KALETRA 200 mg lopinavir and 50 mg to FDA at 1-800-FDA-1088. ritonavir tablets: copovidone, sorbitan monolaurate, colloidal silicon dioxide, and sodium stearyl fumarate. The film coating contains: hypromellose, titanium dioxide,

It’s in the

cards Where to get help to pay for your meds

by Jeff Berry

There are a number of ways to get assistance in paying for your HIV medications depending on your financial situation and the coverage you may or may not currently have.

The good news is that in 2010 many pharmaceutical companies expanded coverage for their co-pay and patient assistance programs. The bad news is that financially strapped AIDS Drug Assistance Programs (ADAPs) around the country had to make some tough decisions just to stay afloat. They did this in some cases by reducing formularies, capping enrollment, and instituting waiting lists, among other strict measures.

The last thing anyone with HIV needs to worry about is not being able to pay for their medications, so hopefully this article will help you to navigate the system and keep your medicine chest full, while keeping your stress level to a minimum.

Co-pay and Patient Assistance Programs All pharmaceutical companies provide some level of assistance to individuals who are unable to afford their HIV medications through the use of their patient assistance program, or PAP. These PAPs are typically for patients without insurance and who don’t qualify for Medicare, Medicaid, or ADAP. Qualifications and criteria vary by P o s i t i v e lyAwa r e . c o m

program and are based on a percentage of Federal Poverty Level (FPL), for example 300%. The FPL is currently $10,830 for a single individual, so 300% would be $32,490. Some of the companies are now covering up to 500% FPL and even higher, so check the details of each program.

Patients or providers should contact the manufacturer directly to see if they are eligible (see chart, next page).

Many companies also have co-pay assistance programs which are designed for those who have drug coverage through privately held insurance. These programs may cover all or part of the drug co-pay up to a specified amount, and for a pre-determined period of time (for example, up to one year). Certain restrictions and eligibility requirements apply (for example, recipients of ADAP, Medicare, and Medicaid are not eligible), and may vary from program to program. Individuals usually get the co-pay card directly from their provider, the manufacturer’s website, or by calling a toll-free number. Once enrolled, they bring the co-pay card to the pharmacy when filling their prescription and the pharmacy is reimbursed for the amount covered.

The Fair Pricing Coalition, founded by the late HIV treatment advocate Martin Delaney, regularly meets with drug companies on pricing issues and in an effort to help control costs and improve access to life-saving medications. The existing HIV and hepatitis drug co-pay programs are the direct result of ongoing discussions between the Fair Pricing Coalition (FPC) and representatives of the pharmaceutical industry. After concerns were voiced by both the FPC and members of the community over rising costs and people not being able to get their medications, many companies increased coverage for their co-pay programs, raised the qualifying level of income for some PAPs and eased restrictions, thereby making the programs even more accessible to people who in the past may not have qualified.

Medicare and Medicaid Medicare is a federally-funded program focusing primarily on the older population.

It is a social insurance program for people age 65 or older, people under age 65 with certain disabilities, including HIV/AIDS, and people of all ages with end stage renal disease. Medicare Part A covers hospital bills, Medicare Part B covers medical insurance coverage, and Medicare Part D covers prescription drugs. Medicare operates similar to a single-payer health care system, the M a r c h +A p r i l 2 0 1 1

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key difference being that its coverage only extends to 80% of any given medical cost; the remaining 20% must be paid by other means, such as privately-held supplemental insurance, or by the patient.

Medicaid is a program that is not entirely funded at the federal level—states provide up to half of the funding, and counties also contribute funds in some states. Eligibility is determined largely by limited income and financial resources.

Medicaid covers a wider range of health care services than Medicare, and it is currently the largest single payer for prescription drugs.

To find out if you are eligible, talk to your health care provider or case manager, or contact your state’s Medicare or Medicaid agency.

ADAP and Welvista Around one-third of all people receiving HIV treatment in the U.S. get their medications through AIDS Drug Assistance Programs (ADAPs), which are a set of federal- and state-funded programs in each state that provide medications to low income patients. To find out if you may qualify or for more information, talk to your health care provider, contact your local AIDS service organization or case manager, or call your state AIDS hotline.

The Welvista program is a non-profit organizarion funded by the Heinz Family Philanthropies and through grants from many of the major pharmaceutical companies. Currently, six companies that market HIV drugs are participating in the program, which is designed to facilitate access to HIV meds for those on ADAP waiting lists by streamlining paperwork and using a single mail order pharmacy, rather than having to access multiple patient assistance programs. You will need to be certified by your state ADAP and on a waiting list to participate in this program.

