MARCH+APRIL 2013 HIV DRUG GUIDE by POSITIVELY AWARE

March+APRIL 2013

the 17th annual

HIV Drug

Guide Harness the power of hiv treatment When to start help with paying For your meds Treating Hepatitis

What is STRIBILD? STRIBILD is a prescription medicine used to treat HIV-1 in adults who have never taken HIV-1 medicines before. It combines 4 medicines into 1 pill to be taken once a day with food. STRIBILD is a complete single-tablet regimen and should not be used with other HIV-1 medicines. STRIBILD does not cure HIV-1 infection or AIDS. To control HIV-1 infection and decrease HIV-related illnesses you must keep taking STRIBILD. Ask your healthcare provider if you have questions about how to reduce the risk of passing HIV-1 to others. Always practice safer sex and use condoms to lower the chance of sexual contact with body fluids. Never reuse or share needles or other items that have body fluids on them.

IMPORTANT SAFETY INFORMATION What is the most important information I should know about STRIBILD? STRIBILD can cause serious side effects: • Build-up of an acid in your blood (lactic acidosis), which is a serious medical emergency. Symptoms of lactic acidosis include feeling very weak or tired, unusual (not normal) muscle pain, trouble breathing, stomach pain with nausea or vomiting, feeling cold especially in your arms and legs, feeling dizzy or lightheaded, and/or a fast or irregular heartbeat. • Serious liver problems. The liver may become large (hepatomegaly) and fatty (steatosis). Symptoms of liver problems include your skin or the white part of your eyes turns yellow (jaundice), dark “tea-colored” urine, light-colored bowel movements (stools), loss of appetite for several days or longer, nausea, and/or stomach pain. • You may be more likely to get lactic acidosis or serious liver problems if you are female, very overweight (obese), or have been taking STRIBILD for a long time. In some cases, these serious conditions have led to death. Call your healthcare provider right away if you have any symptoms of these conditions.

• Worsening of hepatitis B (HBV) infection. If you also have HBV and stop taking STRIBILD, your hepatitis may suddenly get worse. Do not stop taking STRIBILD without first talking to your healthcare provider, as they will need to monitor your health. STRIBILD is not approved for the treatment of HBV. Who should not take STRIBILD? Do not take STRIBILD if you: • Take a medicine that contains: alfuzosin, dihydroergotamine, ergotamine, methylergonovine, cisapride, lovastatin, simvastatin, pimozide, sildenafil when used for lung problems (Revatio®), triazolam, oral midazolam, rifampin or the herb St. John’s wort. • For a list of brand names for these medicines, please see the Brief Summary on the following pages. • Take any other medicines to treat HIV-1 infection, or the medicine adefovir (Hepsera®). What are the other possible side effects of STRIBILD? Serious side effects of STRIBILD may also include: • New or worse kidney problems, including kidney failure. Your healthcare provider should do regular blood and urine tests to check your kidneys before and during treatment with STRIBILD. If you develop kidney problems, your healthcare provider may tell you to stop taking STRIBILD. • Bone problems, including bone pain or bones getting soft or thin, which may lead to fractures. Your healthcare provider may do tests to check your bones. • Changes in body fat can happen in people taking HIV-1 medicines. • Changes in your immune system. Your immune system may get stronger and begin to fight infections. Tell your healthcare provider if you have any new symptoms after you start taking STRIBILD. The most common side effects of STRIBILD include nausea and diarrhea. Tell your healthcare provider if you have any side effects that bother you or don’t go away.

What should I tell my healthcare provider before taking STRIBILD? • All your health problems. Be sure to tell your healthcare provider if you have or had any kidney, bone, or liver problems, including hepatitis virus infection. • All the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. STRIBILD may affect the way other medicines work, and other medicines may affect how STRIBILD works. Keep a list of all your medicines and show it to your healthcare provider and pharmacist. Do not start any new medicines while taking STRIBILD without first talking with your healthcare provider. • If you take hormone-based birth control (pills, patches, rings, shots, etc). • If you take antacids. Take antacids at least 2 hours before or after you take STRIBILD. • If you are pregnant or plan to become pregnant. It is not known if STRIBILD can harm your unborn baby. Tell your healthcare provider if you become pregnant while taking STRIBILD. • If you are breastfeeding (nursing) or plan to breastfeed. Do not breastfeed. HIV-1 can be passed to the baby in breast milk. Also, some medicines in STRIBILD can pass into breast milk, and it is not known if this can harm the baby. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088. Please see Brief Summary of full Prescribing Information with important warnings on the following pages.

STRIBILD is a prescription medicine used as a complete single-tablet regimen to treat HIV-1 in adults who have never taken HIV-1 medicines before. STRIBILD does not cure HIV-1 or AIDS.

I started my personal revolution Talk to your healthcare provider about starting treatment. STRIBILD is a complete HIV-1 treatment in 1 pill, once a day.

Ask if itâ&#x20AC;&#x2122;s right for you.

Patient Information STRIBILDTM (STRY-bild) (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg) tablets Brief summary of full Prescribing Information. For more information, please see the full Prescribing Information, including Patient Information. What is STRIBILD? • STRIBILD is a prescription medicine used to treat HIV-1 in adults who have never taken HIV-1 medicines before. STRIBILD is a complete regimen and should not be used with other HIV-1 medicines. • STRIBILD does not cure HIV-1 or AIDS. You must stay on continuous HIV-1 therapy to control HIV-1 infection and decrease HIV-related illnesses. • Ask your healthcare provider about how to prevent passing HIV-1 to others. Do not share or reuse needles, injection equipment, or personal items that can have blood or body fluids on them. Do not have 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 is the most important information I should know about STRIBILD? STRIBILD can cause serious side effects, including: 1. Build-up of lactic acid in your blood (lactic acidosis). Lactic acidosis can happen in some people who take STRIBILD or similar (nucleoside analogs) medicines. Lactic acidosis is a serious medical emergency that can lead to death. Lactic acidosis can be hard to identify early, because the symptoms could seem like symptoms of other health problems. Call your healthcare provider right away if you get any of the following symptoms which could be signs of lactic acidosis: • feel very weak or tired • have unusual (not normal) muscle pain • have trouble breathing • have stomach pain with nausea or vomiting • feel cold, especially in your arms and legs • feel dizzy or lightheaded • have a fast or irregular heartbeat 2. Severe liver problems. Severe liver problems can happen in people who take STRIBILD. In some cases, these liver problems can lead to death. Your liver may become large (hepatomegaly) and you may develop fat in your liver (steatosis). Call your healthcare provider right away if you get any of the following symptoms of liver problems: • your skin or the white part of your eyes turns yellow (jaundice) • dark “tea-colored” urine • light-colored bowel movements (stools) • loss of appetite for several days or longer • nausea • stomach pain You may be more likely to get lactic acidosis or severe liver problems if you are female, very overweight (obese), or have been taking STRIBILD for a long time. 3. Worsening of Hepatitis B infection. If you have hepatitis B virus (HBV) infection and take STRIBILD, your HBV may get worse (flare-up) if you stop taking STRIBILD. A “flare-up” is when your HBV infection suddenly returns in a worse way than before. • Do not run out of STRIBILD. Refill your prescription or talk to your healthcare provider before your STRIBILD is all gone

• Do not stop taking STRIBILD without first talking to your healthcare provider • If you stop taking STRIBILD, your healthcare provider will need to check your health often and do blood tests regularly for several months to check your HBV infection. Tell your healthcare provider about any new or unusual symptoms you may have after you stop taking STRIBILD Who should not take STRIBILD? Do not take STRIBILD if you also take a medicine that contains: • adefovir (Hepsera®) • alfuzosin hydrochloride (Uroxatral®) • cisapride (Propulsid®, Propulsid Quicksolv®) • ergot-containing medicines, including: dihydroergotamine mesylate (D.H.E. 45®, Migranal®), ergotamine tartrate (Cafergot®, Migergot®, Ergostat®, Medihaler Ergotamine®, Wigraine®, Wigrettes®), and methylergonovine maleate (Ergotrate®, Methergine®) • lovastatin (Advicor®, Altoprev®, Mevacor®) • oral midazolam • pimozide (Orap®) • rifampin (Rifadin®, Rifamate®, Rifater®, Rimactane®) • sildenafil (Revatio®), when used for treating lung problems • simvastatin (Simcor®, Vytorin®, Zocor®) • triazolam (Halcion®) • the herb St. John’s wort Do not take STRIBILD if you also take any other HIV-1 medicines, including: • Other medicines that contain tenofovir (Atripla®, Complera®, Viread®, Truvada®) • Other medicines that contain emtricitabine, lamivudine, or ritonavir (Combivir®, Emtriva®, Epivir® or Epivir-HBV®, Epzicom®, Kaletra®, Norvir®, Trizivir®) STRIBILD is not for use in people who are less than 18 years old. What are the possible side effects of STRIBILD? STRIBILD may cause the following serious side effects: • See “What is the most important information I should know about STRIBILD?” • New or worse kidney problems, including kidney failure. Your healthcare provider should do blood and urine tests to check your kidneys before you start and while you are taking STRIBILD. Your healthcare provider may tell you to stop taking STRIBILD if you develop new or worse kidney problems. • Bone problems can happen in some people who take STRIBILD. Bone problems include bone pain, softening or thinning (which may lead to fractures). Your healthcare provider may need to do tests to check your bones. • Changes in body fat can happen in people who take HIV-1 medicine. These changes may include increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the middle of your body (trunk). Loss of fat from the legs, arms and face may also happen. The exact cause and long-term health effects of these conditions are not known. • Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking HIV-1 medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your healthcare provider right away if you start having any new symptoms after starting your HIV-1 medicine.

The most common side effects of STRIBILD include: • Nausea • Diarrhea Tell your healthcare provider if you have any side effect that bothers you or that does not go away. • These are not all the possible side effects of STRIBILD. For more information, ask your healthcare provider. • Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. What should I tell my healthcare provider before taking STRIBILD? Tell your healthcare provider about all your medical conditions, including: • If you have or had any kidney, bone, or liver problems, including hepatitis B infection • If you are pregnant or plan to become pregnant. It is not known if STRIBILD can harm your unborn baby. Tell your healthcare provider if you become pregnant while taking STRIBILD. – There is a pregnancy registry for women who take antiviral medicines during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk with your healthcare provider about how you can take part in this registry. • If you are breastfeeding (nursing) or plan to breastfeed. Do not breastfeed if you take STRIBILD. - You should not breastfeed if you have HIV-1 because of the risk of passing HIV-1 to your baby. - Two of the medicines in STRIBILD can pass to your baby in your breast milk. It is not known if the other medicines in STRIBILD can pass into your breast milk. - Talk with your healthcare provider about the best way to feed your baby. Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements: • STRIBILD may affect the way other medicines work, and other medicines may affect how STRIBILD works. • Be sure to tell your healthcare provider if you take any of the following medicines: - Hormone-based birth control (pills, patches, rings, shots, etc) - Antacid medicines that contains aluminum, magnesium hydroxide, or calcium carbonate. Take antacids at least 2 hours before or after you take STRIBILD - Medicines to treat depression, organ transplant rejection, or high blood pressure - amiodarone (Cordarone®, Pacerone®) - atorvastatin (Lipitor®, Caduet®) - bepridil hydrochloric (Vascor®, Bepadin®) - bosentan (Tracleer®) - buspirone - carbamazepine (Carbatrol®, Epitol®, Equetro®, Tegreto®) - clarithromycin (Biaxin®, Prevpac®) - clonazepam (Klonopin®) - clorazepate (Gen-xene®, Tranxene®) - colchicine (Colcrys®) - medicines that contain dexamethasone - diazepam (Valium®)

- digoxin (Lanoxin®) - disopyramide (Norpace®) - estazolam - ethosuximide (Zarontin®) - flecainide (Tambocor®) - flurazepam - fluticasone (Flovent®, Flonase®, Flovent® Diskus, Flovent® HFA, Veramyst®) - itraconazole (Sporanox®) - ketoconazole (Nizoral®) - lidocaine (Xylocaine®) - mexiletine - oxcarbazepine (Trileptal®) - perphenazine - phenobarbital (Luminal®) - phenytoin (Dilantin®, Phenytek®) - propafenone (Rythmol®) - quinidine (Neudexta®) - rifabutin (Mycobutin®) - rifapentine (Priftin®) - risperidone (Risperdal®, Risperdal Consta®) - salmeterol (Serevent®) or salmeterol when taken in combination with fluticasone (Advair Diskus®, Advair HFA®) - sildenafil (Viagra®), tadalafil (Cialis®) or vardenafil (Levitra®, Staxyn®), for the treatment of erectile dysfunction (ED). If you get dizzy or faint (low blood pressure), have vision changes or have an erection that last longer than 4 hours, call your healthcare provider or get medical help right away. - tadalafil (Adcirca®), for the treatment of pulmonary arterial hypertension - telithromycin (Ketek®) - thioridazine - voriconazole (Vfend®) - warfarin (Coumadin®, Jantoven®) - zolpidem (Ambien®, Edlular®, Intermezzo®, Zolpimist®) Know the medicines you take. Keep a list of all your medicines and show it to your healthcare provider and pharmacist when you get a new medicine. Do not start any new medicines while you are taking STRIBILD without first talking with your healthcare provider. Keep STRIBILD and all medicines out of reach of children. This Brief Summary summarizes the most important information about STRIBILD. If you would like more information, talk with your healthcare provider. You can also ask your healthcare provider or pharmacist for information about STRIBILD that is written for health professionals, or call 1-800-445-3235 or go to www.STRIBILD.com. Issued: August 2012

COMPLERA, EMTRIVA, GILEAD, the GILEAD Logo, GSI, HEPSERA, STRIBILD, the STRIBILD Logo, TRUVADA, and VIREAD are trademarks of Gilead Sciences, Inc., or its related companies. ATRIPLA is a trademark of Bristol-Myers Squibb & Gilead Sciences, LLC. All other marks referenced herein are the property of their respective owners. © 2013 Gilead Sciences, Inc. All rights reserved. QC15554 01/13

Resources

What’s new in print and online The 2013 Positively Aware HIV Drug Chart, sponsored by Walgreens, is also available as a stand-alone chart printed on heavy card-stock paper. The charts are free, but supplies are limited and orders will be filled on a first-come, first-served basis (maximum of 25 copies per order please). Email distribution@tpan.com or write/ fax your request to Positively Aware, Attn: 2013 HIV Drug Chart, 5537 N. Broadway St., Chicago, IL 60640; fax 773-989-9494. Custom URLs make it easier to go directly to the page that you want to read in the online Drug Guide. Positivelyaware.com/drugchart takes you to the pull-out HIV Drug Chart. Positivelyaware.com/copay will take you to the co-pay and patient assistance charts found on pages 70–73. Also, each drug name has its own custom URL—for example positivelyaware.com/stribild for Stribild, or positivelyaware.com/isentress for Isentress. Go to positivelyaware.com/drugguide for the Drug Guide homepage. Conveniently page through the digital issue of the 2013 HIV Drug Guide on your computer or tablet, seeing it just as you would in print. Go to PositivelyAware.com and click on the link, or issuu.com/positivelyaware. Go online for additional content not found in the print or digital versions of the issue, including an article on how the different drug classes work, and a drug interactions chart. Subscribe to our weekly email newsletter, the PA E-News at positivelyaware.com/subscribe. For more copies of the drug guide, email distribution@tpan.com. © 2013. Positively Aware (ISSN: 1523-2883) is published bi-monthly by Test Positive Aware Network (TPAN), 5537 N. Broadway St, Chicago, IL 60640. TPAN is an Illinois not-for-profit corporation, providing information and support to anyone concerned with HIV and AIDS issues. Positively Aware is a registered trademark of TPAN. All rights reserved. Circulation: 100,000. For reprint permission, send email to inbox@tpan.com. Six issues mailed bulk rate for $30 donation; mailed free to those living with HIV or those unable to contribute.

HIV DRUG GUIDE

2013

We accept 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. 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. Opinions expressed in Positively Aware are not necessarily those of staff 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. A model, photographer, or author’s HIV status should not be assumed based on their appearance in Positively Aware, association with TPAN, or contributions to this journal.

March+April 2013 | positivelyaware.com

Contributors

T h e D o c to r

T h e P h a r m ac i s t

Howard A. Grossman, MD

Renata Smith, PHARMD

Dr. Howard A. Grossman is a boardcertified internist and a specialist in HIV medicine. He began his work at St. Clare’s Hospital, one of the first dedicated AIDS units in the country, and entered private practice in 1987. He is Associate Attending Physician at St. Luke’sRoosevelt Hospital Center in Manhattan and an Assistant Clinical Professor of Medicine at Columbia University, College of Physicians and Surgeons. In addition to being nationally recognized as an educator on HIV issues and as an advocate for gay and lesbian rights and the rights of people with HIV, Dr. Grossman was one of the plaintiffs in the landmark Supreme Court lawsuit which sought to overturn laws preventing terminally ill patients from obtaining their physicians’ help to end their own lives. Dr. Grossman has written and reviewed articles for many publications (including Positively Aware) and for The Body.com. He is now practicing internal and HIV medicine at AlphaBetterCare, in midtown Manhattan.

A clinical assistant professor in HIV/ Infectious Diseases at the University of Illinois at Chicago, Renata Smith, PharmD, has specialized in HIV patient care for the past 16 years in the university’s hospital and clinics. Renata received her PharmD from UIC, followed by advanced training in infectious diseases and HIV. She practices at several of UIC’s outreach clinics and teaches at the school’s College of Pharmacy of the University of Pharmacy, Nursing, and Dentistry. This is Smith’s second consecutive year serving as the pharmacist for the Drug Guide.

THE A s s o c i at e Ed i to r

Enid Vázquez Having worked on the Drug Guide since its inception in 1997 (when her sister Sylvia appeared on the cover—see right), Enid looks forward every year to working on the Drug Guide and incorporating the latest treatment and research news. She earned her B.A. in journalism from the University of Wisconsin, Madison, and has worked as an intern for The Chicago Reporter and a cub reporter for The Hartford Courant. Her freelance work has appeared in publications around the country.

T h e Ac t i v i s t

Matt Sharp Matt Sharp was diagnosed with HIV in 1988. He retired from a ballet career in 1991 and became an AIDS activist in San Francisco, volunteering with ACT UP Golden Gate, later serving on five local community advisory boards for AIDS clinical research. From 2003–2008, he served as Director of Education and Advocacy at Test Positive Aware Network (TPAN) in Chicago. He has become a nationally known and respected HIV treatment activist and has written about AIDS for publications such as the Bay Area Reporter, POZ, and TPAN’s Positively Aware, including the ongoing column “Get Sharp.” This is Sharp’s second time providing the activist comments for the Drug Guide. As an international consultant, he is continuing his work by providing education, training, and advocacy services to HIV services providers, non-profit organizations, and the pharmaceutical industry.

March+April 2013 | positivelyaware.com

Special thanks

This issue never would have been possible without the tireless efforts of a team of talented individuals, who we cannot thank enough. The main contributors are listed at left. Special thanks to Joel Gallant, MD, MPH, for his thoughtful input on this issue, and who served as the physician in the very first Drug Guide in 1997, along with the late Spencer Cox (who contributed the activist viewpoint in that same issue). Many thanks also to Swarup Mehta, PharmD; Thomas D. Chiampis, PharmD; Liz Highleyman; Sue Saltmarsh; Josh Thorne; Jason Lancaster, and Chris Knight.

Positively Aware’s

first HIV Drug Guide, in 1997.

HIV DRUG GUIDE

2013

JOURNALISM. INTEGRITY. HOPE.

Jeff Berry editor-in-Chief

Enid Vázquez associate editor

Sue Saltmarsh copy Editor

Jason Lancaster proofreader

Joshua Thorne Web Master

Rick Guasco Creative director contributing writers

Keith R. Green, Liz Highleyman, Sal Iacopelli, Laura Jones, Jim Pickett, Matt Sharp photographers

Chris Knight Joshua Thorne Medical advisors

Daniel S. Berger, MD Gary Bucher, MD Michael Cristofano, PA Joel Gallant, MD Swarup Mehta, PharmD advertising inquiries

Lorraine Hayes l.hayes@tpan.com Subscription services

Ian Ponsetto distribution@tpan.com

2013 HIV Drug Pull-out chart sponsored by

Departments

5 Contributors POSITIVELY AWARE

8 In Box

IS PUBLISHED BY for a list of Walgreens HIV specialty pharmacies, and other resources, Go to HIV.walgreens.com

5537 N. Broadway St. Chicago, IL 60640 phone: (773) 989–9400 fax: (773) 989–9494 email: inbox@tpan.com www.positivelyaware.com

cover and contents spread photos by chris knight. Model: christopher clark.

March+April 2013 | positivelyaware.com

8 Readers’ Poll How comfortable are you with using technology to keep track of your medical records?

9 editor’s Note Generically speaking.

1 7 t h

a n n u a l

H I V

D r u g

G u i d e

MARCH+APRIL 2013 V O L U M E

2 5

NU M B ER

the drug guide

Mapping out a strategy How to use this guide. by Jeff Berry and Sue Saltmarsh

The 17th Annual HIV Drug Guide A handbook of all the drugs used to treat HIV (and those nearing approval)— including tips on how to use them, potential side effects and interactions— and what a doctor and activist have to say about each drug. Updated by Renata Smith, PharmD, and Enid Vázquez

Drug class side effects A quick look at potential side effects associated with each drug class. Updated by Renata Smith, PharmD, and Enid Vázquez

O n li n e e x t r a s

F e at u r e s

Timing and t-cells

Treating hepatitis B and C

The evolution of when to start treatment —through one doctor’s eyes.

The current standard of care for HBV and HCV, plus new drugs in the pipeline.

A comprehensive chart of potential drug-drug interactions.

by Howard A. Grossman, MD

by LIZ HIGHLEYMAN

Updated by swarup Mehta, PHARmD,

Keeping standards

Don’t break the bank

Current DHHS treatment guidelines for first-time therapy.

