MAY-JUNE 2010 by POSITIVELY AWARE

Gary Blick, MD HIV, your HAART, and you

Positively Aware May/June 2010

Is it all in your head? How your mental health can affect living with HIV The HIV Treatment & Health Journal of

Test Positive Aware Network

CROI 2010 Update Latest findings could lead to new strategies

Important Safety Information and Indication

• Have liver problems, including hepatitis B or C virus infection. • Have ever had seizures: Seizures have occurred in patients taking a component of ATRIPLA, usually in those with a history of seizures. If you have ever had seizures, or take medicine for seizures, your healthcare provider may want to switch you to another medicine or monitor you. • Have ever had mental illness or use drugs or alcohol. Contact your healthcare provider right away if you experience any of the following serious or common side effects: Serious side effects associated with ATRIPLA: • Severe depression, strange thoughts, or angry behavior have been reported by a small number of patients. Some patients have had thoughts of suicide and a few have actually committed suicide. These problems may occur more often in patients who have had mental illness. • Kidney problems (including decline or failure of kidney function). If you have had kidney problems, or take other medicines that may cause kidney problems, your healthcare provider should do regular blood tests. Symptoms that may be related to kidney problems include a high volume of urine, thirst, muscle pain, and muscle weakness. • Bone changes. Lab tests show changes in the bones of patients treated with tenofovir DF, a component of ATRIPLA. Some HIV patients treated with tenofovir DF developed thinning of the bones (osteopenia) which could lead to fractures. Also, bone pain and softening of the bone (which may lead to fractures) may occur as a consequence of kidney problems. If you have had bone problems in the past, your healthcare provider may want to check your bones. Common side effects: • Dizziness, headache, trouble sleeping, drowsiness, trouble concentrating, and/or unusual dreams. These side effects tend to go away after taking ATRIPLA for a few weeks. These symptoms may be more severe with the use of alcohol and/or mood-altering (street) drugs. If you are dizzy, have trouble concentrating, and/or are drowsy, avoid activities that may be dangerous, such as driving or operating machinery. • Rash is a common side effect that usually goes away without any change in treatment, but may be serious in a small number of patients. • Other common side effects include: tiredness, upset stomach, vomiting, gas, and diarrhea. Other possible side effects: • Changes in body fat have been seen in some people taking anti-HIV-1 medicines. The cause and long-term health effects are not known. • Skin discoloration (small spots or freckles) may also happen. • If you notice any symptoms of infection, contact your healthcare provider right away. • Additional side effects are inflammation of the pancreas, allergic reaction (including swelling of the face, lips, tongue, or throat), shortness of breath, pain, stomach pain, weakness and indigestion. You should take ATRIPLA once daily on an empty stomach. Taking ATRIPLA at bedtime may make some side effects less bothersome.

INDICATION ATRIPLA® (efavirenz 600 mg/emtricitabine 200 mg/ tenofovir disoproxil fumarate [DF] 300 mg) is a prescription medication used alone as a complete regimen or with other medicines to treat HIV-1 infection in adults. ATRIPLA does not cure HIV-1 and has not been shown to prevent passing HIV-1 to others. Do not stop taking ATRIPLA unless directed by your healthcare provider. See your healthcare provider regularly. IMPORTANT SAFETY INFORMATION Contact your healthcare provider right away if you get the following side effects or conditions associated with ATRIPLA: • Nausea, vomiting, unusual muscle pain, and/or weakness. These may be signs of a buildup of acid in the blood (lactic acidosis), which is a serious medical condition. • Light-colored stools, dark-colored urine, and/or if your skin or the whites of your eyes turn yellow. These may be signs of serious liver problems. • If you have HIV-1 and hepatitis B virus (HBV), your liver disease may suddenly get worse if you stop taking ATRIPLA. Do not take ATRIPLA if you are taking the following medicines because serious and life-threatening side effects may occur when taken together: Vascor® (bepridil), Propulsid® (cisapride), Versed® (midazolam), Orap® (pimozide), Halcion® (triazolam), or ergot medications (for example, Wigraine® and Cafergot®). In addition, ATRIPLA should not be taken with: Combivir® (lamivudine/zidovudine), EMTRIVA® (emtricitabine), Epivir® or Epivir-HBV® (lamivudine), Epzicom® (abacavir sulfate/lamivudine), SUSTIVA® (efavirenz), Trizivir® (abacavir sulfate/ lamivudine/zidovudine), TRUVADA® (emtricitabine/tenofovir DF), or VIREAD® (tenofovir DF), because they contain the same or similar active ingredients as ATRIPLA. ATRIPLA should not be used with HEPSERA® (adefovir dipivoxil). Vfend® (voriconazole) or REYATAZ® (atazanavir sulfate), with or without Norvir® (ritonavir), should not be taken with ATRIPLA since they may lose their effect and may also increase the chance of having side effects from ATRIPLA. Fortovase® or Invirase® (saquinavir) should not be used as the only protease inhibitor in combination with ATRIPLA. Taking ATRIPLA with St. John’s wort or products containing St. John’s wort is not recommended as it may cause decreased levels of ATRIPLA, increased viral load, and possible resistance to ATRIPLA or cross-resistance to other anti-HIV drugs. This list of medicines is not complete. Discuss with your healthcare provider all prescription and nonprescription medicines, vitamins, or herbal supplements you are taking or plan to take. Tell your healthcare provider if you: • Are pregnant: Women should not become pregnant while taking ATRIPLA and for 12 weeks after stopping ATRIPLA. Serious birth defects have been seen in children of women treated during ATRIPLA is one of several treatment options pregnancy with one of the medicines in ATRIPLA. your doctor may consider. Women must use a reliable form of barrier contraception, such as a condom or diaphragm, even if they also use other methods of birth control You are encouraged to report negative while on ATRIPLA and for 12 weeks after stopping side effects of prescription drugs to the ATRIPLA. FDA. Visit www.fda.gov/medwatch • Are breastfeeding: Women with HIV should not breastfeed because they can pass HIV through their or call 1-800-FDA-1088. milk to the baby. Also, ATRIPLA may pass through breast milk and cause serious harm to the baby.

Please see Patient Information on the following pages.

Patient model. Individual results may vary.

© 2010 Bristol-Myers Squibb & Gilead Sciences, LLC. All rights reserved. ATRIPLA is a trademark of Bristol-Myers Squibb & Gilead Sciences, LLC. EMTRIVA, VIREAD, and TRUVADA are trademarks of Gilead Sciences, Inc. SUSTIVA and REYATAZ are registered trademarks of Bristol-Myers Squibb. All other trademarks are owned by third parties. 697US09AB07011/TR3982 01/10

“My entire HIV regimen in one pill daily. For me, that’s great.” Phill ip

on ATRIPLA for 2 years

ATRIPLA is the #1 prescribed HIV regimen.* • Only ATRIPLA combines 3 HIV medications in 1 pill daily. • Proven to lower viral load to undetectable† and help raise T-cell (CD4+) count to help control HIV through 3 years of a clinical study. • ATRIPLA does not cure HIV-1 and has not been shown to prevent passing HIV-1 to others. • Selected Important Safety Information: Some people who have taken medicine like ATRIPLA have developed the following: a serious condition of acid buildup in the blood (lactic acidosis), and serious liver problems (hepatotoxicity). For patients with both HIV-1 and hepatitis B virus (HBV), hepatitis may worsen if ATRIPLA is discontinued.

Talk to your doctor to see if ATRIPLA is right for you. Your doctor may prescribe ATRIPLA alone or with other HIV medications. Please see Important Safety Information, including bolded information, on adjacent page. *Synovate Healthcare Data; US HIV Monitor, Q2 2009.

†

Defined as a viral load of less than 400 copies/mL.

To learn more, visit www.ATRIPLA.com

FDA-Approved Patient Patient Labeling Labeling FDA-Approved Patient Information Patient Information ® (uh TRIP luh) Tablets ATRIPLA ® (uh TRIP luh) Tablets ATRIPLA ALERT: Find out about medicines that should NOT be taken with ATRIPLA. ALERT: Findread out the about medicines that should NOT be NOT taken withWITH ATRIPLA. Please also section “MEDICINES YOU SHOULD TAKE ATRIPLA.” Please readefavirenz, the section “MEDICINESandYOU SHOULD NOT TAKE WITH ATRIPLA.” Genericalso name: emtricitabine tenofovir disoproxil fumarate (eh FAH vih renz, em tri SITname: uh bean and te emtricitabine NOE’ fo veer dye PROX ildisoproxil FYOU marfumarate ate) (eh FAH vih renz, Generic efavirenz, and soe tenofovir Readtri SIT the uh Patient Information thatveer comes withPROX ATRIPLA em bean and te NOE’ fo dye soe il FYOU(efavirenz/emtricitabine/tenofovir mar ate) disoproxil before youthat startcomes taking itwith andATRIPLA each time(efavirenz/emtricitabine/tenofovir you get a refill since there may Read the fumarate) Patient Information be new information. This information does not take the place talking your healthcare disoproxil fumarate) before you start taking it and each time youofget a refillto since there may provider about your This medical conditiondoes or not treatment. should stay under healthcare be new information. information take theYou place of talking to youra healthcare provider’s care when taking ATRIPLA. Do not change or stop your medicine without first provider about your medical condition or treatment. You should stay under a healthcare talking with your healthcare provider. Talk to your healthcare provider or pharmacist if you provider’s care when taking ATRIPLA. Do not change or stop your medicine without first have any questions about ATRIPLA. talking with your healthcare provider. Talk to your healthcare provider or pharmacist if you Whatany is the most important information I should know about ATRIPLA? have questions about ATRIPLA. • Some people who have taken medicine like ATRIPLA (which contains nucleoside What is the most important information I shouldcalled know lactic aboutacidosis ATRIPLA? analogs) have developed a serious condition (buildup of an acid in the blood). acidosis can medicine be a medical maycontains need to be treated in • Some peopleLactic who have taken likeemergency ATRIPLA and (which nucleoside the hospital. Call your healthcare right away if you get the following analogs) have developed a seriousprovider condition called lactic acidosis (build up of ansigns acid symptoms of lactic acidosis: inorthe blood). Lactic acidosis can be a medical emergency and may need to be treated in the Call your • hospital. You feel very weak healthcare or tired. provider right away if you get the following signs or of lactic(not acidosis: • symptoms You have unusual normal) muscle pain. You feel havevery trouble •• You weakbreathing. or tired. You have have unusual stomach(not painnormal) with nausea vomiting. •• You muscleand pain. You have feel cold, especially in your arms and legs. •• You trouble breathing. • You feel dizzy or lightheaded. •• You withheartbeat. nausea and vomiting. You have have stomach a fast or pain irregular • Youpeople feel cold, especially in your arms andlike legs. • Some who have taken medicines ATRIPLA have developed serious liver •problems You feelcalled dizzy or lightheaded. with liver enlargement (hepatomegaly) and fat in the hepatotoxicity, (steatosis). Callor your healthcare •liverYou have a fast irregular heartbeat.provider right away if you get the following signs or symptoms of liver problems: • Some people who have taken medicines like ATRIPLA have developed serious liver • Your skin or the white part of your yellow (jaundice). problems called hepatotoxicity, witheyes liverturns enlargement (hepatomegaly) and fat in the • Your urine turns liver (steatosis). Calldark. your healthcare provider right away if you get the following • Your movements turn light in color. signs or bowel symptoms of liver(stools) problems: • You don’t feel like eating food for several days or longer. •• Your skin or the white part of your eyes turns yellow (jaundice). You feel sick to your stomach (nausea). •• Your urinelower turns stomach dark. area (abdominal) pain. You have movements turnacidosis light in color. • •YouYour maybowel be more likely to (stools) get lactic or liver problems if you are female, very have food beenfortaking analog-containing medicines, like •overweight You don’t(obese), feel likeoreating severalnucleoside days or longer. forsick a long time.stomach (nausea). •ATRIPLA, You feel to your • •If you virus(abdominal) (HBV) infection Youalso havehave lowerhepatitis stomachBarea pain. and you stop taking ATRIPLA, you may get a “flare-up” of your hepatitis. A “flare-up” is when the disease suddenly • You mayinbeamore get before. lactic acidosis liver problems you areATRIPLA female, need very returns worselikely waytothan Patients or with HBV who stopif taking overweight (obese), or have been taking nucleoside close medical follow-up for several months, including analog-containing medical exams andmedicines, blood testslike to ATRIPLA, a long that time.could be getting worse. ATRIPLA is not approved for the treatment check forfor hepatitis HBV,also so you must discussByour therapy with your provider. • Ifofyou have hepatitis virusHBV (HBV) infection and healthcare you stop taking ATRIPLA, you What is get ATRIPLA? may a “flare-up” of your hepatitis. A “flare-up” is when the disease suddenly ® ® ATRIPLA contains 3 medicines, SUSTIVA EMTRIVA and VIREAD returns in a worse way than before.(efavirenz), Patients with HBV who(emtricitabine) stop taking ATRIPLA need® (tenofovir disoproxil fumarate called tenofovir DF) combined in one and pill. blood EMTRIVA close medical follow-up foralso several months, including medical exams testsand to VIREAD (human immunodeficiency virus)ATRIPLA nucleoside reverse transcriptase checkare forHIV-1 hepatitis that could be getting worse. is notanalog approved for the treatment inhibitors and SUSTIVA is an non-nucleoside analog reverse of HBV,(NRTIs) so you must discuss your HBVHIV-1 therapy with your healthcare provider.transcriptase inhibitor (NNRTI). VIREAD and EMTRIVA are the components of TRUVADA®. ATRIPLA can be What is ATRIPLA? used alone as a complete regimen, or in combination with other anti-HIV-1 ® (efavirenz), EMTRIVA® (emtricitabine) and VIREAD® ATRIPLA contains medicines, SUSTIVA medicines to treat3people with HIV-1 infection. ATRIPLA is for adults age 18 and over. ATRIPLA (tenofovir disoproxil fumarate also called tenofovir DF) combined in one pill. EMTRIVA and has not been studied in children under age 18 or adults over age 65. VIREAD are HIV-1 (human immunodeficiency virus) nucleoside analog reverse + HIV infection destroys CD4 T cells, which are important to the immune system.transcriptase The immune inhibitors (NRTIs) SUSTIVA HIV-1 non-nucleoside reverse transcriptase system helps fightand infection. Afterisa an large number of T cells areanalog destroyed, immune ®.acquired inhibitor (NNRTI). VIREAD and EMTRIVA are the components of TRUVADA ATRIPLA can be deficiency syndrome (AIDS) develops. used alone as a complete regimen, or in combination with other ATRIPLA helps block HIV-1 reverse transcriptase, a viral chemical in your body (enzyme)antithat HIV-1 medicines to treat peopleATRIPLA with HIV-1 infection. ATRIPLAof isHIV-1 for adults and load). over. is needed for HIV-1 to multiply. lowers the amount in the age blood18(viral ATRIPLA in children under of age 18 or(CD4 adults + over age 65. ATRIPLA has maynot alsobeen helpstudied to increase the number T cells cells), allowing your immune HIV infection destroys CD4+ T the cells, which ofareHIV-1 important the immune system. system to improve. Lowering amount in the toblood lowers the chanceThe of immune death or system helps infection. large number cells (opportunistic are destroyed,infections). acquired immune infections thatfight happen whenAfter your aimmune systemofisTweak deficiency syndrome Does ATRIPLA cure (AIDS) HIV-1 develops. or AIDS? ATRIPLA HIV-1HIV-1 reverse transcriptase, a viral chemical ineffects your body (enzyme) ATRIPLAhelps doesblock not cure infection or AIDS. The long-term of ATRIPLA arethat not isknown needed multiply. ATRIPLA lowersmay the still amount of HIV-1 in theinfections blood (viral at for thisHIV-1 time.toPeople taking ATRIPLA get opportunistic or load). other + ATRIPLA maythat alsohappen help to with increase number ofOpportunistic T cells (CD4 infections cells), allowing your immune conditions HIV-1theinfection. are infections that system improve.the Lowering amountisofweak. HIV-1Some in the of blood lowers the chance of death or developtobecause immunethesystem these conditions are pneumonia, infections that infections, happen when immune system is weak (opportunistic infections). herpes virus andyour Mycobacterium avium complex (MAC) infection. It is very important thatcure you see your healthcare provider regularly while taking ATRIPLA. Does ATRIPLA HIV-1 or AIDS? Does ATRIPLA reduce the risk of passing HIV-1 to others? ATRIPLA does not cure HIV-1 infection or AIDS. The long-term effects of ATRIPLA are not ATRIPLA shown to lower passing HIV-1 to otherorpeople known at has this not time.been People taking ATRIPLAyour maychance still getof opportunistic infections other through sexual contact,with sharing or being exposedinfections to your blood. conditions that happen HIV-1needles, infection. Opportunistic are infections that • Do not share needles or other injection equipment. develop because the immune system is weak. Some of these conditions are pneumonia, • Do not personal that can avium have blood or (MAC) body fluids on them, like herpes virusshare infections, and items Mycobacterium complex infection. It is very toothbrushes razor blades. important that youorsee your healthcare provider regularly while taking ATRIPLA.

ATRIPLA® (efavirenz/emtricitabine/tenofovir disoproxil Does ATRIPLA (efavirenz/emtricitabine/tenofovir disoproxil fumarate) reducefumarate) the risk of passing HIV-1 to others? • Do not have any kind of sex without protection. Always practice safer sex by using a ATRIPLA not been shown your chance of the passing to other people latex orhas polyurethane condomtoorlower other barrier to reduce chanceHIV-1 of sexual contact with through sexual contact, sharing needles, or being exposed to your blood. semen, vaginal secretions, or blood. not take ATRIPLA? •WhoDoshould not share needles or other injection equipment. your personal healthcareitems provider, need to decide is right for like you. •Together Do notwith share thatyoucan have blood whether or bodyATRIPLA fluids on them, Do toothbrushes not take ATRIPLA if you are allergic to ATRIPLA or any of its ingredients. The active or razor blades. ingredients of ATRIPLA are efavirenz, emtricitabine, and tenofovir DF. See the end of this •leaflet Do for notahave any kind sex without protection. Always practice safer sex by using a complete list ofofingredients. latex or polyurethane condom or provider other barrier to reduce chance of sexual contact with What should I tell my healthcare before takingthe ATRIPLA? semen, vaginal secretions, or blood. Tell your healthcare provider if you: Who should not take ATRIPLA?to become pregnant (see “What should I avoid while taking • Are pregnant or planning Together with your healthcare provider, you need to decide whether ATRIPLA is right for you. ATRIPLA?”). • not Are take breast-feeding shouldtoI avoid whileortaking Do ATRIPLA if (see you “What are allergic ATRIPLA any ofATRIPLA?”). its ingredients. The active • Have kidney problems are undergoing kidney treatment. ingredients of ATRIPLA are or efavirenz, emtricitabine, anddialysis tenofovir DF. See the end of this leaflet for bone a complete list of ingredients. • Have problems. • Have liverI tell problems, including hepatitis B virus infection. Your healthcare provider What should my healthcare provider before taking ATRIPLA? may want to do tests to check your liver while you take ATRIPLA. Tell your healthcare provider if you: • Have ever had mental illness or are using drugs or alcohol. •• Are planningortoare become “What should I avoid while taking Havepregnant ever hadorseizures taking pregnant medicine(see for seizures. ATRIPLA?”). What important information should I know about taking other medicines with •ATRIPLA? Are breast-feeding (see “What should I avoid while taking ATRIPLA?”). •ATRIPLA Have kidney problems are undergoing kidney dialysis treatment. may change the or effect of other medicines, including the ones for HIV-1, and cause serious side effects. Your healthcare provider may change your other medicines •mayHave bone problems. theirproblems, doses. Other medicines, including herbalinfection. products,Your mayhealthcare affect ATRIPLA. For •or change Have liver including hepatitis B virus provider this reason, it is very important to let all your healthcare providers and pharmacists know may want to do tests to check your liver while you take ATRIPLA. what medications, herbal supplements, or vitamins you are taking. •MEDICINES Have everYOU hadSHOULD mental NOT illness or are using drugs or alcohol. TAKE WITH ATRIPLA •• Have ever hadmedicines seizures may or are taking medicine for seizures. side effects when taken The following cause serious and life-threatening withimportant ATRIPLA. You should notshould take anyI ofknow theseabout medicines whileother takingmedicines ATRIPLA: Vascor What information taking with (bepridil), Propulsid (cisapride), Versed (midazolam), Orap (pimozide), Halcion (triazolam), ATRIPLA? ergot medications and Cafergot). ATRIPLA may change(for theexample, effect ofWigraine other medicines, including the ones for HIV-1, and • ATRIPLA also should be used Combivirprovider (lamivudine/zidovudine), EMTRIVA, Epivir, may cause serious sidenot effects. Yourwith healthcare may change your other medicines Epivir-HBV (lamivudine), Epzicom including (abacavirherbal sulfate/lamivudine), Trizivir (abacavir or change their doses. Other medicines, products, may affect ATRIPLA. For TRUVADA, or VIREAD. this sulfate/lamivudine/zidovudine), reason, it is very important toSUSTIVA, let all your healthcare providers and pharmacists know • Vfend (voriconazole) not be taken with ATRIPLA it may lose its effect or may what medications, herbalshould supplements, or vitamins you aresince taking. increase the chance of having side effects from ATRIPLA. MEDICINES YOU SHOULD NOT TAKE WITH ATRIPLA • Do not take St. John’s wort (Hypericum perforatum), or products containing • The followingwort medicines may cause side effects when taken St. John’s with ATRIPLA. St.serious John’s and wortlife-threatening is an herbal product sold as a dietary with ATRIPLA.Talk Youwith should take any provider of these ifmedicines while taking Vascor supplement. yournothealthcare you are taking or are ATRIPLA: planning to take (bepridil), (cisapride), (midazolam), (pimozide), Halcion St. John’sPropulsid wort. Taking St. John’sVersed wort may decrease Orap ATRIPLA levels and lead to(triazolam), increased ergot medications (for example, andorCafergot). viral load and possible resistanceWigraine to ATRIPLA cross-resistance to other anti-HIV-1 drugs. ® (adefovir dipivoxil). ATRIPLA also should not be with with HEPSERA •• ATRIPLA should notused be used Combivir (lamivudine/zidovudine), EMTRIVA, Epivir, (lamivudine), Epzicom (abacavir Trizivir (abacavir It isEpivir-HBV also important to tell your healthcare provider if sulfate/lamivudine), you are taking any of the following: TRUVADA, or VIREAD. • sulfate/lamivudine/zidovudine), Fortovase, Invirase (saquinavir),SUSTIVA, Biaxin (clarithromycin); or Sporanox (itraconazole); these medicines may need to not be be replaced with another when takenor with • Vfend (voriconazole) should taken with ATRIPLA sincemedicine it may lose its effect may ATRIPLA.the chance of having side effects from ATRIPLA. increase • Calcium channel blockers such as Cardizem or Tiazac (diltiazem), Covera HS or Isoptin • Do not take St. John’s wort (Hypericum perforatum), or products containing (verapamil) andwith others; Crixivan (indinavir); St. John’s wort ATRIPLA. St. John’s wort isthean immunosuppressant herbal product sold asmedicines a dietary cyclosporineTalk (Gengraf, Neoral, Sandimmune, others), (tacrolimus), or supplement. with your healthcare provider if and you are takingPrograf or are planning to take Rapamune (sirolimus); Methadone; Mycobutin (rifabutin); Rifampin; cholesterol-lowering St. John’s wort. Taking St. John’s wort may decrease ATRIPLA levels and lead to increased medicines such as Lipitor (atorvastatin), Pravachol (pravastatin sodium), and Zocor viral load and possible to ATRIPLA or cross-resistance to other anti-HIV-1 (simvastatin); or Zoloftresistance (sertraline); these medicines may need to have theirdrugs. dose It is changed also important tell your whentotaken withhealthcare ATRIPLA.provider if you are taking any of the following: Videx, Videx EC (didanosine); tenofovir DF (a component of ATRIPLA) may increase •• Fortovase, Invirase (saquinavir), Biaxin (clarithromycin); or Sporanox (itraconazole); these the amountmay of didanosine in replaced your blood,with which could medicine result in when more side medicines need to be another takeneffects. with You may need to be monitored more carefully if you are taking ATRIPLA and didanosine ATRIPLA. together.channel Also, theblockers dose of didanosine may need be changed. • Calcium such as Cardizem or to Tiazac (diltiazem), Covera HS or Isoptin • (verapamil) Reyataz (atazanavir sulfate) or Kaletra (lopinavir/ritonavir); these medicines mayRifampin; increase and others; Crixivan (indinavir); Methadone; Mycobutin (rifabutin); the amount of tenofovir DF (a component of ATRIPLA) in your blood, which could result in cholesterol-lowering medicines such as Lipitor (atorvastatin), Pravachol (pravastatin more sideandeffects. is notorrecommended with these ATRIPLA. You maymay need to be sodium), Zocor Reyataz (simvastatin); Zoloft (sertraline); medicines need to monitored morechanged carefullywhen if youtaken are taking and Kaletra together. Also, the dose have their dose withATRIPLA ATRIPLA. of Kaletra may need to be changed. •• Videx, Videx (didanosine); tenofovir DF (a(phenytoin), componentTegretol of ATRIPLA) may increase Medicine for EC seizures [for example, Dilantin (carbamazepine), or the amount of your didanosine in your blood, result more side effects. phenobarbital]; healthcare provider maywhich want tocould switch you in to another medicine or You may need to be monitored more carefully if you are taking ATRIPLA check drug levels in your blood from time to time. (efavirenz/emtricitabine/tenofovir disoproxil and didanosine together. Also,take the These are not all the medicines thatfumarate) may cause problems if you dose didanosine mayyour needhealthcare to be changed. ATRIPLA.ofBe sure to tell provider about all medicines that you take. •Keep Reyataz (atazanavir Kaletra (lopinavir/ritonavir); thesemedicines medicinesasmay a complete list ofsulfate) all the orprescription and nonprescription wellincrease as any the amount tenofovir DF (ataking, component of ATRIPLA) in your whichyou could result in herbal remediesof that you are how much you take, andblood, how often take them. more sidelist effects. is not recommended ATRIPLA. You mayorneed be Make a new whenReyataz medicines or herbal remedieswith are added or stopped, if thetodose monitored ATRIPLA and Kaletra and together. Also, theevery dose changes. Give more copiescarefully of this listif you to allareof taking your healthcare providers pharmacists Kaletra to be changed. timeof you visitmay yourneed healthcare provider or fill a prescription. This will give your healthcare a complete picture[forof example, the medicines you(phenytoin), use. Then heTegretol or she (carbamazepine), can decide the best •provider Medicine for seizures Dilantin or approach for your situation. phenobarbital]; your healthcare provider may want to switch you to another medicine or check drug levels in your blood from time to time.