Welvista is a stand-alone non-profit company that dispenses medicines for other disease states, not just HIV. Visit www. welvista.com.

Additional programs There may also be other medications that individuals need for conditions such as high cholesterol or diabetes. To learn more about patient assistance or drug co-pay 68

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programs for these and other medications talk to your provider, contact the manufacturer directly, or visit www.pparx.org or www.needymeds.org. Together Rx is a prescription savings program for uninsured individuals sponsored by many of the nation’s leading pharmaceutical companies; call toll-free 800-966-0407, or enroll online at www.TogetherRxAccess.com.

SurvivorRxPlan is for those who qualify financially to help them get many of the medications not covered by ADAP, including alternative therapies and generics. Patients can take advantage of the program even if they receive medicines through another discount program, and it is available to individuals with incomes of up to $36,425.

Visit www.SurvivorRxPlan.com.

Additional co-pay and patient assistance programs are available for drugs used to treat hepatitis B and C, as well as medications or treatments used for other HIV-related conditions such as lipodystrophy; contact the manufacturer, discuss with your health care provider, or visit www.fairpricingcoalition.org for a complete list.

HIV Co-PAY & Patient Drug

Company

Aptivus

Boehringer Ingelheim

Atripla

Bristol-Myers Squibb and Gilead

Combivir

ViiV Healthcare

Crixivan

Merck & Co.

Emtriva

Gilead Sciences

Epivir

ViiV Healthcare

Epzicom

ViiV Healthcare

Fuzeon

Genentech/Roche

Intelence

Tibotec Therapeutics

Invirase

Genentech/Roche

Isentress

Merck & Co.

Kaletra

Abbott Laboratories

Lexiva

ViiV Healthcare

Norvir

Abbott Laboratories

Prezista

Tibotec Therapeutics

The recently approved Egrifta (tesamorelin), which is used to treat lipohypertrophy, or increased abdominal fat in people with HIV, has a planned co-pay and patient assistance program which is scheduled to launch in early 2011; visit www.egrifta.com.

You must get the card from your provider, or you can call 877-714-2947 for details. e

Rescriptor

ViiV Healthcare

Retrovir (AZT or zidovudine)

ViiV Healthcare

Reyataz

Bristol-Myers Squibb

rilpivirine

Tibotec Therapeutics

rilpivirine/Truvada

Gilead/Tibotec

Selzentry

ViiV Healthcare

Special thanks to David Evans and the Fair Pricing Coalition for some of the information contained in this article. Note: The author is a member of the Fair Pricing Coalition.

Sustiva

Bristol-Myers Squibb

Trizivir

ViiV Healthcare

Trofile assay for Selzentry

Monogram Biosciences

Truvada

Gilead Sciences

Videx and Videx EC (didanosine)

Bristol-Myers Squibb

Viracept

ViiV Healthcare

Viramune and Viramune XR

Boehringer Ingelheim

Viread

Gilead Sciences

Zerit (stavudine)

Bristol-Myers Squibb

Ziagen

ViiV Healthcare

Egrifta assistance

The chart at right gives a brief description of currently available HIV co-pay and patient assistance programs. If you have a problem accessing or using a specific program, call the Project Inform Hotline at 800-822-7422, or call the number listed for each program.

Visit www.PositivelyAware.com for more information as details of specific programs may change.

M a r c h +A p r i l 2 0 1 1 P o s i t i v e lyAwa r e . c o m

Assistance programs*

*By law residents of the state of Massachusetts are not eligible for drug co-pay programs.

Co-Pay Program

Patient Assistance

N/A

800-556-8317 / needymeds.org Patient assistance program only.

866-784-3431 atripla.com

866-290-4767 atripla.com

Co-pay program covers up to $200 per month per prescription.

Card available through provider.

888-825-5249 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $100 per month per prescription.

Card available through provider or your can print the card online.

N/A

800-850-3430 merck.com/merckhelps

Patient assistance program only.

888-358-0398 truvada.com

800-226-2056 truvada.com

Truvada co-pay program covers Emtriva up to $200 per month per prescription.

Card available through provider.

888-825-5249 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $100 per month per prescription.

Card available through provider or your can print the card online.

888-825-5249 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $100 per month per prescription.

Card available through provider or your can print the card online.

N/A

877-757-6243 / fuzeon.com

Patient assistance program only. Also go to genentech.com.

866-961-7169 intelence.com

800-652-6227 intelence.com

Co-pay: patient pays first $5, then up to $100 a month per month per prescription.