Assistance programs can help you pay for your meds.

by Jeff Berry

March+April 2013 | positivelyaware.com

Drug interactions chart

and Enid VáZquez

www.positivelyaware.com/interactions

(Drug) class is in session

A look at the different drug classes, and how they work. by Joel Gallant, MD, MPH

www.positivelyaware.com/drugclass 7

In box

Readers’ poll

inbox@tpan.com + @posaware

In the JAN+FEB issue, we asked

How comfortable are you with using computer technology to keep track of your medical records? 6% I refuse to use it 6% Uncomfortable 6% I wish I knew more 7% Somewhat comfortable

On the face of it Kudos for David Fawcett’s insightful, if sad, exposure and commentary (“Spoiled identity,” November+December 2012) on the stigma that those with HIV face both within and without the community; an important piece to share and remember when we interact with each other. We should also remember those wonderful lesbian women who stepped up, in the days before antiretroviral therapy, to take care of so many men, giving unstintingly of their time to care for those that were ill when some men turned their backs on those who were sick and dying. —Darryl Grant, MSW, LCSW Chicago

Finding hope I am currently incarcerated in a Florida prison. Without HIV testing, I may have found out too late that I’m HIV-positive and passed the disease to someone else. Until I found out about your publication, I thought I was alone in this fight. My family will not look up information for me because it’s too much for them to deal with. Throughout my life, I didn’t think I had ever met anyone with this disease and I have many questions and concerns. I recently started taking Complera, my first

75% Very comfortable

HIV medication. I don’t know how I’ll afford it in 19 months when I’m released. I wonder about how to meet and learn from others living with HIV and about dating again now that I’m divorced. POSITIVELY AWARE helps me with some of these everyday questions and thanks to you, I now know I’m not alone. My hat is off to you—keep fighting the fight! —Robert Sneads, FL

Expensive proposition As an HIV Prevention Specialist for the West Virginia Bureau for Public Health, I think pre-exposure prophylaxis [See “A Pill to Prevent HIV,” in the January+February issue] can be an important part of the overall fight against HIV/AIDS. But it’s also an EXPENSIVE strategy: If you take Truvada every day (as recommended), it will likely cost in the neighborhood of $14,000 per year. That’s over $38 per day. If insurance companies consider this to be a purely elective therapy and are unwilling to cover it, it will be a bit too expensive for many people. —Chuck Anziulewicz Charleston, WV, via thebody.com

Your comments: “I have used computer medical records for over seven years at the Cleveland Clinic. It’s nice to have a record of all the doctors I have seen so I can see the same provider again without re-explaining everything.” “I use the www.roadid.com electronic system for only $10 per year. I love it because all of my information is in one place for easy recall and updating and I can share it with my doctors and emergency responders.” “Internet security is still in its infancy and until it proves safe and secure, I won’t consider doing anything of a personal nature online.” this issue’s poll question:

Email: inbox@tpan.com Facebook: www.facebook.com/PositivelyAware Twitter: @PosAware Letters: Positively Aware, 5537 N. Broadway St., Chicago, IL 60640. Positively Aware treats all communications (letters, email, etc.) as letters to the editor unless otherwise instructed. We reserve the right to edit for length, style, or clarity. Let us if know you prefer we not use your name and city. 8

March+April 2013 | positivelyaware.com

Do you trust that your doctor and/or pharmacist is knowledgeable about possible drug interactions or side effects? cast your vote at

positivelyaware.com

Photo:

C o n n ec t to P ositively Aware

Editor’s note Jeff Berry @PAEditor

Generically speaking

Photo: Chris Knight

Welcome to your official handbook for HIV treatment, the Positively Aware 17th Annual HIV Drug Guide. Every year the Drug Guide is our most requested issue, with pre-orders for hundreds of this year’s Guide already rolling in. It’s not hard to understand why—there is a lot of incredibly useful information that’s easy to find, and all in one place. Information not only for those who are on treatment, but also for those considering treatment, to get the knowledge they need to get healthy with HIV, and stay that way. The world of HIV is no different than any other— outlooks evolve, priorities shift, and so the Drug Guide changes along with them. This year, for the first time, we have added helpful details about some other drugs that are not necessarily HIV drugs, but are used commonly by people with HIV, including an article on current treatment of hepatitis B and C, plus drugs that are in the pipeline. Another change instituted a few years ago was to provide information on generic formulations of drugs, including pricing and availability. There are now a handful of HIV drugs available as generics in the U.S., with more soon on the way. Typically in the non-HIV world, generics are considerably cheaper than brand-name drugs—and while that hasn’t exactly panned out in HIV (at least in the U.S.), there is still a cost savings when choosing generic over brand-name drugs. So, you may ask, what’s the problem? Lower price, get the generic, end of story, right? Well, as with a lot of things in HIV, it’s not that simple. Patents protect drugs for 20 years from the time they were invented, but it can easily take eight years or more to develop a drug and get it approved, leaving sometimes only 8–12 years before the patent expires. Of course, there are ways for companies to extend a drug’s patent life, and to delay generics from coming to market or being priced competitively (at least not right away). HIV drugs need to be taken in combination, but all of the individual drugs were approved at different times, sometimes years or even a decade or more apart. Efavirenz, which is found in the single-tablet regimen Atripla will become available as generic before the patents on the rest of the drugs in Atripla (emtricitabine and tenofovir DF) expire. Lamivudine, which is already available as a generic, has a similar mechanism of action

to emtricitabine, so insurance companies, ADAPs, and other payers may decide to break up your one Atripla pill into a regimen of three pills a day, made up of generic efavirenz and lamivudine, plus Viread, in order to reduce costs. A recent study found that replacing brand-name HIV drugs with generics that will soon become available could save the U.S. health care system up to $1 billion dollars annually, but could lessen the effectiveness of treatment. According to one of the study authors, providers, who may soon be faced with a difficult emotional or even ethical choice, may be more inclined to embrace a change in policy if they knew the savings were going to be redirected to “other aspects of HIV medicine,” such as providing hepatitis C treatment to co-infected individuals through a state ADAP which currently doesn’t cover HCV. Some have expressed concern as to whether all generics are created equal. In the U.S., when submitting for FDA approval of a generic drug (via an abbreviated new drug application, or ANDA), the applicant only has to prove that the generic is bioequivalent to the original drug, and is not usually required to include clinical data on safety and effectiveness, as was required for the original drug. Lawsuits have been successfully won against makers of generics when bioequivalence standards were not met. In 2011, the FDA issued new guidelines for the makers of generic drugs. So like it or not, generics are here to stay. In some ways, we are victims of our own successes, as many of us are now starting to outlive the patents on the very drugs we fought for, and that have saved our lives. Hopefully we aren’t headed towards a “generic cliff” as more and more drugs come off patent, forcing us to face our own collective “Sophie’s Choice” of having to choose between optimal treatment, and treatment that may be similar or not be as effective, but less costly.

Many of us are now starting to outlive the patents on the very drugs we fought for, and that have saved our lives.

Take care of yourself and each other.

March+April 2013 | positivelyaware.com

TIMING and The evolution of when to start treatment—through one doctor’s by Howard A. Grossman, MD

ver since the first antiretrovirals were approved, one of the most

HIV DRUG GUIDE

2013

When to start has been compared to a pendulum swinging back and forth, with higher and lower limits set for the decision on when to initiate antiretroviral therapy (ART). A pendulum, however, swings back and forth between fixed points. The debate about “when to start” has been more like a playground swing hanging from a decision framework made up of CD4 counts and viral loads. With one major exception, that swing has consistently moved higher, suggesting initiation of treatment earlier and earlier in the disease process. Making the decision has meant weighing the pros and cons of treatment. On the pro side has been our desire to control and possibly cure the disease. HIV

has been one of the only diseases in modern medicine that is not treated immediately upon discovery, one we wait years or even decades to treat. On the negative side rest much heavier concerns, including drug toxicities, cost of medication, the need for perfect adherence, denial of access by insurance companies and governments, and lack of research data. For most of the last 25 years, the swing swung back towards waiting to start therapy. But while we waited, our thinking evolved.

In the beginning When AZT was first available, it was only approved for patients who had experienced an opportunistic

March+April 2013 | positivelyaware.com

Photo: ISTOCKPHOTO.COM

vexing questions for patients and doctors has been when to start therapy. In the past two years, a host of new data has been released that is bringing us closer to a time when therapy can be offered to everyone with HIV. I would like to share with you the evolution in my own thinking which may help you make a decision.

nd T-CELLS eyes

infection. After so many years without any therapy, it quickly became clear, however, that people who were suffering from other complications of HIV were going to demand access to the drug. In retrospect, most of the people getting it in those days had very, very low CD4 counts, probably less than 50. We all know now that any benefit from AZT was probably limited to a six-month increase in survival in those very advanced people. More drugs became available during the late 1980s and early 1990s and our comfort level in treating people increased. We progressed to treating everyone with fewer than 200 CD4 cells/mm3. In 1993, the case definition was changed so that a low CD4 count alone meant an AIDS diagnosis. Part of the impetus for this was to ensure access for people with low CD4 counts who weren’t yet ill with infections.

HAART arrives The 200 CD4 limit remained for many years, and in fact, remained in place in the World Health Organization guidelines until 2010. In the U.S. and Western Europe, the 200 CD4 limit began to be called

into question with the advent of highly active antiretroviral therapy (HAART) in the late 1990s. There was a great deal of excitement about the benefits we were seeing in those starting on the triple combination cocktail, despite the very serious side effects and complications of those early treatments. People with CD4 counts over 200 began wanting access to the medications. We also understood more about the dynamics of HIV infection. It became clear that rather than there being a “latent” period when the virus was controlled and nothing much was happening, HIV infection was, instead, a very dynamic process. By the late ’90s, studies were being initiated in people with higher CD4 counts and there was interest in treating early infection. We had clear-cut data from controlled clinical trials and observational studies that the 200 CD4 limit was important, but many of those caught in the middle (not in acute or early infection but above the 200 CD4 level) became increasingly uncomfortable with not being treated. There were serious discussions about moving the bar up to 500, with David Ho and others advocating that we “hit hard, hit early.” Not waiting for studies

March+April 2013 | positivelyaware.com

HIV DRUG GUIDE

2013

Data swings toward 500

HIV DRUG GUIDE

2013

In 2008, the first presentations were given of the NA-ACCORD trial, a huge retrospective review of some of the largest cohorts in the U.S. and Canada. The results were striking. There was a 70% decrease in all-cause mortality in patients who initiated therapy with a count between 350 and 500. A later analysis showed a 60% decrease in mortality in those who started at a count of 500 compared to those who waited until fewer than 500. This was paradigmshattering as it really indicated clinical consequences to waiting to initiate therapy. There are limitations to retrospective observational studies. It is possible that those who started therapy earlier could be longer-lived for reasons having nothing to do with when they started. Retrospective studies also tend to smooth over some big variations. As I mentioned earlier, in the late 1990s and early 2000s, there were large numbers of people who started therapy early but then stopped for extended periods. This was not accounted for and those people were considered throughout as “early starters.” In any case, data from other retrospective studies has supported the observations in NA-ACCORD. The ART Cohort Collaboration looked at the data a bit differently and there was a clear benefit up to a count of 400 CD4/mm3 but not above. A

growing consensus emerged and in the 2009 U.S. Department of Health and Human Services (DHHS) guidelines, it was recommended that therapy should be initiated in all patients below 350 CD4/mm3 and that therapy should be considered between 350 and 500 CD4/mm3, especially in pregnant women and people who were symptomatic, including those with cancers. By the time the guidelines were rewritten for 2010, many on the panel felt that the accumulated data was really showing a benefit to initiating treatment at 500. Less than 350 still had the most hard data behind it, but there was increasingly more observational data to show decreases in some of the secondary illnesses being observed as people lived longer with HIV—things like cardiovascular disease and cancer.

Treatment reduces transmission I have to admit that I was skeptical. Starting in 2008, there was increasing evidence that treating HIV-positive people decreased viral transmission in the population. There was increasing discussion of inflammatory markers and the role that inflammation might play in HIV. The idea was also expressed that everyone was going to need drugs in a few years anyway, so why not move it up? I didn’t buy it. I failed to see clear-cut evidence of benefit over 500 CD4s and I did not see how to convince individual patients that there were benefits for them in the idea that lowering their viral loads served the public good. Many drugs still had significant side effects, we had seen the difficulties when patients developed resistance and had few options, and the last time we pushed the starting line higher it had not been a good idea. This was a very uncomfortable place for me to be—it was the first time I had ever found myself thinking more conservatively than the guidelines panel. I wondered if I had been at this too long. Over the last couple of years the lines of thinking mentioned above have become more firmly established and the evidence for them continues to grow. Rates of HIV infection in the U.S. have continued at the same levels for almost two decades now. In my own practice, I have seen so many young men become positive in the past two years. We have seen high rates of STDs for years, but much of it seemed to be coming from oral sex. In the last two years, I have seen more anal gonorrhea and Chlamydia than I remember seeing in a long time. Some men are looking for any excuse to stop using condoms, the most effective method we have of preventing transmission for people having sex (although preexposure prophylaxis, PrEP, adds another tool). It has become very clear that our prevention messages are failing to help people maintain changes in behavior that would lower transmission rates. For young

March+April 2013 | positivelyaware.com

Photo: iSTOCKPHOTO.COM

the idea was that everyone was going to need drugs in a few years anyway, so why not move it up? I didn’t buy it.

to be completed, many patients, beginning with the activist community, put their bodies on the line to test this in practice. And so the swing got a push and swung upward. By the turn of the century, the side effects and complications of HAART were becoming more clear, written in the wasted faces and growing bellies of so many patients. An increasing number of those who had chosen to start therapy when the swing swung toward 500 decided to go on extended drug holidays. I treated many of these patients who did well off medications, some maintaining low viral loads and improved CD4 counts for several years. This was the one instance that I can recall when the so-called swing actually swung back down. Many providers who had been willing to treat people with higher CD4 counts were uncomfortable going back to waiting until 200. It was also clear that if one waited to initiate the conversation on starting until patients hit 200, by the time adherence and access issues were addressed, therapy was often not initiated until well below 200. So, many of us started talking about therapy with patients who had between 300 and 400 T-cells and were starting them on meds a little earlier. Observational studies at the time seemed to indicate that treatment appeared to improve outcomes in this range, but there was little evidence that it was having a big clinical impact above a count of 500.

people today, the horrors of the AIDS epidemic are just things they learn about in history books, and the fear of HIV doesn’t last beyond the next hook-up. The right wing in the U.S. has destroyed sex education in many places and the level of ignorance about STDs is appalling. The CDC and other public health authorities have undertaken a powerful campaign for treatment as prevention. I think it becomes increasingly clear that reducing viral load across communities by treating as many people as possible may be our only real chance of bringing this epidemic under control. So government is clearly moving to support universal treatment, thus guaranteeing coverage and access, removing another obstacle on the “con” side of the argument. As a primary care provider however, one has to be able to convince the patient that the therapy being offered is of benefit to him or her. For those in a relationship with someone of the opposite serostatus, treatment as prevention does serve the interest of increasing the chance that the negative partner will stay uninfected. But the reality is that we are experiencing a new kind of apartheid based on viral load status. Over and over I hear from patients that they are questioned by potential partners about their viral load. If they are on meds and undetectable, they are acceptable sex partners. If they are not on meds, they get rejected. This has pushed some to start therapy earlier.

Trending toward STRs For real personal benefits to be seen, however, powerful trends needed to come into play. First has been the development of truly tolerable and easy-to-take medication regimens. We have had Atripla for quite a few years now and its once-daily dosing made it easy. But many people still experienced side effects. The development of more once-daily regimens, of two more once-daily fixed dose combinations, the approval of several twice-daily, well tolerated meds in new classes—all of these have suddenly presented us with more options, not just for initial therapy but for sequential regimens as well. And we expect to see a number of new once-daily and fixed dose combinations in new formulations—PIs and entry inhibitors without nucleosides, new integrase inhibitors with next generation nukes, and many others. This is truly the first time in fighting HIV that, as a provider, I can say to a patient that he or she will most likely not have any side effects from the medication I’m prescribing.

Inflammation The third area of growing consensus has been in regard to the importance of inflammation as a cause

of disease. This is a trend across the entire field of medicine. Inflammation appears to play important roles in aging, in the development of cardiovascular disease, in neurologic disease, as well as in rheumatology, endocrinology, and virtually every other area. People with HIV at every CD4 count have shown elevated levels of inflammation and immune activation, as well as heightened risk for a myriad of diseases from blood clots to early heart attacks. By the time of the International AIDS Conference in Washington, D.C. last year, the evidence for the deleterious effects of inflammation and the positive impact of ART on markers of immune activation was becoming overwhelming. Data continues to accumulate rapidly. As I wrote this article, two new studies appeared in the New England Journal of Medicine which showed significant benefit for patients started on medications very early in the disease process. The 2012 guidelines gave a stronger recommendation than previously to treating all patients with fewer than 500 CD4/mm3. There also appeared to be a growing consensus of expert opinion leading to more universal treatment.

The reality is that we are experiencing a new kind of apartheid based on viral load status.

Jumping off For me, the meeting in D.C. brought a kind of epiphany. It finally seemed that the scales had shifted. The things on the negative side of the scale—the side effects, complicated regimens, drug access issues, and lack of documented benefit—seemed to be lightening if not absent. And the side of the scale in favor of treatment was becoming heavier and heavier with reasons to start early. In fact, it appears to me that it is time to jump off of the swing at the highest point of its arc, to stop using CD4 count as a parameter in deciding when to start, and to offer treatment to all patients who are infected with HIV. I have begun to do this with overwhelming acceptance by many of my patients. Hopefully, we’ll land on our feet.

March+April 2013 | positivelyaware.com

HIV DRUG GUIDE

2013

ABOUT PREZISTA

PREZISTA® is always taken with and at the same time as ritonavir (Norvir ®), in combination with other HIV medicines for the treatment of HIV infection in adults. PREZISTA® should also be taken with food. • The use of other medicines active against HIV in combination with PREZISTA®/ritonavir (Norvir ®) may increase your ability to ﬁght HIV. Your healthcare professional will work with you to ﬁnd the right combination of HIV medicines • It is important that you remain under the care of your healthcare professional during treatment with PREZISTA® PREZISTA® does not cure HIV infection or AIDS and you may continue to experience illnesses associated with HIV-1 infection, including opportunistic infections. You should remain under the care of a doctor when using PREZISTA.® Please read Important Safety Information below, and talk to your healthcare professional to learn if PREZISTA® is right for you.

IMPORTANT SAFETY INFORMATION What is the most important information I should know about PREZISTA®? • PREZISTA® can interact with other medicines and cause serious side effects. See “Who should not take PREZISTA®?” • PREZISTA® may cause liver problems. Some people taking PREZISTA,® together with Norvir ® (ritonavir), have developed liver problems which may be life-threatening. Your healthcare professional should do blood tests before and during your combination treatment with 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 • Tell your healthcare professional if you have any of these signs and symptoms of liver problems: dark (tea-colored) urine, yellowing of your skin or whites of your eyes, pale-colored stools (bowel movements), nausea, vomiting, pain or tenderness on your right side below your ribs, or loss of appetite • PREZISTA® may cause a severe or life-threatening skin reaction or rash. Sometimes these skin reactions and skin rashes can become severe and require treatment in a hospital. You should call your healthcare professional immediately if you develop a rash. However, stop taking PREZISTA® and ritonavir combination treatment and call your healthcare professional immediately if you develop any skin changes with these symptoms: fever, tiredness, muscle or joint pain, blisters or skin lesions, mouth sores or ulcers, red or inflamed eyes, like “pink eye.” Rash occurred more often in patients taking PREZISTA® and raltegravir together than with either drug separately, but was generally mild Who should not take PREZISTA®? • Do not take PREZISTA® if you are taking the following medicines: alfuzosin (Uroxatral®), dihydroergotamine (D.H.E.45,® Embolex,® Migranal®), ergonovine, ergotamine (Cafergot,® Ergomar ®), methylergonovine, cisapride (Propulsid®), pimozide (Orap®), oral midazolam, triazolam (Halcion®), the herbal supplement St. John’s wort (Hypericum perforatum), lovastatin (Mevacor,® Altoprev,® Advicor ®), simvastatin (Zocor,® Simcor,® Vytorin®), rifampin (Rifadin,® Rifater,®

Rifamate,® Rimactane®), sildenafil (Revatio®) when used to treat pulmonary arterial hypertension, indinavir (Crixivan®), lopinavir/ ritonavir (Kaletra®), saquinavir (Invirase®), boceprevir (Victrelis™), or telaprevir (Incivek™) • Before taking PREZISTA,® tell your healthcare professional if you are taking sildenafil (Viagra,® Revatio®), vardenafil (Levitra,® Staxyn®), tadalafil (Cialis,® Adcirca®), atorvastatin (Lipitor ®), rosuvastatin (Crestor ®), pravastatin (Pravachol®), or colchicine (Colcrys,® Col-Probenecid®). Tell your healthcare professional if you are taking estrogen-based contraceptives (birth control). PREZISTA® might reduce the effectiveness of estrogen-based contraceptives. You must take additional precautions for birth control, such as condoms This is not a complete list of medicines. Be sure to tell your healthcare professional about all the medicines you are taking or plan to take, including prescription and nonprescription medicines, vitamins, and herbal supplements. What should I tell my doctor before I take PREZISTA®? • Before taking PREZISTA,® tell your healthcare professional if you have any medical conditions, including liver problems (including hepatitis B or C), allergy to sulfa medicines, diabetes, or hemophilia • Tell your healthcare professional if you are pregnant or planning to become pregnant, or are breastfeeding — The effects of PREZISTA® on pregnant women or their unborn babies are not known. You and your healthcare professional will need to decide if taking PREZISTA® is right for you — Do not breastfeed. It is not known if PREZISTA® can be passed to your baby in your breast milk and whether it could harm your baby. Also, mothers with HIV should not breastfeed because HIV can be passed to your baby in the breast milk What are the possible side effects of PREZISTA®? • High blood sugar, diabetes or worsening of diabetes, and increased bleeding in people with hemophilia have been reported in patients taking protease inhibitor medicines, including PREZISTA® • Changes in body fat have been seen in some patients taking HIV medicines, including PREZISTA.® The cause and long-term health effects of these conditions are not known at this time • Changes in your immune system can happen when you start taking HIV medicines. Your immune system may get stronger and begin to fight infections that have been hidden • The most common side effects related to taking PREZISTA® include diarrhea, nausea, rash, headache, stomach pain, and vomiting. This is not a complete list of all possible side effects. If you experience these or other side effects, talk to your healthcare professional. Do not stop taking PREZISTA® or any other medicines without first talking to your healthcare professional You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088. Please refer to the ritonavir (Norvir ®) Product Information (PI and PPI) for additional information on precautionary measures. Please read accompanying Patient Information for PREZISTA® and discuss any questions you have with your doctor.

28PRZDTC0288R8

PREZISTA® (darunavir) is a prescription medicine. It is one treatment option in the class of HIV (human immunodeficiency virus) medicines known as protease inhibitors.

IS THE PREZISTA

EXPERIENCE RIGHT FOR YOU?

There is no other person in the world who is exactly like you. And no HIV treatments are exactly alike, either. That’s why you should ask your healthcare professional about PREZISTA® (darunavir). Once-Daily PREZISTA® taken with ritonavir and in combination with other HIV medications can help lower your viral load and keep your HIV under control over the long term. In a clinical study* of almost 4 years (192 weeks), 7 out of 10 adults who had never taken HIV medications before maintained undetectable† viral loads with PREZISTA® plus ritonavir and Truvada.® Find out if the PREZISTA® EXPERIENCE is right for you. Ask your healthcare professional and learn more at DiscoverPREZISTA.com Please read the Important Safety Information and Patient Information on adjacent pages.

Snap a quick pic of our logo to show your doctor and get the conversation started. *A randomized open label Phase 3 trial comparing PREZISTA®/ritonavir 800/100 mg once daily (n=343) vs. Kaletra®/ritonavir 800/200 mg/day (n=346). †Undetectable was deﬁned as a viral load of less than 50 copies per mL. Registered trademarks are the property of their respective owners.

Janssen Therapeutics, Division of Janssen Products, LP © Janssen Therapeutics, Division of Janssen Products, LP 2012 06/12 28PRZ12036G

IMPORTANT PATIENT INFORMATION PREZISTA (pre-ZIS-ta) (darunavir) Oral Suspension PREZISTA (pre-ZIS-ta) (darunavir) Tablets Read this Patient Information before you start taking PREZISTA and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment. Also read the Patient Information leaflet for NORVIR® (ritonavir). What is the most important information I should know about PREZISTA? • PREZISTA can interact with other medicines and cause serious side effects. It is important to know the medicines that should not be taken with PREZISTA. See the section “Who should not take PREZISTA?” • PREZISTA may cause liver problems. Some people taking PREZISTA in combination with NORVIR® (ritonavir) have developed liver problems which may be life-threatening. Your healthcare provider should do blood tests before and during your combination treatment with PREZISTA. If you have chronic hepatitis B or C infection, your healthcare provider should check your blood tests more often because you have an increased chance of developing liver problems. • Tell your healthcare provider if you have any of the below signs and symptoms of liver problems. • Dark (tea colored) urine • yellowing of your skin or whites of your eyes • pale colored stools (bowel movements) • nausea • vomiting • pain or tenderness on your right side below your ribs • loss of appetite PREZISTA may cause severe or life-threatening skin reactions or rash. Sometimes these skin reactions and skin rashes can become severe and require treatment in a hospital. You should call your healthcare provider immediately if you develop a rash. However, stop taking PREZISTA and ritonavir combination treatment and call your healthcare provider immediately if you develop any skin changes with symptoms below: • fever • tiredness • muscle or joint pain • blisters or skin lesions • mouth sores or ulcers • red or inflamed eyes, like “pink eye” (conjunctivitis) Rash occurred more often in patients taking PREZISTA and raltegravir together than with either drug separately, but was generally mild. See “What are the possible side effects of PREZISTA?” for more information about side effects. What is PREZISTA? PREZISTA is a prescription anti-HIV medicine used with ritonavir and other anti-HIV medicines to treat adults with human immunodeficiency virus (HIV-1) infection. PREZISTA is a type of anti-HIV medicine called a protease inhibitor. HIV is the virus that causes AIDS (Acquired Immune Deficiency Syndrome). When used with other HIV medicines, PREZISTA may help to reduce the amount of HIV in your blood (called “viral load”). PREZISTA may also help to increase the number of white blood cells called CD4 (T) cell which help fight off other infections. Reducing the amount of HIV and increasing the CD4 (T) cell count may improve your immune system. This may reduce your risk of death or infections that can happen when your immune system is weak (opportunistic infections). PREZISTA does not cure HIV infection or AIDS and you may continue to experience illnesses associated with HIV-1 infection, including opportunistic infections. You should remain under the care of a doctor when using PREZISTA. Avoid doing things that can spread HIV-1 infection. • Do not share needles or other injection equipment. • Do not share personal items that can have blood or body fluids on them, like toothbrushes and razor blades.