® (efavirenz/emtricitabine/tenofovir ATRIPLAare fumarate) These not all the medicines that disoproxil may cause problems if you take ATRIPLA (efavirenz/emtricitabine/tenofovir disoproxil fumarate). Be sure to tell your How should I take ATRIPLA? healthcare provider about all medicines that you take. • Take the exact amount of ATRIPLA your healthcare provider prescribes. Never change Keepthea dose complete list own. of all Do thenot prescription nonprescription well as tells any on your stop this and medicine unless yourmedicines healthcareasprovider herbal youremedies to stop. that you are taking, how much you take, and how often you take them. Make new listtake when medicines herbal remedies are added or stopped, or if the dose • Youa should ATRIPLA on an or empty stomach. changes. Give copies of this list to all of your healthcare providers and pharmacists every • Swallow ATRIPLA with water. time you visit your healthcare provider or fill a prescription. This will give your healthcare • Takinga ATRIPLA bedtimeof may make someyou sideuse. effects bothersome. provider completeatpicture the medicines Thenless he or she can decide the best • Do notfor miss a dose of ATRIPLA. If you forget to take ATRIPLA, take the missed dose right approach your situation. away, unless it is almost time for your next dose. Do not double the next dose. Carry on Howwith should take ATRIPLA? your Iregular dosing schedule. If you need help in planning the best times to take your • Take the exact amount of ATRIPLA youror healthcare medicine, ask your healthcare provider pharmacist.provider prescribes. Never change dose on your Do notthan stopthe thisprescribed medicineamount unless your healthcare provider tells • the If you believe you own. took more of ATRIPLA, contact your local you to stop. poison control center or emergency room right away. • You take ATRIPLA on anif empty stomach. Tell should your healthcare provider you start any new medicine or change how you take old ones. YourATRIPLA doses may • Swallow with need water.adjustment. When your ATRIPLA supplymay startsmake to run low,side get effects more from your healthcare provider or •• Taking ATRIPLA at bedtime some less bothersome. pharmacy. is very importantIfbecause thetoamount of virus take in your maydose increase • Do not missThis a dose of ATRIPLA. you forget take ATRIPLA, theblood missed right if the unless medicine stopped forfor even shortdose. time.Do Thenotvirus maythedevelop resistance to away, it isisalmost time youra next double next dose. Carry on ATRIPLA and become harder to treat. with your regular dosing schedule. If you need help in planning the best times to take your • medicine, Your healthcare provider may want to doorblood tests to check for certain side effects while ask your healthcare provider pharmacist. you take ATRIPLA. • If you believe you took more than the prescribed amount of ATRIPLA, contact your local What should I avoid while taking ATRIPLA? poison control center or emergency room right away. • Women should not become pregnant while taking ATRIPLA and for 12 weeks after • Tell your healthcare if youhave start been any new or change how you old stopping it. Seriousprovider birth defects seenmedicine in the babies of animals andtake women ones. may (a need adjustment. treatedYour withdoses efavirenz component of ATRIPLA) during pregnancy. It is not known whether • When yourcaused ATRIPLA supply startsTell to run get more provider from yourright healthcare or efavirenz these defects. yourlow, healthcare away provider if you are pharmacy. very important becauseprovider the amount of want virus to in your blood may increase pregnant. This Also istalk with your healthcare if you become pregnant. the medicine is stopped a short time. Thecontrol, virus may • ifWomen should not rely onlyfor oneven hormone-based birth suchdevelop as pills, resistance injections, to or ATRIPLA become hardermay to treat. implants,and because ATRIPLA make these contraceptives ineffective. Women must use a reliable form ofprovider barrier may contraception, a condom or for diaphragm, eveneffects if theywhile also • Your healthcare want to dosuch bloodastests to check certain side use take otherATRIPLA. methods of birth control. Efavirenz, a component of ATRIPLA, may remain in you your bloodI avoid for a time therapy is stopped. Therefore, you should continue to use What should whileafter taking ATRIPLA? contraceptive measures for 12 weeks after you stop taking ATRIPLA. •• Women should not become pregnant taking for 12 weeks Do not breast-feed if you are taking while ATRIPLA. TheATRIPLA Centers and for Disease Controlafter and stopping Serious birth have in the babies of animals andpass women Preventionit.recommend thatdefects mothers withbeen HIV seen not breast-feed because they can the treated with efavirenz (a component of ATRIPLA) during pregnancy. It is not known whether HIV through their milk to the baby. Also, ATRIPLA may pass through breast milk and cause efavirenz caused these defects. Tell your healthcare provider right away if you are serious harm to the baby. Talk with your healthcare provider if you are breast-feeding. You pregnant. talk with your provider if you want to become pregnant. should stopAlso breast-feeding or healthcare may need to use a different medicine. •• Women should not only on hormone-based control, such pills, injections, or Taking ATRIPLA withrely alcohol or other medicines birth causing similar sideaseffects as ATRIPLA, implants, because ATRIPLA may make these ineffective. Women must use such as drowsiness, may increase those sidecontraceptives effects. formany of barrier contraception, such as a condom and or diaphragm, even ifmedicines they also • aDoreliable not take other medicines, including prescription nonprescription use of without birth control. Efavirenz, a component ATRIPLA, may remain in your and other herbalmethods products, checking with your healthcareof provider. blood for a time after therapy is stopped. Therefore, you should continue to use • contraceptive Avoid doing things thatforcan HIV-1youinfection since ATRIPLA does not stop you measures 12 spread weeks after stop taking ATRIPLA. from passing the HIV-1 infection to others. •What Doare notthe breast-feed if you are taking ATRIPLA. The Centers for Disease Control and possible side effects of ATRIPLA? Prevention recommend that mothers with HIV not breast-feed because they can pass the ATRIPLA may cause the following serious side effects: HIV through their milk to the baby. Also, ATRIPLA may pass through breast milk and cause • serious Lactic harm acidosis of an the blood). Lacticifacidosis can be a medical to the(buildup baby. Talk withacid yourinhealthcare provider you are breast-feeding. You emergency may need or to may be treated the ahospital. your healthcare provider should stop and breast-feeding need toinuse differentCall medicine. right away if you get signs of lactic acidosis. (See “What is the most important • Taking ATRIPLA with know alcoholabout or other medicines causing similar side effects as ATRIPLA, information I should ATRIPLA?”) such as drowsiness, may(hepatotoxicity), increase those side • Serious liver problems witheffects. liver enlargement (hepatomegaly) and fat • Do notliver take(steatosis). any otherCall medicines, includingprovider prescription and nonprescription medicines in the your healthcare right away if you get any signs of liver and herbal products, without checking with your healthcare provider. problems. (See “What is the most important information I should know about ATRIPLA?”) • Avoid doing of things that can spread infection sincethe ATRIPLA not stop you “Flare-ups” hepatitis B virus (HBV)HIV-1 infection, in which diseasedoes suddenly returns from passing thethan HIV-1 infection to others. in a worse way before, can occur if you have HBV and you stop taking ATRIPLA. Your healthcare provider will condition for several months after stopping ATRIPLA What are the possible sidemonitor effectsyour of ATRIPLA? if you have both HIV-1 and HBV infection and may recommend treatment for your HBV. ATRIPLA may cause the following serious sideofeffects: ATRIPLA is not approved for the treatment hepatitis B virus infection. If you have • Lactic acidosis (buildup antreatment acid in the Lactic acidosis can be a medical advanced liver disease andofstop withblood). ATRIPLA, the “flare-up” of hepatitis B may emergency and may needto todecline. be treated in the hospital. Call your healthcare provider cause your liver function away if you get signs ofAlactic “Whatmay is the most important • right Serious psychiatric problems. small acidosis. number of(See patients experience severe information should thoughts, know about ATRIPLA?”) depression, Istrange or angry behavior while taking ATRIPLA. Some patients have thoughtsliver of suicide and a(hepatotoxicity), few have actually with committed suicide. These problems mayand occur • Serious problems liver enlargement (hepatomegaly) fat more in patients Call whoyour havehealthcare had mentalprovider illness.right Contact your healthcare in the often liver (steatosis). away if you get any provider signs of right liver away if you(See think you are having psychiatric symptoms, so your provider problems. “What is the mostthese important information I should knowhealthcare about ATRIPLA?”) can decide if of youhepatitis should continue to takeinfection, ATRIPLA. in which the disease suddenly returns • “Flare-ups” B virus (HBV) • in Kidney problems decline of kidney function). have had kidney a worse way than(including before, can occuroriffailure you have HBV and you stopIf you taking ATRIPLA. Your problems inprovider the past take other medicinesforthat can months cause kidney problems, your healthcare willormonitor your condition several after stopping ATRIPLA should do regular blood check yourtreatment kidneys. for Symptoms ifhealthcare you have provider both HIV-1 and HBV infection andtests may to recommend your HBV.that may be related to kidney problemsAinclude high volume of urine,may thirst, muscle pain, and • Serious psychiatric problems. small anumber of patients experience severe muscle weakness. depression, strange thoughts, or angry behavior while taking ATRIPLA. Some patients have • thoughts Changesofinsuicide bone mineral (thinning bones).suicide. Laboratory tests show changes in and a fewdensity have actually committed These problems may occur the bones patientswho treated tenofovir DF, aContact component of ATRIPLA. Someright HIV more often inof patients have with had mental illness. your healthcare provider patients treated tenofovir developed thinning of thesobones (osteopenia)provider which away if you think with you are havingDF these psychiatric symptoms, your healthcare coulddecide lead toif fractures. have to hadtake bone problems in the past, your healthcare provider can you shouldIf you continue ATRIPLA.

® (efavirenz/emtricitabine/tenofovir disoproxil fumarate) • Kidney problems.ATRIPLA If you have had kidney problems in the past or take other medicines that can cause kidney problems, yourbone healthcare regular blood tests to may need to do tests to check your mineralprovider densityshould or maydoprescribe medicines to check yourbone kidneys. help your mineral density. Additionally, bone pain and softening of the bone (which • Changes in bone mineral density (thinning bones). It is ofnotkidney knownproblems. whether long-term may contribute to fractures) may occur as a consequence use of ATRIPLA (efavirenz/emtricitabine/tenofovir disoproxil fumarate) will cause damage Common side effects: to your bones. you haveheadache, had bone problems in the past, your healthcare provider may Patients may haveIfdizziness, trouble sleeping, drowsiness, trouble concentrating, needunusual to do tests to check bone mineral densityThese or mayside prescribe medicines to helpif and/or dreams duringyour treatment with ATRIPLA. effects may be reduced mineral density.on an empty stomach. They also tend to go away after you have youyour takebone ATRIPLA at bedtime taken the side medicine for a few weeks. If you have these common side effects, such as Common effects: dizziness, it does not mean that you will also have serious psychiatric problems, such as Patients may have dizziness, headache,ortrouble sleeping, drowsiness, trouble concentrating, severe depression, strange thoughts, angry behavior. Tell your healthcare provider right and/or during treatment withorATRIPLA. may be that reduced away ifunusual any of dreams these side effects continue if they These botherside you.effects It is possible theseif you take ATRIPLA at bedtime on an empty stomach. They also tend to go away after youdrugs. have symptoms may be more severe if ATRIPLA is used with alcohol or mood altering (street) taken the medicine for a few weeks. If you have these common side effects, such as If you are dizzy, have trouble concentrating, or are drowsy, avoid activities that may be dizziness, doesasnotdriving meanorthat you willmachinery. also have serious psychiatric problems, such as dangerous,itsuch operating severe depression, strange thoughts, or angry behavior. Tell your healthcare provider right Rash may be common. Rashes usually go away any change In a these small away if any of these side effects continue or ifwithout they bother you. It inistreatment. possible that number of may patients, rashsevere may beif ATRIPLA serious. Ifis you a rash, your healthcare symptoms be more useddevelop with alcohol or call mood altering (street)provider drugs. right away. IfOther you common are dizzy,side have trouble concentrating, or arestomach, drowsy,vomiting, avoid activities may be effects include tiredness, upset gas, andthat diarrhea. dangerous, suchside as driving operating machinery. Other possible effectsorwith ATRIPLA: Rash may be incommon. usually go away without any change in treatment. In a small • Changes body fat.Rashes Changes in body fat develop in some patients taking anti-HIV-1 number of patients, may may be serious. develop amount a rash, call your healthcare provider medicine. These rash changes includeIfanyouincreased of fat in the upper back and rightneck away. (“buffalo hump”), in the breasts, and around the trunk. Loss of fat from the legs, arms, and face also happen. The cause long-term healthgas, effects of these fat Other common side may effects include tiredness, upsetand stomach, vomiting, and diarrhea. changes are not known. Other possible side effects with ATRIPLA include: • Skin discoloration (small spots or freckles) may also happen with ATRIPLA. •• Changes in bodywith fat. advanced Changes in fat develop in some patients taking anti-HIV-1 In some patients HIVbody infection (AIDS), signs and symptoms of inflammation medicine. These changesmay mayoccur include an after increased amount of fatisinstarted. the upper and from previous infections soon anti-HIV treatment It isback believed neck (“buffalo hump”), thetobreasts, and around thebody’s trunk.immune Loss of response, fat from the legs, that these symptoms areindue an improvement in the enabling arms, andtoface also happen. long-term effects of these fat the body fightmay infections that mayThe havecause beenand present with nohealth obvious symptoms. If you changes not known. notice anyaresymptoms of infection, please inform your doctor immediately. Additional side effects of the allergic reaction (including • Skin discoloration (small are spotsinflammation or freckles) may alsopancreas, happen with ATRIPLA. of the provider face, lips, tongue, or throat), shortness of effects breath,while pain,taking stomach pain, Tell swelling your healthcare or pharmacist if you notice any side ATRIPLA. weakness and indigestion. Contact healthcare provider before stopping ATRIPLA of side for any Tell youryour healthcare provider or pharmacist if you notice anybecause side effects whileeffects takingorATRIPLA. other reason. Contact your healthcare provider before stopping ATRIPLA because of side effects or for any This not a complete list of side effects possible with ATRIPLA. Ask your healthcare otherisreason. provider or pharmacist list of side of ATRIPLA all the This is not a complete for list aofmore side complete effects possible with effects ATRIPLA. Ask your and healthcare medicines will take. for a more complete list of side effects of ATRIPLA and all the provider oryou pharmacist medicines you will take. How do I store ATRIPLA? How do I store ATRIPLA? • Keep ATRIPLA and all other medicines out of reach of children. • Keep ATRIPLA and all other medicines out of reach of children. •• Store Store ATRIPLA ATRIPLA at at room room temperature temperature 77 77 °F °F (25 (25 °C). °C). •• Keep Keep ATRIPLA ATRIPLA in in its its original original container container and and keep keep the the container container tightly tightly closed. closed. • Do not keep medicine that is out of date or that you no longer need. If you throw any medicines away make sure that children will not find them. General information about ATRIPLA: Medicines are are sometimes sometimes prescribed prescribed for for conditions conditions that that are are not not mentioned mentioned in in patient patient Medicines information leaflets. leaflets. Do Do not not use use ATRIPLA ATRIPLA for for aa condition condition for for which which itit was was not not prescribed. prescribed. Do Do information not give give ATRIPLA ATRIPLA to to other other people, people, even even ifif they they have have the the same same symptoms symptoms you you have. have. ItIt may may not harm them. them. harm This leaflet summarizes the most important information about ATRIPLA. If you would like more This leaflet the most important information aboutask ATRIPLA. If you wouldprovider like more information,summarizes talk with your healthcare provider. You can your healthcare or information, talkinformation with yourabout healthcare You canforask yourprofessionals. healthcare provider or pharmacist for ATRIPLAprovider. that is written health pharmacist for information about ATRIPLA that is written for health professionals. Do not use ATRIPLA if the seal over bottle opening is broken or missing. Do notare usethe ATRIPLA if the seal over bottle opening is broken or missing. What ingredients of ATRIPLA? Activeare Ingredients: efavirenz, emtricitabine, and tenofovir disoproxil fumarate What the ingredients of ATRIPLA? InactiveIngredients: Ingredients: croscarmellose sodium, hydroxypropyl cellulose, Active efavirenz, emtricitabine, and tenofovir disoproxil fumaratemicrocrystalline cellulose, magnesium stearate, sodium lauryl sulfate. The film coating contains black iron Inactive Ingredients: croscarmellose sodium, hydroxypropyl cellulose, oxide, polyethylene glycol, polyvinyl alcohol, red iron oxide, talc, and titaniummicrocrystalline dioxide. cellulose, magnesium stearate, sodium lauryl sulfate. The film coating contains black iron oxide, polyethylene glycol, polyvinyl alcohol, red iron oxide, talc, and titanium dioxide.

January 2010 ATRIPLA is a trademark of Bristol-Myers Squibb & Gilead Sciences, LLC. EMTRIVA, TRUVADA, September 2008 HEPSERA and VIREAD are trademarks of Gilead Sciences, Inc. SUSTIVA is a trademark of Bristol-Myers Squibb Pharma Company. Reyataz and Videx are trademarks of Bristol-Myers ATRIPLA is a trademark of Bristol-Myers Squibb Gilead &Sciences, LLC. EMTRIVA, Squibb Company. Pravachol is a trademark of ER&Squibb Sons, LLC. Other brandsTRUVADA, listed are and VIREAD are of trademarks of Gilead Sciences, Inc. SUSTIVA is a trademark of Bristol-Myers the trademarks their respective owners. Squibb Pharma Company. Reyataz and Videx are trademarks of Bristol-Myers Squibb Company. Pravachol is a trademark of ER Squibb & Sons, LLC. Other brands listed are the trademarks of their respective owners. SF-B0001B-01-10 21-937-GS-006 ST3962 January 2010 SF-B0001B-10-08

21-937-GS-005

ST0064

Sept 2008

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© 2010. Positively Aware (ISSN: 1523-2883) is published bi-monthly by Test Positive Aware Network (TPAN), 5537 N. Broadway, Chicago, IL 60640. Positively Aware is a registered trademark of TPAN. All rights reserved. Circulation: 85,000. For reprint permission, contact Sue Saltmarsh. Six issues mailed bulkrate for $30 donation; mailed free to TPAN members or those unable to contribute. TPAN is an Illinois not-for-profit corporation, providing information and support to anyone concerned with HIV and AIDS issues. A person’s HIV status should not be assumed based on his or her article or photograph in Positively Aware, membership in TPAN, or contributions to this journal. We encourage contribution of articles covering medical or personal aspects of HIV/AIDS. We reserve the right to edit or decline submitted articles. When published, the articles become the property of TPAN and its assigns. You may use your actual name or a pseudonym for publication, but please include your name and phone number. Opinions expressed in Positively Aware are not necessarily those of staff or membership or TPAN, its supporters and sponsors, or distributing agencies. Information, resources, and advertising in Positively Aware do not constitute endorsement or recommendation of any medical treatment or product. TPAN recommends that all medical treatments or products be discussed thoroughly and frankly with a licensed and fully HIV-informed medical practitioner, preferably a personal physician. Although Positively Aware takes great care to ensure the accuracy of all the information that it presents, Positively Aware staff and volunteers, TPAN, or the institutions and personnel who provide us with information cannot be held responsible for any damages, direct or consequential, that arise from use of this material or due to errors contained herein.