Call toll free number or go to jjpaf.org.

N/A

877-757-6243 / genentech.com

Patient assistance program only.

866-350-9232 isentress.com

800-850-3430 isentress.com

Co-pay program covers up to $400 per month per prescription.

Get the card from your provider or your can print the card online.

800-441-4987 kaletra.com

800-222-6885 kaletra.com

Co-pay program covers up to $50 per month plus up to $50 off up to two other HIV meds that are part of a Kaletra regimen, totalling $100. Card available through provider.

888-825-5249 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $100 per month per prescription.

Card available through provider or your can print the card online.

800-441-4987 norvir.com

800-222-6885 norvir.com

Co-pay program covers up to $50 per month per prescription. Card available through provider. See abbottpatientassistancefoundation.org for patient assistance program.

866-961-7169 prezista.com

800-652-6227 jjpaf.org

Co-pay: patient pays first $5, then covers up to $100 per month per prescription.

Call toll free number or go to jjpaf.org.

888-825-5249 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $100 per month per prescription.

Card available through provider or your can print the card online.

888-825-5249 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $100 per month per prescription.

Card available through provider or your can print the card online.

888-281-8981

888-477-2669 bms.com

Co-pay program covers up to $200 per month per prescription.

Card available through provider or by calling the toll free number.

N/A

N/A

At press time, information was not available; drug not yet approved.

N/A

N/A

At press time, information was not available; fixed dose regimen not yet approved.

888-825-5249 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $100 per month per prescription.

Card available through provider or your can print the card online.

888-281-8981 sustiva.com

888-477-2669 bms.com

Co-pay assistance covers up to $200 per month per prescription.

Card available through provider, or by calling toll free number.

888-825-5249 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $100 per month per prescription.

Card available through provider or your can print the card online.

N/A

877-436-6243 monogramvirology.com

Tropism testing for Selzentry. Gateway patient assistance program for uninsured and underinsured.

888-358-0398 truvada.com

800-226-2056 truvada.com

Co-pay program covers up to $200 per month per prescription.

Card available through your provider.

N/A

bms.com

No company co-pay or patient assistance program for Videx. Available as generic.

888-825-5249 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $100 per month per prescription.

Card available through provider or your can print the card online.

888-998-4726 viramune.com

800-556-8317 needymeds.org

Co-pay program covers up to $50 per month per prescription. Get MasterCard debit card from provider; activate it at viramune.com or by calling the toll free number.

888-358-0398 truvada.com

800-226-2056 truvada.com

Truvada co-pay program covers Viread up to $200 per month per prescription.

Card available through provider.

N/A

bms.com

No company co-pay or patient assistance program for Zerit. Available as generic.

888-825-5249 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $100 per month per prescription.

Card available through provider or your can print the card online.

P o s i t i v e lyAwa r e . c o m

Details

M a r c h +A p r i l 2 0 1 1

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69

Taking VIRAMUNE?

You can save up to $50 off your monthly VIRAMUNE co-pay for up to 1 year!

The VIRAMUNE Co-Pay Savings Program also provides you with Vlife on Therapy—a free educational support program that includes medication reminders.

Ask your healthcare provider about the VIRAMUNE Co-Pay Savings Program today!

We can help. For nearly 125 years, Boehringer Ingelheim has concentrated on furthering science to improve healthcare for patients and their families. Our guiding principles have created a culture of corporate responsibility and commitment.

Value through innovation. Our vision reflects our dedication to discovery—for better real-world health solutions to improve life for individuals, communities, and countries around the world.

Our work involves developing innovative treatments and making them accessible to everyone who needs them.

Please see Important Safety Information and Medication Guide for VIRAMUNE on the following pages.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

www.viramune.com

Terms and Conditions of VIRAMUNE Co-Pay Savings Program For cardholder service, please call the Macaluso Group 1-877-411-8641 between 9 AM and 5 PM ET, Monday through Friday, except holidays. The issuers shall not be liable to the users for losses, expenses, claims, or other damages that the user may incur as a result of this card.

This program expires on 06/30/2012. This offer is not valid for patients participating in Medicare, Medicaid, or any other federal- or state-funded benefit programs, and where prohibited by law.

Cash-paying customers are not eligible for this offer. Offer good in the United States (including the District of Columbia and Puerto Rico) only.

Boehringer Ingelheim Pharmaceuticals, Inc. reserves the right to change the terms and conditions of this offer at any point. This VIRAMUNE Co-Pay Savings Card is issued by KeyBank pursuant to the license by MasterCard International Incorporated.