• D o not have any kind of sex without protection. Always practice safe sex by using a latex or polyurethane condom to lower the chance of sexual contact with semen, vaginal secretions, or blood. Ask your healthcare provider if you have any questions on how to prevent passing HIV to other people. Who should not take PREZISTA? Do not take PREZISTA with any of the following medicines: • alfuzosin (Uroxatral®) • dihydroergotamine (D.H.E. 45®, Embolex®, Migranal®), ergonovine, ergotamine (Cafergot®, Ergomar®) methylergonovine • cisapride • pimozide (Orap®) • oral midazolam, triazolam (Halcion®) • the herbal supplement St. John’s Wort (Hypericum perforatum) • the cholesterol lowering medicines lovastatin (Mevacor®, Altoprev®, Advicor®) or simvastatin (Zocor®, Simcor®, Vytorin®) • rifampin (Rifadin®, Rifater®, Rifamate®, Rimactane®) • sildenafil (Revatio®) only when used for the treatment of pulmonary arterial hypertension. Serious problems can happen if you take any of these medicines with PREZISTA. What should I tell my doctor before I take PREZISTA? PREZISTA may not be right for you. Before taking PREZISTA, tell your healthcare provider if you: • have liver problems, including hepatitis B or hepatitis C • are allergic to sulfa medicines • have high blood sugar (diabetes) • have hemophilia • are pregnant or planning to become pregnant. It is not known if PREZISTA will harm your unborn baby. Pregnancy Registry: You and your healthcare provider will need to decide if taking PREZISTA is right for you. If you take PREZISTA while you are pregnant, talk to your healthcare provider about how you can be included in the Antiretroviral Pregnancy Registry. The purpose of the registry is follow the health of you and your baby. • are breastfeeding or plan to breastfeed. Do not breastfeed. We do not know if PREZISTA can be passed to your baby in your breast milk and whether it could harm your baby. Also, mothers with HIV-1 should not breastfeed because HIV-1 can be passed to the baby in the breast milk. Tell your healthcare provider about all the medicines you take including prescription and nonprescription medicines, vitamins, and herbal supplements. Using PREZISTA and certain other medicines may affect each other causing serious side effects. PREZISTA may affect the way other medicines work and other medicines may affect how PREZISTA works. Especially tell your healthcare provider if you take: • medicine to treat HIV • 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. • medicine for your heart such as bepridil, lidocaine (Xylocaine Viscous®), quinidine (Nuedexta®), amiodarone (Pacerone®, Cardarone®), digoxin (Lanoxin ®), flecainide (Tambocor ®), propafenone (Rythmol®) • warfarin (Coumadin®, Jantoven®) • medicine for seizures such as carbamazepine (Carbatrol®, Equetro®, Tegretol®, Epitol®), phenobarbital, phenytoin (Dilantin®, Phenytek®) • medicine for depression such as trazadone and desipramine (Norpramin®) • clarithromycin (Prevpac®, Biaxin®) • medicine for fungal infections such as ketoconazole (Nizoral®), itraconazole (Sporanox®, Onmel®), voriconazole (VFend®) • colchicine (Colcrys®, Col-Probenecid®) • rifabutin (Mycobutin®) • medicine used to treat blood pressure, a heart attack, heart failure, or to lower pressure in the eye such as metoprolol (Lopressor®, Toprol-XL®), timolol (Cosopt®, Betimol®, Timoptic®, Isatolol®, Combigan®) • midazolam administered by injection • medicine for heart disease such as felodipine (Plendil®), nifedipine (Procardia®, Adalat CC®, Afeditab CR®), nicardipine (Cardene®)

IMPORTANT PATIENT INFORMATION • s teroids such as dexamethasone, fluticasone (Advair Diskus®, Veramyst®, Flovent®, Flonase®) • bosentan (Tracleer®) • medicine to treat chronic hepatitis C such as boceprevir (VictrelisTM), telaprevir (IncivekTM) • medicine for cholesterol such as pravastatin (Pravachol®), atorvastatin (Lipitor®), rosuvastatin (Crestor®) • medicine to prevent organ transplant failure such as cyclosporine (Gengraf®, Sandimmune®, Neoral®), tacrolimus (Prograf®), sirolimus (Rapamune®) • salmeterol (Advair®, Serevent®) • medicine for narcotic withdrawal such as methadone (Methadose®, Dolophine Hydrochloride), buprenorphine (Butrans®, Buprenex®, Subutex®), buprenorphine/naloxone (Suboxone®) • medicine to treat schizophrenia such as risperidone (Risperdal®), thioridazine • medicine to treat erectile dysfunction or pulmonary hypertension such as sildenafil (Viagra®, Revatio®), vardenafil (Levitra®, Staxyn®), tadalafil (Cialis®, Adcirca®) • medicine to treat anxiety, depression or panic disorder such as sertraline (Zoloft®), paroxetine (Paxil®) This is not a complete list of medicines that you should tell your healthcare provider that you are taking. Ask your healthcare provider or pharmacist if you are not sure if your medicine is one that is listed above. Know the medicines you take. Keep a list of them to show your doctor or pharmacist when you get a new medicine. Do not start any new medicines while you are taking PREZISTA without first talking with your healthcare provider. How should I take PREZISTA? • Take PREZISTA every day exactly as prescribed by your healthcare provider. • You must take ritonavir (NORVIR®) at the same time as PREZISTA. • Do not change your dose of PREZISTA or stop treatment without talking to your healthcare provider first. • Take PREZISTA and ritonavir (NORVIR®) with food. • Swallow PREZISTA tablets whole with a drink. If you have difficulty swallowing PREZISTA tablets, PREZISTA oral suspension is also available. Your health care provider will help determine whether PREZISTA tablets or oral suspension is right for you. • PREZISTA oral suspension should be given with the supplied oral dosing syringe. Shake the suspension well before each usage. • If you take too much PREZISTA, call your healthcare provider or go to the nearest hospital emergency room right away. What should I do if I miss a dose? People who take PREZISTA one time a day: • If you miss a dose of PREZISTA by less than 12 hours, take your missed dose of PREZISTA right away. Then take your next dose of PREZISTA at your regularly scheduled time. • If you miss a dose of PREZISTA by more than 12 hours, wait and then take the next dose of PREZISTA at your regularly scheduled time. People who take PREZISTA two times a day • If you miss a dose of PREZISTA by less than 6 hours, take your missed dose of PREZISTA right away. Then take your next dose of PREZISTA at your regularly scheduled time. • If you miss a dose of PREZISTA by more than 6 hours, wait and then take the next dose of PREZISTA at your regularly scheduled time. If a dose of PREZISTA is skipped, do not double the next dose. Do not take more or less than your prescribed dose of PREZISTA at any one time. What are the possible side effects of PREZISTA? PREZISTA can cause side effects including: • See “What is the most important information I should know about PREZISTA?” • Diabetes and high blood sugar (hyperglycemia). Some people who take protease inhibitors including PREZISTA can get high blood sugar, develop diabetes, or your diabetes can get worse. Tell your healthcare provider if you notice an increase in thirst or urinate often while taking PREZISTA. • Changes in body fat. These changes can happen in people who take antiretroviral therapy. The changes may include an increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the back, chest, and stomach area. Loss of fat from the legs, arms, and face may also happen. The exact cause and longterm health effects of these conditions are not known.

• Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking HIV medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Call your healthcare provider right away if you start having new symptoms after starting your HIV medicine. • Increased bleeding for hemophiliacs. Some people with hemophilia have increased bleeding with protease inhibitors including PREZISTA. The most common side effects of PREZISTA include: • diarrhea • headache • nausea • abdominal pain • rash • vomiting Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of PREZISTA. For more information, ask your health care provider. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088. How should I store PREZISTA? • Store PREZISTA oral suspension and tablets at room temperature [77°F (25°C)]. • Do not refrigerate or freeze PREZISTA oral suspension. • Keep PREZISTA away from high heat. • PREZISTA oral suspension should be stored in the original container. Keep PREZISTA and all medicines out of the reach of children. General information about PREZISTA Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use PREZISTA for a condition for which it was not prescribed. Do not give PREZISTA to other people even if they have the same condition you have. It may harm them. This leaflet summarizes the most important information about PREZISTA. If you would like more information, talk to your healthcare provider. You can ask your healthcare provider or pharmacist for information about PREZISTA that is written for health professionals. For more information, call 1-800-526-7736. What are the ingredients in PREZISTA? Active ingredient: darunavir Inactive ingredients: PREZISTA Oral Suspension: hydroxypropyl cellulose, microcrystalline cellulose, sodium carboxymethylcellulose, methylparaben sodium, citric acid monohydrate, sucralose, masking flavor, strawberry cream flavor, hydrochloric acid (for pH adjustment), purified water. PREZISTA 75 mg and 150 mg Tablets: colloidal silicon dioxide, crospovidone, magnesium stearate, microcrystalline cellulose. The film coating contains: OPADRY® White (polyethylene glycol 3350, polyvinyl alcohol-partially hydrolyzed, talc, titanium dioxide). PREZISTA 400 mg and 600 mg Tablets: colloidal silicon dioxide, crospovidone, magnesium stearate, microcrystalline cellulose. The film coating contains: OPADRY® Orange (FD&C Yellow No. 6, polyethylene glycol 3350, polyvinyl alcohol-partially hydrolyzed, talc, titanium dioxide). PREZISTA 800 mg Tablets: colloidal silicon dioxide, crospovidone, magnesium stearate, microcrystalline cellulose, hypromellose. The film coating contains: OPADRY® Dark Red (iron oxide red, polyethylene glycol 3350, polyvinyl alcohol-partially hydrolyzed, talc, titanium dioxide). This Patient Information has been approved by the U.S Food and Drug Administration. Manufactured by: PREZISTA Oral Suspension PREZISTA Tablets Janssen Pharmaceutica, N.V. Janssen Ortho LLC, Beerse, Belgium Gurabo, PR 00778 Manufactured for: Janssen Therapeutics, Division of Janssen Products, LP, Titusville NJ 08560 NORVIR® is a registered trademark of its respective owner. PREZISTA® is a registered trademark of Janssen Pharmaceuticals © Janssen Pharmaceuticals, Inc. 2006 Revised: November 2012 10101718P

Mapping out A

By Jeff Berry and Sue Saltmarsh

S HIV DRUG GUIDE

2013

ILLUSTRATION BY ABBEY DENLINGER

o you have your Drug Guide, which contains a wealth of information, but where exactly should you start? Just like any map, youâ&#x20AC;&#x2122;ll need a reference tool to help chart your course. Here are a few things you might find useful when navigating this yearâ&#x20AC;&#x2122;s Drug Guide. Medications that are included in the HIV Drug Guide are only those drugs in the U.S. that are either FDA approved or expected to be approved in the coming year, as well as those that are available through an expanded access program (EAP). Drugs should always be taken in combination when treating HIV, by pairing medications from two

or more drug classes (for example, a boosted protease inhibitor along with two non-nukes). Some drug combinations are available as one pill (see singletablet regimen below). To learn more about how the different drug classes work, go to positivelyaware. com/drugclass and see the illustration above. Drugs are color-coded by class and are listed alphabetically by brand name (capitalized), or generic name (lower case) if not yet FDA approved. The brand name is listed first, then followed by the generic name (scientific designation), and any abbreviations. Example: Isentress is the brand name, raltegravir is the generic name, and RAL is the

March+April 2013 | positivelyaware.com

strategy

abbreviation. When a drug is available as a generic, it will be indicated in the “Standard dose” section of the drug’s page, and also on the pull-out drug chart. When a drug is available in generic form, or when it is part of a multi-drug combination, it will be referred to by its generic name. Example: Retrovir, commonly known as AZT, is available in generic form as zidovudine. Therefore, on the Combivir page, it is referred to as zidovudine since it’s part of Combivir. However, you should still look for the Retrovir page to find information on zidovudine. Note: In the doctor’s and activist’s comments on each drug page, this rule does not apply. Also, in the “Interactions” section

of each page, drugs are referred to by their mostused name, as determined by the pharmacist. Lastly, Viread’s generic name will appear as “tenofovir DF” or “tenofovir.” A fixed dose combination (FDC) combines two or more drugs in one tablet, such as Epzicom (lamivudine/abacavir). A single-tablet regimen (STR) contains drugs from different drug classes and is a complete regimen in one pill, such as Atripla (efavirenz/emtricitabine/tenofovir). Atripla, Complera, and Stribild are the three single-tablet regimens that are now available, with approval of another STR, “572Trii,” expected sometime in 2014. The Average Wholesale Price (AWP) is used by pharmacies and other buyers to negotiate the amount they pay for drugs. The AWP is included as a way to compare costs of the drugs. It is not necessarily what you would pay if you had to pay the full retail price. A drug-class side effect page, which lists potential side effects that can be expected for each drug within an entire drug class, has been included in the Drug Guide (see page 57). The drug interaction chart makes it easier to identify some of the most important drug interactions that you need to be aware of and look out for. This year the chart is available exclusively online at positivelyaware.com/ interactions. Always refer to the individual drug pages, package insert, or talk to your physician or pharmacist for more information. Paying for your medications can often be a challenge, but there are programs that can help cover all or part of the costs and facilitate access. For a list of drug co-pay and patient assistance programs, see pages 70–73. This year we’ve also added information on programs for drugs used to treat not only HIV but also hepatitis B and C, as well as several other drugs that are important for people living with HIV. The HIV treatment guidelines are established by a panel of experts in conjunction with the Department of Health and Human Services (DHHS) to help physicians and patients inform their treatment decisions. They’re available as a downloadable PDF at www.aidsinfo.nih.gov, or go to www.positivelyaware.com/guidelines. You can easily read up on each drug online by entering the drug name after our URL. For example, you’ll find the Drug Guide’s page for Prezista by typing www.positivelyaware.com/prezista; these unique URLs are also seen at the bottom of each drug’s page.

March+April 2013 | positivelyaware.com

HIV DRUG GUIDE

2013

Find your HIV drug here NRTIs:

INSTIs: Integrase inhibitors

Nucleoside / Nucleotide reverse

Isentress (raltegravir, or RAL)

dolutegravir (dolutegravir, or DTG)

transcriptase inhibitors (“NUKES”)

Combivir

page 21

(lamivudine / zidovudine, or 3TC / AZT)

Emtriva (emtricitabine, or FTC)

Epivir (lamivudine, or 3TC)

Epzicom

(abacavir / lamivudine, or ABC / 3TC)

Retrovir (zidovudine, AZT, or ZDV)

Trizivir (abacavir / lamivudine / zidovudine,

or ABC / 3TC / AZT)

Truvada

(brand name not yet established)

elvitegravir (elvitegravir, or EVG) (brand name not yet established)

EIs: Entry inhibitors Fuzeon (enfuvirtide, T-20, or ENF)

Selzentry (maraviroc, or MVC)

(emtricitabine / tenofovir DF, or FTC / TDF)

Videx EC (didanosine, or ddI)

STRs: Single-tablet regimens

Viread

Atripla

(tenofovir disoproxil fumarate [tenofovir DF], or TDF)

Zerit (stavudine, or d4T)

Ziagen (abacavir, or ABC)

2013

(rilpivirine / emtricitabine / tenofovir DF, or RPV / FTC / TDF)

Stribild

Non-nucleoside reverse transcriptase

(elvitegravir / cobicistat / emtricitabine / tenofovir DF, or EVG / COBI / FTC / TDF)

Edurant (rilpivirine, or RPV)

“572-Trii”

Intelence (etravirine, or ETR)

Rescriptor (delavirdine, or DLV)

(dolutegravir / abacavir / lamivudine, or DTG / ABC / 3TC) (brand name not yet established)

Sustiva (efavirenz, or EFV)

Viramune XR (nevirapine, or NVP)

PIs: Protease inhibitors

HIV DRUG GUIDE

Complera

NNRTIs: inhibitors (“NON-NUKES”)

(efavirenz / emtricitabine / tenofovir DF, or EFV / FTC / TDF)

NON-HIV DRUGS

Aptivus (tipranavir, or TPV)

Crixivan (indinavir, or IDV)

Invirase (saquinavir, or SQV)

Kaletra (lopinavir / ritonavir, or LPV / r)

(COBI) (brand name not yet established)

Lexiva (fosamprenavir, or FPV)

Egrifta

Norvir (ritonavir, or RTV)

Prezista (darunavir, or DRV)

(tesamorelin) Treatment for HIV-related excess belly fat

Reyataz (atazanavir, or ATV)

Viracept (nelfinavir, or NFV)

PKE: Pharmacokinetic enhancer cobicistat

Fulyzaq (crofelemer) Treatment for HIV/AIDS-associated diarrhea

March+April 2013 | positivelyaware.com

lamivudine / zidovudine, or 3TC / AZT

Combivir

NRTI: Nucleoside reverse transcriptase inhibitor (nucleoside, or nuke) | fixed dose combination

Potential side effects and toxicity

See the individual drugs contained in Combivir, Epivir (lamivudine) and Retrovir (zidovudine), for more details. Side effects include fatigue and myopathy (muscle damage). Flare-up of hepatitis B upon stopping may occur (due to the withdrawal of lamivudine; see Epivir). The zidovudine in Combivir has been associated with alteration of various cells in the blood through bone marrow suppression, resulting in anemia (low red blood cell counts) and/or neutropenia (low white blood cell counts), particularly during the first three months of therapy in people with advanced HIV. Zidovudine is also associated with lipoatrophy (fat loss in the arms, legs, face, and/or buttocks—sometimes called “AZT butt”). The lipoatrophy could be irreversible or fat could take a long time to rebuild after your regimen is changed. See page 57 for potential drug class side effects.

Potential drug interactions

Also see the individual drugs contained in Combivir, Epivir (lamivudine) and Retrovir (zidovudine), for more information. Do not take Combivir with Atripla, Complera, Emtriva, Epivir, Epivir-HBV, Epzicom, Hepsera, Retrovir, Stribild, Trizivir, Truvada, or the investigational “572Trii,” since all or part of these medications are already in Combivir or they have equivalent medications. Stavudine (Zerit) cannot be taken with Combivir, as it can limit effectiveness of the zidovudine part of Combivir.

More information

May be taken with food to decrease potential nausea

associated with zidovudine. Generic became available last year. One head-to-head study against Truvada (emtricitabine and tenofovir DF) found greater toxicity with Combivir, due to anemia (see Retrovir). The DHHS HIV treatment guidelines have downgraded Combivir from an “alternative” to an “acceptable” dual nuke background for people taking antiviral therapy for the first time, citing twice-daily dosing and greater toxicity than Truvada or Epzicom. Anyone taking zidovudine might consider taking Combivir even if they are already resistant to the lamivudine component. Resistance to lamivudine makes HIV less fit to replicate. It also slightly improves the antiviral activity of zidovudine and tenofovir DF (Viread), and for that reason, some doctors keep lamivudine onboard in combination with those drugs after M184V resistance develops. Thanks to extensive data, Combivir continues to be preferred to Truvada for pregnant women who are taking therapy for the first time, according to the treatment guidelines. Although generics should be as effective and tolerable as brand name drugs, some insurers may require patients to take regimens containing generics rather than simpler brand-name, co-formulated products. For example, when generic efavirenz becomes available, a person taking single-tablet Atripla might have to switch to Viread plus generic lamivudine and generic efavirenz. The availability of generics might also limit choices of therapy. For example, newer brand-name agents such as Stribild or Complera might be restricted to patients who can’t physically tolerate generic regimens. See package insert for more complete information on potential side effects and interactions.

STANDARD DOSE:

One tablet (150 mg lamivudine / 300 mg zidovudine) twice a day (12 hours apart), with or without food, with no dietary restrictions. Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Should not be used for children weighing less than 66 pounds, nor for people with kidney function less than 50 mL/min because the doses for both drugs need to be adjusted, or those with liver disease because the dose cannot be adjusted with this fixed dose combination. Generic is available. manufacturer:

ViiV Healthcare

www.viivhealthcare.com (877) 844-8872

Doctor’s comments

A fixed dose combination of two of the oldest drugs used to control HIV, Retrovir (zidovudine or AZT) and Epivir (lamivudine or 3TC), Combivir was, for many years, the nucleoside backbone most used in combination therapy. It has fallen out of favor because of its twice-daily dosing and the increased toxicities of Retrovir compared to other new nucleoside analogues. Zidovudine and lamivudine are now available as generics. In resource-poor settings and places where insurance coverage is lacking, they may be the only drugs available and can be effective when used properly, but there is little reason to use them where alternatives are available. — Howard A. Grossman, MD

AWP:

$1,081.70 / month; $931.61 for generic

Activist’s comments

A hopeful advance in HIV treatment when approved in 1997, Combivir is a fixed dose combination of the then commonly used AZT and 3TC (Epivir). It set the stage for combining the cornucopia of AIDS meds being developed, helping to make people’s drugtaking easier and improving adherence and associated drug levels in the blood. Yet, the combo fell out of favor as newer, once-daily pills became available. Still, people who need to take AZT/3TC in their regimen may at least feel better that they have one pill to take instead of two. — Matt Sharp

March+April 2013 | positivelyaware.com/combivir

HIV DRUG GUIDE

2013

Emtriva

emtricitabine, or FTC NRTI: Nucleoside reverse transcriptase inhibitor (nucleoside, or nuke)

Potential side effects and toxicity STANDARD DOSE:

One 200 mg capsule once a day, with or without food, with no dietary restrictions. The dosing needs to be adjusted for children and people who have decreased kidney function. Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. It is also available as an oral solution for children from birth and older and adults who are not able to swallow the capsules. manufacturer:

Gilead Sciences, Inc. www.gilead.com (800) GILEAD-5 (445–3235) awp:

$574.14 / month for 200 mg capsules

Very tolerable. The most common side effects (rarely seen) may include headache, diarrhea, and nausea. Flare-up of HBV (hepatitis B) in people co-infected with HBV has occurred when emtricitabine (Emtriva) was discontinued because it also treats HBV (see “More information”). Skin discoloration (darkening of the skin on the palms and the soles of the feet) can occur, but is generally mild and otherwise harmless. See page 57 for potential drug class side effects.

Potential drug interactions

No significant drug interactions. Do not take Emtriva with Atripla, Combivir, Complera, Epivir, Epivir-HBV, Epzicom, Hepsera, Stribild, Trizivir, Truvada, or “572-Trii,” since they contain emtricitabine or medication equivalent to it.