May/June 2010

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MAY/JUNE 2010 VOLUME 21 NUMBER 3

Departments 10

In Box

Online Poll

Editor’s Note

Briefly

CROI treatment update

Reports from the 2010 Conference on Retroviruses and Opportunistic Infections in San Francisco.

22 Hepatitis highlights from CROI

Sexual transmission of hepatitis B; hepatitis C survives in syringes; and more.

New Norvir tablet; Invirase warning; H1N1 and HIV

Is it all in your head?

36 Ask the HIV Speciailst

Dual stigma

Features

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HIV, your HAART, and you

40 The Buzz

Three integrase inhibitors offer great promise

43 What’s Goin’ On?

A survivor of sexual abuse searches for his voice

44 Wholistic Picture

Every biological aspect of living with HIV has a psychological response.

Economic impact

A difficult economy can be another complication when living with HIV.

Threads of connection

One man’s AIDS quilt and its journey.

on the cover model: michael tatum | photo: Chris Knight this page Photos: Enid Vázquez, Chris Knight A model, photographer, or author’s HIV status should not be assumed based on their appearance in Positively Aware. View these, and other stories from previous issues, online at www.positivelyaware.com Distribution of Positively Aware is supported in part through an unrestricted grant from GlaxoSmithKline.

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May/June 2010

you whether your symptoms can be managed IMPORTANT SAFETY INFORMATION on therapy or whether PREZISTA should • PREZISTA, together with Norvir ®, has PREZISTA® (darunavir) is a prescription be stopped rarely been observed to cause liver medicine. It is one treatment option in the • Taking PREZISTA with certain problems which may be life-threatening. class of HIV (human immunodeficiency virus) medicines could cause serious and/or It was not always clear if PREZISTA medicines known as protease inhibitors. life-threatening side effects or may caused these liver problems because PREZISTA is always taken with and at the same result in loss of its effectiveness. Do some patients had other illnesses or were time as ritonavir (Norvir ®), in combination with not take PREZISTA if you are taking taking other medicines. Your healthcare other HIV medicines for the treatment of HIV the following medicines: alfuzosin professional should do blood tests infection in adults. PREZISTA should also be (Uroxatral®), dihydroergotamine (D.H.E.45®, prior to starting combination treatment taken with food. Migranal®), ergonovine, ergotamine including PREZISTA. If you have chronic • The use of other medicines active against (Wigraine®, Ergostat ®, Cafergot ®, Ergomar ®), hepatitis B or C infection, your healthcare HIV in combination with PREZISTA/ritonavir methylergonovine, cisapride (Propulsid®), professional should check your blood tests ® (Norvir ) may increase your ability to fight HIV. pimozide (Orap®), oral midazolam, triazolam more often because you have an increased Your healthcare professional will work with (Halcion®), rifampin (Rifadin®, Rifater ®, chance of developing liver problems you to find the right combination of Rifamate®), indinavir (Crixivan®), Talk to your healthcare professional about HIV medicines lopinavir/ritonavir (Kaletra®), saquinavir the signs and symptoms of liver problems. ® • It is important that you remain under the (Invirase ), lovastatin (Mevacor ®, Altoprev®, These may include yellowing of your ® care of your healthcare professional during Advicor ), pravastatin (Pravachol®), skin or whites of your eyes, dark (tea® ® treatment with PREZISTA simvastatin (Zocor , Simcor , Vytorin®), or colored) urine, pale-colored stools (bowel products containing St. John’s wort movements), nausea, vomiting, loss of PREZISTA does not cure HIV infection or • Before taking PREZISTA, tell your healthcare appetite, or pain, aching or sensitivity on AIDS, and does not prevent passing HIV professional if you are taking sildenafil your right side below your ribs to others. (Viagra®), vardenafil (Levitra®), tadalafil • Skin rashes have been reported in patients (Cialis®), atorvastatin (Lipitor ®), taking PREZISTA. Rarely, PREZISTA has atorvastatin/amlodipine (Caduet ®), or been reported to cause a severe or liferosuvastatin (Crestor®). This is not a complete threatening rash. Contact your healthcare list of medicines. Be sure to tell your professional immediately if you develop a healthcare professional about all the rash. Your healthcare professional will advise

ABOUT PREZISTA

Belief {

in myself in my doctor in my meds

ONCE-DAILY PREZISTA FOR ADULTS TAKING HIV MEDS FOR THE FIRST TIME In a clinical study* of almost 2 years (96 weeks) in people who had never taken HIV meds before, ONCE-DAILY PREZISTA with low-dose ritonavir plus Truvada®… • Helped 8 out of 10 people achieve undetectable viral load (less than 50 copies/mL) • May help to increase T-cell count • Was associated with low rates of diarrhea, stomach pain, nausea, and vomiting — Diarrhea (8%), stomach pain (5%), nausea (3%), and vomiting (2%) were reported as moderate to severe PREZISTA must be taken with and at the same time as 100 mg of Norvir® (ritonavir), and with other HIV meds and with food. Once-daily PREZISTA is not recommended for adults who have taken HIV meds in the past. Please read Important Safety Information below and ask your doctor if once-daily PREZISTA is right for you. *343 adult patients (30% women) received combination therapy with PREZISTA/ritonavir. At the start of the study, the average T-cell count was 245, and 66% of patients had a viral load less than 100,000 copies/mL.

Individual results may vary.

taking protease inhibitor medicines, medicines you are taking or plan to take, including PREZISTA including prescription and nonprescription medicines, vitamins, and herbal supplements • Changes in body fat have been seen in some • Tell your healthcare professional if you patients taking HIV medicines, including are taking estrogen-based contraceptives PREZISTA. The cause and long-term health (birth control). PREZISTA might reduce effects of these conditions are not known at the effectiveness of estrogen-based this time contraceptives. You must take additional • As with other protease inhibitors, taking precautions for birth control, such as condoms PREZISTA may strengthen the body’s immune • Before taking PREZISTA, tell your healthcare response, enabling it to begin to fight infections professional if you have any medical conditions, that have been hidden. Patients may experience including allergy to sulfa medicines, diabetes, signs and symptoms of inflammation that can liver problems (including hepatitis B or C), include swelling, tenderness, or redness or hemophilia •The most common side effects related to • Tell your healthcare professional if you are taking PREZISTA include diarrhea, nausea, pregnant or planning to become pregnant, or rash, headache, stomach pain, and vomiting. are breastfeeding Uncommon but severe side effects such as – The effects of PREZISTA on pregnant women inflammation of the pancreas and increased blood fat levels have also been rarely reported. or their unborn babies are not known. You This is not a complete list of all possible side and your healthcare professional will need to effects. If you experience these or other side decide if taking PREZISTA is right for you – Do not breastfeed if you are taking PREZISTA. effects, talk to your healthcare professional. Do not stop taking PREZISTA or any other You should not breastfeed if you have HIV medicines without first talking to your because of the chance of passing HIV to healthcare professional your baby • High blood sugar, diabetes or worsening of diabetes, and increased bleeding in people with hemophilia have been reported in patients

ONCE DAILY www.PREZISTA.com/patient

• Please refer to the ritonavir (Norvir ®) Product Information (PI and PPI) for additional information on precautionary measures 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 adults taking HIV meds for the ﬁrst time: 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 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 (1-888-477-2669) or go to www.pparx.org.

Distributed by: Tibotec Therapeutics/Division of Centocor Ortho Biotech Products, L.P. Titusville, NJ 08560 ©2010 Tibotec Therapeutics 03/10 28PRZDTC0010BR2 All trademarks are property of their respective owners.

IMPORTANT PATIENT INFORMATION PREZISTA® (pre-ZIS-ta) [(darunavir) (da-ROO-nuh-veer)] Tablets ALERT: Find out about medicines that should NOT be taken with PREZISTA. Please also read the section “Who should not take PREZISTA?”. Please read this information before you start taking PREZISTA. Also, read the leaflet each time you renew your prescription, just in case anything has changed. Remember, this leaflet does not take the place of careful discussions with your doctor. You and your doctor should discuss your treatment with PREZISTA prior to the first time you take your medicine and at regular checkups. You should remain under a doctor’s care when using PREZISTA and should not change or stop treatment without first talking with a doctor. WHAT IS THE MOST IMPORTANT INFORMATION I SHOULD KNOW ABOUT PREZISTA? PREZISTA, together with NORVIR® (ritonavir), has rarely been observed to cause liver problems which may be life-threatening. It was not always clear if PREZISTA caused these liver problems because some patients had other illnesses or were taking other medicines. Your healthcare professional should do blood tests prior to initiating combination treatment including PREZISTA. If you have chronic hepatitis B or C infection, your healthcare professional should check your blood tests more often because you have an increased chance of developing liver problems. Please also read the section “What are the possible side effects of PREZISTA?”. Rarely, PREZISTA has been reported to cause a severe or life-threatening rash. Contact your healthcare provider immediately if you develop a rash. Your healthcare provider will advise you whether your symptoms can be managed on therapy or whether PREZISTA should be stopped. WHAT IS PREZISTA? PREZISTA is an oral tablet used for the treatment of HIV (Human Immunodeficiency Virus) infection in adults. HIV is the virus that causes AIDS (Acquired Immune Deficiency Syndrome). PREZISTA is a type of anti-HIV medicine called a protease (PRO-tee-ase) inhibitor. 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. Because of this, it is very important for you to remain under the care of a doctor. 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 doctor if you have any questions on how to prevent passing HIV to other people. WHAT SHOULD I TELL MY DOCTOR BEFORE I TAKE PREZISTA? Tell your doctor about all of your medical conditions, including if you: • are allergic to sulfa medicines. • have diabetes. In general, 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 doctor will need to decide if taking PREZISTA is right for you. If you take PREZISTA while you are pregnant, talk to your doctor 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 doctor about the best way to feed your baby.

WHO SHOULD NOT TAKE PREZISTA?** Together with your doctor, 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®) CAN PREZISTA BE TAKEN WITH OTHER MEDICATIONS?** Tell your doctor 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 doctor 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 doctor 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 doctor 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®) – 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®) – dexamethasone, fluticasone (Advair Diskus®, Cutivate®, Flonase®, Flovent Diskus®) – atorvastatin (Lipitor®), pravastatin (Pravachol®), rosuvastatin (Crestor®) – cyclosporine (Sandimmune®, Neoral®), tacrolimus (Prograf®), sirolimus (Rapamune®) – methadone, buprenorphine/naloxone – risperidone (Risperdal®, Risperdal® Consta®,Risperdal® M-TAB®), thioridazine – sildenafil (Viagra®), vardenafil (Levitra®), tadalafil (Cialis®) – paroxetine (Paxil®), sertraline (Zoloft®)

IMPORTANT PATIENT INFORMATION Tell your doctor 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 doctor 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 doctors and pharmacists any time you get a new medicine. Both your doctor 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 doctor or pharmacist. You can ask your doctor 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 doctor. You must take ritonavir (NORVIR®) at the same time as PREZISTA. • For adults who have never taken anti-HIV medicines, the usual dose is 800 mg (two 400 mg tablets) of PREZISTA, together with 100 mg (one 100 mg capsule) of ritonavir (NORVIR®), once daily every day. • For adults who have taken anti-HIV medicines in the past, the usual dose is 600 mg (one 600 mg tablet or two 300 mg tablets) of PREZISTA, together with 100 mg (one 100 mg capsule) of ritonavir (NORVIR®), twice daily every day. Do not take PREZISTA once daily if you have taken anti-HIV medicines in the past. PREZISTA and ritonavir (NORVIR®) should be taken together at the same time every day. If you have questions about when to take PREZISTA and ritonavir (NORVIR®), your doctor can help you decide which schedule works for you. Take PREZISTA and ritonavir (NORVIR®) with food. Swallow the whole tablets with a drink such as water or milk. Do not chew the tablets. Continue taking PREZISTA and ritonavir (NORVIR®) unless your doctor tells you to stop. Take the exact amount of PREZISTA and ritonavir (NORVIR®) that your doctor tells you to take, right from the very start. To help make sure you will benefit from PREZISTA and ritonavir (NORVIR®), you must not skip doses or interrupt therapy. If you don’t take PREZISTA and ritonavir (NORVIR®) as prescribed, the beneficial effects of PREZISTA and ritonavir (NORVIR®) may be reduced or even lost. Patients taking PREZISTA once daily 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 the 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®) immediately. Then take your next dose of PREZISTA and ritonavir (NORVIR®) at the regularly scheduled time. Patients taking PREZISTA twice daily 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 the 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®) immediately. Then take your next dose of PREZISTA and ritonavir (NORVIR®) at the regularly scheduled time.

Rash has been reported in 10.3% of patients receiving PREZISTA. In few patients, PREZISTA has been reported to cause a severe or life-threatening rash. Contact your healthcare provider immediately if you develop a rash. Your healthcare provider will advise you whether your symptoms can be managed on therapy or whether PREZISTA should be stopped. Other relevant severe side effects reported at an uncommon or rare frequency were inflammation of the liver or pancreas, increased blood fat levels, diabetes, and changes in body fat. Some side effects are typical for anti-HIV medicines in the same family as PREZISTA. These are: • 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. It is believed that these symptoms are due to an improvement in the body’s immune response, enabling the body to fight infections that may have been present with no obvious symptoms. The most common side effects include diarrhea, nausea, rash, headache, abdominal pain and vomiting. Tell your doctor 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 doctor. 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, Ltd.

You should always take PREZISTA and ritonavir (NORVIR®) together with food. 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? Like all prescription drugs, 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 anti-HIV medicines. Do not rely on this leaflet alone for information about side effects. Your doctor can discuss with you a more complete list of side effects. PREZISTA, together with NORVIR® (ritonavir), has rarely been observed to cause liver problems which may be life-threatening. It was not always clear if PREZISTA caused these liver problems because some patients had other illnesses or were taking other medicines. Your healthcare professional should do blood tests prior to initiating combination treatment including PREZISTA. If you have chronic hepatitis B or C infection, your healthcare professional should check your blood tests more often because you have an increased chance of developing liver problems. Talk to your healthcare professional 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.

Manufactured for Tibotec, Inc. by: JOLLC, Gurabo, Puerto Rico Distributed by: Tibotec Therapeutics, Division of Centocor Ortho Biotech Products, L.P., Raritan NJ 08869 Patent Numbers: 5,843,946; 6,248,775; 6,335,460 and other US patents pending NORVIR® is a registered trademark of its respective owner. PREZISTA® is a registered trademark of Tibotec Pharmaceuticals, Ltd.

Revised: January 2010

10101710P

In Box

Thanks to Terry

hanks for your excellent response to Ashley [see Reader’s Forum, March/ April 2009 issue]. I know both gay cowboys and Indians from South Dakota.

I used to live alone on 13 acres in western New York (in the county which has the greatest number of horse owners per capita in the state). I put some “cowboy bait,” i.e. horses, out in the yard and soon had me a gay cowboy partner. HIVpositive, like me, to boot! Yee Haw! Thanks again for your response. I enjoyed reading that issue with the cowboys on the front, and even read it front to back because of the cover and the content (something I don’t often do). —N.R. Cassadaga, NY Climbing every mountain After reading Jeff’s Editor’s Note in the March/April 2010 issue, I want to share with you how important your work and your organization are. I have been HIV-positive for 20 years now. I met an outreach person from TPAN in May 2000—yes, at IML (International Mr. Leather). I was amazed at the scope of help and harm reduction efforts your staff provides. Anyway, the good man I met gave me a t-shirt. It reads on the back “Fuck Safe…Shoot Clean.” I have worn that t-shirt out. You see, each October 11th (the anniversary of my diagnosis), my family and I climb Blue Mountain in the Adirondacks. In fact, the t-shirt has made it up many mountains in the Adirondacks. As I climb the mountain, many folks ask me about the shirt; some are open to an HIV prevention message and, well, some are not. But I wanted you to know that as I continue to climb my personal mountain, your organization has been there with me for each step. 10

May/June 2010

I work as a case manager at Albany Medical Center in New York. I often use your magazine as a teaching tool, and the very colorful list of meds hangs on my wall only to be replaced each year when the new Drug Guide comes out. Keep up the good work. —Hank Good for the bones Since starting treatment in 1995, I’ve seen Positively Aware in different doctors’ offices and various HIV/AIDS organizations throughout the country. While waiting to see a doctor at the University of Iowa Hospital and Clinics, I just happened to see the May/June 2009 issue. What really caught my attention was “How to Have Stronger, Healthier Bones” on the cover. I started reading the article “Make No Bones About It” because for the last two years, I’ve suffered several fractures and a broken leg, all inexplicable until that moment. When the doctor came into the room, I informed him about the article and that I had been taking Viread for several years. I was immediately taken off Viread and put on Isentress. We also talked about other things that could be causing my bone loss. One thing that he mentioned—which was confirmed in your January/February issue—is a low testosterone level, which I’ve also suffered from for the last 10 years. I currently receive testosterone injections every four

weeks, and more blood work is being done to determine if there may be other underlying conditions contributing to my bone loss. Basically, I just wanted to say that if I had not seen the May/June issue of PA, I would not have been able to point those problems out to my doctor. So, thank you for providing a very informative magazine and also a big thank you for my free subscription! With your help, I’m able to stay on top of my HIV treatment and care. Keep up the good work. —William Smith Anamosa, Iowa GAPA fan Foremost, thank you for this wonderful publication that, in so many ways, raises the awareness of people and is a valuable weapon in the fight against ignorance, cultural bias, and social stigma. I’m from Africa and am always drawn to the articles about HIV/AIDS in Africa. Though I’m at times disheartened, I’m hopeful for a better future for those who are suffering from this pandemic. I read your November/December issue and was greatly moved by the article, “Fighting HIV One Grandmother at a Time.” It would really be a blessing for me if you would send me the address of GAPA in Cape Town, South Africa. I would like to write directly to the organization and share with them my moral and spiritual support. Lastly, I read with interest the article on sexual assault in prison. Something that needs to be exposed is the involvement of correctional officers in these assaults. In many cases, the officers are directly involved and are aware of the situation beforehand. Next time you write such an article, I hope you’ll investigate PositivelyAware.com

and other resources. I just received the March/April edition of Positively Aware, and although I have not been able to look at it in detail, what I Editor Jeff Berry have seen is great. responds: I also thought I Thanks so much for your might share a little letter. I appreciate your story. Just last week, input on the issue of I was working with sexual assault in prison a young man here in and while I know that Denver who is from some correctional officers Familiar face: PA cover boy the Chicago area. are part of the problem, Dr. Chad Zawitz He happened to see the I have hope that there are copy of PA that had the picture of Dr. also many who are willing to be part of the solution. However, as you say, further Chad Zawitz and he said, “I know him!” It goes to show how small our world is investigation is warranted. getting, and for this patient, I think it I am happy to provide you and other was comforting to see a familiar face, readers with the address at which you even though it was just on the cover of can write GAPA (Grandmothers Against your magazine. Poverty and AIDS). I’m sure they’ll Thank you for your efforts at proappreciate any support—financial, ducing Positively Aware. Please know moral, spiritual, or otherwise—towards that I appreciate having it as a resource their efforts. They are truly an inspiring to give to the patients I meet with. Keep group of women and I was honored to up the good work. meet them. —Michael Furhiman Denver, CO GAPA’s mailing address is: 15 St George Campground Road, Drug Guide Correction Rosebank 7700 South Africa In the “New to the Game?” section of e-mail: info@gapa.org.za Positively Aware’s annual drug guide issue phone: +27(0)213643138 (March/April), where recommendations are the officers’ involvement. Continue to do the wonderful work that you do. Thanks a million. —B.P. Comstock, NY

Small world I work at the Denver Public Health Department where I do HIV testing and counseling, and work with the Linkage to Care program that provides referrals for persons with HIV to medical care

listed from the U.S. Department of Health and Human Services (DHHS) for preferred medications in first-time HIV therapy, the regimen for pregnant women should be Kaletra plus Combivir, not Kaletra plus Truvada as stated. Positively Aware regrets the error.

PA ONLINE Last issue’s poll question:

Have you ever participated in a clinical trial?

Yes: 43% No: 57%

This issue’s poll question:

Have you ever been treated for depression? Log on to www.positivelyaware.com to cast your vote!

Stay current with PA E-mail updates Sign up today for our Positively Aware e-mail newsletter and receive regular updates on HIV treatment news and information. Visit www.positivelyaware.com or www.tpan.com, and click on Subscribe. Once you receive a confirmation email, you can update your TPAN profile to include “Positively Aware Updates.” Follow Positively Aware on Twitter: @PosAware

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. Please advise if we can use your name and city. Write to: Positively Aware, 5537 N. Broadway St., Chicago, IL 60640 E-mail: readersforum@tpan.com

PositivelyAware.com

May/June 2010

Editor’s Note Jeff Berry

Dual stigma

epression is a big deal, especially when you’re facing

HIV or any other number of serious health conditions. For many health care providers the old school of thought was to tell you to more or less “get over it,” and “buck up.” You have a life-threatening illness which demands the bulk of your attention, so of course you’re going to feel a little “depressed,” but basically, “it’s all in your head.”

But being a little depressed and clinical depression are two very different things. Depression can often be overlooked by health care professionals, as many have not been trained to look for the signs of depression, let alone treat it. This issue attempts to take on the subject of not only depression, but overall mental health in those living with HIV. Rates of depression can reach as high as 60% for people with HIV. It can be quite debilitating and, left untreated, very likely to affect your overall health and well-being. It has even been linked to a greater risk of death. Of course this issue by itself cannot address all of the many aspects of mental health and HIV, so finding a good provider, having strong support systems in place, and knowing where to go for help, is key. Depression can cause some people to miss doses of their antiretroviral (ARV) medications, as well as lead to higher-risk behaviors. Some ARVs can even cause or exacerbate depression, or interact with drugs used to treat depression, and people with hepatitis B or C are more apt to be

May/June 2010

depressed, especially if they’re on interferon treatment. It’s all kind of depressing, isn’t it? Ironically, that is one of the things I kept hearing over and over again from some of my co-workers when we were putting together this issue. But, and perhaps because I’m the relentless Pollyanna in the office, I choose to look at it a little differently. And I know I’m not the only one who feels that way (there she goes again!). Depression can be treated with medication, complementary therapies, and making some changes in your lifestyle. Regular exercise is critical, not only to help maintain your physical health, but also your emotional and mental well-being. Managing stress, eating well, getting the proper amount of rest, and even exposure to sunlight are all important to achieving success and finding balance in your life. Reducing or eliminating alcohol and substance use can also help, especially if you’re using them to self-medicate, as abusing them will only worsen the problem. Finally, recognizing and admitting that

you, or someone you know, may need help, and seeking adequate counseling or treatment, without the fear, shame, or stigma that is often associated with depression or other mental health disorders, is crucial. We already deal enough with the stigma of HIV, we shouldn’t also have to cope with the dual stigma of HIV and depression. In this issue you may note a few changes on the cover and within the pages of the magazine. This is a reflection of the continuing evolution of Positively Aware. The graphic design, imagery, font selection, logo, and departments have all been updated and given a fresh, new look. We trust you’ll like the changes you see. Look for more changes in the coming months, both in print and online at www.positivelyaware.com. Visit our website to sign up for our weekly e-mail updates, and join the PA forum where you can read blogs, comment on articles, and chat with members and make new friends. And don’t forget to look for us on facebook! As always, we welcome comments from you, our readers, on what you would like to see more of and hear more about in PA, so drop us a line at publications@tpan.com and let us know what you think. We’d love to hear from you. Until then, take care of yourself, and each other.