INDICATION AND IMPORTANT SAFETY INFORMATION VIRAMUNE is indicated for use in combination with other antiretroviral agents for the treatment of HIV infection.

VIRAMUNE does not cure HIV or AIDS, and has not been shown to reduce the risk of passing HIV to others through sexual contact or blood contamination.

VIRAMUNE can cause severe liver disease and skin reactions that can cause death. These reactions occur most often during the first 18 weeks of treatment, but can occur later. Ask your healthcare provider about how to recognize symptoms of skin and liver problems.

Stop taking VIRAMUNE if you have any of these reactions. Do not restart VIRAMUNE if you experience any of these reactions. Call your healthcare provider immediately if you have any of these reactions.

VIRAMUNE is only for people diagnosed with HIV. If you have not been diagnosed as HIV positive, then do not take VIRAMUNE. Any patient can experience liver problems with VIRAMUNE, but women and patients who have higher CD4 counts when they begin VIRAMUNE treatment have a greater risk. If you are a woman with CD4+ >250 cells/mm3, or a man with CD4+ >400 cells/mm3, you should not begin taking VIRAMUNE unless you and your doctor have decided that the benefit of doing so outweighs the risk. Women, including pregnant women, with CD4+ cell counts >250 cells/mm3 are at the greatest risk.

Do not take VIRAMUNE if you have severe liver problems.

The dose of VIRAMUNE for adults is one 200-mg tablet daily for the first 14 days, followed by one 200-mg tablet twice daily. VIRAMUNE is always taken with other anti-HIV medications. The 14-day lead-in period is important because it can help reduce your chances of getting a potentially serious skin rash. If you have a skin rash during the first 14 days, immediately contact your doctor and do not increase your VIRAMUNE dose to twice a day. The total duration of the once daily lead-in dosing period should not exceed 28 days, at which point an alternative regimen may need to be started.

Other side effects that patients have experienced include nausea, fatigue, fever, headache, vomiting, diarrhea, abdominal pain, and myalgia. Changes in body fat may occur in patients receiving antiretroviral therapy.

Immune reconstitution syndrome has been reported in patients treated with combination ARV therapy.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Please see Medication Guide for VIRAMUNE on the following pages.

Copyright Š 2010 Boehringer Ingelheim Pharmaceuticals, Inc. All Rights Reserved.

(08/10)

VR78906CONS

www.viramune.com

Severe rash and skin reactions: Skin rash is the most common side effect of VIRAMUNE. Most rashes happen in the first 6 weeks of taking VIRAMUNE. Rashes and skin reactions may be VIRAMUNE® (VIH-rah-mune) severe, life-threatening, and in some people, (nevirapine) Tablets may lead to death. If you get a rash with any of the following symptoms, stop using VIRAMUNE® (VIH-rah-mune) VIRAMUNE and call your doctor right away: (nevirapine) Oral Suspension • “flu-like” symptoms or you do not feel well Read this Medication Guide before you start • blisters taking VIRAMUNE and each time you get a refill.

• fever There may be new information. This information does not take the place of talking to your doctor • mouth sores about your medical condition or treatment.

• muscle or joint aches What is the most important information • swelling of your face I should know about VIRAMUNE? • red or inflamed eyes, like “pink eye” VIRAMUNE can cause serious side effects. (conjunctivitis) These include severe liver and skin problems • tiredness which can cause death. The risk of these problems is greatest during the first 18 weeks of • swollen glands (enlarged lymph nodes) treatment, but these problems can also happen • liver problems (see symptoms of liver at any time during treatment. problems above) Severe liver problems: Anyone who takes If your doctor tells you to stop treatment with VIRAMUNE may get severe liver problems.

VIRAMUNE because you have had the serious In some cases, these liver problems can lead to liver or skin problems described above, you liver failure and the need for a liver transplant, should never take VIRAMUNE again. or death. You may get a rash if you have liver These are not all the side effects of VIRAMUNE. problems. People with higher risk of these problems include women or anyone with higher See the section “What are the possible side effects of VIRAMUNE?” for more information.

CD4+ cell counts when they begin VIRAMUNE treatment. Women with CD4+ cell counts higher What is VIRAMUNE? than 250 cells/mm3 at the start of treatment VIRAMUNE is a medicine used to treat Human have the greatest risk for liver damage.