More information

Emtricitabine is similar to lamivudine (Epivir); both treat HIV and HBV and have the same resistance profile for HIV and HBV, meaning that if your virus is resistant to one it may also be resistant to the other. However, unlike lamivudine, emtricitabine remains in blood cells for a longer interval. Emtricitabine is active against chronic hepatitis B (though it is not FDA approved for this indication). If you have HIV and HBV and your hep B needs treatment but your HIV doesn’t, guidelines recommend treatment

Doctor’s comments

Emtriva (emtricitabine or FTC) is very similar in structure and resistance pattern to Epivir and together they have proven to be the most tolerable drugs used against HIV. Both are extremely potent agents in the test tube, but must be used in combinations due to their low barriers to the development of resistance. Emtriva is most often used with Viread (tenofovir), whereas Epivir is most often seen in combinations with AZT and Ziagen (abacavir). This is mostly due to who makes the drugs, although there is a good argument that can be made that the longer half-lives of Viread and Emtriva make them more ideal in combination together. Emtriva is now available in multiple combination medications including Truvada, Atripla, Complera, and Stribild and we can expect to see it in newer fixed dose combinations as well. — Howard A. Grossman, MD

for both. You should never be treated only for HBV without treatment for HIV. Emtricitabine and tenofovir DF (Viread) both work against HBV and HIV and can be used together as the NRTI backbone to increase activity and decrease the risk for developing HBV resistance, but there are other HBV treatments available that can be combined with HIV meds. If you are co-infected with HIV and HBV and you stop emtricitabine, your HBV may reactivate and you may experience signs and symptoms of acute HBV. You should be closely monitored by your physician. If your HIV develops resistance to lamivudine or emtricitabine, it does not mean that your HBV is also resistant to them. Emtricitabine is available as a combination tablet with tenofovir DF, which is called Truvada. Truvada was approved last year for HIV prevention as PrEP (pre-exposure prophylaxis). Truvada is a preferred NRTI combination in the DHHS HIV treatment guidelines for the NRTI component of first-time therapy. Drug resistance that the virus develops against emtricitabine, the M184V mutation, makes the virus less fit to replicate, meaning that it multiplies slower. It also slightly improves the antiviral activity of zidovudine (Retrovir) and tenofovir, and for that reason, some doctors keep emtricitabine onboard in combination with other NRTIs after M184V resistance develops. Emtriva oral solution should be kept in the refrigerator. If kept at room temperature, the oral solution should be used within three months. Emtricitabine is part of the single tablet regimens Atripla, Complera, Stribild, and “572-Trii.” See package insert for more complete information on potential side effects and interactions.

Activist’s comments

HIV DRUG GUIDE

2013

One of the first direct competitive stories in HIV drug development is the development of Emtriva, virtually identical to Epivir. It is rarely prescribed alone, but in combination with Viread—also similar to AZT and Epivir. The only real difference in the two drugs is that Emtriva has a longer half-life, and is therefore more forgiving if doses are missed. Other advantages are similar to Epivir in that the drug is very tolerable and if the M184V mutation develops, a less fit virus emerges. Clearly this drug was developed as a competitive strategy for market influence. — Matt Sharp

March+April 2013 | positivelyaware.com/emtriva

Epivir

lamivudine, or 3TC NRTI: Nucleoside reverse transcriptase inhibitor (nucleoside, or nuke)

Potential side effects and toxicity

Very tolerable. Side effects (though rarely seen) may include headache, nausea, vomiting, diarrhea, fever, fatigue, hair loss, insomnia, malaise (general ill feeling), nasal symptoms, and cough. See page 57 for potential drug class side effects.

Potential drug interactions

No significant drug interactions. Do not take Epivir with Atripla, Combivir, Complera, Emtriva, Epivir-HBV, Epzicom, Hepsera, Stribild, Trizivir, Truvada or the investigational “572-Trii,” since they contain Epivir or medication equivalent to it.

More information

One benefit is that the drug resistance the virus develops against lamivudine (Epivir), the M184V mutation, makes the virus less fit to replicate and has even been shown to keep T-cells from dropping during a treatment interruption as much as they would have otherwise. The mutation also slightly improves the antiviral activity of zidovudine (Retrovir or AZT) and tenofovir DF (Viread), and for that reason, some doctors keep lamivudine onboard in combination with those drugs after M184V resistance develops. Lamivudine is also approved for the treatment of hepatitis B virus (HBV), under the brand name Epivir-HBV, which has a lower dose than Epivir (Epivir-HBV is used only in people without HIV), but if you have HIV and HBV, you will need to take full-dose

Doctor’s comments

Epivir (lamivudine or 3TC) is probably the best tolerated and most used medication in the anti-HIV armamentarium. It is highly active against HIV in the test tube, but as a single agent, resistance develops rapidly. In combination, it has been highly useful and it or its analogue, emtricitabine, are the major part of most nucleoside analogue backbones in combination therapy. The weakness of Epivir is its low genetic barrier to resistance. A single mutation, the M184V mutation, blocks the antiviral activity of Epivir. However, it appears that viruses that carry the M184V mutation are less “fit”—they grow less well—than viruses without it. Given that, Epivir will often be continued even in the face of antiviral resistance in order to keep the virus less fit. This is not the optimum situation—we always prefer to fight the virus with antiviral activity—but it has proven to be a useful tool. — Howard A. Grossman, MD

lamivudine along with a complete HIV regimen to treat HIV and HBV. If you have them both and your hep B needs treatment but your HIV doesn’t, guidelines recommend treatment for both. You should never be treated only for HBV without treatment for HIV. Lamivudine and tenofovir DF both work against HBV and HIV and can be used together as the NRTI backbone to increase activity and decrease the risk of HBV drug resistance, but there are other HBV treatments available that can be combined with HIV meds. Make sure you are taking lamivudine at HIV doses—always ask your doctor or pharmacist. If you are co-infected with HIV and HBV and you stop taking lamivudine, your HBV may reactivate and you may experience signs and symptoms of acute HBV. You should be closely monitored by your physician. If your HIV develops resistance to lamivudine, it doesn’t mean that your HBV is also resistant to it. Lamivudine is also available in three combination products: Combivir, with zidovudine; Epzicom, with abacavir; and Trizivir with zidovudine and abacavir. The single tablet regimen in development called “572-Trii” (see “572-Trii” page) contains lamivudine, abacavir, and dolutegravir (see dolutegravir page). Available as a generic—although generics should be as effective and tolerable as brand name drugs, some insurers may require patients to take regimens containing generics rather than simpler brand-name co-formulated products. For example, when generic efavirenz becomes available, a person taking single-tablet Atripla might have to switch to Viread plus generic lamivudine and generic efavirenz. The availability of generics might also limit choices of therapy. For example, newer brand-name agents such as Stribild or Complera might be restricted to patients who can’t physically tolerate generic regimens. See package insert for more complete information on potential side effects and interactions.

STANDARD DOSE:

One 300 mg tablet once a day (or one 150 mg tablet twice daily), with or without food, with no dietary restrictions. Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Dose is lowered for people with kidney impairment. Dose for children 3 months to 16 years of age is 4 mg per 2.2 pounds (1 kg) twice daily to a maximum of 150 mg twice daily. A strawberry/ banana-flavored liquid (10 mg/1 mL) is available. Generic is available. manufacturer:

ViiV Healthcare www.viivhealthcare.com (877) 844-8872 awp:

$498.89 / month for 300 mg tablets; $429.19 for generic

Activist’s comments

Still referred to as 3TC, this drug has an interesting history. A safe and important part of the HIV treatment backbone in combination therapy, it was learned that even though resistance occurs relatively quickly the mutation known as M184V causes HIV to be less “fit” or less able to replicate. Many people are on 3TC or its relative Emtriva simply to keep the mutation and an unfit virus, even though the drug may be inactive. — Matt Sharp

March+April 2013 | positivelyaware.com/epivir

HIV DRUG GUIDE

2013

Epzicom

abacavir sulfate (abacavir) / lamivudine, or ABC / 3TC

NRTI: Nucleoside reverse transcriptase inhibitor (nucleoside, or nuke) | fixed dose combination

Potential side effects and toxicity

STANDARD DOSE:

One tablet (600 mg abacavir / 300 mg lamivudine), once a day, with or without food, with no dietary restrictions. Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Not indicated for patients younger than 18 years old, those with kidney function less than 50 mL/min, or those with liver problems, because dose adjustments are not possible with this fixed dose combination. manufacturer:

ViiV Healthcare

www.viivhealthcare.com (877) 844-8872 awp:

$1,169.26 / month

The most common side effects of Epzicom are the same as the individual drugs it contains—see Epivir (lamivudine) and Ziagen (abacavir). Of note is the hypersensitivity reaction (HSR, an allergic-like reaction) warning on abacavir (see Ziagen page). A blood test, covered by insurance (and also paid for by LabCorp/ViiV—see chart, page 72-73), for HLA-B*5701 (a genetic marker) can identify people at high risk for this reaction and virtually eliminate HSR. About 90% of HSR occurs within the first six weeks of treatment. Symptoms of HSR usually worsen, very slowly, with every dose. If treatment is stopped because of this serious reaction, you can never take products containing abacavir, such as Epzicom or Trizivir, again (called “re-challenging”). Re-challenging could cause a rare life-threatening reaction. (This does not apply to missed doses when there’s no HSR, but watch for symptoms if you’ve stopped the drug for at least a few days.) Symptoms usually, but not always, include some combination of fever; muscle ache; malaise (general ill feeling); severe nausea, vomiting, diarrhea, or abdominal pain; severe tiredness; respiratory symptoms (cough, difficulty breathing, or sore throat); and possible rash. Symptoms are listed on the patient information sheet and warning card that you receive each time you fill your prescription. You should keep the warning card with you. Hypersensitivity might be confused with flu,

Doctor’s comments

Epzicom is a fixed dose combination of abacavir (Ziagen) and lamivudine (Epivir). It is safe and well tolerated. When initially approved, it was a popular combination as an alternative to Combivir, the preeminent nucleoside backbone at the time, but it has largely been supplanted by the use of Truvada. It is a useful alternative, especially in people with kidney disease, which can be worsened by use of tenofovir, a component of Truvada. There is some indication that Epzicom may not be as effective as Truvada at viral loads greater than 100,000 copies/mL. There have also been varying reports of cardiovascular toxicity and, while there is no definitive finding, most clinicians are cautious about its use in people at high risk or with underlying cardiovascular disease. As with abacavir alone, hypersensitivity reactions are a concern. It is vital to obtain a test for HLA-B*5701 prior to starting therapy and a positive test makes abacavir and Epzicom contraindicated. — Howard A. Grossman, MD

Activist’s comments

HIV DRUG GUIDE

2013

This fixed dose pill of Ziagen and Epivir came into being as a convenient alternative for people who cannot take Truvada (Viread plus Emtriva), but according to one study, it turned out to be not so effective in those with viral loads greater than 100,000. For reasons mentioned with Ziagen, including the conflicting evidence on whether it causes heart complications, Epzicom might be put in the dustbin of older HIV drugs. — Matt Sharp

but remember that HSR worsens with every dose. Check with your doctor if you have any side effects after taking this medicine—don’t just stop! Some observational studies seemed to indicate that abacavir may increase the risk of cardiovascular events, including heart attacks, in people with greater risk factors (such as smoking, diabetes, high blood pressure, older age, high cholesterol, and drug use), though other studies have found no increased risk. DHHS HIV treatment guidelines state, “to date, no consensus has been reached either on the association of [abacavir] use with MI [myocardial infarction, or heart attack] risk or a possible mechanism for the association.” People who have high risk for heart disease are monitored more closely; the decision to stop or never start a regimen containing abacavir is up to you and your provider. See page 57 for potential drug class side effects.

Potential drug interactions

See the individual drugs contained in Epzicom—Epivir and Ziagen—for more information. Do not take Epzicom with Atripla, Combivir, Complera, Emtriva, Epivir, EpivirHBV, Hepsera, Stribild, Trizivir, Truvada, Ziagen, or “572Trii,” since all or part of these medications are already in Epzicom or have equivalent medications. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Alcohol can increase the levels of abacavir and therefore increase the possibility of side effects.

More information

Currently, DHHS treatment guidelines recommend Truvada over Epzicom as the preferred backbone for the NRTI component of an HIV drug combination for firsttime therapy. Epzicom is listed as an alternative NRTI backbone. However, guidelines from the International Antiviral [formerly “AIDS”] Society-USA (www.iasusa. org) last year upgraded Epzicom from “alternative” to “recommended” when used with Sustiva or boosted Reyataz in people with viral loads of less than 100,000 who are negative for HLA-B*5701. See discussion “Is it time to rethink abacavir?” at www.clinicalcareoptions. com/hiv. Epzicom is doing well against Truvada with dolutegravir, a new integrase inhibitor not yet on the market; see dolutegravir and “572-Trii” pages. The DHHS guidelines state, “Pending additional data, [Epzicom] should be used with caution in individuals who have plasma HIV RNA [viral load] greater than 100,000 copies/mL, as well as in persons at higher risk for cardiovascular disease. However, Epzicom remains a good alternative dual-NRTI option for some treatment-naïve patients.” The lamivudine portion of Epzicom is also used to treat the hepatitis B virus (HBV); see Epivir page. If you are co-infected with HIV and HBV and you stop Epzicom, your HBV may reactivate and you may experience signs and symptoms of acute HBV. You should be closely monitored by your physician. See package insert for more complete information on potential side effects and interactions.

March+April 2013 | positivelyaware.com/epzicom

Retrovir

zidovudine, or AZT, or ZDV NRTI: Nucleoside reverse transcriptase inhibitor (nucleoside, or nuke)

Potential side effects and toxicity

May include headache, fever and chills (more common in children), muscle pain, fatigue, nausea, and fingernail discoloration. Zidovudine has been associated with alteration of various blood cells through bone marrow suppression, resulting in anemia (low red blood cell counts), which can make you feel short of breath and tired, and/ or neutropenia (low white blood cell counts), which can increase risk for getting colds and other infections, particularly during the first three months of therapy in people with advanced HIV. Potential exists for severe anemia requiring blood transfusion, erythropoietin injections, or hospitalization. Your provider may check your blood in the first 4–6 weeks after you start zidovudine. Zidovudine is associated with lipoatrophy (fat loss in the arms, legs, face, and/or buttocks—sometimes called “AZT butt”). The lipoatrophy could be irreversible or fat could take a long

Doctor’s comments

Retrovir (zidovudine or AZT) was the first drug approved for treatment of HIV. Its release was highly anticipated and generated a lot of unrealistic expectations because absolutely no treatment had been available for over six years. It was difficult to take, as it was initially taken every four hours around the clock. Side effects included anemia, neuropathy, nausea, etc., and there has been a lot of backlash and mythology about the drug. Its efficacy as a single agent was modest, improving disease for approximately six months, but in combination therapy, it was quite potent. AZT is used rarely these days in resource-rich settings and has been replaced by nucleosides that have less toxicity and easier dosing schedules. Zidovudine remains a mainstay of treatment during pregnancy, as there is the most data accumulated with it and it appears to have no ill effects on the baby. It is also a mainstay in resourcepoor settings where inexpensive generic drugs are necessary. It is available as a generic and could be a useful tool for those without drug coverage. — Howard A. Grossman, MD

Activist’s comments

In the ’80s, Retrovir (zidovudine or AZT) was the drug everyone had been waiting for, so illustrious that it became the fodder of AIDS literature in Angels in America and And the Band Played On. Before HIV, AZT was a cancer drug thought to be too toxic so it was shelved. But after approval for HIV, in one of the most historic AIDS protests, ACT UP New York closed the New York Stock Exchange in a civil disobedience action over the high cost of the drug. Two weeks later, the prices were lowered. Today, its history is marred by stories of toxicities, especially from the days when it was taken in monotherapy at 1,200 mg a day, twice the 600 mg used today. Once the dust was settled on how to appropriately use it at lower doses, AZT was useful in combination with other drugs. However over the years, its place in the hierarchy of AIDS drugs has been taken over by Viread. — Matt Sharp

time to rebuild after your HIV regimen is changed. See page 57 for potential drug class side effects.

Potential drug interactions

Do not take with Combivir or Trizivir, since zidovudine is already in these medications. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Clarithromycin and rifampin may decrease zidovudine blood levels. Do not take with the cancer treatment doxorubicin. Probenecid, phenytoin, and valproic acid may increase blood levels and decrease clearance of zidovudine, but no dosing adjustments are recommended. Zidovudine and stavudine (Zerit) should never be used together. Bone marrow suppression should be monitored with use of ganciclovir, Valcyte, amphotericin B, pentamidine, dapsone, flucytosine, sulfadiazine, interferonalpha, and ribavirin. Ribavirin may decrease the efficacy of zidovudine and increase the risk of lactic acidosis and should not be used. Measure hemoglobin once a week after starting other medications that can cause anemia until hemoglobin has stabilized. Notify your health care provider if you’re experiencing pain and/or swelling in the legs, worsening or shortness of breath, increases in blood pressure, dizziness, or loss of consciousness, extreme tiredness, or blood clots in hemodialysis vascular access ports. Methadone can increase zidovudine levels but no dose adjustments are recommended. Monitor for adverse effects.

More information

Zidovudine is rarely used nowadays, though it remains the go-to medication for pregnancy and infants after birth, to prevent mother-to-child transmission. Thanks to extensive data, zidovudine is also a preferred drug for pregnant women who are taking therapy for the first time, according to DHHS HIV treatment guidelines. The not-so-good news for people adding zidovudine—the fatigue and the potential anemia, but it is still a very good HIV medication with many years of data behind it and a good option for people who have developed resistance to some of the newer first-line HIV medications. You can take erythropoietin for some anemias, but that’s an expensive weekly injectable. Some doctors would prefer switching out the zidovudine for another drug. Taking with food may minimize upset stomach. Zidovudine crosses the blood-brain barrier to a useful degree, which may be beneficial for patients at risk for neurological damage (such as dementia) from HIV. Although generics should be as effective and tolerable as brand name drugs, some insurers may require patients to take regimens containing generics rather than simpler brand-name, co-formulated products. For example, when generic efavirenz becomes available, a person taking single-tablet Atripla might have to switch to Viread plus generic lamivudine and generic efavirenz. The availability of generics might also limit choices of therapy. For example, newer brand-name agents such as Stribild or Complera might be restricted to patients who don’t tolerate generic regimens. See package insert for more complete information.

March+April 2013 | positivelyaware.com/retrovir

Standard dose:

One 300 mg tablet twice a day (12 hours apart); two 100 mg capsules three times a day (8 hours apart) also available; with or without food, with no dietary restrictions. Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Clear, strawberryflavored liquid available for infants four weeks of age and up; dose is weight-based. If your kidney function is less than 15 mL/min or you are on dialysis, your dose will need to be adjusted. Used in pregnancy and for newborns to prevent HIV transmission from mother to child. Generic is available. manufacturer:

ViiV Healthcare

www.viivhealthcare.com (877) 844-8872 awp:

$582.94 / month for 300 mg tablets; $309.89 for generic. $72.84 for 240 mL of 10 mg/mL syrup; $56.42 for generic

HIV DRUG GUIDE

2013

Trizivir

abacavir sulfate (abacavir) / lamivudine / zidovudine, or ABC / 3TC / AZT

NRTI: Nucleoside reverse transcriptase inhibitor (nucleoside, or nuke) | fixed dose combination

Potential side effects and toxicity

STANDARD DOSE:

One tablet (300 mg abacavir / 150 mg lamivudine / 300 mg zidovudine), twice a day, with or without food, with no dietary restrictions. Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Trizivir should not be used for adolescents who weigh less than 88 pounds, people with kidney function less than 50 mL/min, and those with liver disease, because dose adjustments are not possible with the fixed dose combination. manufacturer:

ViiV Healthcare

www.viivhealthcare.com (877) 844-8872 awp:

$1839.66 / month

The most common side effects of Trizivir are the same as those of the drugs it contains—see Epivir (lamivudine), Retrovir (zidovudine), and Ziagen (abacavir). Of note is the hypersensitivity reaction (HSR, an allergic-like reaction) warning on abacavir; see important details on Ziagen, page 31. A blood test, covered by insurance (and also paid for by LabCorp/ViiV—see chart, page 72-73), for HLA-B*5701 (a genetic marker) can identify people at high risk for this reaction and virtually eliminate HSR. If treatment is stopped because of this serious reaction, you can never take products containing abacavir, such as Epzicom or Trizivir, again (called “re-challenging”). Re-challenging can cause a rare life-threatening reaction. (This does not apply to missed doses when there’s no HSR, but watch for symptoms if you’ve stopped the drug for at least a few days.) Symptoms usually worsen, very slowly, with every dose. Symptoms usually, but not always, include some combination of fever; muscle ache; severe nausea, vomiting, diarrhea, or abdominal pain; severe tiredness; respiratory symptoms (cough, difficulty breathing, or sore throat); and possible rash. Hypersensitivity might be confused with flu, but remember that HSR worsens with every dose. Check with your doctor if you have any side effects after taking this medicine—don’t just stop! Some studies indicate that abacavir may increase the risk of cardiovascular events,

Doctor’s comments

When the triple nuke combination of Trizivir (AZT, 3TC, and abacavir) first won approval it was a useful tool. At that time, we needed alternatives to PI-containing regimens, which had many side effects, and there were also people on mega-drug cocktails of four to six drugs or more. So a simple, twice-a-day pill that contained three drugs looked like a winner. Results from studies published as early as 2001, though, showed no benefit from using three nukes over two and a much greater benefit from using multi-class combinations (a PI and two nukes or an NNRTI and two nukes). This was especially true at higher viral loads. Today there is no real indication for using Trizivir except when needed to simplify adherence for someone already on the three nukes in combination with other drugs. — Howard A. Grossman, MD

Activist’s comments

HIV DRUG GUIDE

2013

Not one, not two, but three drugs in one pill—AZT, Epivir, and Ziagen! Quite a feat when the drug was first approved. The only problem is that few people take three nucleoside analog drugs in their regimens, and Trizivir has been shown to not be very effective. Since the drug is taken twice daily, it’s simply not much of an advance in the competitive nuke market. Even when it was first approved, it was sort of ho-hum except for the excitement of three drugs crammed into one pill. However, the fixed dose regimen started to catch on with the advent of Trizivir. — Matt Sharp

including heart attacks, in people with greater risk factors (such as smoking, diabetes, high blood pressure, and drug use), though other studies have found no such evidence. People who have high risk for heart disease are monitored more closely; the decision to stop or never start a regimen containing abacavir is up to you and your provider. Other side effects associated with Trizivir may include headache, nausea, upset stomach, and fatigue. May be taken with food to decrease potential nausea associated with zidovudine. The zidovudine in Trizivir has been associated with anemia (low red blood cell counts) and/or neutropenia (low white blood cell counts), particularly during the first three months of therapy in people with advanced HIV. Zidovudine is also associated with lipoatrophy (fat loss in the arms, legs, face, and/or buttocks—sometimes called “AZT butt”). The lipoatrophy could be irreversible or fat could take a long time to rebuild after changing your regimen. See page 57 for potential drug class side effects.

Potential drug interactions

See the drugs contained in Trizivir—Epivir (lamivudine), Retrovir (zidovudine), and Ziagen (abacavir), for details. Do not take Trizivir with Atripla, Complera, Emtriva, Epivir, Epivir-HBV, Epzicom, Hepsera, Retrovir, Stribild, Truvada, Ziagen, or “572-Trii;” as all or part of these medications are already in Trizivir or have equivalent medications. If you’re taking any of the following medications, consult your doctor or pharmacist before starting Trizivir: clarithromycin (Biaxin), Cytovene (ganciclovir), Daraprim (pyrimethamine), doxorubicin, flucytosine, Fungizone (amphotericin B), hydroxyurea, interferon, probenecid, ribavirin, rifampin, stavudine (Zerit), and Valcyte (valganciclovir).