PositivelyAware.com

By starting HIV

treatment,

I went from feeling low

to learning to love myself. If youâ&#x20AC;&#x2122;re HIV positive, the decision to begin taking medication can be difficult. But it can be the first step toward reclaiming your life and living longer. Talking to your doctor and getting the right information on HIV treatment can help take you from feeling low to feeling in control.

BRIEFLY reported by Enid VázQUEZ

New Norvir tablet doesn’t need refrigeration tablets contain 100 mg of Norvir, they are not bioequivalent. When taken with food, the blood concentration of the tablets is higher. This may lead to greater side effects. Norvir is known for its gastrointestinal side effects, particularly diarrhea, and for increasing triglyceride levels. The capsules will remain available. Norvir’s manufacturer, Abbott Laboratories, reported that the new tablets will have the same wholesale acquisition (WAC) price as the capsules. Abbott also launched a Norvir co-pay support program that is now available. The co-pay program will be available for all formulations of Norvir. Once an individual has paid $25 in co-pays, the program covers up to $75 per month in co-pays for the first 12 months. Restrictions apply. Individuals can request the co-pay card from their health care provider, and will soon be able to print the card from the website. Visit www.norvir.com.

Photo: Joshua Thorne

In February, the U.S. of Food and Drug Administration (FDA) approved a new formulation of Norvir (ritonavir), an HIV medication that’s used in small doses to increase blood levels of HIV protease inhibitor drugs, making them more effective. The new Norvir is a tablet. Unlike the previous soft-gel capsules, the tablets must be taken with food and, like the capsules, must be swallowed whole, not crushed, chewed, or broken. The most significant difference between the capsules and the new tablets is that the tablets do not have to be refrigerated. This is of particular importance to homeless people with limited access—if any—to refrigerators, and to resource-poor countries where many patients may also have difficulty accessing refrigeration. The tablets use a heat-stable formulation called Meltrex that allows them to be stored at room temperature. Though both the capsules and the

New study: Getting meds that work Men sought for People with HIV taking a protease inhibitor drug combination, who have a viral load of more than 1,000 copies per ml, are invited to apply for study A5241. The study from the AIDS Clinical Trials Group (ACTG) will use drug resistance tests to determine what new medications should work best for these individuals and provide them with that optimized therapy. ACTG will see if people going on a new drug regimen can have treatment success without taking nucleoside medications (also known as NRTIs). Usually, nucleosides are included in HIV treatment. With so many new and powerful HIV drugs on the market, however, nucleosides may no longer be necessary. Not taking nucleosides would decrease the risk of side effects and lower the number of pills patients need to take. Among the medications that will be made available through the study is Isentress (raltegravir), and participants may not have ever taken a medication from its drug class, called integrase inhibitors. A5241 is called the OPTIONS Study, for “Optimized Treatment that Includes or Omits NRTIs.” ACTG is a division of the National Institutes of Health. The OPTIONS Study is taking place at more than 50 clinics around the country. For details or a study site near you, visit www.aactg.org. In Chicago, call Rush University Medical Center at (312) 942-5865. 14

May/June 2010

HIV vaccine study

Chicago is one of the sites for a new study from the HIV Vaccine Trial Network , HVTN 505. The study is now enrolling HIV-negative men who are circumcised and between the ages of 18 and 45. They cannot get HIV from the vaccine and will receive financial compensation for their participation. This is a randomized study—the men will be given the vaccine being studied or a placebo (fake drug). In addition, the men will receive information on how to lower their risk of acquiring HIV. For more information, call (800) 575-5758 or (312) 413-5897, e-mail wish@uic.edu, or visit www.hopetakesaction.org for a list of study sites around the country. PositivelyAware.com

FDA warning on Invirase According to a February report from the U.S. Food and Drug Administration (FDA), the agency is reviewing study data on “a

potentially serious effect on the heart from the use of Invirase (saquinavir) in combination with Norvir (ritonavir). The data suggest that together, the two drugs may affect the electrical activity of the heart.” Invirase, an HIV protease inhibitor drug, must be taken with a booster dose of Norvir to achieve adequate blood levels. The federal agency cautions that “Patients should not stop taking their prescribed antiviral medications. Patients who are concerned about possible risks associated with using Invirase and Norvir should talk to their healthcare professional.” The FDA does not yet know the extent of the potential side effect or its clinical

implications (in other words, whether people will require medical care). The agency noted that some people may be at increased risk of developing an abnormal heart rhythm. “The changes to the electrical activity of the heart possibly associated with these drugs, known as prolonged QT or PR intervals, can be seen on an electrocardiogram (EKG),” the report continued. “A prolonged QT interval can increase the risk for abnormal heart rhythms, including a serious abnormal rhythm called torsades de pointes. A prolonged PR interval can cause the electrical signal responsible for generating a heartbeat to slow or even stop; this is known as heart block and can affect how fast the heart is able to beat.” The report noted that “The FDA’s analysis of these data is ongoing. However,

healthcare professionals should be aware of this potential risk for changes to the electrical activity of the heart. Invirase and Norvir should not be used in patients already taking medications known to cause QT interval prolongation such as Class IA (such as quinidine) or Class III (such as amiodarone) antiarrhythmic drugs; or in patients with a history of QT interval prolongation.” In addition, medical providers should not prescribe Invirase to patients with cardiomyopathy, ischemic heart disease, pre-existing conduction system disease, or underlying structural heart disease.

Mississippi to stop segregating HIV-positive prisoners The following is taken from a March 17 press release from the American Civil Liberties Union (ACLU). The Mississippi Department of Corrections (MDOC) has agreed to end

the segregation of prisoners with HIV, a longstanding discriminatory policy that has prevented prisoners from accessing key resources that facilitate their successful transition back into the community. The decision by Mississippi’s corrections commissioner Christopher Epps, prompted by recent advocacy by the ACLU and Human Rights Watch, leaves Alabama and South Carolina as the only states that segregate prisoners based on their HIV status. Epps made the decision ahead of a forthcoming report by the ACLU and Human Rights Watch analyzing the harmful impact segregation policies have had in the three states. “Commissioner Epps deserves a tremendous amount of credit for making this courageous decision to replace a policy PositivelyAware.com

based on irrational HIV prejudice with a policy based on science, sound correctional practice, and respect for human rights,” said Margaret Winter, Associate Director of the ACLU National Prison Project. “The remaining segregation policies in South Carolina and Alabama are remnants of the early days of the HIV epidemic and continue to stigmatize prisoners and inflict them and their families with a tremendous amount of needless suffering.” Since 1987, MDOC has performed mandatory HIV tests on all prisoners entering the state prison system, and has permanently housed all male prisoners who test positive in a segregated unit at the Mississippi State Penitentiary, the state’s highest security prison. As a result, prisoners with HIV have been faced with unjustified isolation, exclusion, and marginalization, and low-custody prisoners have been forced unnecessarily to serve their sentences in more violent, more expensive prisons.

The change in policy will enable prisoners with HIV to participate in jobs, training programs, and other services to which they were previously denied access because of their HIV status and which are designed to prepare prisoners for a productive return to society. Additionally, HIV-positive prisoners will no longer be assigned to a segregated HIV unit, which resulted in the public disclosure of their HIV status and left them at risk of being ostracized and subjected to hostility and violence at the hands of other prisoners. “Prisoners with HIV were often forced to live in cruel, inhumane, and degrading conditions, and we’re delighted that Mississippi has changed its policy,” said Megan McLemore, health researcher at Human Rights Watch. “Integrating prisoners with HIV is the norm across the United States and MDOC deserves significant credit for making this decision.”

May/June 2010

BRIEFLY continued

How do women survive financially? Here in Chicago, researchers at Northwestern University are conducting a survey of

HIV-positive women, seeking to learn how they cope financially while living with the virus. The Health, Hardship, and Renewal (HHR) study is run by Dr. Celeste Watkins-Hayes, a former board member of Test Positive Aware Network (TPAN) who has long worked with women living with HIV and has reported her research findings throughout the community. According to an announcement for the study, “We hope to increase awareness and point to strategies that will help women take care of their economic resources and their health.” The study seeks positive women from ages 18 – 65 in the Chicago area to talk about how they:

• find and access resources for help, • cope with financial obstacles, • make ends meet to take care of their family, and • manage their health while paying their bills. There will be compensation for qualifying participants. The survey consists of a face-to-face meeting lasting about two hours. “This is a groundbreaking study, the first of its kind!” reads the announcement. “Your input will have far-reaching effects that will help us learn how to better serve women who are living with HIV/AIDS.” For more information, call toll-free at (877) 737-4758, e-mail hhrinfo@northwestern. edu, or visit www.hhrstrategies.org.

SURVEY SAYS: A groundbreaking study seeks to learn how women cope financially while living with HIV.

Positive patients seek flu treatment sooner

Get well soon: HIV-positive flu sufferers recovered more quickly, but that might be because they received treatment sooner. 16

May/June 2010

By the time this issue comes out, flu season should be over. It’s worth remembering, however, that each year flu kills more people in the United States than AIDS. Spanish researchers looked to see how people with HIV did during the recent H1N1 flu epidemic (the so-called swine flu). In short, not bad. In a clinic in Barcelona, 56 positive patients with H1N1 were compared to HIV-negative patients with H1N1. The groups had similar symptoms. Interestingly, the HIV-negative people had more cases of pneumonia and respiratory failure. But when the researchers looked at only the people without a co-morbidity (another illness, such as hepatitis), there was no difference. Also interesting is that the HIV-positive patients recovered sooner. That might be because people with HIV were more likely to be treated for H1N1. HIV-positive people overall were more likely to receive Tamiflu than HIV-negative people (95% compared to 71%). For those without a co-morbidity, the same was true (94% compared to 40%). The rate of antibiotic use was similar between the two groups (half), but for the folks without a co-morbidity, the HIV-positive people were just shy of having a significantly higher rate of getting antibiotics. Fortunately, there was no change in viral load or CD4 T-cell count for the people with HIV in the four to six weeks after their H1N1 diagnosis. Of the five positive patients with pneumonia and respiratory failure, smoking and a history of injection drug use were risk factors for these illnesses. The report was presented in February at the Conference on Retroviruses and Opportunitistic Infections (see page 18 for more news from CROI). PositivelyAware.com

Cholesterol concerns with Lexiva Cholesterol and triglyceride levels should be checked before going on Lexiva (fos-amprenavir), and then monitored thereafter, according to updated information on the medication’s drug label. In February, GlaxoSmithKline (GSK) issued a Dear Healthcare Professional Letter on this label change to its HIV protease inhibitor drug. The new information shouldn’t surprise anyone. As the letter points out, increases in lipid levels (cholesterol and triglycerides) are a known risk factor of this class of drugs. Monitoring lipid levels is important when using a protease inhibitor. GSK pointed to a report from the French Hospital Database on HIV which showed an association between exposure to Lexiva and an increased risk of heart attack. (The same was true for the protease inhibitor Kaletra and for the nucleoside drug Ziagen.) The letter explains that heart attacks are a recognized risk for the protease inhibitor drug class, possibly related to the risk of increased lipid levels. Providers are advised to help patients with modifiable cardiovascular risk factors such as diabetes, smoking, and high blood pressure. In addition, elevated lipid levels should be treated appropriately for the individual patient. Moreover, “Prescribers are reminded that HIV infection itself has been associated with lipid disorders and ischemic heart disease.” See the 2009 French report at www. retroconference.org. The abstract, #43LB, is entitled “Impact of Specific NRTI and PI Exposure on the Risk of Myocardial Infarction: A Case-Control Study Nested within FHDH ANRS C04.” PositivelyAware.com

More than 850 people in 10 states are currently on ADAP waiting lists

to access HIV/AIDS drugs, and more states are joining the ranks, according to the Fair Pricing Coalition (FPC). The following is from the coalition: This situation will not improve anytime soon—certainly not until the new Health Care Reform Legislation is fully implemented—unless we act now! AIDS Drug Assistance Programs (ADAPs) are at the center of a perfect storm, brought on by the economic meltdown, federal and state budget shortfalls, and continuing escalation of drug prices. The number of people who rely on ADAPs for their medications grew an unprecedented 80% each month in FY2009. Join the Fair Pricing Coalition in calling on all HIV drug companies to do their part to help solve this crisis by: ■

Implementing a multi-year cost protection and rebate enhancement program for ADAPs to reduce their drug costs and allow them to reopen enrollments. ■ Offering streamlined Patient Assistance Program (PAP) eligibility for individuals on any state’s ADAP waiting list. The FPC is seeking organizational and individual endorsements of an open letter to the drug companies in anticipation of upcoming negotiations with ADAPs in May. To sign on and read the full letter, please go to www.hivresearchcatalystforum.org/action. Note: There is a separate ADAP emergency funding sign-on that is still open for signatures (contact rclary@projectinform to sign on to the emergency funding letter). The Fair Pricing Coalition is an ad hoc group of community-based activists who work on drug pricing issues with pharmaceutical companies in the field of HIV/AIDS and hepatitis. The FPC focuses on the impact of drug pricing on patients, public and private payers, and providers. The core group meets with and coordinates discussions over pricing with individual pharmaceutical companies. A much larger group of AIDS and hepatitis organizations and concerned individuals participate in the FPC through consensus statements and petitions.

Viread gets FDA nod for teens In March, the FDA approved the use of Viread (tenofovir) in patients ages 12 to 18 who weigh more than 77 pounds. Viread is also available in the top-selling combination pills Truvada (Viread plus Emtriva) and Atripla (Viread and Emtriva plus Sustiva). Interestingly, the small study of 45 patients taking Viread and 42 taking placebos (sugar pills) did not find a difference in effectiveness (suppressed viral load) between the two groups. According to the FDA announcement, a subgroup analysis suggests that the lack of difference in virologic response may be due to differences in baseline drug resistance for these highly treatment-experienced adolescents. The FDA said that despite the disappointing results, the safety and pharmacokinetic data is similar to that seen in adults and supports approval for patients in this age range. Also, increased bone turnover was seen in the participants taking Viread, and the report noted that, “Although the effect of supplementation with calcium and vitamin D was not studied, such supplementation may be beneficial for all patients. If bone abnormalities are suspected, then appropriate consultation should be obtained.” May/June 2010

Croi conference update

Photo: Enid Vázquez

reported by Jeff Berry & Enid VázQUEZ

ver the past several years, we’ve seen great

strides in HIV therapy with the development of drugs from two new classes, as well as those with fewer side effects, less stringent dosing requirements, and greater efficacy.

At the 17th Conference on Retroviruses and Opportunistic Infections (CROI), held in San Francisco this past February, we learned that while there aren’t as many new blockbuster drugs on the immediate horizon, there are newer targets and novel treatment strategies still being explored. Additional information on integrase inhibitors in development, along with the new pharmacokinetic enhancer, or booster drug, cobicistat (formerly GS-9350), as well as complications, co-infection, HIV and H1N1, and treatment as prevention are covered within this special conference section and elsewhere in this issue (see HIV Wellness Series: HIV, Your HAART, and You, p.37, and The Buzz, p.40). For webcasts and podcasts of conference sessions, interviews, and panel discussions, visit www.retroconference.org and www.ifarablog.org.

May/June 2010

New targets While many people are responding quite well to the medications we currently have in the HIV armamentarium, there continues to be a need for additional drugs and newer classes for those who may have no options available due to toxicities or the development of drug resistance. Several proof-of-concept studies looked at newer targets in the virus life cycle process. Data was presented on LEDGINs, a novel class of antivirals which target LEDGF/p75 (an essential HIV integration co-factor), and show potential as second-generation integrase inhibitors, which may prove to be effective against virus that is resistant to Isentress (raltegravir) and elvitegravir. The capsid (CA) protein is another potential target for new drug development. CA is essential for HIV virions made within the CD4 cell to then go on and infect other CD4 cells. Capsid inhibitors would interrupt that process. Study data presented by Stephen Mason of Boehringer-Ingelheim provided proof-of-concept for these compounds. A complex resistance profile was observed, and the study author concluded that further research in this —Jeff Berry area is warranted. PositivelyAware.com

CCR5 antagonists: TBR-652 and vicriviroc TBR-652 is an oral CCR5 antagonist (entry inhibitor) being developed by Tobira that is taken once daily without the need for boosting. Data were presented from a Phase 2a dose-finding study (25-150 mg) of TBR-652. Study participants had a reduction of at least 1 log in viral load within the first 10 days, with a continued decline up to day 14 with some doses after stopping the drug on day 10. Few adverse events (AEs) were seen; they were generally mild (GI toxicities, headache, fatigue, and cough), and did not lead to discontinuation of the drug, although more AEs were seen at the 150 mg dose. There was a median nadir (lowest point) response of up to 1.8 log. The drug has a long half-life of 34-40 hours, which might account for the continued drop in viral load observed after stopping the drug. Selzentry (maraviroc) is currently the only oral entry inhibitor approved for use. CCR5 antagonists are only useful in those with R5-tropic virus, and an expensive assay (Trofile) is needed to determine tropism. However, genotypic assays are currently in development and will soon be available (hopefully sometime later this year) that should prove to be just as accurate as the current Trofile test, but at only around a quarter of the cost.

TBR-652 also has dual activity against CCR2, another chemokine receptor found on the cell surface of monocytes, dendritic (immature) cells, and memory T-cells. Other CCR2 antagonists are currently in development and being studied in relation to inflammation-associated diseases such as atherosclerosis, metabolic syndrome/ insulin resistance, and others. While this added activity is intriguing, it is still too early to tell whether it will lead to the drug potentially having added benefits aside from its anti-HIV activity. There are potential risks to blocking CCR2, including an increased risk of bacterial infections such as listeriosis, tuberculosis, toxoplasmosis, and cryptococcosis, but to date, no significant safety signals have been identified with CCR2 antagonists. Plans for a Phase 2b study are currently underway and should begin sometime next year. Stay tuned for further developments. 48-week data were presented on two Phase 3 studies of the latest CCR5 antagonist in development, vicriviroc. A total of 721 treatment-experienced individuals with R5 virus were randomized to receive either an optimized background regimen (OBR) or OBR plus vicriviroc. The study did not meet the primary efficacy endpoint of non-inferiority in the

treatment-experienced population that was studied. The percentage of patients who reached a viral load of less than 50 copies was 64% for the vicriviroc group vs. 61% for the placebo group (p=0.6), which was not statistically significant. Vicriviroc was well tolerated in both studies, and there were no significant differences in AIDS-defining events, malignancies, or other adverse events between the two groups. Subsequent planned post-hoc analyses showed that the use of Isentress (raltegravir) and/or Prezista (darunavir) in the background regimen strongly influenced the outcome, making it difficult for vicriviroc to show an additional benefit. The presenter, Dr. Joseph Gathe, noted that the optimized background regimen in these studies included more potent antiretroviral drugs than in the vicriviroc Phase 2 study, or Phase 3 studies of recently approved HIV drugs. A majority of patients (64%) had three or more fully active drugs in their OBR. For those with two or fewer available active drugs, vicriviroc showed efficacy (70% vs. 55%; p=0.02). Dr. Gathe concluded by stating that with the success of recently available therapies for treatment-experienced subjects, new drugs will require novel study designs to demon—Jeff Berry strate efficacy.

New drugs will need new designs Following the above noted vicriviroc presentation, this reporter approached the microphone and asked Dr. Joseph Gathe about his closing statement and whether he would like to comment on what those novel study designs might look like. Dr. Gathe replied, “I think we’ve had such success with our newer agents in triple-class failing people, that I would not anticipate a clinician adding a drug on top of three active drugs to show benefit. So I think the design will have to be some other kind of novel way to look at a group of patients that would not necessarily take those drugs. You need to add it in where there’s only two active drugs, adding to where it benefits, instead of three active agents. And the question is, can that study be ethically done, now, when you have three active drugs? And that’s going to be a challenge to the pharmaceutical companies as well as the FDA—whether or not we’re going to be able to get any of these drugs pushed forward at this point in time, in that group of patients. I think it’s going to be ethically difficult to do that.” —Jeff Berry PositivelyAware.com

LOOKING AHEAD: Dr. Joseph Gathe May/June 2010

Croi conference update

Mix and match: Finding the best of all options Study ACTG 5202 is important because it compares best-selling HIV drugs to each other. Reyataz was compared to Sustiva, and Epzicom was compared to Truvada. Dr. Eric Daar from UCLA presented final, two-year results from 5202. The large study from the AIDS Clinical Trials Group (ACTG) enrolled more than 1,800 participants. They were divided into four groups, depending on the drug combination they received: Norvir-boosted Reyataz/Epzicom; Sustiva/ Epzicom; boosted Reyataz/Truvada; or Sustiva/Truvada. Participants were treatment-naïve, meaning that this was their first time taking HIV therapy.

Reyataz vs. Sustiva Reyataz (atazanavir) is the first protease inhibitor drug not to get its ass kicked by Sustiva (efavirenz), a non-nuke drug. The study stopped just short of showing that Reyataz was equivalent to Sustiva, a drug that’s been around longer and has beat out every competitor. The lack of equivalence—close, but no cigar—was essentially a problem of statistics. Dr. Daar said “the efficacy was very similar,” but that equivalence could not be declared under what he called the “very strict” standards of the study’s design. Dr. Daar explained that under usual study standards, Reyataz would have been found both equivalent and non-inferior to Sustiva. Ironically, what threw off the statistics was the fact that participants had much greater treatment success than expected. Instead of a 32% predicted failure rate, there was a 15% failure rate. “Basically, this study reinforces current DHHS [U.S. Department of Health and Human Services] HIV treatment guidelines: efavirenz and boosted atazanavir are both good choices,” said Dr. Joel Gallant, an HIV specialist, researcher, and writer at Johns Hopkins University, who was kind enough to review this article. He added, “Truvada is the nucleoside backbone of choice, but Epzicom is a good alternative, especially 20

May/June 2010

for patients with kidney issues and low baseline viral loads.” The most common reason for going off Reyataz was jaundice and non-compliance with study medications or study visits. (Jaundice, yellowing of the skin and eyes, is a potential side effect of Reyataz, but is a cosmetic concern and not a result of any damage to the liver or other organs.) The most common reasons for going off Sustiva were virologic failure, central nervous system symptoms, rash, and allergic reactions. Across the board, no matter what people were taking, the rate was the same (a low 4%) for kidney problems, bone fractures, cardiovascular events, and malignant tumors not related to AIDS.