Immunodeficiency Virus (HIV), the virus that + If you are a woman with CD4 cell >250 cells/ causes AIDS (Acquired Immune Deficiency 3 + 3 mm or a man with CD4 cell >400 cells/mm , Syndrome). you and your doctor will decide if VIRAMUNE is VIRAMUNE is a type of anti-HIV medicine right for you. called a “non-nucleoside reverse transcriptase People who have abnormal liver test results inhibitor” (NNRTI). VIRAMUNE works by lowering and people with hepatitis B or C have a greater the amount of HIV in your blood (“viral load”). chance of getting liver problems and further You must take VIRAMUNE with other anti-HIV increases in liver test results during treatment. medicines. When you take VIRAMUNE with other If you get any of the following symptoms of anti-HIV medicines, VIRAMUNE can lower your liver problems, stop taking VIRAMUNE and viral load and increase the number of CD4+ cells call your doctor right away: (“T cells”). CD4+ cells are a type of immune helper cell in the blood. VIRAMUNE may not have • fever these effects in every person.

• “flu-like” symptoms or you do not feel well VIRAMUNE does not cure HIV or AIDS, and it is • dark (tea colored) urine not known if it will help you live longer with HIV. People taking VIRAMUNE may still get infections • tiredness common in people with HIV (opportunistic • light-colored bowel movements (stools) infections). It is very important that you stay • nausea (feeling sick to your stomach) under the care of your doctor.

• pain or tenderness on your right side below your ribs Who should not take VIRAMUNE? • loss of appetite Tell your doctor if you have or have had liver problems. Your doctor may tell you not to take • yellowing of your skin or whites of VIRAMUNE if you have certain liver problems. your eyes VIRAMUNE is only for people diagnosed with HIV. Your doctor should see you and do blood tests If you have not been diagnosed as HIV positive, often to check your liver function during the then do not take VIRAMUNE. first 18 weeks of treatment with VIRAMUNE. You should continue to have your liver checked regularly during your treatment with VIRAMUNE. It is important for you to keep all of your doctor appointments.

MEDICATION GUIDE

What should I tell my doctor before taking VIRAMUNE? Before you take VIRAMUNE, tell your doctor if you: • have or have had hepatitis (inflammation of your liver) or problems with your liver.

See “What is the most important information I should know about VIRAMUNE?” and “Who should not take VIRAMUNE?” • receive dialysis • have skin problems, such as a rash • are pregnant or plan to become pregnant. It is not known if VIRAMUNE will harm your unborn baby.

Pregnancy Registry: There is a pregnancy registry for women who take antiviral medicines during pregnancy.

The purpose of the registry is to collect information about the health of you and your baby. Talk to your doctor about how you can take part in this registry.

• are breast-feeding or plan to breast-feed. VIRAMUNE can pass into your breast milk and may harm your baby. It is also recommended that HIV-positive women should not breast-feed their babies. Do not breast-feed during treatment with VIRAMUNE. Talk to your doctor about the best way to feed your baby.

Tell your doctor and pharmacist about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. VIRAMUNE may affect the way other medicines work, and other medicines may affect how VIRAMUNE works. Especially tell your doctor if you take: • St. John’s Wort. You should not take products containing St. John’s Wort during treatment with VIRAMUNE because it can lower the amount of VIRAMUNE in your body.

• efavirenz (Sustiva®, Atripla®). You should not take efavirenz during treatment with VIRAMUNE. You may have an increased chance of side effects if this is taken together with VIRAMUNE. • atazanavir (Reyataz®). You should not take atazanavir during treatment with VIRAMUNE. • itraconazole (Sporanox®). You should not take itraconazole during treatment with VIRAMUNE. • ketoconazole (Nizoral®). You should not take ketoconazole during treatment with VIRAMUNE.

• rifampin (Rifadin®, Rifamate®, Rifater®).

You should not take rifampin during treatment with VIRAMUNE. • Birth control pills. Birth control pills taken by mouth (oral contraceptives) and other hormone types of birth control may not work to prevent pregnancy if you use them during VIRAMUNE treatment.

Talk with your doctor about other types of birth control that you can use to prevent pregnancy during treatment with VIRAMUNE. Also tell your doctor if you are taking the following drugs: • clarithromycin (Biaxin) • fluconazole (Diflucan) • methadone • rifabutin (Mycobutin) Know the medicines you take. Keep a list of them to show your doctor or pharmacist when you get a new medicine.

How should I take VIRAMUNE? • Take VIRAMUNE exactly as your doctor tells you to take it.

• The dose of VIRAMUNE for children is based on their size and thus may not be the same as in adults.

• You may take VIRAMUNE with or without food.