More information

Trizivir is the only triple combination NRTI that has been studied in a randomized, controlled study, which has shown it to be inferior to the standard treatment of two NRTIs plus efavirenz (Sustiva). DHHS treatment guidelines recommend that Trizivir should only be used if other options are not available due to toxicities or drug interactions associated with other HIV regimens. Trizivir contains lamivudine (Epivir), which is used to treat hepatitis B virus (HBV). If you are co-infected with HIV and HBV and you stop Trizivir, your HBV may reactivate and you may experience signs and symptoms of acute HBV. You should be closely monitored by your physician. See package insert for more complete information on potential side effects and interactions.

March+April 2013 | positivelyaware.com/trizivir

emtricitabine / tenofovir DF, or FTC / TDF

Truvada

NRTI: Nucleoside/nucleotide reverse transcriptase inhibitor (nucleoside, or “nuke”) | fixed dose combination

Potential side effects and toxicity

See the individual drugs contained in Truvada—Viread and Emtriva. Overall, fairly well tolerated, but some may experience diarrhea, dizziness, nausea, depression, fatigue, insomnia, abnormal dreams, and rash. Skin discoloration on palms and soles may also occur. The tenofovir DF (Viread) in Truvada is associated with decreases in bone mineral density (BMD). BMD monitoring should be considered in people who have a history of pathologic bone fracture or are at risk for osteopenia or osteoporosis. The effects of calcium supplements with or without vitamin D have not been studied, but their use may be beneficial. Calcium and vitamin D levels can be checked to assess the need for these supplements. Less common side effects include kidney toxicities and low blood phosphate. See page 57 for potential drug class side effects.

Potential drug interactions

See the individual drugs contained in Truvada—Viread and Emtriva. Do not take with Atripla, Combivir, Complera, Emtriva, Epivir, Epivir-HBV, Epzicom, Hepsera, Stribild, Trizivir, Truvada, Viread, or the investigational “572-Trii,” since all or part of these medications are already in Truvada or have equivalent medications. Tenofovir increases levels of didanosine (Videx EC), so use with caution and make sure your dose of didanosine is adjusted accordingly and monitored for toxicities. Tenofovir DF decreases the concentration levels of Reyataz, therefore Reyataz can only be used boosted when in combination with tenofovir or Truvada. In addition, Reyataz and Kaletra increase tenofovir

Doctor’s comments

Truvada (tenofovir plus emticitabine) is now the preferred nucleoside backbone in combination therapy according to most guidelines. It has shown greater efficacy and better tolerability than Combivir and Epzicom. It is available as a two-drug combination pill and is also available in combination with efavirenz (Sustiva) as Atripla, with rilpivarine (Edurant) as Complera, and with cobicistat and elvitegravir as Stribild. Renal (kidney) function must be monitored as with all drugs containing tenofovir. Adjustments to the dose or discontinuation may be necessary if changes in kidney function occur. There can also be bone loss with tenofovir. This has not been shown to lead to clinically relevant changes, like increased numbers of bone fractures, but still requires awareness and monitoring. — Howard A. Grossman, MD

concentrations for unknown reasons. It is recommended that patients taking Reyataz or Kaletra and Truvada should be monitored for Truvada-associated adverse events, particularly decrease in kidney function. When taken with Truvada or tenofovir DF, it is recommended that Reyataz 300 mg is taken with ritonavir (Norvir) 100 mg (all as a single daily dose with food). Reyataz without ritonavir should not be taken with Truvada or tenofovir. No dose adjustment is needed when used with Kaletra. Avoid taking Truvada with kidney-toxic drugs.

More information

Truvada was FDA approved in July 2012 for HIV prevention (pre-exposure prophylaxis, or PrEP) in HIV-negative individuals (go to www.truvadapreprems.com and www. avac.org). However, awareness about proper usage is urgently needed, both for effectiveness and to avoid viral drug resistance if later infected. (Refer to interim guidelines for PrEP from the Centers for Disease Control and Prevention, www.cdc.gov). Discuss the pros and cons with your provider, preferably an HIV specialist (go to referral link at www.aahivm.org). Currently, DHHS HIV treatment guidelines recommend Truvada over Epzicom as the only preferred medication for the NRTI component for first-time therapy. Should prevention with Truvada fail, Epzicom could become more important. One study reported that while both Epzicom and Truvada reduced viral load, for those people who started treatment with a viral load of more than 100,000, Epzicom was “less effective at controlling HIV” in the regimens tested. Moreover, time to a serious adverse event was sooner in the people taking Epzicom. Kidney function must be monitored before and during treatment with Truvada and it may not be a good option for patients with underlying kidney problems. Tenofovir alafenamide, or TAF, a prodrug (substance that becomes activated after entering the body) of tenofovir still in development, works in the same way, but is expected to provide greater effectiveness at a dose approximately 10 times lower than that used for tenofovir DF. Truvada is contained in three single-tablet regimens taken once daily: Atripla, Complera, and the new Stribild. Although the effect of supplementation with calcium and vitamin D has not been studied, such supplementation may be beneficial for all patients, according to the FDA. See package insert for more information on side effects and interactions.

STANDARD DOSE:

For adults and children 12 years or older weighing more than 77 pounds, one tablet (200 mg emtricitabine / 300 mg tenofovir DF) once daily, with or without food, with no dietary restrictions. Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Dosing frequency needs to be adjusted for people with decreased kidney function. Truvada should not be used if kidney function is less than 30 mL/min or if you are on dialysis. Truvada is approved for prevention (pre-exposure prophylaxis, or PrEP) in HIV-negative adults at high risk for HIV. Do not use for PrEP if kidney function is less than 60 mL/min. manufacturer:

Gilead Sciences, Inc. www.gilead.com (800) GILEAD-5 (445–3235) awp:

$1,467.97 / month

Activist’s comments

The marriage of tenofovir (Viread) and emtricitabine (Emtriva), has become a cannon in the HIV drug armamentarium, and a mainstay of treatment today. The combined blue pill is not only pretty but has been approved for use as a prevention pill. Used in Atripla, Complera, and Stribild, the combo pill has become a blockbuster for Gilead. Consideration of side effects related to tenofovir is recommended before taking this combo pill. — Matt Sharp

March+April 2013 | positivelyaware.com/truvada

HIV DRUG GUIDE

2013

Videx EC

didanosine, or ddI NRTI: Nucleoside reverse transcriptase inhibitor (nucleoside, or nuke)

Potential side effects and toxicity STANDARD DOSE:

One 400 mg entericcoated didanosine (Videx) EC, delayedrelease capsule once a day for people who weigh 132 pounds or more. Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Dose needs to be adjusted for those weighing less than 132 pounds; kidney function less than 60 mL/min; and when combined with tenofovir DF (Viread), Truvada, or Atripla. Take strictly on an empty stomach (unless taking with tenofovir), one hour before or two hours after food or drink, except water. Approved for children weighing at least 44 pounds. Capsules must be swallowed whole. Videx is also available as a buffered powder for oral solution. Generic didanosine EC (pictured) is available.

Peripheral neuropathy (tingling, burning, numbness, or pain in the hands or feet) may go away once didanosine (Videx EC) is stopped, but can be painful and permanently debilitating if not treated in time or if you continue to use the drug after symptoms of neuropathy start. It occurs more frequently when didanosine EC is used with stavudine (Zerit) or in people with more advanced HIV. Upset stomach, diarrhea, headache, and, more rarely, pancreatitis (inflammation of the pancreas), have also been reported. Pancreatitis can be life-threatening and may cause pain in the stomach and back, along with nausea, vomiting, and blood in the urine. Risks for pancreatitis include higher than recommended doses of NRTIs, advanced HIV, and alcohol use. Stop all HIV medications and see a health care provider right away. Body fat redistribution/accumulation has also been reported. Recently, cases of non-cirrhotic portal hypertension (increased blood pressure in the vessels that connect to and from the liver) associated with the use of didanosine EC have been reported. Symptoms (elevated liver enzymes, enlarged spleen, blood in vomit, and fluid collection in abdomen) may begin months to years after starting didanosine EC. Routine doctor visits and lab tests will assist in early detection and prompt discontinuation of didanosine EC. Other possible toxicities include eye changes and optic neuritis. Have periodic eye exams by

Doctor’s comments

www.bms.com (800) 321-1335

Videx (didanosine or ddI) was the second approved drug for treating HIV. In its earliest form, it was a very large tablet that needed to be taken on an empty stomach, making for complicated treatment regimens when combined with other drugs. The first combination therapy involved using ddI with AZT which improved outcomes for a short time but carried many toxicities. Videx has mostly fallen out of use. Its side effect profile was high, including pancreatitis, liver function abnormalities, lipoatrophy, and neuropathy. There is a lot of overlap in resistance patterns with tenofovir and abacavir, which are most likely to be used as first-line nucleosides, so that patients who fail those other regimens are often resistant to Videx. —Howard A. Grossman, MD

awp:

Activist’s comments

manufacturer:

Bristol-Myers Squibb

$515.84 / month for 400 mg capsules; $368.72 for generic

HIV DRUG GUIDE

2013

One of the infamous “D” drugs, Videx, or ddI as it was known in the early years of AIDS, was literally one of the most distasteful of AIDS therapies. Originally taken in an Alka-Seltzer sized, white, chalky pill, it was either chewed or dissolved in water—talk about adherence problems! It was the first drug offered in an expanded access program for people who had developed resistance to AZT. Unfortunately, pancreatitis and peripheral neuropathy were reported. Today, a newer version that is enteric coated (EC) is an improvement over the older version, yet it is rarely used anymore, especially if Viread is used. Oh, and if for some reason you are taking Videx EC, don’t eat at the same time. — Matt Sharp

someone who knows you are HIV-positive. Increased uric acid levels (indicating several disorders, including kidney damage and metabolic diseases), and insomnia are other potential side effects. People with a history of peripheral neuropathy, pancreatitis, or heavy alcohol use should avoid didanosine EC. See page 57 for potential drug class side effects.

Potential drug interactions

Should not be taken with tenofovir DF (Viread), if possible. However, if co-administration is necessary, use tenofovir with caution and close monitoring, since didanosine EC levels are increased with tenofovir DF (a medication also found in Atripla, Complera, Stribild, and Truvada). Didanosine EC dose should be decreased to 250 mg daily for patients weighing more than 132 lbs. and 200 mg daily for those weighing less. Adjust dose of didanosine EC when taking tenofovir, Truvada, Atripla, Complera, or Stribild to avoid Videx-related toxicity, including neuropathy and pancreatitis. The combined use of didanosine and zidovudine, stavudine, or hydroxyurea may increase risk of peripheral neuropathy. Didanosine EC taken with stavudine increases the risk of facial wasting and/or lactic acidosis. Combining it with stavudine, hydroxyurea, alcohol, ganciclovir, valganciclovir, or intravenous (not inhaled) pentamidine may increase risk of pancreatitis. Do not take with ribavirin or allopurinol. Also, ganciclovir substantially increases didanosine EC levels, and it’s generally recommended they not be taken together. If there is no alternative to ganciclovir, use it with caution and monitor for Videx toxicity. Videx powder in oral solution should be taken on an empty stomach one hour before or two hours after protease inhibitors, Tagamet (cimetidine), ketoconazole, itraconazole, and dapsone, and one hour apart from Rescriptor. Didanosine EC capsules can be taken with them, but still on an empty stomach. With tenofovir, it may be taken with a light snack (low-fat, 373 calories). Methadone decreases Videx powder concentrations significantly and should not be used together, but if necessary, the didanosine EC capsule formulation should be used.

More information

Videx EC is rarely used. Compared to stavudine, it may have lower risk of peripheral neuropathy, but the rate found in clinical trials was still 12-34%. This is hardly an issue anymore, since stavudine is even more rarely used (if ever). The enteric coating helps reduce diarrhea. Those with reduced kidney function may require a lower dose. Notify your doctor right away if peripheral neuropathy is suspected. Although generics should be as effective as brand name drugs, insurers may require people to take generics to cut costs, rather than brand-name products. For example, if generic efavirenz were available, the singletablet Atripla might be switched to Viread plus generics lamivudine and efavirenz. Also, generics might limit choices of therapy. For example, newer, brand-name drugs might be restricted to those who can’t physically tolerate generic regimens. See package insert for more complete information on potential side effects and interactions.

March+April 2013 | positivelyaware.com/videx

tenofovir disoproxil fumarate (tenofovir DF), or TDF

Viread

NtRTI: Nucleotide reverse transcriptase inhibitor (nucleotide, NtRTI, or nuke)

Potential side effects and toxicity

Overall, fairly well tolerated; however, some may experience headache, diarrhea, pain, depression, nausea, weakness, and gas. Decreases in bone mineral density (BMD) have been observed. BMD monitoring should be considered in people who have a history of pathologic bone fracture or are at risk for osteopenia or osteoporosis. Creatinine clearance (CrCl) should be assessed before initiating treatment with Viread. CrCl and serum phosphorus should be monitored more often in patients at risk for kidney problems. Less common side effects of Viread include kidney toxicities and low blood phosphate. Since Viread is not metabolized by the liver (and appears to have less toxicity in the liver than the majority of the NRTIs), it is believed there should be minimal impact on individuals with liver disease. See page 57 for potential drug class side effects.

Potential drug interactions

Do not take with Atripla, Complera, Hepsera, Stribild, Truvada, or “572-Trii” since tenofovir DF (Viread) is in these drugs or they contain equivalent medication. Didanosine (Videx) levels are increased with tenofovir DF; therefore, use with caution and make sure your didanosine dose is adjusted accordingly and monitored for toxicities. Didanosine EC dose should be decreased

Doctor’s comments

Viread (tenofovir) is probably the most commonly prescribed nucleoside analogue antiviral being used today in resource-rich settings. It is in Truvada, Atripla, Complera, and Stribild. The drug is very well tolerated and has potent activity when used in combination. The two major toxicities for which monitoring is important are declining kidney function and bone loss. The former is more serious and may result in needing to decrease the dose or stop the drug. Kidney function can be monitored easily with basic blood chemistry tests. Bone loss has been documented, especially when people first start taking the drug. While the loss (osteopenia) reaches statistical significance, it has not been associated with an increased rate of fracture, the main concern when people develop osteoporosis. — Howard A. Grossman, MD

Activist’s comments

Gilead’s wunderkind is taken so widely for treatment and recently as a part of prevention pill that some have joked that it should be put in our drinking water. Laughs aside, the drug has taken over as the most important backbone in HIV treatment, especially when used in the fixed dose pill Truvada, or better yet, the numero uno HIV drug called Atripla. The trouble may be in the fact that if people with existing kidney function issues take the drug, there may be more serious problems down the road. Also, the story is still unclear whether Viread causes more bone issues than other antiretroviral drugs. — Matt Sharp

to 250 mg daily for patients who weigh more than 132 pounds (60 kg) and 200 mg daily for those less weighing less. Tenofovir DF decreases the concentration levels of Reyataz. Therefore, Reyataz can only be used boosted when in combination with tenofovir DF or Truvada. Both Reyataz and Kaletra increase Viread levels. Higher Viread levels could increase the risk of Viread-associated adverse events, including kidney disorders. Patients taking Reyataz and tenofovir DF should be monitored for Viread-associated adverse events. When Reyataz is taken with Viread, the dose of Reyataz is 300 mg and has to be taken with ritonavir (Norvir) 100 mg (all as a single daily dose with food). Unboosted Reyataz (without ritonavir) should not be taken with Viread or Truvada. No dose adjustment is needed when used with Kaletra. Avoid using tenofovir DF with kidney-toxic drugs. Incivek increases tenofovir DF levels: monitor closely for tenofovir DF side effects.

More information

Tenofovir DF (Viread) combined with emtricitabine (Emtriva), as Truvada, is considered the preferred NRTI combination by DHHS HIV treatment guidelines for first-time therapy. A pro-drug (substance that becomes activated after entering the body) of tenofovir, tenofovir alafenamide, or TAF, is being studied. The pro-drug has the same mechanism of action, but is expected to provide greater effectiveness and less toxicity at a dose approximately 10 times lower than that used for Viread. TAF is less likely to affect the kidneys, but still has activity against hepatitis B. Its lower dose also makes coformulations with other drugs more possible. Gilead has entered into an agreement to develop a fixed dose combination of emtricitabine, TAF, cobicistat, and Janssen Therapeutics’ darunavir (Prezista). Tenofovir DF was approved last year as part of Truvada for HIV prevention as PrEP (pre-exposure prophylaxis).The body clears most of tenofovir DF through the kidneys and the dosing interval needs to be adjusted for those with impaired kidney function. Serious kidney problems have been rare and mostly in those with pre-existing kidney disease or taking kidney-toxic drugs. Two large observational studies found a greater risk of kidney toxicity with tenofovir. It is recommended that individuals with impaired kidney function be monitored closely, especially those with advanced HIV disease, high blood pressure, and diabetes. Tenofovir DF is FDA approved for hep B therapy and is used by itself for hep B treatment, but should not be used alone by people with both hep B and HIV. If you have HIV and HBV and your hep B needs treatment but your HIV doesn’t, guidelines recommend treatment for both. If your HIV develops resistance to tenofovir and/or emtricitabine, it doesn’t mean that your HBV is also resistant to them. Tenofovir DF may have prolonged activity against hepatitis B even when resistant to Epivir. If you are co-infected with HIV and HBV and you stop tenofovir, you may experience signs and symptoms of acute HBV. You should be closely monitored by your physician. The FDA noted that calcium and vitamin D supplements may be beneficial for all patients taking Viread. See package insert for more complete information on potential side effects and interactions.

March+April 2013 | positivelyaware.com/viread

STANDARD DOSE:

One 300 mg tablet once a day, with or without food, with no dietary restrictions. Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Dosing frequency needs to be adjusted for people with decreased kidney function. One 150 mg, 200 mg, or 250 mg once a day for children ages 2 or older weighing at least 37 pounds. Oral powder formulation available for children ages 2 and up. FDA approved for chronic HBV in patients 12 years and older. manufacturer:

Gilead Sciences, Inc. www.gilead.com (800) GILEAD-5 (445–3235) awp:

$998.80 / month

HIV DRUG GUIDE

2013

Zerit

stavudine, or d4T NRTI: Nucleoside reverse transcriptase inhibitor (nucleoside, or nuke)

Potential side effects and toxicity STANDARD DOSE:

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

Bristol-Myers Squibb www.bms.com (800) 321-1335 awp:

$553.12 / month for 40 mg capsules; $411.16 for generic

Headache, diarrhea, nausea, rash, and peripheral neuropathy (tingling, burning, numbness or pain in the hands or feet) are the most common side effects. Peripheral neuropathy is more common in people who have more advanced HIV or are taking other medications that can cause peripheral neuropathy. It goes away once stavudine (Zerit) is stopped, but can be painful and permanently debilitating if stavudine is not stopped as soon as neuropathy is noticed. Caregivers of young children should be instructed on noticing and reporting peripheral neuropathy. Additive lipoatrophy (facial wasting) and mitochondrial toxicities can occur when combined with didanosine (Videx EC). Adverse reactions and serious laboratory abnormalities in children were similar in type and frequency to those seen in adults. Pancreatitis (inflammation of the pancreas) can be life-threatening and may cause pain in the stomach and back, along with nausea, vomiting, and blood in the urine. Risks for pancreatitis include higher than recommended doses of NRTIs, advanced HIV, and alcohol use. Stop all HIV medications and see a health care provider right away. Your physician will check for pancreatitis by doing blood tests. People with a history of peripheral neuropathy, pancreatitis, or heavy alcohol use should avoid stavudine. Lipoatrophy, fat loss in the face and limbs (arms and legs) and, to a lesser degree, lipohypertrophy (such as “buffalo hump” and increased abdominal fat) have been associated with stavudine. Stavudine and zidovudine (Retrovir)

Doctor’s comments

The third approved drug for HIV, Zerit (stavudine or d4T), was once widely used. It did not have the same toxicities as AZT, especially in regard to anemia and nausea and so it was hoped that it would be much better tolerated. Zerit turned out to have even more serious side effects. It caused neuropathy, lipodystrophy, hepatic steatosis (fatty liver), and pancreatitis. The use of stavudine fell off in resourcerich settings over a decade ago, but it remained a mainstay of treatment in resource-poor settings, as it was one of the first and least expensive generic drugs. Even in those settings, though, a broad move away from stavudine is under way. — Howard A. Grossman, MD

are the HIV drugs most implicated by studies as causing lipoatrophy. Stavudine also seems to be implicated in blood lipid (fat) increases, particularly triglycerides. See page 57 for potential drug class side effects.

Potential drug interactions

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

More information

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

Activist’s comments

HIV DRUG GUIDE

2013

I remember this drug as d4T, probably the most insidious of the “D” drugs. Back in the early days, it was one of the newer, more hopeful drugs that had similar promise as AZT. In early use of the drug, like many other AIDS therapies, no one knew of the troubles that lay ahead. Serious adverse events caused by the effect of the drug on the cell mitochondria leading to neuropathy, lactic acidosis, and disfiguring facial atrophy put the death knell on widespread use in the developed world. Elsewhere, it is the only option, so many people are forced to deal with the side effects simply because the newer drugs are not obtainable. — Matt Sharp

March+April 2013 | positivelyaware.com/zerit

Ziagen

abacavir sulfate (abacavir), or ABC NRTI: Nucleoside reverse transcriptase inhibitor (nucleoside, or nuke)

Potential side effects and toxicity

Approximately 5–8% of people who took abacavir (Ziagen) experienced hypersensitivity reaction (HSR, an allergic-like reaction). A blood test, covered by insurance (and also paid for by LabCorp/ViiV—see chart, page 72-73), for HLA-B*5701 (a genetic marker) can identify patients at risk for this reaction and virtually eliminate HSR. Do not use a skin patch test to confirm HSR. If the HLA-*B5701 test is positive, this means that you will likely have the HSR if you start taking abacavir, and an allergy to it should be entered in your medical record even if you have never taken abacavir in the past. If you start abacavir without having the HLA-B*5701 test done, you should be monitored closely the first six weeks or so (HSR usually occurs within that time). If you develop HSR, treatment with abacavir will be stopped and you can never take abacavir or any other product containing

Doctor’s comments

Ziagen (abacavir) is a well-tolerated drug that is part of useful nucleoside backbones in combination therapy. It is most often combined with lamivudine, both being manufactured by ViiV Healthcare. Abacavir is also part of the three-nuke combination Trizivir and the investigational single-tablet regimen known as “572-Trii.” The medication has few side effects. The major concern is that some people develop a serious hypersensitivity reaction to the drug. Screening for the genetic marker HLA-B*5701 helps to identify those at risk for hypersensitivity—people who are positive cannot take abacavir. There is some evidence that it may not be as potent at high viral loads as tenofovir (Viread). Finally, there is data from some very large observational databases that seem to indicate an increased incidence of cardiovascular events for patients on abacavir. Other large data sets have shown no correlation. While there is, therefore, no clear evidence of a cardiac problem, most clinicians opt to avoid abacavir in patients at high risk for cardiovascular disease and in those who already have it. — Howard A. Grossman, MD

Activist’s comments

Another problematic yet well tolerated nuke, Ziagen (abacavir) held early promise as a new option because it was a once-daily drug and more potent. ACT UP Golden Gate staged demonstrations crushing the pills under pavement steamrollers when GlaxoSmithKline, then the manufacturer, refused to offer it in an early access program. When the company finally acquiesced, providing the drug in expanded access programs, a serious life-threatening hypersensitivity was reported in a small percentage of people taking the drug. The company spent gazillions in discovery of a test to tell who would develop this hypersensitivity. To top it off, there are conflicting studies as to whether Ziagen can cause heart problems. With all this baggage, unless people cannot tolerate Truvada, Ziagen might not even be worth steamrolling. — Matt Sharp

abacavir, such as Epzicom, Trizivir, or the investigational “572-Trii,” again (called “re-challenging”). Re-challenging can cause a rare life-threatening reaction. (This does not apply to missed doses when there’s no HSR, but watch for symptoms if you’ve stopped the drug for at least a few days.) Symptoms of HSR usually worsen, very slowly, with every dose. People who think they are experiencing HSR must be evaluated by an experienced HIV provider right away before they stop taking abacavir. Symptoms resolve quickly (24–48 hours) after permanent discontinuation. Symptoms usually include some combination of fever; muscle ache; malaise (general ill feeling); severe nausea, vomiting, diarrhea, or abdominal pain; severe tiredness; respiratory symptoms (cough, difficulty breathing, or sore throat); and possible rash. Symptoms are listed on the patient information sheet and warning card that you receive each time you fill your prescription. You should keep the warning card with you. HSR might be confused with flu, but remember that HSR worsens with every dose. Check with your doctor if you have any side effects after taking this medicine—don’t just stop! More common side effects may include nausea, vomiting, diarrhea, fatigue, headache, fever, rash, trouble sleeping, unusual dreams, and anorexia (loss of appetite). Some observational studies seemed to indicate that abacavir may increase the risk of cardiovascular events, including heart attacks, in people with risk factors (such as older age, smoking, diabetes, high blood pressure, high cholesterol, and drug use). Multiple studies have looked at the association between abacavir use and the risk for MI (myocardial infarction, or heart attack) but to date, no consensus has been reached either on the association of abacavir with MI risk or a possible mechanism for the association; see Epzicom for more information. People who have high risk for heart disease are monitored more closely and the decision to stop or never start a regimen containing abacavir is up to you and your provider. See page 57 for potential drug class side effects.