Epzicom vs. Truvada Two years ago, the ACTG reported that of the study participants beginning with a viral load of more than 100,000 copies/ml, the ones taking Epzicom had a significantly greater risk of virologic failure (lack of complete suppression). At that point, the participants in this group who were undetectable on Epzicom were given the choice of staying on it or switching to Truvada. At that time, there was a small failure rate for both drugs: 26 participants in the Truvada group and 56 in the Epzicom group, out of more than 900 participants in each arm. Still, that means the failures on Epzicom were more than double the ones on Truvada, and it was a statistically significant difference. In this report, for the people who started 5202 with less than 100,000 viral load, Epzicom and Truvada were equally effective at suppressing virus. This confirms earlier findings for this group. But that’s not to say that there weren’t differences. Those participants taking Epzicom with Sustiva had a shorter time to a grade 3 or 4 (serious) safety event (clinical symptoms or problematic changes in their labwork), but not the ones taking Epzicom with Reyataz.

Epzicom users also had a shorter time to treatment modification than Truvada users, whether they were taking Reyataz or Sustiva. With Truvada, there was no difference in time to a grade 3 or 4 safety event or treatment modification, whether taken with Reyataz or Sustiva. ACTG 5202 pointed to an important consideration regarding Epzicom. Epzicom consists of the medications Ziagen and Epivir. Ziagen is associated with a hypersensitivity, or allergic-like, reaction. Today, there is a simple and inexpensive blood test that helps determine if people are hypersensitive to the drug before they take it. At the time 5202 was designed, however, the use of that test was not standard of care. In essence, Epzicom was studied with one hand tied behind its back. There was other bad news for the drug. People taking Epzicom had a greater increase in their lipid levels whether they were taking Reyataz or Sustiva. “The combination of Epzicom and efavirenz may cause more lipid elevation, but this is of unclear importance because the total/HDL cholesterol ratios are the same,” said Dr. Gallant. Outside of 5202, researchers are looking to see if Ziagen is associated with an increased risk of heart attacks. The evidence is mixed, with some studies showing an increased risk, and others showing no difference. Truvada’s bad news came from its tendency to negatively affect the kidneys; specifically, decreased creatinine clearance, a measure of kidney function. There was a statistically significant drop in creatinine clearance only when Truvada was combined with Reyataz. Still, many observers were quick to point out that the drop in creatinine clearance was modest and that less than 5% of participants in all of the arms had a decrease of greater than 25% from the start of the study. For more information, visit the conference website at www.retroconference.org , or go to www.clinicalcareoptions.com. —Enid Vázquez PositivelyAware.com

Once-daily Prezista Evidence shows that treatment helps prevent transmission of HIV More evidence was presented that HIV treatment prevents transmission. A variety of “test and treat” strategies are being examined. It’s known that antiretroviral therapy that is successful in suppressing a person’s viral load (the amount of HIV in their blood) can also make that person less likely to transmit the virus. The San Francisco Department of Health presented a study relating “community viral load” (CVL) with transmission of HIV. The city’s HIV/AIDS surveillance system collects information on the viral loads of people with HIV. Looking at the years 2002 to 2008, there was a decrease in community viral load (which they defined as the average of the most recent viral loads of all reported HIV-positive individuals in a specific population, divided by the number of reported positive individuals in the population). Along with the decrease was a drop in both the number of HIV diagnoses and the number of new HIV infections. The department’s report stated that, “Findings support the hypothesis that wide-scale early ART can have a preventive effect at a population level.” It should be noted that data from the department showed a decline in transmission before the decline in CVL, and that advocates had discussed serosorting (HIV-positive people choosing HIV-positive sex partners) as one explanation for that. The conference report recommended that other public health departments consider adding community viral load to their surveillance system to help measure the effectiveness of HIV prevention and treatment efforts. Moving on to Canada, Dr. Julio Montaner of the British Columbia Center for Excellence in HIV/AIDS in Vancouver updated its CVL data. His research team had previously reported on an association between expanded use of HAART (highly active antiretroviral therapy), a decrease in CVL, and decreased HIV transmission in two research studies of injection drug users (IDU). In their new report, they continued to find declines in HIV infection as more people were treated with antiretroviral therapy. The team’s abstract reported that, “As previously described, the initial HAART roll out [1996-1999] was associated with an approximately 50% decrease in new HIV diagnoses. The HAART expansion in 2004 to 2009 was associated with a second decrease in new HIV diagnoses. Of note, an approximately 50% decrease in new HIV diagnoses among IDU was evident after 2007.” Moreover, there was a drop from about 50% to about 20% of injection drug users with a viral load above 1,500. The team considered that level of viral load to be a sign of high community viral load. The Canadian medical team made special efforts to reach the drug-using community. Interestingly, there was no decrease in other sexually transmitted infections, which supports the idea of using treatment as prevention and possibly serosorting as well. Of note, their HAART and medical services are free. Back to the States—Washington, D.C. has one of the highest rates of HIV in the country: 3% compared to less than one percent nationally. In 2006, the city began a program to increase routine HIV testing. This effort not only helped identify new HIV/AIDS cases, reported researchers from George Washington University and the District of Columbia Department of Health, but was also associated with a faster entrance into medical care and a decrease in the number of “late testers.” Late testers are people who’ve been HIVpositive for a long time but undiagnosed, as shown by the fact that they are found to have low T-cell levels or have AIDS at the time of their HIV test results, or are diagnosed with AIDS soon after. The U.S. Centers for Disease Control and Prevention (CDC) estimate that 25% of people with HIV don’t know that they have it, and it is presumed that they are a significant source of new infections. The researchers from the nation’s capital said further surveillance will help determine if the positive results reported here will lead —Enid Vázquez to better health and to reduced HIV transmission. PositivelyAware.com

Prezista is a great drug from recent years, but it has to be taken twice a day by people who’ve already been on HIV therapy. Might Prezista be just as good for these folks when taken only once a day? The ODIN study (Once-daily Darunavir in Treatment-Experienced Patients) took on this challenge. At one year, the answer was yes. Once-daily Prezista was non-inferior to its twice-daily dose for treatmentexperienced people. Moreover, lipid elevations were half of those seen with twice-a-day therapy. Prezista has to be taken with Norvir, which often raises lipid levels. The once-daily dose cuts the amount of Norvir in half compared to the twice-daily dose. None of these participants had drug resistance to Prezista before entering the study. That’s an important consideration for treatment. Moreover, participants had little if any drug resistance to the HIV protease inhibitor (PI) class of medications, which includes Prezista. Both the once-daily and the twice-daily groups had a 70% success rate (achieving less than 50 copies in viral load) and a CD4 increase of 100 T-cells. Once-daily Prezista had earlier been studied in treatment-experienced people and performed well, but that was a smaller dose-ranging trial. ODIN looked at 300 individuals in each group. And again, the fact that there was practically no PI drug resistance in the participants obviously helps to make the once-daily dose work. —Enid Vázquez

Special thanks to Joel Gallant, MD, of Johns Hopkins University, for his review of the preceding articles. For a non-technical summary of CROI, visit http://i-base.info/htb/9428

May/June 2010

Croi conference update

Hepatitis highlights from CROI Sexual transmission of hepatitis B, hepatitis C survival in syringes, and more By Liz Highleyman

his year’s

Conference on Retroviruses and Opportunistic Infections (CROI), held February 16-19 in San Francisco, included a number of presentations on hepatitis B and C, and their relation to HIV.

Long HCV survival in syringes Hepatitis C virus (HCV) is more easily transmitted than HIV via syringes; while needle exchange programs have dramatically reduced HIV incidence among injection drug users, they have had less effect on new HCV infections. Elijah Paintsil and colleagues from Yale (abstract 168) conducted a laboratory study to determine how long HCV could live in syringes. They first loaded syringes with HCV-spiked blood and depressed the plunger to expel it—similar to what happens when a user “boots,” or draws blood up into a drug-filled syringe. They then flushed out the syringes and tried to grow the recovered virus in cell cultures, either immediately or after storing them for up to two months at different temperatures. They looked at both low-volume (2 microliters of blood) insulin syringes with permanently attached needles and highvolume (32 microliters) tuberculin syringe with detachable needles. In the low-volume syringes, the likelihood of finding infectious HCV decreased rapidly, with no recovered viable virus after three days in syringes stored at room temperature (72º F) or after seven days at 40º F (average refrigerator temperature). But nearly all high-volume syringes stored at 40º F still contained viable HCV after seven days, half still did after 35 days, and 5% still did after 63 days. Even at higher temperatures (72º or 98º F), viable HCV could still be recovered from a small proportion of high-volume syringes after two months. Dr. Paintsil said that while it may be 22

May/June 2010

“advisable” for needle exchange programs to offer smaller insulin syringes, the most important thing is to distribute enough needles so that people never have to share.

Treatment response and AIDS progression People co-infected with HIV and HCV typically experience more rapid liver disease progression; they may also have more rapid HIV disease progression, but research is conflicting. It is well known that interferon-based treatment for hepatitis C can slow or stop worsening of liver disease. Juan Berenguer and colleagues from Spain (abstract 167) reported that successful hepatitis C treatment can also reduce illness and death due to AIDS and other non-liver-related causes. This study included more than 1,400 HIV/HCV co-infected participants starting interferon; about 60% had hard-to-treat HCV genotypes 1 or 4. A majority were also on combination antiretroviral therapy (ART) and had undetectable HIV viral load. Overall, 36% achieved sustained virological response (SVR), or continued undetectable HCV viral load six months after completing treatment. After four years of follow-up, people who were sustained responders were significantly less likely to develop liver disease complications, including liver cancer and liver-related death, than non-responders or relapsers. In addition, sustained responders were about three times less likely to experience new AIDSdefining conditions and had less than half the risk of death due to non-liver-related

causes. Dr. Berenguer said there were also “some hints” that people who had an endof-treatment response but then relapsed also had improved outcomes.

Rapid liver disease progression? Research continues to produce conflicting evidence about how rapidly liver disease progresses in HIV/HCV co-infected people. Juan Macias and colleagues from Spain (abstract 659) used the FibroScan method, which uses ultrasound waves, to estimate liver fibrosis progression in 179 co-infected patients. Most were on ART with undetectable HIV viral load, but they were not on hepatitis C treatment. After 18-24 months of follow-up, 16% of participants showed fibrosis regression or improvement, 54% showed no change, and 30% progressed by at least one liver fibrosis category (for example, from mild stage F1 fibrosis to moderate stage F2 fibrosis, or from advanced stage F3 fibrosis to stage F4 cirrhosis). People with undetectable HIV and higher CD4 counts were less likely to experience fibrosis progression. The researchers concluded that despite ART, “liver fibrosis progresses in a significant proportion of HIV/HCV co-infected patients over a short period of time.” In another FibroScan study, Martin Vogel and colleagues (abstract 642) looked at fibrosis progression among 30 participants in the European NEAT cohort; again, most were on ART and the average CD4 cell count was relatively high. These were mostly gay/bisexual men who acquired acute hepatitis C—likely due to sexual transmission—after they were already HIV-positive. A majority of participants had elevated liver enzymes, an indication of liver inflammation, and about one-quarter showed PositivelyAware.com

symptoms of acute hepatitis. Over a short 4-5 month follow-up period, the calculated fibrosis progression rate was very high, 3.8 fibrosis stages per year. A statistical analysis showed that short observation times were strongly associated with high progression rates. This led the researchers to conclude that the apparent large increase in calculated fibrosis scores did not accurately reflect actual fibrosis progression, and that liver inflammation during early HCV infection might cause FibroScan to falsely overestimate fibrosis. However, researchers in New York using liver biopsies have also seen unusually rapid fibrosis progression in HIV-positive men with acute hepatitis C, so more study is needed.

HCV clearance and CD4 cell recovery Some past studies indicate that HIV/HCV co-infected people experience slower and smaller CD4 cell gains after starting ART than those with HIV alone, but others have seen no difference. Martin Potter and colleagues (abstract 676) looked at the effect of hepatitis C treatment on CD4 count among 319 participants in the Canadian Co-infection Cohort Study; most were on ART and the median CD4 cell count was 376 cells/mm3. Seventeen people spontaneously cleared HCV without treatment, 212 had continued detectable HCV viral load but were not treated for hepatitis C, 59 were treated but were non-responders, and 31 achieved sustained response. Sustained responders had a significantly higher average CD4 count at baseline (486 cells/ mm3). Over two years of follow-up, spontaneous clearers had the steepest CD4 cell increase. Sustained responders also experienced good CD4 cell recovery, while people who were treated but failed to achieve SVR still had larger CD4 cell gains than untreated participants. “Successful HCV treatment with clearance of HCV RNA improved the CD4 reconstitution, independent of ART,” the researchers concluded. “Our findings suggest that active HCV RNA replication has a PositivelyAware.com

negative impact on HIV progression which may partially be restored through successful HCV treatment.”

IL28B gene variation Andri Rauch from University Hospital Bern (abstract 162) presented an overview of the IL28B gene, the main topic of the CROI oral hepatitis session. Specific variations (genotypes) in the IL28B gene were linked to spontaneous HCV clearance and hepatitis C treatment response in HCV mono-infected people just last year. The gene encodes interleukin 28—also known as interferon lambda—a chemical messenger with antiviral activity. Session moderator Ken Sherman said the discovery had “revolutionized the way we think about treatment and management issues.” Researchers identified the link by scanning the human genome for differences between people who responded well and those who did not respond to interferon. Among HCV mono-infected people, sustained responders were about half as likely as non-responders to have the high-risk IL28B genotype, and it was even less common among spontaneous clearers. Black people, who have the poorest response to interferon, were most likely to have the high-risk genotype. After research groups in the U.S., Europe, Australia, and Japan confirmed this association in HCV mono-infected individuals, European investigators looked for the same link in HIV/HCV co-infected people. Jacob Nattermann and colleagues (abstract 164) found that co-infected individuals with the high-risk IL28B genotype were less likely to achieve SVR, but the effect was not as strong as for HCV mono-infected people. Norma Rallon and colleagues (abstract 165) saw a strong association between IL28B genotype and both spontaneous HCV clearance and sustained response among co-infected people, but the latter was only statistically significant for HCV genotype 1. (HCV genotype and IL28B human genotype are two distinct factors, an unfortunate confusion of terminology.) Although its exact mechanism is not yet known, the high-risk IL28 gene variant

may produce interferon lambda with weaker antiviral activity against HCV. An IL28B genotypic test might help predict which patients are likely to respond to interferon-based therapy, but Rauch said it should not be the only factor influencing treatment decisions.

HBV DNA in semen Hepatitis B virus (HBV) is a sexually transmitted infection, and men who have sex with men are at elevated risk . Ann Marie Liapakis and colleagues sought to determine whether HBV DNA (like HIV RNA) might remain detectable in semen from HIV-positive and HIV-negative men with chronic hepatitis B who achieved undetectable blood HBV viral load. They looked at 10 men (seven HIVnegative and three HIV-positive) with undetectable blood HBV DNA on a treatment regimen containing the nucleotide analogs tenofovir (Viread, also in the Truvada and Atripla combination pills) or adefovir (Hepsera). These drugs are active against both HIV and HBV (though adefovir is only approved for hepatitis B) and can penetrate the genital “compartment,” which is protected by a physiological barrier that keeps some drugs out. Ten other men had detectable blood HBV viral load; one was HIV-positive and taking tenofovir, while the rest were HIV-negative and not taking either drug. Among men with undetectable serum HBV DNA, none had detectable semen HBV viral load. However, three of the 10 men with detectable blood HBV viral load (all quite high) also had detectable HBV in their semen—including the sole HIV-positive man in this group. “In this cross-sectional analysis, HBV DNA was not detected in the semen of patients with undetectable blood level as a result of nucleotide antiviral therapy,” the investigators concluded, suggesting that such men are unlikely to transmit HBV via sex. Liz Highleyman (liz@black-rose.com) is a freelance medical writer based in San Francisco. May/June 2010

“October 25, 2002. It’s the day I learned I have HIV. It’s also the day I learned I have the most amazing friends and family. I wanted to hide away from the world—but they wouldn’t let me. They helped keep me going. Keep me moving. And keep me living. These days, I’m feeling good. And to make sure it stays that way, I’m always reading up on treatment options. When I learned that LEXIVA could reduce the amount of HIV in my blood, I asked my doctor about it.

LEXIVA has been part of my combination therapy for just over a year. And while I can’t speak for everyone who uses it, I know LEXIVA is working great for me. My viral load is down and my T-cell counts are up. My friends, family, and I couldn’t be happier with my results.”*

*Not actual patient testimonial. Based on compilation of stories. Individual results may vary. By prescription only.

I have HIV.

I am cherished.

Models used for illustrative purposes only.

Models for illustrative purposes only.with other LEXIVAused is indicated in combination antiretroviral agents for the treatment of HIV infection. • The PI-experienced–patient study was not large enough to reach a deﬁnitive conclusion that LEXIVA/ritonavir and lopinavir/ritonavir are clinically equivalent • Once-daily administration of LEXIVA plus ritonavir is not recommended for PI-experienced patients or any pediatric patients LEXIVA does not cure HIV or prevent passing HIV to others. Please see Important Patient Information below and on the following page. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit fda.gov/medwatch, or call 1-800-FDA-1088. IMPORTANT�SAFETY�INFORMATION • You should not take LEXIVA if you have had an allergic reaction to LEXIVA or AGENERASE® (amprenavir).

• High blood sugar, diabetes or worsening of diabetes, and bleeding in hemophiliacs have occurred in some patients taking protease inhibitors. • 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 a�er starting your HIV medicines, be sure to tell your doctor. • Changes in body fat may occur in some patients taking antiretroviral therapy. The cause and long-term health effects of these conditions are not known at this time. • Skin rashes can occur in patients taking LEXIVA. Rarely, rashes were severe or life threatening. • Opportunistic infections can develop when you have HIV and your immune system is weak. It is very important that you see your healthcare provider regularly while you are taking LEXIVA to discuss any side effects or concerns. • Kidney stones have been reported in patients taking LEXIVA. Tell your healthcare provider if you have pain in your side, blood in your urine, or pain when you urinate. • Most common side effects in clinical studies were diarrhea, headache, nausea, rash, and vomiting. In most cases, these side effects did not cause people to stop taking their medicine.

Ask your doctor if LEXIVA is right for you. Learn more at www.LexivaHIVTreatment.com

BY�YOUR�SIDE� • This list of drug DRUG�INTERACTIONS • LEXIVA should not be taken with: AGENERASE® interactions is not complete. (amprenavir), Halcion® (triazolam), ergot medications Be sure to tell your healthcare provider about all medicines (Cafergot®, Migranal®, D.H.E. 45®, and others), Propulsid® you are taking or plan to take, including over-the-counter (cisapride), Versed® (midazolam), Orap® (pimozide), drugs, vitamins, and herbals. Zocor® (simvastatin), Mevacor® (lovastatin), Rifadin® �RESISTANCE (rifampin), Rescriptor® (delavirdine mesylate), or St. John’s • Missing or skipping doses of your medicine may make it wort (Hypericum perforatum). If you are taking Norvir® easier for the virus to mutate and multiply. Your medicines (ritonavir), you should not take Tambocor® (flecainide) or may not work as well against a mutated virus, and you Rythmol® (propafenone hydrochloride). may become cross-resistant to other HIV medicines. It’s • Serious and/or life-threatening events could occur between important to take your medicine exactly as prescribed. LEXIVA and other medications, including Cordarone® (amiodarone), lidocaine (intravenous only), Elavil® (amitriptyline HCl), and Tofranil® (imipramine pamoate), SAVE�ON�YOUR�MEDICATIONS� tricyclic antidepressants, and Quinaglute® (quinidine). Ask your doctor about the Patient Savings Card • Women who use birth control pills should choose a different or visit www.mysupportcard.com to learn kind of birth control. The use of LEXIVA with Norvir how to save on your out-of-pocket expenses. (ritonavir) in combination with birth control pills may hurt Subject to eligibility. Restrictions apply. your liver. Also, birth control pills may not work if you take LEXIVA or LEXIVA with Norvir. Talk to your healthcare provider about choosing the right birth control for you. • Patients taking Viagra® (sildenafil citrate) or LEVITRA® (vardenafil HCl) with LEXIVA may be at increased risk of side effects.

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PATIENT INFORMATION LEXIVA® (lex-EE-vah) (fosamprenavir calcium) Tablets and Oral Suspension Read the Patient Information that comes with LEXIVA 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 healthcare provider about your medical condition or treatment. It is important to remain under a healthcare provider’s care while taking LEXIVA. Do not change or stop treatment without first talking with your healthcare provider. Talk to your healthcare provider or pharmacist if you have any questions about LEXIVA. What is the most important information I should know about LEXIVA? LEXIVA can cause dangerous and life-threatening interactions if taken with certain other medicines. Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. • Some medicines cannot be taken at all with LEXIVA. • Some medicines will require dose changes if taken with LEXIVA. • Some medicines will require close monitoring if you take them with LEXIVA. Know all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. Keep a list of the medicines you take. Show this list to all your healthcare providers and pharmacists anytime you get a new medicine or refill. Your healthcare providers and pharmacists must know all the medicines you take. They will tell you if you can take other medicines with LEXIVA. Do not start any new medicines while you are taking LEXIVA without talking with your healthcare provider or pharmacist. You can ask your healthcare provider or pharmacist for a list of medicines that can interact with LEXIVA. What is LEXIVA? LEXIVA is a medicine you take by mouth to treat HIV infection. HIV is the virus that causes AIDS (acquired immune deficiency syndrome). LEXIVA belongs to a class of anti-HIV medicines called protease inhibitors. LEXIVA is always used with other anti-HIV medicines. When used in combination therapy, LEXIVA may help lower the amount of HIV found in your blood, raise CD4+ (T) cell counts, and keep your immune system as healthy as possible, so it can help fight infection. However, LEXIVA does not work in all patients with HIV.