• If you or your child takes VIRAMUNE suspension (liquid), shake it gently before use. Use an oral dosing syringe or dosing cup to measure the right dose.

The oral dosing syringe and dosing cup are not provided with VIRAMUNE suspension.

• After drinking the medicine, fill the dosing cup with water and drink it to make sure you get all the medicine. If the dose is less than 1 teaspoon (5 mL), use the syringe instead of the dosing cup.

• Do not change your dose unless your doctor tells you to.

• Your doctor should start you with one dose each day to lower your chance of getting a serious rash. It is important that you only take one dose of VIRAMUNE each day for the first 14 days.

• Call your doctor right away if you get a skin rash during the first 14 days of VIRAMUNE treatment and do not increase your dose to 2 times a day.

• You should never take your starting dose (200 mg one time each day) for longer than 28 days. If after 28 days you are still receiving this starting dose because you have a rash, you and your doctor should discuss replacing VIRAMUNE with another HIV medicine. Never increase your dose to 2 times a day if you have a rash.

• Do not miss a dose of VIRAMUNE, because this could make HIV harder to treat. If you miss a dose of VIRAMUNE, take the missed dose as soon as you remember. If it is almost time for your next dose, do not take the missed dose, just take the next dose at your regular time.

• If you stop taking VIRAMUNE for more than 7 days, ask your doctor how much to take before you start taking it again.

You may need to start with one time each day dosing again.

• If you take too much VIRAMUNE, call your local poison control center or emergency room right away.

What are the possible side effects of VIRAMUNE? VIRAMUNE may cause serious side effects.

• See “What is the most important information I should know about VIRAMUNE?” • Other common side effects of VIRAMUNE include nausea, fatigue, fever, headache, vomiting, diarrhea, abdominal pain, and muscle pain.

• Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking HIV medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your doctor if you start having new symptoms after starting your HIV medicine.

• Changes in body fat can happen in some people who take antiretroviral therapy. These changes may include increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the middle of your body (trunk). Loss of fat from your legs, arms, and face can also happen. The cause and long-term health effects of these problems are not known at this time.

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of VIRAMUNE. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store VIRAMUNE? • Store VIRAMUNE at 59° to 86°F (15° to 30°C).

• Throw away VIRAMUNE that is no longer needed or out-of-date.

Keep VIRAMUNE and all medicines out of the reach of children.

General information about VIRAMUNE Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use VIRAMUNE for a condition for which it was not prescribed. Do not give VIRAMUNE to other people, even if they have the same condition you have. It may harm them.

This Medication Guide summarizes the most important information about VIRAMUNE. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about VIRAMUNE that is written for health professionals.

For more information, call Boehringer Ingelheim Pharmaceuticals, Inc., at 1-800-542-6257, or (TTY) 1-800-459-9906.

What are the ingredients in VIRAMUNE? Active Ingredient: nevirapine Inactive ingredients: Viramune Tablets: microcrystalline cellulose, lactose monohydrate, povidone, sodium starch glycolate, colloidal silicon dioxide, and magnesium stearate Viramune Oral Suspension: carbomer 934P, methylparaben, propylparaben, sorbitol, sucrose, polysorbate 80, sodium hydroxide, and purified water Distributed by: Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT 06877 USA Rev: June 2010 This Medication Guide has been approved by the US Food and Drug Administration Atripla, Reyataz, and Sustiva are trademarks of Bristol-Myers Squibb. Biaxin is a trademark of Abbott Laboratories. Diflucan is a trademark of Pfizer, Inc. Mycobutin is a trademark of Pharmacia & Upjohn Company. Nizoral and Sporanox are trademarks of Janssen Pharmaceutica. Rifadin, Rifamate, and Rifater are trademarks of Aventis Pharmaceuticals, Inc. ©Copyright 2010 Boehringer Ingelheim Pharmaceuticals, Inc. ALL RIGHTS RESERVED OT1801LE1910 10003354/06 OT1803D 090340228/5 VR77527CONS

Coming

into view Drugs we can look forward to in the future

structurally similar to Epivir and Emtriva and early studies show it may have activity against HIV strains that are resistant to older nukes including Retrovir (AZT). Side effects include nausea, diarrhea, nasal and chest congestion, and increases in triglycerides. Hopefully, another company will purchase this product and continue development.

600 mg by mouth once daily. Racivir is structurally similar to Epivir and Emtriva.

Continuing trials will see if it has activity against HIV strains already resistant to Epivir and Emtriva. Side effects including headache and fatigue have been reported.