STANDARD DOSE:

Two 300 mg tablets once a day (or one 300 mg tablet twice a day), with or without food, with no dietary restrictions; scored tablets available for children. A strawberry/banana flavored liquid is available (20 mg/mL). Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Dose does not need to be adjusted for people with kidney impairment. Ziagen can be used in children as young as 3 months old. manufacturer:

ViiV Healthcare

www.viivhealthcare.com (877) 844-8872 AWP:

$602.66 / month for capsules; $176.23 for 240 mL solution (20 mg/mL)

Potential drug interactions

Do not take with Epzicom, Trizivir, or “572-Trii” since abacavir is already in these medications. Excessive alcohol increases abacavir levels and may increase side effects.

More information

It is recommended that people with symptoms of acute respiratory disease consider HSR even if another diagnosis such as pneumonia, bronchitis, or flu is possible. FDA researchers reported finding a mechanism for autoimmune drug reactions, including abacavir HSR and hope it helps improve drug safety in the future. Abacavir is part of Epzicom; see Epzicom page. Dose adjustment is needed in people with mild liver disease and the oral solution will need to be used for these patients. There are no data in people with moderate/severe liver disease and therefore it should not be used for those individuals. See package insert for more complete information on potential side effects and interactions.

March+April 2013 | positivelyaware.com/ziagen

HIV DRUG GUIDE

2013

Edurant

rilpivirine hydrochloride (rilpivirine), or RPV NNRTI: Non-Nucleoside reverse transcriptase inhibitor (non-nucleoside, or non-nuke)

Potential side effects and toxicity STANDARD DOSE:

One 25 mg tablet once daily with a meal. Take missed dose as soon as possible with a meal, unless it is closer to the time of your next dose. Do not double up on your next dose. A protein drink alone does not constitute a meal. manufacturer:

Janssen Therapeutics

www.janssentherapeutics.com (877) JANSSEN (526-7736) AWP:

$855.86 / month

Insomnia, headache, rash, and depressive disorders (depression and negative or suicidal thoughts or actions). Nephrotic syndrome, a kidney disorder, was added to the post-marketing experience section, with the explanation that the level of risk is unknown, and that the syndrome may not even be related to rilpivirine (Edurant). Combined information from two different studies comparing Edurant to Sustiva showed that Edurant was slightly better tolerated. Edurant also has minimal negative effects on “bad” cholesterol, total cholesterol, and triglycerides when compared to efavirenz (Sustiva). See page 57 for potential drug class side effects.

Potential drug interactions

Doctor’s comments

Edurant (rilpivirine) was approved as a single agent in 2011, but it is now part of a fixed dose combination with Truvada (emtricitabine/tenofovir DF) called Complera. Complera has proven equally as potent as Atripla in patients with viral loads of less than 100,000 copies. In patients with viral loads greater than 100,000 copies, however, there were more virologic failures and a greater development of resistance with rilpivirine. Rilpivirine may treat viruses that contain only the K103N mutation, most likely the first mutation in failure with earlier NNRTI drugs, especially efavirenz (Sustiva). If patients remain on a failing regimen too long, they may accumulate other viral mutations that can compromise the ability to sequence using rilpivirine. Development of resistance to rilpivirine may create cross-resistance with Intelence (etravirine). The drug is very well tolerated with few side effects. It must be taken with a 400-calorie meal of solid food given at close to the same time each day. Failure to heed the food requirement may result in inadequate blood levels. Rilpivirine has a number of drug interactions requiring dose adjustment of other drugs, especially protease inhibitors. — Howard A. Grossman, MD

Activist’s comments

HIV DRUG GUIDE

2013

The newest non-nuke, I’m not sure who came up with the name for this drug. Essentially a me-too drug, it is on the market to compete with the top selling Sustiva for those new to HIV treatment. Yet there are some who may find it beneficial if they cannot tolerate the neuro side effects of Sustiva. Activists pushed the company to perform studies in people with higher viral loads since it was found out that it is less effective in that group. It has to be taken on a full stomach, and cannot be taken with antacids. — Matt Sharp

rilpivirine or have equivalent medication. Can be taken with Isentress without dose adjustments. Antacids should be taken two hours before or at least four hours after a rilpivirine dose. H2 receptor antagonists, such as Pepcid, Tagamet, and Zantac, should be taken 12 hours before or four hours after a rilpivirine dose. Proton pump inhibitors, such as Aciphex, Nexium, Prevacid, Protonix, and Prilosec, should not be taken. Cannot be taken with the anti-seizure medications carbamazepine, oxcarbazepine, phenobarbital, and phenytoin; the anti-TB drugs rifabutin, rifampin, and Priftin (rifapentine); or the herb St. John’s wort. Do not take with more than one injectable dose of the steroid dexamethasone; repeated topical use is okay. Clinically monitor the anti-fungals fluconazole (Diflucan), itraconazole (Sporanox), ketoconazole (Nizoral), posaconazole (Noxafil), and voriconazole (Vfend); dose adjustment for these medications may be needed. Use azithromycin when possible instead of the antibiotics clarithromycin (Biaxin), erythromycin, and telithromycin. Methadone levels are reduced slightly and patients should be monitored for symptoms of withdrawal. Should be used with caution when taken with medications with a known risk of Torsade de Pointes or QT prolongation (these are abnormal heart rhythms and can make the heart stop). Okay to take with Incivek, but there is no information yet on using it with Victrelis (both are medications for hep C).

More information

Use with caution in patients with a viral load of greater than 100,000 copies/mL. ECHO and THRIVE studies showed that Edurant is non-inferior (a term used in scientific research that means the drug is no worse nor better than those it’s compared to) to Sustiva in efficacy—84% vs. 82% of patients achieved a viral load of less than 50 copies/mL (undetectable) and CD4 count increases of 190 vs. 172 when comparing Edurant and Sustiva, respectively. While its tolerability and safety profiles are advantages for Edurant, the greater potential for virologic failure and cross-resistance to the other NNRTIs compared to Sustiva puts Edurant at a disadvantage for first-time treatment, since people may not be able to switch to another NNRTI if their HIV develops NNRTI resistance mutations with Edurant. For proper absorption, it must be taken with a meal that you chew, not nutritional drinks or protein shakes. The amount of fat doesn’t matter. Meal examples include two slices of whole wheat toast with peanut butter, fresh fruit, and orange juice; a roast beef sandwich on a hard roll with mayo and cheese; or two cups of spaghetti with marinara sauce and a slice of bread. Edurant is a tiny pill about the size of a baby aspirin. While Sustiva is associated with a risk of birth defects, Edurant is Pregnancy Category B (found safe in animal studies), but no studies in humans have been conducted, and Edurant should be used in pregnancy only if the potential benefit justifies the potential risk. Most HIV medications are Pregnancy Category B and carry the same warning. See package insert for complete information on potential side effects and drug interactions.

March+April 2013 | positivelyaware.com/edurant

Intelence

etravirine, or ETR NNRTI: Non-Nucleoside reverse transcriptase inhibitor (non-nucleoside, or non-nuke)

Potential side effects and toxicity

Generally tolerable, but most common side effects (though rarely seen) include nausea, rash, and peripheral neuropathy. The FDA advises, “Discontinue Intelence immediately if signs or symptoms of severe skin reactions or hypersensitivity reactions develop (including, but not limited to, severe rash or rash accompanied by fever, malaise [general ill feeling], fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis [eye inflammation], facial edema [swelling], hepatitis, and eosinophilia [increased levels of the white blood cells called eosinophils, a sign of an allergic reaction]).” In addition, levels of liver enzymes called transaminases should be monitored. Rash is associated with all of the current non-nukes, but if you develop a rash from Intelence, you may still be able to take one of the other non-nukes. See page 57 for potential drug class side effects.

Potential drug interactions

See package insert for the most complete list. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Intelence should not be taken with other non-nukes or medications that contain them (Atripla and Complera). It should not be taken with unboosted

Doctor’s comments

Intelence (etravirine) is a second-generation NNRTI. It may be useful for people where Sustiva or Viramune have failed, if a switch is made early in treatment failure. The first NNRTI mutation that usually occurs is K103N and Intelence works in the presence of this mutation, allowing a sequencing of non-nukes. Remaining on the failing regimen, however, may lead to a greater number of mutations and this could compromise Intelence use. It is welltolerated. The major drawback in today’s market with its mania for once-a-day therapy is that it is a twice-a-day drug. Some prescribers were giving it once-a-day, but a controlled clinical trial reported in 2012 showed that once-a-day was not as effective as twice-a-day. The drug, originally available only as 100 mg tablets, is now available as 200 mg tablets, meaning one pill twice a day. There are a number of important drug interactions that can affect the dosing of other drugs. — Howard A. Grossman, MD

Activist’s comments

We waited a long time for Intelence since it was not cross-resistant to the older non-nukes. It was not easy to study, or produce. However, a good alternative non-nuke for people who have developed resistance to either Viramune or Sustiva, in fact it was developed to be just that. Fortunately, the new 200 mg pill taken once daily is better than taking two of the older 100 mg pills, however the pills are a bit rough to swallow for some. Toxicities are few, and in combination with other new agents, Intelence is a helpful addition for people with few effective nonnuke options. — Matt Sharp

(without Norvir) PIs, or with Aptivus/Norvir, Reyataz/ Norvir, or Lexiva/Norvir. It can, however, be taken with Prezista/Norvir, Kaletra, and Invirase/Norvir. It can be taken with the integrase inhibitor Isentress. Taking it with Selzentry requires a Selzentry dose adjustment to 600 mg twice daily when used without a boosted PI. Adjust Selzentry dose to 150 mg twice daily if taken with both Intelence and Prezista 600 mg/Norvir 100 mg twice a day. In people who’ve failed therapy with other NNRTIs, Intelence should not be taken only with NRTIs. Do not take with carbamazepine, phenobarbital, phenytoin, Priftin, rifampin, or the herb St. John’s wort. Use with caution when combined with antifungals (fluconazole and voriconazole). Atorvastatin dose may need adjustment based on clinical response. Dose adjustments may be needed for fluvastatin, lovastatin, pitastatin, and simvastatin. Monitor the effectiveness of warfarin and adjust dose if needed. Alternatives to Plavix should be considered when used with Intelence. Clarithromycin may be used in cases of MAC (mycobacterium avium complex), in which alternatives like azithromycin should be considered. Lower diazepam dose may be needed. Use caution with systemic dexamethasone or consider alternatives. Do not take Intelence with Mycobutin if you’re on a Norvir-boosted PI. If you’re not, Mycobutin dose should be 300 mg once daily. No interaction was found between Intelence and acid suppressants (Prilosec, Zantac, and others). Intelence can be safely combined with methadone; monitoring may be necessary. Intelence can also be safely combined with Viagra, Cialis, and Levitra, though a higher dose of these drugs may be needed.

More information

This second-generation drug was developed to have a higher genetic barrier (more than one mutation) to drug resistance. It has shown significant viral load reduction in people with drug resistance to Sustiva or Viramune. The older NNRTIs can develop resistance quickly, and with only one viral mutation. For patients who have had virologic failure on an NNRTI-containing regimen, do not use Intelence in combination with only a nucleoside backbone. Some physicians are prescribing Intelence once daily to increase adherence, although not FDA approved. Some patients complain of hard-to-swallow, large chalky pills; see dissolving instructions in dose section. Comparative studies between the 100 mg and 200 mg tablets showed a high rate of patient preference for the 200 mg tablets because they were dissolveable and thus, easier to swallow. See package insert for more complete information on potential side effects and interactions.

March+April 2013 | positivelyaware.com/intelence

STANDARD DOSE:

One 200 mg tablet, or two 100 mg tablets, twice a day, with food. 25 mg tablets available for children 6–18 years old (dose based on weight). Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. People unable to swallow pills can dissolve tablets in 5 mL (1 teaspoon) of water, or at least enough liquid to cover the medication, stir well until the water looks milky, add more water if desired, or alternatively orange juice or milk (tablets should be placed in water first). Avoid grapefruit juice and warm (over 40°C) or carbonated beverages. Drink it immediately, rinse the glass several times with water, orange juice, or milk and completely swallow the rinse each time to make sure the entire dose is taken. manufacturer:

Janssen Therapeutics

www.janssentherapeutics.com (877) JANSSEN (526-7736) AWP:

$1,041.26 / month

HIV DRUG GUIDE

2013

Rescriptor

delavirdine, or DLV

NNRTI: Non-Nucleoside reverse transcriptase inhibitor (non-nucleoside, or non-nuke)

Potential side effects and toxicity STANDARD DOSE:

Two 200 mg tablets or four 100 mg tablets three times a day (every 8 hours). Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Take with or without food. Only the 100 mg tablets can be dissolved in liquid. manufacturer:

ViiV Healthcare

www.viivhealthcare.com (877) 844-8872 AWP:

$381.89 / month for 200 mg tablets

Most common side effects are elevated liver enzymes and itchy skin or rash. A serious side effect of the NNRTI class is rash, which can be life threatening. Most rashes occur one to three weeks after starting Rescriptor. If you experience blistering, mouth lesions, conjunctivitis (redness or inflammation of the eye, which if untreated may result in permanent vision loss), swelling, muscle or joint aches, fever, or malaise (general ill feeling), you should stop the medication, and seek medical attention right away. See page 57 for potential drug class side effects.

Potential drug interactions

Non-nukes interact with many other drugs. See package insert for the most complete list. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. You should not take Rescriptor with triazolam (Halcion), migraine medicines in any form, pimozide (Orap), midazolam (oral Versed), Xanax (alprazolam), or the herb St. John’s wort. Do not use Mevacore, Vitorin, or Zocor cholesterol (lipid) lowering meds; suggested alternatives are atorvastatin (Lipitor), fluvastatin (Lescol), and pravastatin (Pravacol). Liver enzymes should be checked regularly if you are on these cholesterol meds, as they can increase risk for liver toxicity with Rescriptor. Rescriptor needs stomach acid in order to be absorbed correctly. Over-the-counter antacids, like Tums or Maalox, decrease absorption of Rescriptor, so take it one hour apart from these remedies. Other acidreducing drugs (like Zantac, Tagamet, and Prilosec) may

Doctor’s comments

Rescriptor (delavirdine) was the first approved NNRTI, but is rarely used anymore. It needs to be taken three times a day, can cause a rash, has a low barrier to resistance and may be less effective than other drugs in its class and has, therefore, been overshadowed by more recently developed medications. It is generally a well tolerated drug. There are no studies of Rescriptor with newer medications, though it is unique among NNRTIs in that it can increase protease inhibitor levels. Therefore, it has continued to be used as a boosting agent in some patients who cannot tolerate Norvir. The recent development of the new boosting agent, cobicistat, may have an impact on the market for Rescriptor, but this will remain unclear until cobicistat is available as a single agent or in combination with protease inhibitors. — Howard A. Grossman, MD

Activist’s comments

HIV DRUG GUIDE

2013

also reduce absorption of Rescriptor—try not to take them together for long periods of time. People with low stomach acid should take Rescriptor with acidic beverages (orange or cranberry juice, etc.) to increase acidity. Certain amphetamines and antiarrhythmic drugs should not be used with Rescriptor—therefore, inform your health care provider if you have a history of heart or blood pressure problems. Dose adjustment may be needed when taken with clarithromycin (Biaxin) if you have decreased kidney function. Rescriptor should be used with caution with Procardia or Adalat (nifedipine), Norvasc (amlodipine), Plendil (felodipine), quinidine, and warfarin (Coumadin). Use caution with anti-convulsants: carbamazepine (Tegretol), phenobarbital, and phenytoin (Dilantin). Mycobutin (rifabutin) and rifampin (Rifadin), used to treat tuberculosis, decrease Rescriptor levels. Rescriptor is not recommended with either Mycobutin, rifampin, or Priftin (rifampentine). Rescriptor increases levels of protease inhibitors Crixivan, Lexiva, Invirase, Kaletra, Norvir, and Viracept, as well as immunosuppressants (including transplant drugs), birth control pills (ethinyl estradiol), and methadone, so caution is advised if using together. Cialis, Levitra, and sildanafil (Viagra) levels are increased by Rescriptor; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Also, increased levels of trazodone can occur with Rescriptor and therefore should be used with caution. Increased levels of the inhaled and nasal sprays that contain fluticasone, a steroid for asthma or allergies (found in Advair, Flonase, and Flovent) can occur with Rescriptor which can result in Cushing’s syndrome (increased fat in the abdomen, fatty hump between the shoulders, rounded face, red/purple stretch marks on the skin, bone loss, possible high blood pressure, and sometimes diabetes), and therefore should not be used unless no other options are available.

More information

Very rarely used due to its three-times-a-day dosing, it has not been compared to the newer NNRTIs and the studies done with Rescriptor included the older NRTIs (Retrovir, Videx, Hivid, and Epivir) with only 45% of patients achieving a viral load of less than 400 copies/mL. Research demonstrates that smaller doses of Rescriptor increase blood levels of some protease inhibitors, making it unique among the NNRTIs. Some people who cannot tolerate Norvir (ritonavir) are successfully using Rescriptor instead to boost their protease inhibitor. Studies of this use, however, have not been published. A new booster medication for HIV drugs is expected to be approved this year and is already in Stribild; see cobicistat. See package insert for more complete information on potential side effects and interactions.

Now regarded as a “dud,” this drug was an unfortunate failure. Better stated, it is just a drug that fell out of favor with the arrival of other, better drugs. Now, there is almost no reason to use it, especially with new second-generation non-nukes on the market. It also has some complex interactions with other drugs. Next year perhaps we won’t be seeing this on the HIV drug list. — Matt Sharp

March+April 2013 | positivelyaware.com/rescriptor

Sustiva

efavirenz, or EFV NNRTI: Non-Nucleoside reverse transcriptase inhibitor (non-nucleoside, or non-nuke)

Potential side effects and toxicity

Central nervous system (CNS) or psychiatric symptoms (dizziness, insomnia, impaired concentration, abnormal dreams and hallucinations, depression, suicidal thoughts or actions, aggressive behavior, paranoid and/or manic reactions), usually diminishing within four weeks. A history of drug or alcohol use, psychiatric illness, or the taking of psychiatric medications may increase risk. Other side effects may include rash, nausea, vomiting, diarrhea, fever, and increased liver enzymes, generally resolving within four weeks. Rash in children is more common and more severe, as are low levels of some blood cells. May raise levels of triglycerides and cholesterol. May lead to false positive urine tests for marijuana; a confirmatory test is available. Women should not become pregnant on efavirenz or for 12 weeks after discontinuation, because of the risk of birth defects. Close monitoring for increased liver enzyme levels is recommended initially and levels should be checked regularly in people with hepatitis B and/or C or liver disease. Use with caution when mild liver impairment exists; not recommended with moderate or severe liver impairment. See page 57 for potential drug class side effects.

Doctor’s comments

Sustiva (efavirenz) has become the most widely prescribed antiretroviral, especially in fixed dose combination as Atripla. It is very potent, mostly well tolerated, and has a long half-life. The two major side effects limiting the use of efavirenz are rash and central nervous system effects. The neuro-psychiatric effects (see above) usually disappear after two to four weeks. To minimize side effects, Sustiva and Atripla are usually taken at bedtime on an empty stomach. Food will actually increase the absorption of efavirenz, so the concern was increased toxicity, not decreased efficacy. Longer term, the only other side effect of note is an elevation in lipids, including, in some studies, HDL or “good” cholesterol. HIV easily develops resistance to efavirenz—a single mutation renders it ineffective—so adherence is very important. Missing doses is likely to cause rapid drug failure. Efavirenz is contraindicated for pregnant women, especially during the first trimester. — Howard A. Grossman, MD

Activist’s comments

I first took this drug when it was fresh in the pharmacy and doctors guessed on how to prescribe it in order to manage the side effects. One night, I took the three pills together before bed and woke up to what was literally like a bad acid trip. The drug has serious flaws, but it has a very long half-life and is very potent, so added into Atripla, it is the number one combo pill for newly diagnosed people, and a preferred once-a-day fixed dose pill. Beware, women who may become pregnant, that the drug can cause birth defects. Rash is fairly common as well, and those who have liver issues may bear a double whammy if they are on Sustiva. — Matt Sharp

Potential drug interactions

See package insert for the most complete list. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Do not take with Atripla, Complera, Edurant, Intelence, Rescriptor, or Viramune, since efavirenz is in these drugs or they have equivalent medication. Do not take bepridil, clarithromycin, Gingko biloba, midazolam, pimozide, Priftin, St. John’s wort, or triazolam. Efavirenz may affect warfarin levels. Efavirenz decreases methadone levels; dose adjustment may be necessary to avoid withdrawal. Increase Kaletra to three tablets twice daily with food (recommended) when taken with Sustiva in treatment-experienced people. Kaletra cannot be taken once daily with Sustiva. Monitor liver enzymes closely if Sustiva and Norvir are used together. Reyataz once-daily dose should be 400 mg and boosted with Norvir when taken with Sustiva, but treatment-experienced people should not take this combination at all. With once-daily Lexiva, boost with 300 mg Norvir. Increase the Sustiva dose to 800 mg once daily with rifampin for people weighing 110 pounds or more. Rifabutin can be used as an alternative to rifampin but double the dose. When taken with anticonvulsants carbamazepine, phenobarbital, or phenytoin, periodic monitoring of blood levels of anticonvulsants and efavirenz should be done or alternative anti-seizure medications considered. Effectiveness of birth control pills may be decreased; consider the use of other contraceptives, including a barrier method. The maintenance dose of Noxafil, Sporanox, and voriconazole should be increased to 400 mg every 12 hours and the Sustiva dose should be decreased to 300 mg capsules once daily. Levels of immunosuppressants should be monitored when starting or stopping efavirenz. Atorvastatin, Zoloft, pravastatin, simvastatin, and diltiazem doses may need to be adjusted. Titrate dose of bupropion and sertraline based on clinical response. Efavirenz can decrease levels of buprenorphine. No dose adjustment is recommended, but monitor for withdrawal. Efavirenz can decrease the effects of Malarone; consider alternative drug. Avoid taking Victrelis. Increase Incivek doses to 1,125 mg, which increases the Incivek cost by 50% or so.