LEXIVA has not been fully studied in children under the age of 2 or in adults over the age of 65. Who should not take LEXIVA? Do not take LEXIVA if you: • are taking certain other medicines. Read the section “What is the most important information I should know about LEXIVA?” Do not take the following medicines* with LEXIVA. You could develop serious or life-threatening problems. • HALCION® (triazolam; used for insomnia) • Ergot medicines: dihydroergotamine, ergonovine, ergotamine, and methylergonovine such as CAFERGOT®, MIGRANAL®, D.H.E. 45®, ergotrate maleate, METHERGINE®, and others (used for migraine headaches) • PROPULSID® (cisapride), used for certain stomach problems • VERSED® (midazolam), used for sedation • ORAP® (pimozide), used for Tourette’s disorder • are allergic to LEXIVA or any of its ingredients. The active ingredient is fosamprenavir calcium. See the end of this leaflet for a list of all the ingredients in LEXIVA. • are allergic to AGENERASE (amprenavir). You should not take AGENERASE (amprenavir) and LEXIVA at the same time. There are other medicines you should not take if you are taking LEXIVA and NORVIR® (ritonavir) together. You could develop serious or life-threatening problems. Tell your healthcare provider about all medicines you are taking before you begin taking LEXIVA and NORVIR (ritonavir) together.

Before taking LEXIVA, tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. LEXIVA can cause dangerous and life-threatening interactions if taken with certain other medicines. You may need dose changes in some of your medicines or closer monitoring with some medicines if you also take LEXIVA (see “What is the most important information I should know about LEXIVA.”). Know all the medicines that you take and keep a list of them with you to show healthcare providers and pharmacists. Women who use birth control pills should choose a different kind of contraception. The use of LEXIVA with NORVIR (ritonavir) in combination with birth control pills may be harmful to your liver. The use of LEXIVA with or without NORVIR may decrease the effectiveness of birth control pills. Talk to your healthcare provider about choosing an effective contraceptive. How should I take LEXIVA? • Take LEXIVA exactly as your healthcare provider prescribed. • Do not take more or less than your prescribed dose of LEXIVA at any one time. Do not change your dose or stop taking LEXIVA without talking with your healthcare provider. • You can take LEXIVA Tablets with or without food. • Adults should take LEXIVA Oral Suspension without food. • Pediatric patients should take LEXIVA Oral Suspension with food. If vomiting occurs within 30 minutes after dosing, the dose should be repeated. • Shake LEXIVA Oral Suspension vigorously before each use. • When your supply of LEXIVA or other anti-HIV medicine starts to run low, get more from your healthcare provider or pharmacy. The amount of HIV virus in your blood may increase if one or more of the medicines are stopped, even for a short time. • Stay under the care of a healthcare provider while using LEXIVA. • It is important that you do not miss any doses. If you miss a dose of LEXIVA by more than 4 hours, wait and take the next dose at the regular time. However, if you miss a dose by fewer than 4 hours, take your missed dose right away. Then take your next dose at the regular time. • If you take too much LEXIVA, call your healthcare provider or poison control center right away. What should I avoid while taking LEXIVA? • Do not use certain medicines while you are taking LEXIVA. See “What is the most important information I should know about LEXIVA” and “Who should not take LEXIVA?” • Do not breastfeed. See “Before taking LEXIVA, tell your healthcare provider”. Talk with your healthcare provider about the best way to feed your baby. • Avoid doing things that can spread HIV infection since LEXIVA doesn’t 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 or razor blades. • Do not have any kind of sex without protection. 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 LEXIVA? LEXIVA may cause the following side effects: • skin rash. Skin rashes, some with itching, have happened in patients taking LEXIVA. Swelling of the face, lips, and tongue (angioedema) has also been reported. Tell your healthcare provider if you get a rash or develop facial swelling after starting LEXIVA.

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LEXIVA does not: • cure HIV infection or AIDS. We do not know if LEXIVA will help you live longer or have fewer of the medical problems (opportunistic infections) that people get with HIV or AIDS. 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 you are taking LEXIVA. The long-term effects of LEXIVA are not known. • 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 safer sex by using a latex or polyurethane condom to lower the chance of sexual contact with semen, vaginal secretions, or blood. Never use or share dirty needles.

What should I tell my healthcare provider before taking LEXIVA? Before taking LEXIVA, tell your healthcare provider about all of your medical conditions including if you: • are pregnant or planning to become pregnant. It is not known if LEXIVA can harm your unborn baby. You and your healthcare provider will need to decide if LEXIVA is right for you. If you use LEXIVA while you are pregnant, talk to your healthcare provider about how you can be on the Antiretroviral Pregnancy Registry. • are breastfeeding. You should not breastfeed if you are HIV-positive because of the chance of passing the HIV virus to your baby through your milk. Also, it is not known if LEXIVA 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. • have liver problems. You may be given a lower dose of LEXIVA or LEXIVA may not be right for you. • have kidney problems • have diabetes. You may need dose changes in your insulin or other diabetes medicines. • have hemophilia • are allergic to sulfa medicines

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• diabetes and high blood sugar (hyperglycemia). Some patients had diabetes before taking LEXIVA while others did not. Some patients may need changes in their diabetes medicine. Others may need a new diabetes medicine. • increased bleeding problems in some patients with hemophilia. • worse liver disease. Patients with liver problems, including hepatitis B or C, are more likely to get worse liver disease when they take anti-HIV medicines like LEXIVA. • changes in blood tests. Some people have changes in blood tests while taking LEXIVA. These include increases seen in liver function tests and blood fat levels, and decreases in white blood cells. Your healthcare provider may do regular blood tests to see if LEXIVA is affecting your body. • changes in body fat. These changes have happened in patients taking antiretroviral medicines like LEXIVA. The 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. • kidney stones have been reported in some patients taking LEXIVA. 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 right away. Common side effects of LEXIVA are nausea, vomiting, and diarrhea. Tell your healthcare provider about any side effects that bother you or that won’t go away. This list of side effects of LEXIVA 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 LEXIVA? • LEXIVA Tablets should be stored at room temperature between 59° and 86°F (15° to 30°C). Keep the container of LEXIVA Tablets tightly closed. • LEXIVA Oral Suspension may be stored at room temperature or refrigerated. Refrigeration of LEXIVA Oral Suspension may improve taste for some patients. Do not freeze. • Keep LEXIVA and all medicines out of the reach of children. • Do not keep medicine that is out of date or that you no longer need. Be sure that if you throw any medicine away, it is out of the reach of children.

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General information about LEXIVA Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use LEXIVA for a condition for which it was not prescribed. Do not give LEXIVA to other people, even if they have the same symptoms you have. It may harm them. This leaflet summarizes the most important information about LEXIVA. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about LEXIVA that is written for health professionals. For more information you can call toll-free 888-825-5249 or visit www.LEXIVA.com. What are the ingredients in LEXIVA? Tablets: Active Ingredient: fosamprenavir calcium. Inactive Ingredients: colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, and povidone K30. The tablet film-coating contains the inactive ingredients hypromellose, iron oxide red, titanium dioxide, and triacetin. LEXIVA Tablets, 700 mg, are pink in color and are capsule-shaped, with the letters “GX LL7” printed on one side of the tablet.

Oral Suspension: Active Ingredient: fosamprenavir calcium Inactive ingredients: artificial grape-bubblegum flavor, calcium chloride dihydrate, hypromellose, methylparaben, natural peppermint flavor, polysorbate 80, propylene glycol, propylparaben, purified water, and sucralose. LEXIVA and AGENERASE 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.

GlaxoSmithKline Research Triangle Park, NC 27709

Vertex Pharmaceuticals Incorporated Cambridge, MA 02139

LXV:7PIL LXV689R1

December 2009

Positively Aware

www.positivelyaware.com

Is it all in your head?

Every biological aspect of living with HIV has a psychological response by Marshall Forstein, MD

eople living with HIV, not surprisingly, commonly experience concerns, and even disorders, that affect their mental health. The same is true for people at high risk of infection.

HIV and the brain HIV invades the central nervous system (CNSâ&#x20AC;&#x201D;the brain and spine) at the time of initial infection. During the acute period of infection, in addition to symptoms of an acute viral infection throughout the body, a substantial proportion of people experience the impact of HIV in the central nervous system, such as confusion, disorientation, slowness of thinking, and changes in mood. Most of the time, however, the infection of the CNS goes unnoticed. Whether or not a particular individual develops symptoms of CNS disturbance depends on a variety of factors including, but not limited to: the particular strain of HIV, viral load, immunological response, inflammatory response in the body and brain, and current medical or psychiatric problems. HIV and emotions Aside from the initial impact of HIV in the brain and body, there is an ongoing emotional adjustment to becoming positive. Incorporating an HIV-positive status into oneâ&#x20AC;&#x2122;s identity may include 28

May/June 2010

PositivelyAware.com

Model: Michael Tatum | Photo: Chris Knight

While anyone who engages in unprotected sex or shares needles is at risk to contract HIV, people with pre-existing psychiatric disorders (including addictive substance use) are at increased risk for behaviors that transmit HIV. In addition, HIV-positive people are at increased risk for mood, anxiety, substance use, and cognitive disorders.

managing information about one’s health with both health care providers and other relationships, and adjusting to medical care and lifestyle changes to reduce risks to health. There is a great range of reactions and accommodations to becoming positive and adjusting one’s view of the self and of one’s relationship to the world. These emotional and psychological reactions may change throughout a changing course of illness. Emotional support is often very helpful, particularly from experienced therapists or members of HIV-positive support groups who are negotiating this process of integrating the reality of being HIV-positive into their future. The interaction of HIV on the body, brain, and mind is complex. Symptoms that seem to arise in one area often impact all the others. Whatever the symptom, a thorough evaluation and assessment must be done to ensure the correct diagnosis and treatment. This is most comprehensively accomplished using a bio-psycho-socialcultural-spiritual model. For example, a complaint of fatigue or lack of energy may be a symptom of depression, but may also be explained by a disturbance in sleep, endocrine function (such as adrenal insufficiency,1, 2 low thyroid, or low testosterone in both males and females3), anemia due to HIV or medications, or poor pulmonary function due to lack of exercise or some lung infection. Alternatively, low energy or fatigue may be a reaction to an existential crisis around fear of dying, losing relationships, being rejected, or a manifestation of guilt or shame about sexuality, drug use, or other concerns.

To assess a particular symptom or set of symptoms requires medical providers to take time not only to evaluate the physical aspects of having HIV, but the emotional aspects caused by living with a chronic condition that is uncertain, may progress, and cause premature functional impairment. In other words, every biological aspect of living with HIV is accompanied by a psychological response. People with HIV can use positive coping strategies to diminish the impact of changes in physical or mental well-being. Quality of life, and the maintenance of overall function, should be the focus of treatment for anyone living with HIV. A coordinated, collaborative approach among all providers is essential to maximize the individual’s capacity to function at the highest possible level for as long as possible. While living longer with HIV is now the norm rather than the exception, there are adjustments in function and lifestyle that must be anticipated, and discussed openly between patient and provider. Neuropsychiatric disorders Over the past decade, evidence has mounted that HIV in the central nervous system (CNS) causes variable degrees of inflammation that manifests itself in a variety of ways, including • mood disorders (depression and mania), • anxiety, • sleep disturbances, and • cognitive impairment. See Table I for early and late signs of cognitive deficits. (Tables and References available online.)

Surviving longer with HIV, independent of viral load and CD4 count, increases the likelihood of some impairments of cognitive function. People at greatest risk for cognitive changes are those whose CD4 counts dropped to below about 200-300 before responding to HIV meds, and those with the highest viral loads in both the cerebral spinal fluid that bathes the brain and in the blood. The chances of developing cognitive impairments increase with • advancing age,4 • living longer with HIV, • co-infection with hepatitis C, • the use of toxic substances such as methamphetamine, • cognitive changes early in the course of infection, and • depression.5 Changes in personality are also common in people with mild cognitive impairments, and the inability to function as well as expected can cause significant fear, depression, and anxiety. Advancing cognitive impairment may lead to impulsivity, poor adherence to both medications and protective sexual behaviors, and hopelessness, including suicidal thoughts and attempts. Cognitive disorders may be due to primary HIV in the brain, or secondary dysfunction due to metabolic, endocrine, infectious, or neoplastic effects on the CNS. Medications, herbal remedies, excessive vitamins, and substances of abuse are also frequently associated with cognitive impairment.6, 7 HIV antiretrovirals (ARVs) may also cause neuropsychological impairment, and

While living longer with HIV is now the norm rather than the exception, there are adjustments in function and lifestyle that must be anticipated, and discussed openly between patient and provider.

PositivelyAware.com

May/June 2010

Depression is the most common psychiatric problem in the HIV-positive population, affecting as many as 50% of primary care HIV patients.

head trauma may also contribute to CNS dysfunction. Classification of primary HIV cognitive impairment is based on criteria having to do with the presence or absence of symptoms and the degree of functional impairment. HIV Associated Neurocognitive Disorder (HAND) (see Table II) classifies impairment under three categories: 1. asymptomatic neurocognitive impairment (ANI) with evidence upon neu-

ropsychological testing of cognitive deficits; 2. mild neurocognitive disorder (MND) with some functional limitations due to the cognitive domains affected; and 3. the often progressive and disabling HIV-associated dementia (HAD) that

always requires significant impairment for diagnosis.8

As ARVs have been more widely prescribed, the incidence of HAD has declined from the number of cases seen before these medications arrived,9 but as HIV-positive people live longer, there are increasing rates of MND and ANI being diagnosed. In spite of the fact that ARVs may slow the development of illness, and have almost eliminated the appearance of diseases that were so common before ARVs, there is evidence that the impact of HIV in the brain may cause mild to moderate cognitive impairment as people live longer and age with HIV.5 The prevalence rates of primary HIV mild neurocognitive disorder may range from 20-60%. The most common symptoms include • short-term memory loss, • problems with attention, concentration, multitasking, and word finding, and • motor slowing. No single rapid screening tool currently has been validated to diagnose 30

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MND, but there are a couple of screening tests that have been shown to correlate with the more advanced form of cognitive impairment, HAD. Providers can ask a few questions of every HIV-positive patient to get a sense of cognitive concerns. (See Table III.) The treatment of cognitive disorders in HIV includes ARVs,10 psychostimulants, and cognitive rehabilitative strategies for compensating for deficits and enhancing mental function. (See Table IV.) As people live longer with HAD and MND, the range of symptoms may vary more than previously thought.11 There are many co-morbid conditions that can contribute to CNS dysfunction that require a comprehensive medical workup. (See Table V.) In an aging HIV-positive population, there are also increased risks for other types of non-HIV-related cognitive disorders that may synergistically cause cognitive impairment, such as hypertension, cerebrovascular disease, depression, and diabetes. Depression Depression is the most common psychiatric problem in the HIV-positive population, affecting as many as 50% of primary care HIV patients. HIVnegative gay men have been reported to have rates of depression 2-3 times that of heterosexual men, and gay men with HIV appear to have higher rates than HIV-negative gay men. Women have higher rates of depression than men in both the general and HIV populations, and untreated depression in HIV is associated with increased risk of dying. The treatment of depression in HIVpositive people has been shown to be most effective when combining antidepressant medications and psychotherapy. While acute anxiety, shock, fear, and sadness are common initial reactions to discovering HIV-positivity, depression is not a normal reaction to illness, and

should be treated aggressively to prevent decreased adherence to medications and protective sexual practices. Depression must be distinguished from sadness, grief, fear, and existential concerns such as a fear of dying or losing one’s health. Since so many people with HIV may have some of the symptoms of depression due to the medical illness, it is important to look at the more emotional and less biological aspects of depression, such as loss of interest in self or others, a sense of hopelessness, and guilt for behaviors or thoughts that are unacceptable to the person. For example, a mother who is fatigued and cannot muster the energy to play with her children, but wants to, may not be depressed compared to a mother who becomes hopeless and disinterested in doing so. When diagnosed in a patient with co-existing substance use, depression and the substance use disorder must both be treated in a comprehensive model. Substance use and abuse There is growing evidence in the research that certain legal substances, as well as drugs of abuse, vary in their toxicity in the CNS. Alcohol, nicotine, and excessive vitamins like B6 are all legal but potentially toxic to brain function. Episodic binge drinking is likely more toxic to brain function compared to small amounts of alcohol on a daily basis, but any alcohol with certain medications may be detrimental to brain function and may affect blood levels of medications. Illicit drugs have varying degrees of toxicity. Additionally, the brain is more vulnerable to the effects of such drugs depending on the presence of a co-existing psychiatric disorder or previous delirium. Some illicit drugs, more than others, have direct effects on nerve development in the CNS. Methamphetamine appears to be the PositivelyAware.com

Psychosocial support has been shown to be very important to sustaining adherence to antiretroviral medications and dealing with side effects.

most neurotoxic of all illicit substances, even in small doses, causing loss of actual nerve tissue and function in the brain. Methamphetamine is not only rapidly addictive, but also very resistant to treatment and has very high relapse rates. To date, no medication is clearly beneficial in the treatment of methamphetamine addiction. Behavioral treatments have been shown to help in some situations, but the relapse rates are very high relative to the treatment for other addictive behaviors. The long-term cure for methamphetamine addiction may be as low as 10%. HIV infection rates are significantly increased in methamphetamine users and secondary transmission is high, as judgment and impulse control are impaired with methamphetamine use. For an informative summary on methamphetamine effects and treatment, see www.ncjrs.gov/ondcppubs/publications/drugfact/methconf/appen-b3.html. Other illicit drugs such as marijuana, cocaine, ecstasy, GHB, and ketamine may also have neurotoxic effects, and may disrupt or deplete neurotransmitters that are essential for a well-functioning brain. Psychological issues Mental health issues are best addressed in the context of a professional relationship with a provider who is nonjudgmental, open, and able to formulate a psychological understanding of behavior and the resistance to change. Primary care and mental health providers must stay collaborative and vigilant for changes in mental status, and for interactions between medications, especially in the context of recreational substances. There are phases to the psychological adjustment of becoming HIV-positive, even when there is awareness that one has put oneself at risk for infection. Research shows that sero-conversions most often occur in the context PositivelyAware.com

of sexual encounters under the influence of substances. Occasional use, as well as addiction, can reduce the capacity for using condoms. Depression, cognitive impairment, intoxication, and impulsive personality traits can reduce executive function of the frontal lobes that control rational thinking and behavior. Additionally, there is growing evidence that previous sexual abuse and trauma are highly correlated with risky behaviors. The psychological impact of sexual or emotional trauma can reduce an individualâ&#x20AC;&#x2122;s capacity to insist on condom use, or to refrain from undesired sexual or drug use behaviors. Couples in which one partner is positive and one negative may experience a variety of emotional responses. Fear of infecting a partner, or being infected, can precipitate a loss of intimacy, a change in sexual function, or an increase in pre-existing psychiatric symptoms. Psychosocial support has been shown to be very important to sustaining adherence to antiretroviral medications and dealing with side effects. Attention should also be paid to the impact of bodily changes due to HIV or its treatment. Body image can impact a sense of self-worth, cause one to be stigmatized, and can affect oneâ&#x20AC;&#x2122;s sense of sexual attractiveness and desirability. With the promise of a longer life now possible with good medication adherence, HIV-positive people are often interested in starting or maintaining sexual relationships, and often feel hesitant, or afraid of being rejected. Many HIV-related problems (such as neuropathy, metabolic syndrome, and renal or liver disease) can cause sexual dysfunction in both men and women. Additionally, many of the medications used for cardiovascular disease or hypertension (beta blockers), as well as many psychiatric meds (antidepressants and antipsychotics) can cause sexual side effects.

Most importantly, providers must create a safe environment in which expressing concerns about sexuality is welcomed. Goals of treatment The most important mental health issues facing people who are HIV-positive today include maintaining excellent adherence to antiretroviral medications, avoiding toxic substances that impair brain function, preventing co-infection with other strains of HIV (to prevent resistance to medications that are suppressing viral replication), being treated for underlying psychiatric symptoms and disorders, and dealing with subtle changes in brain function over time. All of the above factors affect each other. Preserving brain function is at least as important as preserving liver, lung, and cardiac function. Living longer with greater quality of life should be the focus of treatment. Finding purpose and community can provide the impetus for self-care and hope. e References and tables are available online at www.positivelyaware.com. Marshall Forstein, MD, is Director of Training for the Division of Adult Psychiatry at The Cambridge Hospital, and an Associate Professor of Psychiatry at Harvard Medical School. He teaches medical students and is a core faculty member in the Division of Palliative Care at Harvard Medical School. Dr. Forstein has been a principal investigator on an HIV Education and Training Grant through the federal Center for Mental Health Services, and teaches and has published on the neuropsychiatry and psychosocial aspects of HIV/AIDS. He is a Distinguished Fellow of the American Psychiatric Association and is currently serving on the Residency Review Committee for Psychiatry of The Accreditation Council for Graduate Medical Education.

May/June 2010

Economic impact

Economic hard times can be another complication when living with HIV

he most current research in mental health supports the strong connection between mind, body, and brain. Western approaches to psychotherapy and medicine have tended to split the body from the brain/mind, treating symptoms of psychological distress and physical distress as though they were unrelated. More and more, however, we are recognizing how the brain responds to outside influences, the impact of those outside influences on the body, and the impact of the brain’s and body’s responses to those outside influences on our mind (how we think about and understand our world). Enter: Our current economy.

Joe’s story I hadn’t heard from Joe for almost four years. When he recently called 32

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to schedule an appointment, I was surprised to hear from him. He’d stopped seeing me abruptly and despite

several attempts to contact him, he hadn’t responded to my calls or a final letter. “I need to see you as quickly as possible,” he shared in a voice mail. “I know it’s been a long time, but I’m hoping you’ll still see me.” I returned his call and we scheduled an appointment within the week. When I opened the door to greet him, he looked exhausted. His clothes were wrinkled and his shirt was untucked. His eyes seemed glazed and his skin was ashen. He walked slowly into the office, settled into the couch, and began to cry. He told me what brought him back to see me. “I lost my job a month ago and I’ve been using PositivelyAware.com

Model: Michael Tatum | PhotoS: Chris Knight

By Jeff Levy, LCSW

Even for those who don’t have pre-existing mental health concerns or physical concerns, the economic climate has the potential to create a sense of despair. crystal meth for the past four years— that’s part of why I stopped therapy— I didn’t want to tell you,” he hesitated and continued, “I’m HIV-positive now as well. Luckily, I’m participating in a drug trial, so my medication is free, but I have no money. I’m afraid I’m going to lose my condo. I know I need to look for work, but I can’t even get myself out of bed in the morning. And…what will I tell people about why I lost my job?” Joe originally came to see me because of anxiety and depression. Both his parents struggled with alcoholism and depression and though Joe did not report using substances when we first met, he was worried that he might, given his family history. Joe had no significant long-term relationships and was fairly isolated. Raymond’s story Raymond has been seeing me consistently for a few years. He has been HIV-positive for about 10 years and was diagnosed with bi-polar disorder and anxiety prior to beginning therapy with me. He has held the same job for seven years and has received numerous promotions and increased responsibilities at work, despite his concern that his lack of formal education (no college degree) would hold him back. He has been in a stable and committed relationship with his partner, Francisco, for eight years. Raymond’s physical health has been good, with an undetectable viral load, no other serious health issues, and a commitment to exercise and healthy eating. This past week, he began our session by telling me he felt paralyzed. “I can’t function or focus,” he said. “My responsibilities at work are increasing. There have been multiple lay-offs and I’m expected to do more with less. I know I don’t want to do what I’m doing anymore, but I can’t quit. I’ll never find a job that pays me what I’m making. Francisco doesn’t make enough to support us both. And how will I ever get health insurance?” PositivelyAware.com

Raymond grew up in a fundamentalist Christian home. When his mother and stepfather found out he was gay, he was disowned and has had no contact with his parents and minimal contact with his siblings. His father, though more accepting, has chronic and persistent mental health issues, is frequently homeless, and often relies on Raymond for emotional and financial support. Anthony’s story When Anthony began therapy with me, he was preparing to die. He had been HIV-positive since the late 1980s, had numerous opportunistic infections and wasting syndrome, and had exhausted all possible medication regimens. He could no longer work as a physical therapist and was living on social security disability income (SSDI). His reported reason for entering therapy, however, was “co-dependence” and depression. Anthony reported he consistently put others before himself, focused on others’ well-being, tried to manage the behavior of others—including those who had addictions and were violent toward him (he had a history of being the victim of intimate partner violence). With advances in HIV medications, Anthony’s physical health improved significantly. So much so, in fact, that he began to consider working again. Several years ago, he began to return to work very part-time and, more recently, discontinued SSDI and began full-time work. He also returned to school to pursue a graduate degree. Despite all these improvements in Anthony’s life, he still has periodic health challenges. “I’m scared,” he said in one of his recent sessions. “I’ve decided I’m going to live. I’ve taken on work and school, but the home health agency I work for might shut down. We’ve cut staff, we’re not being paid in a timely fashion, and we’re so small that the hospital we’re affiliated with isn’t motivated to keep us. I wish I’d never gone off disability. What will I do?”