Festinavir is another NRTI being developed by Bristol-Myers Squibb and Oncolys BioPharma, Inc. It is currently in Phase 2. Early studies show the once-daily oral medication has an improved safety profile when compared to older nukes, like its cousin agent Zerit.

Elvucitabine is currently in Phase 2 and is being developed by Achillion Pharmaceuticals. Studied doses are 5 or 10 mg by mouth once daily. This drug shows activity against hepatitis B as well as HIV and may have activity against HIV strains that are resistant to other NRTIs, including Epivir and Retrovir. This drug has a very long half-life, making it more forgiving if a dose is forgotten.

Some good news

Non-nukes

Racivir is an NRTI being developed by Pharmasset, Inc. and has activity against hepatitis B as well as HIV. Phase 2 trials have just been completed using a dose of

In addition to the promising rilpivirine, other second-generation non-nucleoside reverse transcriptase inhibitors are currently being developed.

by Swarup Mehta, PharmD

It has now been more than three years since a new anti-HIV medication has come on the market. However, the wait is finally over with the inevitable approval of rilpivirine in May 2011 (see page 34) and with many other promising drugs in Phase 2 or 3 development. Here are some highlights of exciting drugs we may see in the future.

Nukes There was some disappointing news coming from the nucleoside reverse transcriptase inhibitors (NRTIs, or nukes), the oldest class of anti-HIV drugs, with development of some drugs in this class being discontinued. This is unfortunate because the advantage of these new drugs is that they will hopefully have few side effects and have activity against HIV strains that are resistant to the older nukes.

For example, Avexa has halted the development of apricitabine because it cannot find a partner to help launch and finance the product. Apricitabine is 74

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RDEA806 by Ardea has completed Phase 2 trials. It has been shown to be active against HIV strains resistant to Sustiva. Secondary data have shown it can reduce uric acid levels. Another NNRTI in Phase 2 is GSK2248761 (formally IDX899).

It is being developed by ViiV Healthcare.

This drug is less susceptible to resistance when compared to the older NNRTIs on the market (Sustiva and Viramune). ViiV has another NNRTI called lersivirine that is also less susceptible to resistance when compared to older NNRTIs on the market.

A Phase 2 trial is currently underway comparing it to Sustiva.

Integrase inhibitor and new booster The integrase inhibitor class of medications has many exciting drugs in development. Elvitegravir is an integrase inhibitor (same class as Isentress) being developed

by Gilead, now in Phase 3. It does not require dose adjustments for individuals with kidney problems. This drug needs to be “boosted” for it to be effective.

One of the most exciting drugs in development is a new “booster” drug called

cobicistat (GS-9350), also being developed

by Gilead. It may be the first alternative to taking low-dose Norvir to increase concentrations of other drugs, including elvitegravir. It should be noted that it has no activity against HIV. Cobicistat has just started two Phase 3 studies comparing a once-daily, fixed dose “Quad” regimen (four-in-one combination of GS9350, elvitegravir, and Truvada) vs. once-daily, fixed dose Atripla and Norvir-boosted Reyataz and Truvada.

This stems from the good results of the Phase 2 head-to-head study presented at the Conference on Retroviruses and Opportunistic Infections (CROI) in 2010.

The “Quad” was non-inferior to Atripla in safety and efficacy. Gilead is also going to start a Phase 3 study with cobicistat as a stand-alone booster. The study will evaluate efficacy, safety, and tolerability of cobicistat-boosted Reyataz vs. Norvir-boosted Reyataz, each with a Truvada backbone.

Shionogi-ViiV Healthcare has started Phase 3 trials for a once-daily, unboosted integrase inhibitor called S/GSK1349572 (572 for short); and a co-formulation of 572 with Epzicom (known as 572-Trii), also in Phase 3. Phase 2 studies of 572

demonstrated potent anti-viral activity with good tolerability, and activity against strains already resistant to Isentress. Both elvitegravir and 572 offer an advantage over Isentress, being dosed once-daily instead of twice-daily. Both are expected to have limited cross-resistance with Isentress as well, but more data from studies are needed.

CCR5/CCR2 antagonist Tobira Therapeutics is developing a new dual CCR5/CCR2 antagonist called TBR-652 that not only shows potent anti-viral activity but has a potential antiinflammatory benefit as well. Inflammation in HIV-positive individuals can increase risk of heart disease, dementia, and other age related problems. Unlike Selzentry, TBR-652 is dosed once daily, giving it an advantage when compared with other anti-virals. It is continuing Phase 2 studies.

It is exciting to see what the future of HIV therapy might bring. But remember, highly active drugs are already available.