STANDARD DOSE:

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

Bristol-Myers Squibb www.sustiva.com (800) 321-1335 AWP:

$785.90 / month for 600 mg tablets

More information

According to DHHS HIV treatment guidelines, Sustiva is the preferred NNRTI for NNRTI-based regimens. It has been proven to work just as well as the newer NNRTIs in people without resistance to the drug class. Avoid driving or operating heavy machinery for a few hours after dose. A sleep medication may be needed at first, though it might cause morning grogginess. If you can’t sleep, ask about switching the timing of your dose little by little until it’s taken in the daytime. Based on the HIV pregnancy registry, very few infants born to women who have become pregnant while on efavirenz have had birth defects. According to perinatal guidelines, it’s recommended that women in their first trimester stay on efavirenz as long as viral load remains undetectable. See package insert for more complete information on potential side effects and interactions.

March+April 2013 | positivelyaware.com/sustiva

HIV DRUG GUIDE

2013

Viramune XR

nevirapine, or NVP

NNRTI: Non-Nucleoside reverse transcriptase inhibitor (non-nucleoside, or non-nuke)

Potential side effects and toxicity

STANDARD DOSE:

One 200 mg IR (immediate release) tablet once daily for two weeks, then full dose of one 400 mg tablet once daily of Viramune XR or one 200 mg IR tablet twice daily, with or without food, with no dietary restrictions. Take missed dose as soon as possible, unless it is closer in time to your next dose. Do not double up on your next dose. If you interrupt therapy for more than seven days, you will need to restart with 200 mg IR daily for 14 days, followed by 400 mg XR once daily or 200 mg IR twice daily. Pediatric 100 mg XR tablets approved last year for children 6 to 18 years of age. Viramune IR frequently prescribed as two 200 mg tablets once daily, although once-daily dosing is not FDA approved with the IR formulation; Viramune XR once daily is approved only for adults. Dose for children 15 days or older is 150 mg/m2 once daily for 14 days, then 150 mg/m2 twice daily thereafter, not to exceed 400 mg daily. For dialysis patients, an additional 200 mg IR is required after each dialysis. 50 mg/5 mL oral suspension also available. Generic available for immediate release formulation. manufacturer:

Boehringer Ingelheim www.viramunexr.com (800) 274–8651 AWP:

$710.87 for XR / month; $650.70 / for generic; $165.98 for 240 mL suspension (50 mg/5 mL) 36

Most common side effects include headache, nausea, vomiting, fever, and rash (reduced with 14-day lead-in dosing). Rarely, severe and life-threatening liver damage, including fatal cases, has occurred. Women with CD4 counts greater than 250 T-cells, including pregnant women, have the highest risk of serious liver damage, though men with more than 400 T-cells are also at risk. The package insert says Viramune or Viramune XR should not be started in these groups unless the benefit outweighs the risk. The highest risk period is within the first six weeks of treatment, but patients should be monitored closely for the first 18 weeks. Severe rash, including Stevens-Johnson syndrome, while rare, can be life-threatening; notify your health care provider immediately. Seek medical attention right away if you experience blistering, mouth sores, conjunctivitis (redness or inflammation of the eye, which if untreated may result in blindness), swelling, muscle or joint aches, fever, or malaise (general ill feeling). Do not increase dose if rash develops

Doctor’s comments

Viramune (nevirapine) was the second approved non-nuclesoside reverse transcriptase inhibitor (NNRTI). It quickly became popular because of its minimal side effects. In resource-limited areas of the world, nevirapine has been a mainstay of treatment due to the low cost of its generic formulation. Both nevirapine and efavirenz (Sustiva) can cause life-threatening skin rashes, but nevirapine has been associated with sudden onset of severe liver inflammation which can lead to liver failure. It is not recommended for women with CD4 counts above 250 and men with counts above 400. For others, nevirapine can be a useful alternative to efavirenz. Long-term safety is very good. There is now a one pill once-aday formulation, Viramune XR, which is 400 mg. If patients fail on an efavirenz-containing regimen, viral resistance must be assessed since the development of the K103N mutation will render nevirapine ineffective. Now that we have another very well tolerated NNRTI in the form of Edurant (rilpivirine) with the added advantage of being in a single tablet regimen (Complera), it is unclear what the impact will be on the use of Viramune, but it would seem to move it down the ladder as a choice. — Howard A. Grossman, MD

Activist’s comments

Actually a good enough drug for the larger part of the world that can afford the lower cost of the original Viramune, this drug is an acceptable alternative to Sustiva, yet serious rashes may occur in those with higher CD4 cell counts. Liver toxicity is another issue, but it is oddly a more lipid-friendly drug than Sustiva. The bonus is that Viramune XR is a once-daily tablet after you start with the lead-in dose of the immediate release version for two weeks. Many people are still using Viramune mostly because they cannot tolerate Sustiva or Atripla. — Matt Sharp

during dose escalation or if it is accompanied by the conditions listed above. Once-daily lead-in dose should not exceed 28 days. An increase in liver enzyme levels has been observed and in rare instances, hepatitis has developed. In such cases, it may be necessary to stop taking Viramune (either formulation) until liver function returns to normal. Permanently discontinue it if abnormalities return. See page 57 for potential drug class side effects.

Potential drug interactions

Non-nukes interact with many other drugs. See package insert for the most complete list. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Do not take with Atripla, Complera, Edurant, Intelence, Rescriptor, Reyataz, or Sustiva. Never take St. John’s wort with Viramune. Rifampin or Priftin (rifampentine) should not be used with Viramune; Mycobutin (rifabutin) is the recommended alternative to rifampin for tuberculosis treatment. Use with caution with midazolam, triazolam, fluconazole, itraconazole, voriconazole, Cordarone, lidocaine or disopyramide, ethosuximide, clonazepam, calcium channel blockers (Procardia and others), immunosuppressants (including transplant drugs), and warfarin (Coumadin). Viramune decreases methadone levels; dose adjustment may be necessary to avoid withdrawal symptoms. Can reduce levels of protease inhibitors; dose adjustment may be needed if they are taken together. Kaletra should be increased to three tablets twice a day in treatment-experienced people. Use caution with anti-convulsants: carbamazepine (Tegretol), phenobarbital, and phenytoin (Dilantin). Effectiveness of birth control pills may be decreased; consider the use of other contraceptives. During the first six weeks of therapy, prednisone should be avoided; it can cause increased severity and incidence of rash.

More information

The once-daily Viramune XR was FDA approved in 2011, but many providers already prescribed once-daily dosing with the old formulation. The regular Viramune (IR) formulation is now available as generic nevirapine. Monitor liver function and signs of rash during first six months. Do not ignore yellowing of eyes or skin, as this may be a sign of a severe liver effect. Nevirapine crosses the blood-brain barrier to a useful degree, which may be beneficial for patients at risk for neurological damage (such as dementia) from HIV. Viramune should not be used for PEP (post-exposure prophylaxis). Viramune has been shown to improve triglycerides and total cholesterol levels. When taken around the time of labor, Viramune has been effective in preventing transmission of HIV from mother to child, but there was an increase in HIV drug resistance when taken alone—use at least one other HIV drug to prevent resistance. Single- or doubledose Viramune may be used for babies born to HIVpositive mothers. In order to prevent HIV transmission to HIV-negative newborns, HIV-positive mothers should not breastfeed. See package insert for more complete information on potential side effects and interactions.

March+April 2013 | positivelyaware.com/viramune

Aptivus

tipranavir, or TPV PI: ProTease Inhibitor

Potential side effects and toxicity

Contains a sulfa component. Mild diarrhea, nausea, vomiting, abdominal pain, and fatigue. Other side effects may include headache, fever, dry mouth, and dizziness. Rash, including sensitivity to the sun, has occurred (commonly among children). Rash may occur with joint pain or stiffness, throat tightness, generalized itching, muscle aches, fever, redness, blisters, or peeling skin. Women taking birth control pills may be at higher risk. Stop using Aptivus if a severe rash occurs or if rash appears with the symptoms listed above; call your medical provider immediately. Caution should be used for people with mild liver impairment; it cannot be taken by people with moderate to severe liver disease. Be sure to know your liver function status if you are about to start or are taking this drug! Use with caution by people who may be at risk of increased bleeding from trauma, surgery, or other medical conditions, or who are taking medications known to increase the risk of bleeding. See page 57 for potential drug class side effects.

Potential drug interactions

See package insert for the most complete list. Tell your provider or pharmacist of the medications, herbs,

Doctor’s comments

Aptivus (tipranavir) was a welcome addition to the arsenal of anti-HIV protease inhibitors when first approved, as it had activity against some virus resistant to other PIs. Its use has declined dramatically for several reasons. Foremost was the development of Prezista (darunavir), which had greater activity against many types of HIV. Aptivus use was also limited by the increased side effects (especially liver toxicity and elevated lipids) from the need to add a higher dose of Norvir (200 mg twice a day), and the side effects and allergies associated with being a sulfa-containing drug. Finally, a move away from using PIs in general had an effect on the use of Aptivus. It may still be a useful drug in patients who have been on Lexiva or Agenerase (discontinued in 2005) who may have developed PI mutations causing crossresistance to Prezista, so there is still a place for the drug. — Howard A. Grossman, MD

Activist’s comments

Oh what a tortuous history this protease inhibitor has! It was intended to fill the niche for people who had run out of treatment options (before Isentress and Prezista approval), but unfortunately it only had a brief time in the spotlight. There is a lot of other baggage that comes with the drug. It is not recommended for use in those starting treatment due to liver toxicity, and there is a laundry list of drugs that it interacts with. It also has to be taken with twice the amount of Norvir to boost the levels to the right amount. Looking at it positively, maybe this is a story of the success of treatment activism since newer drugs have replaced older not-so-good drugs. — Matt Sharp

and supplements you are taking or thinking of taking, prescribed or not. Do not take with alfuzosin, Revatio, Tambocor, Rythmol, Cordarone, quinidine, midazolam, pimozide, triazolam, or the herb St. John’s wort. Do not use Advicor, Altoprev, Livalo, lovastatin, Simcor, simvastatin, or Vytorin. Cholesterol-lowering alternatives are atorvastatin, Crestor, fluvastatin, and pravastatin, but should be used with caution and started at the lowest dose possible; monitor closely for increased side effects from them. Increases levels of fluticasone (found in Advair, Flonase, and Flovent); use with caution and only if the benefits outweigh the risks, and monitor for signs of Cushing’s syndrome (increased fat in the abdomen, fatty hump between the shoulders, rounded face, red/purple stretch marks on the skin, bone loss, possible high blood pressure, and sometimes diabetes). Aptivus can lower blood levels of Intelence, Ziagen, Videx EC, and Retrovir and they should not be combined. Take Videx EC and Aptivus two hours apart. Aptivus should not be taken with other protease inhibitors because it greatly lowers their blood levels. Lowest level of Aptivus is increased 45% with Fuzeon, but dose adjustments are not recommended. Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Effectiveness of birth control pills may be decreased; consider the use of other contraception. Methadone doses may need to be increased. Buprenorphine/naloxone can lower Aptivus levels significantly; Aptivus levels can be monitored, but dose adjustments are not recommended. A lower dose of trazodone is recommended. Calcium channel blockers should be monitored for side effects. Monitoring may be required when taking warfarin. Carbamazepine, phenytoin, or phenobarbital may decrease Aptivus levels, so alternate seizure medications should be used and monitoring of Aptivus levels is recommended. Caution should be used with valproic acid, which may be less effective. Use caution when taking itraconazole or fluconazole. Rifampin and Priftin should not be used; reduced dose and frequency of Mycobutin, the recommended alternative. Use with caution with bosentan, salmeterol, immunosuppressants, and colchicine (lower colchicine dose). Norvir and Aptivus capsules contain alcohol (should not be enough to trigger relapse), so be cautious with Antabuse (disulfiram) or Flagyl. Oral solution contains vitamin E; do not take more vitamin E than found in a multivitamin. Aptivus should be taken two hours before or one hour after antacids. Aptivus decreases Prilosec (omeprazole) concentrations and Prilosec dose may need to be increased. Taking Victrelis along with Aptivus can potentially reduce the effectiveness of both drugs—combined use is not recommended.

STANDARD DOSE:

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

Boehringer Ingelheim www.aptivus.com (800) 542–6257 AWP:

$1,415.26 / month for capsules; $471.73 for 95 mL solution

More information

Due to its drug resistance profile, drug interactions, higher pill burden, and the need for refrigeration if the indoor temperature is too hot, Aptivus is not as popular as other PIs. It is only FDA approved for treatment-experienced patients. Take with food to minimize stomach problems. Refrigerate capsules before opening, though Aptivus can be stored at room temperature (up to 77˚F), but must be used within 60 days. See package insert for details.

March+April 2013 | positivelyaware.com/aptivus

HIV DRUG GUIDE

2013

Crixivan

indinavir sulfate (indinavir), or IDV PI: ProTease Inhibitor

Potential side effects and toxicity

STANDARD DOSE:

Rarely used by itself (two 400 mg capsules every eight hours with no food or a low-fat snack). Almost always boosted with Norvir, both twice daily: 800 mg with 100 mg Norvir or 800 mg with 200 mg Norvir. All doses taken with food and with plenty of water to avoid kidney sludge or stones. Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Avoid grapefruit juice and vitamin C (more than one gram a day). Drink lots of non-caffeinated fluids throughout the day to help reduce the risk of kidney stones. Also available in 100 mg, 200 mg, and 333 mg capsules. manufacturer:

Merck and Co.

www.merck.com (800) 850–3430 AWP:

$548.12 / month for 180 400 mg capsules

Headache, fatigue or weakness, malaise (general ill feeling), nausea, diarrhea, stomach pain, loss of appetite, yellowing of skin/eyes, changed skin color, dry mouth/ sore throat, taste changes, painful urination, indigestion, joint pain, hives, and liver toxicity. Itchy/dry skin, ingrown toe nails, and hair loss are unique to Crixivan. Kidney stones, which may lead to more serious problems, can also occur—if pain develops in the middle to lower stomach or the back, or if there is blood in the urine, call your health care provider immediately. An increase in bilirubin (a test of liver function) has been reported, but it is not associated with liver problems. It may sometimes cause yellowing of the skin or eyes. Crixivan has also been associated with hemolytic anemia (premature destruction of red blood cells) and it should be stopped once the anemia is diagnosed. See page 57 for potential drug class side effects.

Potential drug interactions

PIs interact with many other drugs. See the package insert for the most complete list. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Do not take with alfuzosin, Revatio, Tambocor (flecainide), Rythmol (propafenone), Cordarone (amiodarone), midazolam (oral Versed), triazolam, rifampin, pimozide, Priftin (rifapentine), garlic supplements, or the herb St. John’s wort. Do not use Advicor, Altoprev, Livalo, lovastatin (Mevacor),

Doctor’s comments

Crixivan (indinavir) was one of the first protease inhibitors developed, the third approved, and it quickly became the mainstay of the early triple combination drug “cocktail” that changed the face of the HIV epidemic. It was one of the first PIs to be boosted successfully by Norvir (ritonavir), taking it from a three-times-a-day drug with dietary restrictions to a twice-a-day drug. Crixivan is almost never used anymore, however. It caused a plethora of very severe side effects from dry skin and broken nails to kidney stones, renal failure, and diabetes. It was the first drug associated with the development of severe lipodystrophy, hence the street term “Crix belly” denoting the central obesity that developed. Later PIs and non-PI regimens have rendered Crixivan obsolete. — Howard A. Grossman, MD

Simcor, simvastatin (Zocor), or Vytorin for the treatment of high cholesterol. Cholesterol-lowering alternatives are atorvastatin (Lipitor), Crestor, fluvastatin, and pravastatin (Pravacol), but should be used with caution and started at the lowest dose possible; monitor closely for increased side effects from these medications. Not recommended in combination with Reyataz. Reduce Crixivan to 600 mg every eight hours when taken with Rescriptor, itraconazole (200 mg twice a day), or ketoconazole (200 mg once a day). The dose of Mycobutin should be reduced to 150 mg daily or 300 mg three times a week and Crixivan dose increased to 1,000 mg every eight hours or use Norvirboosted dose when taken together. Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Effectiveness of birth control pills may be decreased; consider the use of other contraception. Additional monitoring may be required when taking warfarin (Coumadin) or calcium channel blockers (Norvasc, Procardia, and others). Use caution with anti-convulsants: carbamazepine (Tegretol), phenobarbital, and phenytoin (Dilantin). Crixivan may decrease levels of methadone, which may need to be increased, but withdrawal rarely occurs. Also, increased levels of trazodone can occur with Crixivan. Increased levels of the inhaled and nasal sprays with fluticasone (found in Advair, Flonase, and Flovent) can occur with Crixivan; use only if the benefits outweigh the risks, and monitor for signs of Cushing’s syndrome (increased fat in the abdomen, fatty hump between the shoulders, rounded face, red/purple stretch marks on the skin, bone loss, possible high blood pressure, and sometime diabetes). Use with caution with bosentan, salmeterol, immunosuppressants (including transplant drugs), and colchicine; use lower dose of colchicine. Use of the hepatitis C drug Victrelis (boceprevir) along with a Norvirboosted PI can potentially reduce the effectiveness of both drugs—combined use is not recommended.

More information

Very rarely used. Drink at least 48 oz. of fluids daily, preferably water or clear liquids (not soda pop!) to decrease the chances of kidney stones. Don’t forget to drink more water in summer or with increased sweating. Large amounts of coffee or alcohol can increase risk of stones due to increased dehydration. Stones may continue after stopping Crixivan. Store in original container and keep dry. See package insert for more complete information on potential side effects and interactions.

Activist’s comments

HIV DRUG GUIDE

2013

One of the oldest PIs, this drug is neither the most convenient nor friendly of AIDS meds. It is known to cause kidney stones, dry skin, rash, and lipodystrophy, including increased lipids in the blood and abnormal body fat distribution. In fact, the drug bears the misfortune of having been associated solely with increased belly fat, aka “Crix belly”—a term now known as being outdated. Not a preferred PI according to the guidelines, and owning a slew of drug interactions, this drug is another older veteran on the bottom of the drug list. — Matt Sharp

March+April 2013 | positivelyaware.com/crixivan

Invirase

saquinavir, or SQV PI: ProTease Inhibitor

Potential side effects and toxicity

Most common are diarrhea, abdominal discomfort, vomiting, and nausea. Drug label warning states that Invirase/Norvir may change the electrical activity of the heart, which may lead to abnormal heart rhythms called prolonged QT or PR intervals. People with underlying heart conditions, who have heart rate or heart rhythm problems, or low potassium or magnesium levels, are at greater risk. Symptoms may include lightheadedness and fainting. A medication guide is required with a prescription. See page 57 for potential drug class side effects.

Potential drug interactions

PIs interact with many other drugs. See package insert for the most complete list. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Viramune and Sustiva decrease Invirase levels. Not recommended to be used with Aptivus/Norvir or Prezista. Should be used with caution and may require dose adjustment with Reyataz (additive effect on QT and PR interval prolongation may occur). Rescriptor, Crixivan, Norvir, Viracept, and Kaletra all significantly increase Invirase concentrations. No dosage change when taken with Kaletra, but additive effect on QT and PR interval prolongation may occur. Do not take with alfuzosin, Revatio, Tambocor (flecainide), Rythmol (propafenone), clarithromycin

Doctor’s comments

Invirase (saquinavir) was the first PI approved for use back in 1995, although it was, at the time, in a different formulation that was later found to have very limited absorption and, therefore, little efficacy. The next formulation, called Fortovase, worked better when combined with Norvir, but caused a lot of gastrointestinal distress. Still, it was a useful alternative to some of the other PIs. It was the first PI to be successfully boosted with Norvir in studies. Norvirboosting actually helped to bring back into use the original formulation, Invirase, as it improved the levels and the drug was more tolerable, but by that time, other more tolerable drugs had been developed with better dosing schedules, greater efficacy, and needing less Norvir for boosting. Invirase is rarely used these days. — Howard A. Grossman, MD

Activist’s comments

AKA saquinavir, this was the first protease inhibitor approved for HIV and led the way for the HAART (highly-active antiretroviral therapy) era. We no longer use the HAART nomenclature since today, all drugs must be highly active or potent before they become approved. While Invirase, having gone through many iterations and formulations over the years, is not a preferred PI today, it has made a comeback from the early days due to the boosting effect of Norvir, and can be an alternative. Because it uses the common liver enzyme pathway of several other medications, check all your meds before using Invirase. — Matt Sharp

(Biaxin), dexamethasone, amiodarone (Cordarone), midazolam (oral Versed), triazolam (Halcion), pimozide (Orap), digoxin (Lanoxin), quinidine, trazodone, dofetilide (Tykosyn), lidocaine (systemic), voriconazole, garlic supplements, or the herb St. John’s wort. Colchicine levels may be increased and dose reduction is necessary. Do not use Advicor, Altoprev, Livalo, lovastatin (Mevacor), Simcor, simvastatin, or Vytorin for the treatment of high cholesterol. Cholesterol-lowering alternatives are atorvastatin (Lipitor), Crestor, fluvastatin, and pravastatin (Pravacol), but should be used with caution and started at the lowest dose possible; you should be monitored closely for increased side effects from these medications. Cannot be taken with Priftin (rifampentine) or rifampin. Rifabutin can be used as alternative, but its dose needs to be decreased. Methadone doses may need to be increased. Invirase increases levels of fluticasone (active component of Advair, Flonase, and Flovent); use only if the benefits outweigh the risks, and monitor for signs of Cushing’s syndrome (increased fat in the abdomen, fatty hump between the shoulders, rounded face, red/ purple stretch marks on the skin, bone loss, possible high blood pressure, and sometimes diabetes). Use calcium channel blockers with caution. Monitor digoxin levels; digoxin dose may need to be decreased. Use caution with anti-convulsants carbamazepine (Tegretol), phenobarbital, and phenytoin (Dilantin), as these medications will decrease Invirase levels. Invirase may increase dapsone levels and alter warfarin levels; additional monitoring may be required. Do not take with birth control pills as Invirase reduces the level of the hormone ethinyl estradiol. Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Prilosec, Prevacid, or any other PPI (medications used to treat acid reflux or heartburn) increase Invirase levels, therefore monitor for possible side effects from Invirase if taken together. Use with caution with bosentan, salmeterol, and immunosuppressants (including transplant drugs). Use of the hepatitis C drug Victrelis (boceprevir) along with a Norvir-boosted PI can potentially reduce the effectiveness of both drugs—combined use is not recommended. Refer to the package insert for the complete guide to the drug interactions.

STANDARD DOSE:

Two 500 mg filmcoated tablets with 100 mg Norvir two times a day with food, or within two hours of a meal for patients over 16 years old. Must be taken with Norvir. Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. manufacturer:

Genentech

www.genentech.com (800) 626-3553 AWP:

$1,121.51 / month for 500 mg tablets

More information

Rarely used, Invirase has efficacy similar to Kaletra with less hyperlipidemia (elevated cholesterol and triglycerides). Invirase/Norvir was downgraded from “alternative choice” to the list of “regimens that are acceptable but should be used with caution” in the DHHS HIV treatment guidelines for what to take when starting HIV therapy. People with previous QT or PR prolongation issues, those who take medications that increase the risk for these heart problems, and those with low potassium or magnesium levels should be aware of this, as Invirase/Norvir taken under these circumstances may lead to an increased risk for heart problems. Must be taken with food and always with Norvir. Patent expired in May 2011, but no generic is available. See package insert for more complete information on potential side effects and interactions.