Common Themes As I thought about Joe, Raymond, and Anthony, I also thought about the other people I work with who have HIV, who constitute about 40% of those I see on a regular basis, and the extent to which financial and economic challenges impact their bodies, minds, and brains. Some common themes arise. Anxiety, Depression, and Hopelessness All three men—Joe, Raymond, and Anthony—are dealing with an increased sense of anxiety and a sense of feeling trapped by their current circumstances. Even for those who don’t have pre-existing mental health or physical concerns, the economic climate has the potential to create a sense of despair. Savings dwindle, earning potential decreases, and financial debt increases. For those living with HIV, added economic challenges magnify concerns around physical health. Loss of employment may mean loss of health insurance and loss of health insurance could significantly impair maintaining physical health. For those whose health is more tenuous, anxiety about health care has a more immediate impact on physical health and deteriorating physical health magnifies anxiety. This interrelated spiral can lead to a sense of feeling trapped and even a great sense of hopelessness. Stigma and Shame For most of us, losing a job or becoming unemployed carries with it a sense of shame, even when unemployment occurs during a recession. Questions about competence, how we might have handled a situation differently, or even the shock of job loss create a sense of isolation. As a society, we have preconceptions and judgments about those who “can’t keep work” or “can’t find work.” When unemployment is concurrent with HIV, another historically stigmatized condition, these two unrelated experiences have the potential to magnify one another, May/June 2010

Despite economic, physical, and emotional challenges, there are ways we can take care of ourselves to enhance mental health in times of economic difficulty. with a greater vulnerability to feeling unworthy and somehow “bad.” And if we feel unworthy and bad, we are even more likely not to take care of our physical selves. When multiple stigmatized identities “collide,” each is individually more difficult to manage. Substance Use and Abuse Joe’s substance use, he came to find, was one of the causes for his job loss and, he realized, made him more vulnerable to less safe sexual behavior (resulting in HIV). Now, his substance use was interfering with his employment search and escalating financial concerns. Long histories of recovery and abstinence can be challenged when we’re uncertain if we can maintain our home and/or if we’re uncertain where our next meal may come from. Even without a history of substance use, financial and economic stressors can lead to a desire to escape. And for many, escape comes in the form of alcohol and other drugs. Substance use and abuse certainly impact physical health and an ability to find and retain employment. When unemployment creates a desire to escape, and the strategy to escape makes re-employment even more difficult, another cycle is created where body, mind, and brain unwittingly enter into and maintain an unproductive and downward spiraling cycle. The good news: “Practice makes better” If we understand and integrate a mind-body-brain approach to our lives, we can intervene in any one of these areas and be confident the other two will be influenced. Thus, despite economic, physical, and emotional challenges, there are ways for Joe, Raymond, Anthony, and the rest of us to take care of ourselves to enhance mental health in times of economic illness. When forces like the economy are involved, however, it’s also important to remember there is no “one” or “quick” fix that will solve the problem. I will, however, offer a 34

May/June 2010

daily “practice” comprised of five basic components that, if engaged, will most certainly enhance mental health. Normalize distress. Feeling anxious, depressed, fearful, or angry are all “normal” responses to “abnormal” circumstances. These are extremely difficult economic times. In fact, the economy has not been as challenged since the great depression. If we allow ourselves to see that our distress about current circumstances is normal, we are less likely to label ourselves as somehow unhealthy or alone in our feelings. Suspend judgment. When we notice ourselves having some sort of negative self-commentary or criticism about our reactions or feelings in response to current stressors, practice noticing these responses without labeling them as good or bad. We are prone to feel worse especially when we judge our feelings negatively. When we suspend judgment, our feelings become our feelings, neither good nor bad. We learn to accept them as a part of life. Meditate. For some folks, the idea of meditating may be formidable. Research studies show, however, that meditating regularly reduces stress—and if we reduce stress, we enhance hope, and if we enhance hope, we feel better. When we feel better, we perform better. We can more easily do the things we want to get done. Begin by spending just several minutes per day quietly noticing breathing, physical sensations, or sounds. When thoughts interrupt your meditation, simply notice them (without judgment) and return to meditation. Slowly build to twice-daily meditation—morning and evening—with the goal of 10-12 minutes per meditation period. Move your body. I have recently been experimenting with “therapy on the fly.” Instead of sitting in my office with clients— especially those who feel immobilized by depression—we are walking. In a therapy hour, we can perhaps walk 2-3 miles depending on our clip. Everyone who has engaged with me in

this manner talks about feeling better after walking. You don’t need to be in therapy to move your body. There are simple ways to move your body on a daily basis, recognizing that acts of physical movement help release us from emotional “stuckness” or feelings of being trapped. The body changes the brain and the brain changes the mind. Be with others committed to the strategies above. Practicing strategies of self-care with others creates new patterns of being and moving through the world. The more we practice, the more natural these strategies become. We know from current research that it has taken lots of “practice” for our brains to work the way they do, our minds to think the way they do, and our bodies to respond the way they do. To change what we’ve learned takes repetition and practice. By engaging in this five-step practice on a regular basis, we change our brains, we change our minds, and we change our bodies. Consequently, we feel better physically and emotionally. It’s Complicated Joe, Raymond, and Anthony are dealing with extremely difficult and complicated circumstances. As I’ve previously mentioned, there is no one or quick way to manage such challenges. It is also not possible for me to reduce such complicated dynamics to a recipe for mental health. I offer suggestions for understanding the impact of economic hardship on physical and mental health and for experimenting with and practicing strategies that change our brains, change our minds, and change our bodies. First and foremost, perhaps, is practicing hope. e Jeff Levy is a social worker, co-founder, and CEO of Live Oak, Inc. (www.liveoakchicago. com) in Chicago. He is also adjunct faculty at the University of Chicago’s School of Social Service Administration. He can be reached at jlevy@liveoakchicago.com.

PositivelyAware.com

Photo: Enid VÁzquez

Memorialized: Quilt dedicated to the memory of Howard Okorofsky.

Threads of connection One man’s quilt and its journey by Sue Saltmarsh

tuart Okorofsky was there in the late 1980s when his brother Howard learned that he had contracted HIV. “My brother was the least promiscuous gay man I knew,” said Stuart, noting that many of Howard’s friends had unsafe sex with multiple partners, yet somehow remained HIVnegative. “It only takes once,” was a lesson that both Stuart and his brother learned in the hardest way. At that point in the epidemic, treatment options were as limited as life expectancy and medications came with the danger of unknown toxicities. Stuart was there again in 1992 when, after being hospitalized, comatose, and then rallying briefly, Howard passed away. For the last 15 years, Stuart has continued to honor his brother by riding in various AIDS rides around the country, including rides in California, Alaska, Canada, Vermont, Maine, New Hampshire, New York, Massachusetts,

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Connecticut, Washington, D.C., New Jersey, Maryland, and Virginia. He has personally raised around $100,000, and this year, he and his nephew are riding in New York in August. (To support their effort, go to www.empirestateaidsride. org, hit Donate and enter Stuart’s name.) Stuart was also responsible for starting an AIDS quilt panel for Howard, to which many family members and friends contributed. It’s obvious from looking at the panel that Howard was much loved and is greatly missed. Small world But there’s more to the story. At the 2009 ICAAC (Interscience Conference on Antimicrobial Agents and Chemotherapy) in San Francisco, Positively Aware’s Enid Vázquez took a picture of Howard’s quilt when she saw it on display. That photo made it onto the pages of the November/December issue, which covered the conference.

A friend of Stuart’s who lives in Florida and works with HIV-positive people was given a copy of the magazine by a client and when he saw the photo, he recognized the quilt and sent the magazine to Stuart. Curious as to how his brother’s quilt ended up being displayed at the conference, Stuart contacted PA Editor Jeff Berry to see if he knew anything about it. Unfortunately, the answer to his question wasn’t immediately available. However, after PA got in touch with Brian Holman, Manager of Quilt Displays for The Names Project, it was learned that the panel rests at the national office of The Names Project in Atlanta, Georgia, and was chosen based on the customary criteria used when selecting panels to make up a display. According to Holman, “The Quilt is chosen based on many different factors, such as location, the primary audience, and by specific request. I take into consideration who will be viewing the display. I would choose a Quilt for a college display much differently than a display at a church.” At present, Howard’s panel isn’t scheduled for any displays. Quilt facts The panel—and thousands like it— can be seen online at www.aidsquilt.org. The site gives you the ability to search for any panels connected to the person whose name you enter in the search box. Conceived in 1987 by San Francisco activist Cleve Jones, the first time the entire quilt was displayed in Washington, D.C. that year, there were 1,920 panels and it covered more than a football field. As of November 2008, the AIDS quilt was comprised of 46,312 panels—it’s mind-boggling to think how much space it would cover now. Anyone who has seen such a display, or even photos of it, can testify as to the impact, not only of the size, but of the depth of feeling that went into every panel. Such tangible memorials to those we’ve lost serve as reminders that HIV/AIDS has woven a tapestry through our lives, the threads of which connect us all. e

May/June 2010

Ask the HIV SPecialist Jason Faulhaber, MD, AAHIVS

Dear HIV Specialist, am a 45-year-old, male insulin-dependent, Type-II diabetic with HIV. When I was diagnosed last spring my CD4 count was 182 and I started therapy with Truvada/ Isentress, and Bactrim to prevent infections. Despite my low CD4s, I remain asymptomatic, and now have a CD4 count of 266 and an undetectable viral load. My question is, how long should I continue to take Bactrim? I was told that I would be taken off it when my CD4 count went above 200. I am concerned about building up resistance now that I have been taking it for more than eight months. Also, having both HIV and diabetes (which can both lead to kidney problems, neuropathy, and vision problems) is a double whammy. I haven’t been able to find much information on how one affects the other. I’m wondering if my HIV drug regimen has any effect on my pancreas and its ability to produce insulin. Besides taking my medications on schedule and maintaining good glucose control, do you have any other advice about my care and what I should watch out for long term? —D.C. Diabetic Dear DCD, Your questions and concerns are quite valid, and I encourage you to continue to be involved in your own medical care and certainly pursue a discussion with your HIV provider regarding any changes in your management. With regards to Bactrim (trimethoprim/ sulfamethoxazole) for prophylaxis against Pneumocystis pneumonia, the current guidelines recommend discontinuation after at least six months of a CD4 count greater than 200. This is a general recommendation, and your provider may tailor it specifically to your care. There are certain conditions, such as thrush, which have been shown to increase the potential risk of 36

May/June 2010

developing Pneumocystis pneumonia. This would supercede the CD4 count in deciding to maintain or discontinue primary prophylaxis with Bactrim. Of the medications, Truvada (fixed-dose co-formulation of tenofovir and emtricitabine) and Isentress (raltegravir) have the potential to affect both your sugar levels and your kidneys. Your kidneys and sugar levels should be routinely monitored (tests such as hemoglobin A1c, BUN/creatinine, phosphate, urine for protein and phosphate) to determine if there are any adverse effects from your regimen. If your viral load is undetectable and you have minimal side effects, then the antiretroviral regimen is working well for you. If there are minor disturbances in your sugar levels, then your insulin requirements may change in order to continue utilizing the effective antiretroviral regimen. HIV (and the medications used to treat it) can cause many metabolic disturbances, especially in your fats and cholesterol, which may increase your risk of cardiovascular, kidney, and liver disease. Certain antiretroviral medications can also cause pancreatitis, causing damage to the pancreas and potentially resulting in a diabetes-like state. Diabetes is a known risk factor for cardiovascular, kidney, and retinal disease. Routine examinations of your eyes by an ophthalmology specialist are recommended. Routine screening for heart and kidney disease will also help in the prevention of adverse events. Neuropathy can be a side effect of certain antiretroviral medications, and it can also be a consequence of advanced diabetes. This should

also be routinely screened by your medical provider, but you should also do it yourself, routinely checking your feet for changes in sensation, coloring of the skin, and temperature. With regards to building up resistance to Bactrim, your body does not build the resistance to the medication, the infectious organism does. The Pneumocystis organism rarely develops resistance to Bactrim; however, there have been reports of it. It typically is not a major concern given that the benefits of prophylaxis with Bactrim greatly outweigh the risk of developing resistance. I hope this provides some useful information. Again, I encourage you to continue to play an active role in your own health care and keep an open line of communication with your provider for any questions you may have about your health. In good health, —Jason R. Faulhaber, MD, AAHIVS Internal Medicine/ID Provider, Fenway Community Health, Clinical Instructor Harvard Medical School, Boston, MA

Submit your questions to AAHIVM@tpan.com Due to space limitations, not all submitted questions can be answered in this column. For more information about AAHIVM, call 202-659-0699 or visit www.aahivm.org.

Search for an HIV Specialist™ Finding an HIV Specialist™ is easy with AAHIVM’s Find-A-Provider directory at www.aahivm.org. Click on the “Find-A-Provider” window on the home page, enter your location, and click on the search button for a list of HIV Specialists™ near you.

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HIV WELLNESS SERIES Gary Blick, MD, AAHIVS

HIV, your HAART, and you

1987 until 1995, the “dark ages” of HIV treatment, only five antiretroviral medications (ARVs) were FDA approved, all nucleoside reverse transcriptase inhibitors (NRTIs, or “nukes”), and monotherapy and dual therapy were the “standards of care.” 2010 is the 15th anniversary of the FDA approval of the first protease inhibitor (PI), saquinavir, as well as the advent of Highly Active Antiretroviral Therapy, or HAART, three-drug “cocktails” that are now capable of suppressing HIV replication in even the most treatment-experienced individuals. rom

Today we have both good news and bad news. The good news is that people with HIV/AIDS are living longer.1, 2 The Antiretroviral Therapy Cohort Collaboration (ART-CC), which includes 19 cohort studies from Europe and North America, found that if you are 20 years old and acquire HIV today, your life expectancy is now over 69 years. 3 (A cohort study is an observational study in which subjects with a certain condition are monitored over time and compared with another group who don’t have the condition.) Ironically, the bad news is that people with HIV/AIDS are living longer! Accompanying this significantly increased longevity is an increase in morbidity and mortality due to non-HIV/AIDS complications such as cardiovascular disease (CVD).4, 5 The cause for concern is so great that a conference was held in 2007 with specialists from various fields of medicine, NIH members, and patient advocates to discuss HIV, CVD, and 1) metabolic abnormalities and lipodystrophy, 2) epidemiological evidence and contribution of HAART, 3) effects of HAART and HIV on the heart and blood vessels, 4) screening recommendations, 5) risk prediction models, and 6) prevention strategies. 5-11 The reasons for these CV complications PositivelyAware.com

are not yet well understood, but we do know that living longer with HIV is accompanied by numerous metabolic and body shape, or anthropometric, abnormalities. These abnormalities may be due to HIV infection, certain ARVs or ARV classes, and/or immunological factors (such as nadir, or lowest, and current CD4 count) and include insulin resistance (IR) and abnormal lipids, as well as lipodystrophy (subcutaneous fat loss, or lipoatrophy, and/or increased visceral fat, or lipoaccumulation), all of which can increase CV risk. Of course, as in the general population, traditional CV risk factors, such as environmental (smoking, diet, lifestyle, obesity, and exercise) and genetic factors (gender, race, age, ethnicity, family history, diabetes [DM], and hypertension [HTN]),12, 13 contribute significantly to these metabolic abnormalities and remain important CV risk factors in HIV-positive individuals.14-16 In understanding CVD and HIV, it is important to know the term metabolic syndrome (MS).17 The table, “Characteristics of Metablic Syndrome,” on page 39 lists the components of MS, and when any three of the five risk factors listed are present, you are at a significantly increased risk of developing CVD.

CVD and HIV The big question is, “Does HIV increase the risk for developing CVD?” The epidemiological evidence suggests HIV-positive individuals are at an increased risk of CVD, despite the steep drop in overall morbidity and mortality with the introduction of HAART.18 Various retrospective and prospective HIV cohort studies, randomized clinical ART studies, and administrative and clinical databases suggest anywhere from a 1.5-to 7.0-fold increase in CVD in HIV-positive versus HIV-negative individuals, although the absolute rates remain low, perhaps reflecting the age and demographics of the studied groups and the short duration of CV risk factor exposure.18-24 Traditional CV risk factors associated with MS play a significant role in the development of coronary heart disease (CHD) in HIV-positive individuals, including elevated total cholesterol (TC), low density lipoprotein (or “bad”) cholesterol (LDL-C), and triglycerides, and lowered HDL-C (or “good”) cholesterol, all of which worsen with lower CD4 cell counts and higher viral loads (PCR),18, 19, 25 as well as increased smoking rates in HIV-positive individuals, male sex, age, DM, and HTN.21, 22, 25-27 Nontraditional CV risk factors, such as chronic HIV inflammation, may also play a significant role in the development of CVD, as is evidenced by the unexpected increases in CV events due to HIV-viremia in the intermittent HAART dosing arm of the SMART study.28 However, impaired endothelial function (endothelial cells, the cells that line the interior surface of blood vessels, have many functions that, when impaired, contribute to the development of CV risk), and increased thickening of artery walls (increased carotid artery intimamedia thickness [IMT]) were found in treated HIV patients with undetectable PCR, as May/June 2010

The greater question that needs to be answered is

whether the effects of ART on development of CVD are only modest compared to the inflammatory effect of HIV. well as in HIV â&#x20AC;&#x153;elite controllersâ&#x20AC;? (those rare HIV-positive individuals with long-term normal CD4 cell counts and undetectable PCR without HAART).24, 29-33 Although the effects of HIV on the heart and vasculature have not been fully determined, there is evidence that HIV-associated metabolic changes, including lipoaccumulation and lipoatrophy, as well as IR, one of the factors thought to be involved in the development of lipodystrophy, also affect endothelial and myocardial (heart wall) function.34 Our prospective study utilizing nuclear exercise stress testing screening in asymptomatic individuals without prior CVD found HIVpositive individuals at six times greater odds of having subclinical coronary artery disease (CAD) that required immediate intervention, when compared to HIVnegative individuals, and abdominal lipoaccumulation was the most significant risk factor predicting CAD in the HIV group.35 Recently, T-cell activation and immunosenescence (accelerated immunologic aging) were shown to be possible mechanisms associated with inflammation and the development of subclinical carotid artery disease.36 Lastly, recent observational studies have found an association with chronic kidney disease (CKD, defined as GFR less than 60) and mild renal insufficiency (GFR 60-89),37 as well as intravenous drug and cocaine use,38 and increased rates of CVD in HIV-positive individuals.

CVD and HAART Although no one denies the benefit of taking HAART versus not taking HAART on markers of CVD,39-43 there are many complex mechanisms whereby ART can affect the heart and vasculature, including endothelial dysfunction, increased endothelial permeability, increased oxidative stress, increased mononuclear cell adhesion, IR, accelerated lipid accumulation in vessel walls, persistent inflammation and immune activation, impaired response to vascular injury, and ART-associated lipodystrophy leading to metabolic disorders (e.g., hyperlipidemia 38

May/June 2010

and IR), increased systemic inflammation, and reduced circulating adiponectin (a protein hormone that regulates a number of metabolic processes).18-21, 24, 44, 49-57 The largest observational cohort study evaluating the impact of ART on cardiovascular risk, the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D), initially found that ART was associated with an overall 26% increased risk of CVD/myocardial infarction (MI),20 and, subsequently, the annual relative risk of MI increased by 16% per year for those using HAART and for those taking PIs but not nonnucleoside reverse transcriptase inhibitors (NNRTIs), possibly somewhat due to the lipid abnormalities associated with PI use.21 Controversy arose when D:A:D and SMART generated a signal that recent use of abacavir (ABC, brand name Ziagen, found in Epzicom and Trizivir) was associated with a significantly increased risk of MI in patients with moderate-to-high CV risk.43, 44, 48 The controversy surrounded the fact that while these observational trials generated banner headlines, randomized clinical trials58-61 and many other observational cohorts27, 37, 38 failed to corroborate this finding. Additionally, despite intensive research investigating inflammation, coagulation, IR, and endothelial dysfunction biomarkers, no studies have uncovered any plausible biological mechanism to explain how ABC could cause rapid development of CAD and subsequent MI.62-65 The possibility that ABC affects platelet hyper-reactivity still needs to be explored in HIV-positive individuals, but if this mechanism is confirmed, antiplatelet therapy, such as a daily 81 mg baby aspirin (ASA), may be the simple answer (see Prevention Strategies below). Although D:A:D failed to find an increased risk of CVD with tenofovir (TDF) use, a non-controlled study showed cumulative exposure (an average 1.5 years) to TDF/FTC (tenofovir/emtricitabine) significantly raised the risk of CVD in adolescents and young adults (average age 18.9 years), 52% of whom had MRI evidence of CAD.66

And if mild-to-moderate renal insufficiency is confirmed as a CV risk factor,37, 66 as it is in the general population, the need to monitor for renal insufficiency while taking TDF becomes critical. The greater question that needs to be answered is whether the effects of ART on development of CVD are only modest compared to the inflammatory effect of HIV.