Make sure to be adherent on your current regimen to avoid resistance and live a long, healthy life. e

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The rules of the game Current DHHS treatment guidelines for first time therapy* * Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. January 10, 2011; 1-166. Available at http://www.aidsinfo.nih.gov/ContentFiles/ AdultandAdolescentGL.pdf. Accessed January 25, 2011; page 39; Table 5a.

Patients new to antiretroviral therapy should start on one of three types of combination regimens: NNRTI + 2 NRTIs

PI

INSTI + 2 NRTIs

(preferably boosted with ritonavir)

+ 2 NRTIs

Preferred Regimens NNRTI-based

Sustiva (efavirenz) 1 + Truvada (emtricitabine/tenofovir) PI-based

Boosted Reyataz (atazanavir/ritonavir) + Truvada (emtricitabine/tenofovir) Boosted Prezista (darunavir/ritonavir) + Truvada (emtricitabine/tenofovir) INSTI-based

Isentress (raltegravir) + Truvada (emtricitabine/tenofovir)

Preferred for Pregnant Women PI-based

Kaletra (lopinavir/ritonavir) (twice daily) + Combivir (zidovudine/lamivudine)

Alternative Regimens NNRTI-based

Sustiva (EFV) + Epzicom or Combivir (ABC or ZDV)/3TC 3 Viramune (NVP) 2 + Combivir (ZDV/3TC) 3 PI-based

Boosted Reyataz (atazanavir/ritonavir) + Epzicom or Combivir (ABC or ZDV)/3TC 3 Boosted Lexiva (FPV/r (once or twice daily) + either Epzicom or Combivir [(ABC or ZDV)/3TC 3] or Truvada (emtricitabine/tenofovir) 3 Kaletra (LPV/r) (once or twice daily) + either Epzicom or Combivir [(ABC or ZDV)/3TC 3] or Truvada (emtricitabine/tenofovir) 3 Boosted Invirase (SQV/r) + Truvada (emtricitabine/tenofovir) 3 76

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Acceptable regimens NNRTI-based

Sustiva (EFV) + Videx (ddI) + (3TC or FTC) PI-based

Reyataz (ATV) + Epzicom or Combivir (ABC or ZDV)/3TC 3 CCR5 Antagonist-based regimens

Selzentry (MVC) + Combivir (ZDV/3TC 3)

May be Acceptable, but MOre Data needed These regimens may be acceptable, but more definitive data are needed.

PI-based

Boosted Prezista (DRV/r) + Epzicom or Combivir (ABC or ZDV)/3TC 3 INSTI-based

Isentress (RAL) + Epzicom or Combivir (ABC or ZDV)/3TC 3 CCR5 Antagonist-based regimens

Selzentry (MVC) + Truvada (TDF/FTC 3) or Epzicom (ABC/3TC 3)

May be acceptable, but Use with caution These regimens may be acceptable, but should be used with caution.

NNRTI-based regimens

Viramune + Epzicom (ABC/3TC 3) Viramune + Truvada (TDF/FTC 3) PI-based regimens

Lexiva (FPV) + Epzicom or Combivir or Truvada [(ABC or ZDV)/3TC3 or TDF/FTC3] Boosted Invirase (SQV/r) + Truvada (TDF/FTC 3) Boosted Invirase (SQV/r) + Epzicom or Combivir (ABC or ZDV)/3TC 3 1. Except during first trimester of pregnancy or in women with high pregnancy potential 2. Viramune (nevirapine) should not be initiated in women with CD4+ T-cell count greater than 250 cells/mm3 or in men with CD4+ T-cell count greater than 400 cells/mm3 3. Emtriva (emtricitabine) and Epivir (lamivudine) are interchangeable.

Abbreviations: INSTI = integrase strand transfer inhibitor, NNRTI = non-nucleoside reverse transcriptase inhibitor, NRTI = nucleos(t)ide reverse transcriptase inhibitor, PI = protease inhibitor, 3TC = lamivudine, ABC = abacavir, ATV = atazanavir, ddI = didanosine, DRV = darunavir, EFV =efavirenz, FPV = fosamprenavir, FTC = emtricitabine, LPV = lopinavir, MVC = maraviroc, NVP = nevirapine, RAL = raltegravir, r = low dose ritonavir SQV = saquinavir, TDF = tenofovir, ZDV = zidovudine Visit www.aidsinfo.nih.gov for the complete set of guidelines and for more detailed information.

Or using a QR code reader app, you can also scan the QR code at left with your iPhone or other smart phone to go directly to the website.

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