CVD Screening Recommendations and Risk Prevention Models Screening for CVD in HIV-positive individuals has been performed with the Framingham Risk Equation (FRE), direct assessment of CAD and myocardial ischemia via exercise stress testing, and indirect assessment using inflammatory biomarkers or surrogate markers for CHD. FRE is the most commonly used tool, incorporating age, sex, BP, LDL-C, HDL-C, DM, and smoking to calculate your 10-year CHD risk. Low, intermediate, and high risk are defined as 10-year risk of CHD of 10%, 10% to 20%, and greater than 20%, respectively. However, despite claims made by D:A:D investigators, 20, 21, 43 FRE has not been validated for use in HIV.5, 8 Our study35 showed that over 56% of HIV-positive individuals with obstructive CAD requiring intervention were low-risk and only 6% were high-risk by FRE immediately prior to their stress test. Newer inflammatory biomarkers, such as high-sensitivity C-reactive protein (hs-CRP), the only biomarker recommended for use in clinical practice by the CDC and the AHA, may prove useful in determining if you may be at increased risk for CHD.9, 29, 68-70 An hs-CRP of 3.0-10.0 mg/L is considered high risk for developing CVD. Other biomarkers, such as D-dimer, IL-6, adiponectin, MCP-1, OPG, ICAM-1, VCAM-1, selectins E and P, and others, are being investigated but are not yet validated or commercially available. Lastly, surrogate markers, including carotid IMT,30, 33, 70 computed tomography of coronary arteries (CT CA) to determine PositivelyAware.com

Now that you’re taking the risk of coronary heart disease seriously, what can you do to prevent or slow

the development of cardiovascular disease?

Characteristics of Metabolic Syndrome (MS) Risk factor Defining level

Abdominal obesity, given as waist circumference: in Men: greater than 40 inches in Women: greater than 35 inches Fasting HDL cholesterol (HDL-C):

in Men: less than 40 mg/dL in Women: less than 50 mg/dL

Fasting triglycerides (TG):

greater than or equal to 150 mg/dL

Blood pressure (BP):

≥ 130 / ≥ 85 mm Hg

Fasting glucose (FBS):

greater than or equal to 110 mg/dL*

* The American Diabetes Association recently established a cutpoint of ≥ 100 mg/ dL, above which persons have either pre-diabetes (impaired FBS) or diabetes. This new cutpoint should be applicable for identifying the lower boundary to define an elevated glucose as one criterion for MS.

coronary calcium scores,71, 72 flow-mediated dilation (FMD) to assess endothelial function,73, 74 and measures of arterial stiffness75, 76 are being investigated but are not yet validated as independent predictors of CHD in HIV.

HIV, CVD, Prevention Strategies, and You So, now that you are taking the risk of CHD seriously, what can you do to prevent or slow the development of CVD? Here is a list of risk-reducing interventions that you can implement. Quit smoking: since smoking is highly prevalent (more than 50%) in HIV-positive individuals and is strongly associated with CVD, this should be number one on your list. D:A:D finally showed the risk reduction in HIV with smoking cessation.77 Dyslipidemia: lipids can be improved through many means including: Dietary interventions (reducing fat intake and/or decreasing simple sugars and starches [“carbs”], as in eliminating PositivelyAware.com

“whites” [white breads, rice, pasta, and potatoes] and replacing them with complex “carbs” [whole grain breads, brown rice, whole wheat pasta, and sweet potatoes]). CV exercise: remember, when your doctor says “stop smoking and get exercise,” he/she is asking you to improve your HDL-C, which reduces CV risk when you obtain the goals listed in the table above. Exercise also benefits DM, HTN, and many other conditions. ARV: Ask your doctor if you can switch from one ARV that may be elevating your lipids to one that may not. (PIs, especially when boosted with ritonavir [RTV, brand name Norvir], may cause hyperlipidemia. NNRTIs, and some newer classes of drugs may have less adverse impact on lipids than PIs.) Lipid-lowering agents: medications like statins, fibrates, nicotinic acid, and omega-3 fatty acids (“fish oils”) have been shown to be of benefit. The question is whether they are potent enough

to achieve goals listed in the adjacent table. It is important to be aware of serious drug-drug interactions with the use of generic statins, such as simvastatin and lovastatin, which can never be combined with ritonavir, and pravastatin, which cannot be used with darunavir (Prezista) and is minimally effective. Co-morbidities: aggressively monitor and treat your obesity, diabetes/IR, and/or HTN with regular lab analyses and doctor visits, diet, exercise, and/or medications. HIV: begin HAART when your CD4 cell count declines to 500 or earlier, if indicated, and never interrupt HAART unless absolutely necessary. Laboratory: check your hs-CRP annually and your lipids, glucose, creatinine, and calculated creatinine clearance at least twice yearly, or more often if indicated. ASA: as a platelet inhibitor, ASA can reduce risk for MI and stroke by as much as 50%, so discuss the use of 81 mg with your healthcare provider, especially since ASA has side effects and drug-drug interactions. Substances: use of alcohol, IV drugs, cocaine, and others have been shown to increase CVD, so substance abuse also requires aggressive intervention to decrease CV risk. e Footnoted references are available online. This article is supported by funding from Merck. Gary Blick, MD, AAHIVS, is Medical and Research Director of CIRCLE Medical, LLC, in Norwalk, Connecticut, a Comprehensive Immunology, and Research Center for Life Extension, specializing in clinical research and specialty medical care for individuals with HIV/AIDS and chronic hepatitis, as well as for the GLBT community. He also sits on the board of directors for Mid-Fairfield AIDS Project (MFAP) and the drug formulary committee for the Connecticut AIDS Drug Assistance Plan (CADAP).

May/June 2010

The Buzz

Daniel S. Berger, MD

Something to CROI about Three integrase inhibitors offer great promise

went to this year’s

CROI (Conference on Retroviruses and Opportunistic Infections), like many I’ve attended over my career, to hear about revelations being presented, if any, and to network among fellow researchers and scientists. I’ll admit this 14th session did not hold the eye-opening surprises that several previous meetings had. The newer compounds have already shown efficacy, but integrase inhibitors are unique, fresh, and still inspire.

This article would not be complete without a personal word about the great expenses involved in attending conferences. There’s the $600 registration fee, plus hotel stay, air travel, food and miscellaneous costs, not to mention lost clinic time; this is a difficult economic environment. A fellow colleague and I were discussing whether it would be more cost effective to listen to audio podcasts at home and do follow-up conference call discussions with fellow thought-leaders. Not a bad idea, but I digress. Of the now several integrase inhibitors (INIs) on the table, raltegravir (Isentress) was the first agent in the class to gain approval. Its first indication was in treatment-experienced patients; those who were in great need of newer options were given a true lifeline with this agent, especially as it’s combined with darunavir (Prezista), etravirine (Intelence) and/or enfurvitide (Fuzeon). More recently, Isentress won a broader indication to include naïve patients (individuals starting their first regimen), becoming the first integrase inhibitor to be approved for treatment of all HIV-positive individuals in combination with other effective antiretroviral agents. This article will approach different issues 40

May/June 2010

within each of the three integrase inhibitors that are in varying stages of development. Much data has previously been presented on raltegravir, but large studies with the second integrase inhibitor, elvitegravir, particularly a trial comparing head-to-head effects of two integrase inhibitors (Isentress and elvitegravir), are not yet available. And for the newest compound in the class, GSK 572, broader studies are only now being recruited; therefore, far less is known about this agent than the previous two.

Intensification with raltegravir Interesting studies concerned patients who do not achieve full immune reconstitution following good HIV treatment and probed the addition of raltegravir to already optimized regimens. Approximately 25% of individuals who initiate HAART (highly active antiretroviral therapy) with CD4 counts below 200 cells/ mm3 never achieve counts above 500. In other words, they exhibit sub-optimal immune recovery. Personally, it’s not uncommon to see patients remain within the less than 200 CD4 cell scale despite excellent treatment, who nevertheless are able to maintain years of undetectable viral

loads. Patients who remain in this lower CD4 count, however, may be at greater risk of developing long-term complications such as malignancy (cancer). Attempting immune reconstitution through the use of an integrase inhibitor is based on unique properties specific to the class, their unique mechanism of action (inhibiting viral integration within the human genome), and observations of more potency with more rapid effect of suppressing HIV RNA (viral load). The question posed was, could CD4 counts be augmented further if select patients had the integrase inhibitior raltegravir added to their treatment? One study examined 30 patients, all undetectable (less than 50 copies/ml) for at least one year, randomized to receive the addition of raltegravir to their regimen versus placebo. At 24 weeks, there was no change in viral activity measured to supersensitive levels, or to below 1 copy of HIV RNA. (Previous to study, baseline values for patients were already at 5 or less copies/ml.) However, no changes were seen with the raltegravir addition to get levels to below 1 copy/ml, nor were there changes in cell-associated RNA (viral particles attached to, or within, the cell) measurements of proviral DNA (virus in a latent stage of its life cycle), nor improvement in CD4 count. In a different protocol, seven individuals who had undetectable viral loads and less than 40 copies/ml for three to 12 years, were studied as follows: four patients had raltegravir added to their regimen, two patients had raltegravir plus efavirenz (Sustiva) added, and one patient had raltegravir plus boosted darunavir (Prezista) added. Viral and immune system markers PositivelyAware.com

Simply adding more antiviral agents to already optimally suppressed patients is not the miraculous key to further controlling HIV.

This work confirms that new avenues in research are needed.

were also looked at in intestinal-lining cells by biopsy after upper and lower endoscopies. In summary, intensification did not result in any decrease in plasma (blood) viral load, viral load in mononuclear cells, nor gut-lining cells. However, there were signs of decreased immune activation (activation is often felt to be harmful), the most being observed in the ileum (third part of the small intestine), as well as trends toward slight increases (1.9-2.9%) in CD4 cell count. Thus intensification had an effect on the ileum of the small intestine, which the authors suggested is a site of ongoing viral replication despite undetectable viral loads in the plasma. These areas within the body (gut-associated lymphoid tissue, or GALT) have been suggested as sanctuary sites for viral activity, and this is one particular reason (among several) that might explain why effective antiviral treatment does not eradicate HIV. In summary, the results of these studies demonstrate that simply adding more antiviral agents to already optimally suppressed patients is not the miraculous key to further controlling HIV. This work confirms that new avenues in research are needed to exert broader control of viral activity and agents are needed to manage hazardous hyper-activation; I believe it is possible to do so with current technology. It’s worth noting that we have been awaiting the data of a large study, also being conducted at Northstar in Chicago, that is comparing the administration of Isentress in its currently approved dosing of one 400 mg tablet, twice daily versus taking both 400 mg tablets once daily (in combination with Truvada). Although preliminary data may suggest that this is a viable option, we do not feel the need to encourage patients to switch their habits PositivelyAware.com

and we warn of the risks for developing possible integrase inhibitor resistance. It is prudent to wait until final results of this trial become available.

Elvitegravir and THE Quad In a presentation that had its entertaining moments, Cal Cohen discussed results from two Phase 2 studies involving Gilead Sciences’ new booster agent cobicistat, a replacement candidate for Norvir (ritonavir). Cobicistat has no antiviral activity, but is used to boost the levels of an integrase inhibitor, elvitegravir, in the blood. The first study randomized 71 patients (2 to 1) to the Quad (a new one-pill regimen, taken once daily) or Atripla. The Quad consists of Truvada plus elvitegravir (integrase inhibitor) plus the new pharmacoenhancer/ booster cobicistat, previously known as GS 9350. Atripla was the first one-pill cocktail and combines Sustiva with Truvada, taken once a day. The second study highlighted the effects of cobicistat versus Norvir, as a booster for atazanavir (Reyataz). Virologic results were similar in Quadtreated patients versus the Atripla arm with 90% versus 83% achieving undetectable viral loads to below 50 copies, demonstrating non-inferiority of the Quad to Atripla. Among side effects, the differences in the two arms were due to central nervous system side effects or sleep disorders, not unexpectedly higher in Sustiva- (Atripla) treated patients (48% versus 10%). Sleep disorders and psychedelic dreams are well known with efavirenz; some have likened their Sustiva experience to dropping acid. There were no lipid level (blood fat) advantages for cobicistat-treated patients over ritonavir, however. Concerns regarding cobicistat’s safety profile, specifically regarding renal issues (kidney-related), were raised due

to observed elevations in creatinine. Creatinine is a waste product the kidneys should be responsible for clearing; elevated levels suggest kidney malfunction. This is paramount, as patients are already taking Viread, which is in itself a concern for some patients at high risk for renal disease. The approximate 10% increase in creatinine associated with cobicistat use was seen within the first one to two weeks of the trial and did not continue into the duration of study (24 weeks). In a separate study conducted by the sponsor, calculated glomerular filtration rates (GFR) based on creatinine changes increased; however, actual GFR did not increase, after IOHexol administration. Cohen indicated that cobicistat had no more impact on renal (kidney) function than, perhaps, Tagamet, and he hypothesized the change was due to an increase in tubular secretion of creatinine. To summarize, at the moment, the Quad looks good going into Phase 3 studies and cobicistat (GS 9350) hopefully moves forward to eventually replace ritonavir (Norvir). The co-formulation of cobicistat with elvitegravir and the Quad lessens pill burdens for patients, but at present does not appear to have a better lipid side effect profile compared to Norvir. The replacement is welcomed by many clinicians and the community based on a general consensus of malcontent with Abbott Labs and their history on the pricing of Norvir.

GSK’s integrase inhibitor GSK 572 ViiV, being called a “new” company, is a joint venture between the HIV franchises of GlaxoSmithKline (GSK) and Pfizer; ViiV is owned primarily by GSK. A new integrase inhibitor, acquired by GSK, is the latest agent in the class and is moving into Phase 3 studies. The compound is often referred May/June 2010

to as “572” (short for S/GSK1349572) and was shown to be a very potent, once-daily administered integrase inhibitor that does not require pharmacokinetic enhancement or boosting. Earlier test tube studies indicated limited cross-resistance to other INIs with 572. At CROI, further information was presented on the antiviral effects of 572, in the presence of integrase inhibitor mutations or substitution at various codons that normally have been able to confer resistance in clinical trials to either ralegravir (Isentress) or elvitegravir (the Gilead compound, also a component of the Quad pill). For the purposes of this article, and to simplify, data presented at CROI continues to be hopeful in suggesting that 572 has a resistance profile distinct from the other two integrase inhibitors and that it may indicate a higher genetic barrier to resistance. 572 will be studied for use in both treatment-naïve patients (first-line therapy), as well as in those having already developed resistance to the other integrase inhibitors. Perhaps the easiest route for an antiviral

to gain approval is in the treatment-naïve population. There are far fewer available individuals who are not able to achieve a fully suppressive regimen in this era, thus fewer patients to enroll in clinical trials who’ve failed or may have treatment resistance to INIs. However, 572’s current use is truly most important for patients who indeed have integrase inhibitor experience, since a true second-generation agent is needed. Moreover, there will already be two integrase inhibitors available for naïve patients. Further, as this candidate agent continues to look good through development, it will also help clinicians have more confidence in using integrase inhibitors up front; they’ll be cognizant of a back-up available within this class. It is early and we’ll need clinical data and experience in patients to make any final judgment on 572.

Conclusions Recent data presented at CROI this year gave us an opportunity to see and discuss progress with three leading developers of integrase inhibitors. Only one is currently approved, and we’ll have to wait for further

studies on continued development of the remaining two integrase inhibitors. The first two have similar resistance profiles, and patients who develop resistance will be cross-resistant to the other. ViiV’s drug may hold promise for patients who may need a new and novel agent. e Dr. Daniel S. Berger is Clinical Associate Professor of Medicine at the University of Illinois at Chicago and founder and medical director of Northstar Healthcare, the largest private HIV treatment and research center in the greater Chicago area. Dr. Berger has published extensively in The Lancet and The New England Journal of Medicine, and serves on the Medical Issues Committee for the Illinois AIDS Drug Assistance Program and the AIDS Foundation of Chicago’s Board of Directors. Dr. Berger has been honored by Test Positive Aware Network with the Charles E. Clifton Leadership Award. He can be reached at DSBergerMD@aol.com and www.nstarmedical.com.

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What’s GOIN’ ON? Keith R. Green

Finding your voice in the aftermath of abuse

hildhood sexual trauma can play out in many different

ways. For 19-year-old Jordan, it impeded his ability to confront a cheating boyfriend who was rumored to be HIV-positive. I met Jordan shortly after he’d contracted both syphilis and HIV while in that relationship. In addition to my role as project director of a multisite pre-exposure prophylaxis (PrEP) study being run through the county hospital here in Chicago, I am also working towards my license as a Clinical Social Worker (LCSW). To do this, I see patients for therapy on Thursday afternoons in the hospital’s Adolescent/Young Adult Clinic (AYAC). Because I’m in the clinic just one day out of the week, I’ve specifically requested to only be referred young people who have symptoms of psychopathology and those who request a male or African American therapist. As you can imagine, there is never a dull moment for me in the clinic. AYAC is set up in such a way that every young person who walks through the door, regardless of what they come in for, receives both a medical and psychological evaluation. Since we’re a part of the county health system, we typically serve the members of the county with the most unmet need. Jordan was referred to the clinic by Dr. Margo Bell, who is the co-principle investigator of the research study that I work on, as well as one of the two attending physicians in AYAC on Thursdays. She is deeply invested in the health and wellbeing of young men who have sex with men, and her work within the community has facilitated a linkage to care for many who may not otherwise have had one.

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I had a million things going on the day that she introduced me to Jordan, but dropped everything I was doing to meet with him at her request. He’d been diagnosed with both HIV and second-stage syphilis, a co-infection that we often see at the clinic. Jordan was a young man with beautiful skin the color of dark chocolate and a bright, pretty smile that instantly warmed my heart. I could see clearly that, behind his pearly whites, he was hiding a great deal of hurt and pain. We bonded instantly, and he agreed to allow me to conduct a psychological evaluation (although he made it clear later on in the interview that if I had been of any other race/ethnic background his response would not have been so favorable). His story was one of survival and resiliency. His mother had died when he was a small child. He was raised by his father and spent a great deal of time in the home of his paternal aunt. It was in that space, beginning when he was in kindergarten, while he was changing clothes after school, that Jordan was sexually molested by his father’s brother. I could see the fear and anger in his eyes as he seemed to relive the experience right there in front of me. The abuse had taken place over the course of about six years, and Jordan never spoke a word about it to anyone during that time. His uncle had

threatened to kill his father should he do so. Ironically, it was an intense argument between his father and that same uncle that resulted in his father’s death. Jordan, unfortunately, had witnessed the entire tragic event. Although he would later disclose to his sister that he’d been molested by their uncle throughout a great portion of his childhood, Jordan never told anyone else or attempted to confront his perpetrator. In fact, even now, in a time when he admits to needing the support of as much of his family as he could muster, he avoids his aunt’s house at all costs because that same uncle still lives there. In addition to helping him to develop healthy ways of coping with his recent HIV diagnosis, our therapeutic relationship is focused on allowing Jordan a space to unravel and address the array of emotions that he has with respect to being sexually abused as a child, and to understand the connection between those two unfortunate circumstances. By his own account, our relationship is one of the first that he’s been in where he feels that he has a voice, and that his voice is actually heard. It is my hope that he will acquire the skills necessary to demand that kind of exchange in future relationships, and to be able to establish healthy support systems with other members of his family he’s cut off in order to avoid contact with his uncle. I’m careful not to lead him to believe that this will be an easy task, but I’ve also assured him that he can have the rest of a healthy lifetime (both physically and mentally) to do so.

May/June 2010

Wholistic picture Sue Saltmarsh

orking on this issue made me remember my days doing

energy work at Project Vida in the ’90s. One of the things my clients back then seemed to have to deal with was the assumption of their doctors that because they were HIV-positive, they were depressed. On the surface, that didn’t seem too unreasonable—who wouldn’t be a little down in the dumps upon finding out that they were HIV-positive? But what was disturbing to me at the time was how many of them had automatically received prescriptions for antidepressants at the same time they got their HIV meds prescribed. For many of them, this seemed to work like a self-fulfilling prophecy—“My doctor thinks I’m depressed, so doesn’t that mean I must be?” And yet, energetically anyway, most of them had the internal resources to manage their diagnosis much more easily than they managed the way the antidepressants made them feel. Now, some 15 years later, doctors don’t seem to assume that being HIV-positive automatically leads to depression. And I have some personal reference points—my sisters Kathy and Kerry are my living, breathing, walking, talking Cymbaltas and, though they would probably never admit it, dealing with my sadness, grief, physical pain, and hopelessness in the last year and a half has taxed Kerry’s patient compassion and Kathy’s irrepressible perkiness. But we soldier on and the dark heaviness lifts occasionally and we are never at a loss for things that make us laugh so hard our bodies ache the next day. That’s a side effect I can live with. Should I be taking an antidepressant? Would a pill provide me with the money to pay my medical debts? Magically replace

May/June 2010

my painful hip without surgery? Find me the perfect apartment a block from work? Most of all, would a pill be able to resurrect the “me” I used to be before August of 2008? No. And when I ask myself if it might be a good idea to be “numbed out” for at least a little while, I am reminded of one long-ago client who said, “I don’t like crying, but it’s better than feeling nothing at all.” My friend Judy recently sent me a piece written by Dr. Darcie Sims. It was both for people going through grief and those around them, and though there was much about it I could argue with (Darcie seemed way too anti-winter and food-phobic for me), there were several truisms that resonated like a gothic cathedral bell. One was this: “When we have lost the framework of our personal identification, we must search for new identities. It is an important and solitary job. No one can help us create the new identity we must find in order to continue our journey.” For me, the question is, “Who am I now, with the diabetes, the liver disease, the bad hip?” For you, it may be, “Who am I now,

with the HIV, the side effects, the limits that are now on my life?” It’s a hard, painful, sad job coming up with the answers, but when they start to trickle in piece by piece, it becomes a hard, hopeful, rewarding accomplishment that deserves attention and celebration. And if that sounds like Disneyesque bullshit, believe me, I know how relentlessly irritating “inspirational” platitudes and “Good Attitude” directives can be and that is certainly not my intent. Fact is that, at some point in time, for everyone, life sucks. And it sucks that life sucks. But only you can decide how, or even if, you’re going to deal with it sucking. So cry, yell, pop a Zoloft or Cymbalta, work out until you pass out, eat nothing but chocolate truffles, meditate, do a sweat lodge, drive a convertible to the ocean, whatever. Just make sure that whatever you do is right for you and not the result of someone else’s assumptions. In the end, the only place of true belonging is within. Our external ties are transient, but the internal ones last as long as we do. It is a miraculously wonderful thing to belong to a family like mine, to work with the people I work with, and to have the true friends I have, but for awhile in 2008, I did not belong to myself and so now, I am challenged to find that belonging again. It’s up to me to accept or reject my doctors’ advice, my parents’ problem solving, my sisters’ cheer-up measures. It’s up to me to know who it is I’m looking at in the mirror now and to get to know her better. It’s my job. And it is your job. And though it’s hard, it doesn’t suck. I’m going to try to keep at it. Breathe deep, live long.

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Photo: CHeryl Mann

Assumption of sadness

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