March+April 2013 | positivelyaware.com/invirase

HIV DRUG GUIDE

2013

Kaletra

lopinavir / ritonavir, or LPV / r PI: ProTease Inhibitor | FIXED DOSE COMBINATION

Potential side effects and toxicity

STANDARD DOSE:

Two tablets (200 mg lopinavir / 50 mg ritonavir) twice a day or four 200 / 50 mg tablets once daily for people with less than three lopinavir resistance-related mutations. No oncedaily dose if taken with Sustiva or Viramune, or anticonvulsants. Three tablets twice a day may be considered for treatment-experienced people, pregnant women from the second trimester on, or those taking it with Sustiva or Viramune. 100 mg lopinavir / 25 mg ritonavir tablets available. Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your dose. Can be taken by children older than 14 days. Halfstrength film-coated tablets available. Tablets should be swallowed whole, not chewed, broken, or crushed. Can be taken with or without food, with no dietary restrictions, but preferably taken with food to lessen side effects. Liquid formula (400 mg/5 mL lopinavir, 100 mg/5mL ritonavir) is available; should be taken with food. Liquid formula should not be taken by pregnant women, as it contains 42% alcohol. manufacturer:

AbbVie

www.kaletra.com (800) 222–6885 AWP:

$922.78 / month for tablets; $461.38 for 160 mL solution 40

Kaletra was the first boosted PI in a single co-formulation pill on the market. It is a combination of ritonavir (Norvir) and lopinavir, the latter being a closely related molecule to ritonavir. Its development and approval in 2001 came at an opportune time. The most prescribed PI at the time, Viracept, could not be boosted with ritonavir. Though it was so much better tolerated than Crixivan and Invirase, by 2001, many patients were failing on the drug. Kaletra proved extremely potent and, for several years, seemed not to be associated with the development of drug resistance. On the other hand, Kaletra caused a lot of gastrointestinal symptoms, and was associated with the development of lipodystrophy. There were a lot of drug interactions as well. At this point, Kaletra’s use has been largely supplanted by Prezista and Reyataz, which can be taken once a day and with less ritonavir, and by NNRTI-based regimens. Kaletra is still a PI of choice for use in pregnant women. — Howard A. Grossman, MD

solution contains alcohol, so do not use with Antabuse or Flagyl. Use calcium channel blockers (such as Norvasc and Procardia) with caution. Dosage of methadone may need to be increased. Physicians usually prescribe three tablets twice a day with food when using with Sustiva or Viramune. Current HIV treatment guidelines state the Kaletra dose should total 500 mg lopinavir and 125 mg ritonavir twice daily when used with Sustiva or Viramune. Not recommended to be taken with Lexiva. Kaletra may lower levels of AZT (Retrovir) and Ziagen. Videx (didanosine) and Kaletra can be taken together without food. If Kaletra is taken with food, Videx should be taken an hour before or two hours after Kaletra. If taking Kaletra with Viread or combinations containing tenofovir, monitor for side effects from tenofovir as Kaletra increases its levels. Rifabutin dosage should be reduced to 150 mg every other day (or 150 mg three times per week) when used with Kaletra. Effectiveness of birth control pills may be decreased; consider the use of other contraception. Mepron levels may be reduced with Kaletra. Avoid Sporanox or Nizoral doses greater than 200 mg per day with Kaletra. Monitor for side effects when taken with Noxafil. Decreases voriconazole levels. People with kidney impairment may require lower clarithromycin (Biaxin) doses with Kaletra. Monitor blood levels of immunosuppressants because levels may increase. Kaletra may alter warfarin levels; additional monitoring may be required. Steroids, especially Decadron, may decrease Kaletra levels. Kaletra increases levels of fluticasone (found in Advair, Flonase, and Flovent). Monitor for signs of Cushing’s syndrome (increased abdominal fat, fatty hump between the shoulders, rounded face, and more). Kaletra increases levels of trazodone. Use caution with anti-convulsants carbamazepine, phenobarbital, and phenytoin, as they may lower levels of Kaletra. Bupropion levels are lowered; titrate dose based on clinical response. Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Use with caution with bosentan, salmeterol, and immunosuppressants, and use lower dose of colchicine. Kaletra can decrease the effects of Malarone. Incivek or Victrelis along with a Norvir-boosted PI can potentially reduce the effectiveness of both drugs—combined use is not recommended.

Activist’s comments

More information

Diarrhea is the most common and can be severe, but may be less severe with tablets than liquid. Rash, nausea, vomiting, stomach pain, headache, muscle weakness, and elevated liver enzymes (a sign of liver damage—may be more common in people with hepatitis B or C). See page 57 for potential drug class side effects.

Potential drug interactions

Doctor’s comments

Kaletra was one of the first fixed dose pills with a combination of two drugs. Abbott (now AbbVie) had marketed Norvir as a stand-alone protease inhibitor until they realized it could be taken at lower doses to boost the levels of the active protease inhibitor known as lopinavir. The convenience for people starting therapy is using once-daily dosing of Kaletra. However, for the treatment-experienced, twice a day dosing is usually recommended. As with other PIs, this drug has significant drug interactions, liver issues, and is associated with lipodystrophy. With the use of integrase inhibitors becoming widespread, it will be interesting to see if Kaletra remains a popular drug. — Matt Sharp

According to DHHS treatment guidelines, the need for 200 mg a day of Norvir (contained in Kaletra) and the higher rate of gastrointestinal side effects compared to other PIs using 100 mg Norvir, make Kaletra an alternative (instead of “preferred”) drug for treatment-naïve people. It is on the preferred list for pregnancy and pediatrics. Four tablets once daily can increase side effects, especially diarrhea. Taking with food and anti-diarrheal medicine helps lessen diarrhea. Kaletra should not be taken once a day by children under 18. Solution cannot be given to premature babies until 14 days after their due date because it contains propylene glycol. See package insert for more complete information on potential side effects and interactions.

March+April 2013 | positivelyaware.com/kaletra

fosamprenavir calcium (fosamprenavir), or FPV

Lexiva

PI: ProTease Inhibitor

Potential side effects and toxicity

AS Lexiva contains a sulfa component, use with caution in patients with sulfa allergies. The most common side effects may include nausea, rash, diarrhea, headache, and vomiting. Rash occurred in about 19% of patients, but severe rashes were uncommon. If you experience a rash, notify your doctor. For mild or moderate rashes, your doctor may choose to continue Lexiva, with close monitoring. Patients with hepatitis B or C should be monitored closely for the possibility of elevated liver enzyme levels. Dose adjustment is recommended for people with liver impairment. Side effects and laboratory abnormalities were similar when Lexiva was taken once or twice daily, with or without Norvir. See page 57 for potential drug class side effects.

Potential drug interactions

PIs interact with many other drugs. See package insert for the most complete list of interactions. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Not recommended to be taken with Kaletra. When taken with Sustiva, boost once-daily Lexiva with 300 mg of Norvir. Do not take with alfuzosin, Revatio, Tambocor, Rythmol, midazolam (oral Versed), triazolam (Halcion), rifampin, Orap (pimozide), Priftin (rifampetine), or the herb St. John’s wort. Do not use Advicor, Altoprev, Livalo,

Doctor’s comments

Lexiva (fosamprenavir) is actually the second version of this drug to hit the market. First came amprenavir, which was a very large pill that was difficult to swallow and required many pills. Fosamprenavir, a pro-drug of amprenavir, proved much easier to take. It had advantages of being able to be taken without worrying about food intake and with or without ritonavir. It was eventually approved for once-a-day dosing in conjunction with ritonavir for treatment-naïve patients. The use of Lexiva has declined dramatically. It offered no benefit over Kaletra in terms of tolerability or efficacy in a boosted twice-a-day dose and ritonavir-boosted Prezista and Reyataz proved superior in the once-a-day dosing arena. Its ability to be used unboosted was surpassed by Reyataz and it turns out that resistance developed on unboosted Lexiva can cause cross-resistance to Prezista, so this use is not recommended either. — Howard A. Grossman, MD

Activist’s comments

Basically an awkward attempt at a shiny new protease inhibitor, approved in 2003, Lexiva is a pro-drug of Agenerase, which was a big fat mistake in the form of a big fat pill. At least GSK (now ViiV) tried to improve upon it with a more attractive Lexiva. However, attempts to prove it was as effective as Kaletra failed, and it’s unclear why people would want to use it instead of the newer PIs. It is a once- or twice-daily drug boosted or unboosted, depending on if it is a new PI to your regimen. — Matt Sharp

lovastatin (Mevacor), Simcor, simvastatin (Zocor), or Vytorin for the treatment of high cholesterol. Cholesterollowering alternatives are atorvastatin (Lipitor), Crestor, fluvastatin, and pravastatin (Pravacol), but use with caution and start at the lowest dose possible; monitor closely for increased side effects from these medications. Calcium channel blockers (Norvasc, Procardia, and others) should be used with caution and careful monitoring. Lexiva should be taken two hours before H2 blockers (Zantac, Pepcid, and others). Lexiva can lower methadone concentrations. A dose adjustment of Mycobutin (rifabutin) will be needed when used in combination with Lexiva. Steroids, such as Decadron, can decrease levels of Lexiva. Increases levels of fluticasone (found in Advair, Flonase, and Flovent); use only if the benefits outweigh the risks, and monitor for signs of Cushing’s syndrome (increased fat in the abdomen, fatty hump between the shoulders, rounded face, red/purple stretch marks on the skin, bone loss, possible high blood pressure, and sometimes diabetes). Trazodone concentrations may increase; a lower dose of trazodone is recommended. Drug levels of Paxil are lowered; titrate dose based on clinical response. Use caution with anti-convulsants carbamazepine, phenobarbital, and phenytoin. Lexiva may alter warfarin (Coumadin) levels; additional monitoring may be required. Effectiveness of birth control pills may be decreased; consider the use of other contraception methods. Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis per 72 hours or 2.5 mg Levitra per 24 hours, or 25 mg Viagra per 48 hours. Use with caution with bosentan, clarithromycin (Biaxin), salmeterol, immunosuppressants (including transplant drugs), and colchicine (lower the colchicine dose). Use of Incivek or Victrelis along with a Norvir-boosted PI can potentially reduce the effectiveness of both drugs—combined use is not recommended.

More information

HIV treatment guidelines dropped Lexiva in regimens not containing Norvir as an option for first-time therapy because of inferior potency and the potential for developing cross-resistance to Prezista, a recommended protease inhibitor for first-time treatment. The lower dose of Norvir may cause less of an increase in cholesterol and triglycerides, but it’s uncertain. Protease inhibitor-experienced patients should take Lexiva 700 mg with Norvir 100 mg, both twice daily. The once-daily dosing is not recommended for treatment-experienced patients for whom a PI therapy has previously failed. It is important to take Lexiva exactly as your doctor instructs, and not to change dosing without discussing it with your doctor. There may be an association between Lexiva and heart attacks, heart disease, and stroke. A liquid formula of Lexiva is available. See package insert for more complete information on potential side effects and interactions.

March+April 2013 | positivelyaware.com/lexiva

STANDARD DOSE:

For people on a PI for the first time: two 700 mg tablets with either one or two 100 mg Norvir, both once daily; or two 700 mg tablets without Norvir, twice daily; or one 700 mg tablet with 100 mg Norvir, twice daily. For PI-experienced patients, one 700 mg tablet Lexiva with 100 mg Norvir, twice daily. Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Available for children ages four weeks and older. For people with liver problems, the dose of Lexiva may need to be adjusted and Norvir may or may not be used depending on the degree of liver disease. A grape/bubblegum/ peppermint-flavored oral suspension is also available. Adults must take suspension without food. Tablet dosage can be taken with or without food, with no dietary restrictions, at any dose. manufacturer:

ViiV Healthcare

www.viivhealthcare.com (877) 844-8872 AWP:

$994.48 / month for capsules; $152.36 for 225 mL solution (50 mg/mL)

HIV DRUG GUIDE

2013

Norvir

ritonavir, or RTV PI: ProTease Inhibitor

Potential side effects and toxicity

STANDARD DOSE:

Used as a boosting agent for other PIs (increases the levels of other PIs), at smaller doses of 100 to 400 mg, either once or twice a day with a meal. Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Do not crush or chew tablets, always swallow whole. See drug label of the other PIs. Always take Norvir at the same time as the other PI prescribed by your provider. Approved for children ages one month and older. Liquid formulation available, but it tastes horrible. Liquid formula should not be taken by pregnant women, as it contains 42% alcohol. manufacturer:

AbbVie

www.norvir.com (800) 222–6885 AWP:

$308.60 / month for 30 tablets; $1,728.24 for 240 mL solution (80 mg/mL)

HIV DRUG GUIDE

2013

Most common side effects include weakness, upset stomach (pain, nausea, diarrhea, and vomiting); tingling/numbness around the mouth, hands, or feet; loss of appetite; taste disturbance; weight loss; headache;

Doctor’s comments

Norvir (ritonavir) was the second PI to be approved. It was the first anti-HIV drug to show, in a study presented at the Retrovirus Conference in early 1996, an actual benefit in slowing death rates due to HIV. Early liquid formulations of ritonavir were incredibly difficult to take. Patients compared the taste to cherry gasoline or mint-flavored motor oil. Nausea and severe diarrhea were very common with the original 600 mg twice-a-day dose. Ritonavir proved, however, to be one of the most important developments in fighting HIV. Due to its effect on liver enzymes that usually break down drugs, ritonavir helps to increase the blood levels of other protease inhibitors and Norvir-boosting has become the mainstay of our use of PIs. Side effects are markedly decreased for most patients with the lower doses of ritonavir now in use, but can still be significant. Effects on lipids are variable and some patients cannot tolerate even 100–200 mg of ritonavir per day. It is also associated with development of lipodystrophy, although there is ongoing controversy regarding the cause. It can also cause GI upset and diarrhea. There are very many drug interactions affecting both anti-HIV drugs and drugs used to treat other things, raising some drug levels and lowering others. It is very important to investigate all other drugs taken before starting ritonavir. Ritonavir is used to boost all PIs except Viracept, which is rarely used anymore. The recent development of cobicistat, which also serves to boost the levels of other anti-HIV drugs, may have an effect on the future market for ritonavir. Right now, cobicistat is only available in Stribild, where it boosts elvitegravir levels, but formulations with other PIs are under investigation and may become available. — Howard A. Grossman, MD

Activist’s comments

No one uses Norvir (ritonavir) as a stand-alone PI unless they have been living in a cave. This drug has so much baggage from the early years when it was prescribed in a motor oil-tasting oral suspension to the time when its manufacturer, Abbott, tried to shock and awe everyone with a 400% price increase. The company claims no single patient has had to suffer the price increase due to assistance programs, but the system has had to suffer the highest price increase of any AIDS drug in history. It is widely suspected that the increase was due to the fact that ritonavir was going to be used in smaller doses as a booster, for which it is highly effective. Abbott should have been happy with the drug-boosting market instead of boosting the prices out of the ballpark. — Matt Sharp

dizziness; pancreatitis; and alcohol intolerance. Other potential side effects are an increase in liver enzymes (AST, ALT, and GGT), hepatitis, jaundice (yellowing of skin), increased muscle enzyme (CPK), and uric acid. People with hepatitis B or C may be at increased risk. See page 57 for potential drug class side effects.

Potential drug interactions

See package insert for the most complete list of interactions. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Do not take with alfuzosin, Revatio, Tambocor, Rythmol, Cordarone, midazolam, triazolam, pimozide, Priftin, Rifadin, voriconazole, garlic supplements, or the herb St. John’s wort. Do not use Advicor, Altoprev, Livalo, lovastatin, Simcor, simvastatin, or Vytorin. Cholesterol-lowering alternatives are atorvastatin, Crestor, fluvastatin, and pravastatin, but should be used with caution and started at the lowest dose possible; monitor closely for increased side effects. Increases levels of fluticasone (found in Advair, Flonase, and Flovent); monitor for signs of Cushing’s syndrome (increased abdominal fat, fatty hump between the shoulders, rounded face, red/purple stretch marks on the skin, bone loss, possible high blood pressure, and sometimes diabetes). Trazodone concentrations may increase; a lower dose of trazodone is recommended. Norvir may decrease levels of methadone, which may need to be increased, but withdrawal rarely occurs. Use caution with anti-convulsants carbamazepine, phenobarbital, and phenytoin. Use calcium channel blockers (Norvasc, Procardia, and others) with caution. Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Effectiveness of birth control pills may be decreased; consider the use of other contraception. Levels of the street drug Ecstasy are greatly increased by Norvir, and at least one death has been attributed to the combination. GHB is also dangerous with Norvir. Tobacco and alcohol may lower blood levels of Norvir. Clarithromycin levels can increase by up to 80%. Use with caution with bosentan, salmeterol, and immunosuppressants; lower colchicine dose. Use of Incivek or Victrelis with Norvir can potentially reduce the effectiveness of both drugs—combined use is not recommended.

More information

The real strength of Norvir is its use with other PIs as a boosting agent. An alternative to Norvir called cobicistat is in Stribild, and is expected to be approved on its own this year (see cobicistat, page 55). Blood levels are higher with Norvir tablets when taken with food (as required), and may cause more side effects. Stomach side effects are reduced by taking Norvir with high-fat foods—however, some other HIV medicines should not be taken with high fat foods. You can mix liquid solution one hour before taking in ice cream, milk (especially chocolate), or pudding to hide the taste. Blood concentration increases in people with liver impairment. See package insert for more complete information on potential side effects and interactions.

March+April 2013 | positivelyaware.com/norvir

Prezista

darunavir, or DRV PI: ProTease Inhibitor

Potential side effects and toxicity

Contains a sulfa component. Most common may include diarrhea, nausea, headache, rash, vomiting, and abdominal pain. Measure liver function before starting and then monitor, with perhaps closer monitoring for those with underlying liver problems, especially during first several months. No dose adjustment necessary in mild to moderate liver disease, but Prezista/Norvir is not recommended in severe liver impairment. While very rare, severe rash (in less than 0.1% of those taking it), accompanied in some cases by fever and/or elevations of AST/ALT (liver enzymes), can be life-threatening. Seek medical attention immediately. You may need to stop all medications. See page 57 for potential drug class side effects.

Potential drug interactions

See package insert for the most complete list of interactions. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Do not take with alfuzosin, Ergomar, ergonovine, Invicek, methylergonovine, midazolam, triazolam, Revatio, rifampin pimozide, Priftin, Victrelis, or St. John’s wort. May decrease levels of phenytoin and

Doctor’s comments

Prezista (darunavir) has rapidly become the leading choice in PI therapy. It is poorly absorbed and always requires boosting (currently with ritonavir) and must be taken with food in order to achieve adequate levels. Prezista has proven superior to Kaletra in patients who are already experienced on PIs, both in terms of efficacy and tolerability. It was approved for once-daily dosing in PI-naïve patients and is now approved for once-daily use in experienced patients who do not have Prezista-associated mutations. And it appears that resistance develops more slowly on a regimen containing Prezista compared to a Kaletracontaining one. In first-line therapy, Prezista has proven superior to Kaletra in terms of causing less GI side effects and less lipid abnormalities and it worked better than Kaletra in patients with higher viral loads. For all of these reasons Prezista has become one of the preferred PIs in the DHHS guidelines for initial therapy. Co-formulations of darunavir with cobicistat are in development and could bring even greater use of the drug if approved. — Howard A. Grossman, MD

Activist’s comments

The last approved PI, in 2008, Prezista is likely the most effective and biggest selling PI today. Really the next best PI since Reyataz, its biggest competition, the drug was later studied to improve its dosing so as to compete with once-daily drugs. For many treatment-experienced folks however, Prezista still has to be taken twice daily. Like many others, I waited for this drug to add to Isentress so I could have a powerful two-drug combo to stop my very resistant virus and along with my backbone drugs, I now remain undetectable six years later. — Matt Sharp

phenobarbital, and increase levels of carbamazepine; levels should be monitored. Reduced dose of rifabutin is recommended. Do not use Advicor, Altoprev, lovastatin, pravastatin, Simcor, simvastatin, or Vytorin. Cholesterollowering alternatives are atorvastatin (should not exceed 20 mg a day) and Crestor, but should be used with caution and started at the lowest dose possible; monitor closely for increased side effects from these medications. Reduce clarithromycin dose by 75% in kidney impairment. The antifungal drugs such as itraconazole or ketoconazole and Prezista may increase each others’ levels, so caution must be exercised when used together (maximum dose is 200 mg a day for the antifungals). Voriconazole should not be used unless the benefits outweigh the risks. Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Prezista may increase levels of calcium channel blockers, such as Norvasc and others, and beta-blockers; clinical monitoring is recommended. A lower dose of trazodone and desipramine may be recommended. Close monitoring of INR levels required when using warfarin. Increases levels of fluticasone (found in Advair, Flonase, and Flovent); use only if the benefits outweigh the risks, and monitor for signs of Cushing’s syndrome (increased abdominal fat, fatty hump between the shoulders, rounded face, red/purple stretch marks on the skin, bone loss, possible high blood pressure, and sometimes diabetes). Effectiveness of birth control pills may be decreased; consider the use of other methods of contraception. Use lowest dose of digoxin; monitor and titrate. No dose adjustment required with buprenorphine or methadone. Monitoring of antidepressant response is recommended with selective serotonin reuptake inhibitors (such as Paxil and Zoloft). Use cautiously with bosentan, salmeterol, immunosuppressants, and colchicine; use lower dose of colchicine.

More information

Prezista is one of two preferred PIs for initial therapy in DHHS HIV treatment guidelines. New 800 mg tablets replace the previous two 400 mg tablet dose. There are ongoing studies with Prezista boosted with cobicistat instead of Norvir plus Emtriva and an investigational NRTI, TAF (Viread pro-drug), as the first PI-based STR (single tablet regimen). A Prezista pill that also contains cobicistat is in the works which would eliminate Norvir and reduce pill burden. Prezista/Norvir is as lipid friendly (not increasing triglycerides and cholesterol, nor affecting insulin levels) as Reyataz/Norvir, which may make metabolic problems such as diabetes and body shape changes less likely. Janssen received community praise for not pricing Prezista higher than other second-generation PIs and last year, the company announced that it would not enforce its Prezista patent as long it was used in resource-limited settings, allowing for generics to be manufactured abroad. See package insert for more complete information on potential side effects and interactions.

March+April 2013 | positivelyaware.com/prezista

STANDARD DOSE:

One 800 mg tablet with 100 mg Norvir once daily with food for first-time therapy and treatmentexperienced adults without Prezista-related HIV resistance, or 600 mg (one 600 mg tablet) with 100 mg Norvir twice daily with food for pregnant women and those whose HIV therapy has failed in the past and who have at least one Prezista-related HIV drug resistance mutation. Prezista should never be taken without Norvir. 75 mg and 150 mg tablets available for children older than three, dose based on weight. Take missed dose as soon as possible, but not if more than 12 hours past the once-daily dose (or six hours past the twice-daily dose). Do not double up on your next dose; take the next dose on schedule. An oral suspension for children three or older and adults who have difficulty swallowing pills is available. Please see the new package insert for specific directions on how to take the oral solution based on weight. As with the Prezista tablet, the oral solution needs to be taken with Norvir. manufacturer:

Janssen Therapeutics www.prezista.com (877) JANSSEN (526-7736) AWP:

$1,308.94 / month for all strengths

Reyataz

atazanavir sulfate (atazanavir), or ATV PI: ProTease Inhibitor

Potential side effects and toxicity

STANDARD DOSE:

One 300 mg capsule plus 100 mg Norvir, once daily (this dose must be used if taking Viread or Truvada, or if pregnant in first trimester), or two 200 mg capsules (without Norvir), once daily for adults taking HIV therapy for the first time; take with food. Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. If on Viread, Truvada, or medications for heartburn/reflux, or pregnant in second or third trimester, take Reyataz 400 mg plus Norvir 100 mg, once daily. It is also recommended in combination with Norvir for children 6 years or older. Reyataz capsules should not be opened and mixed with food or nutritional supplements. Swallow capsules whole. Taken with or without food. Also available in 100 mg and 150 mg capsules. manufacturer:

Bristol-Myers Squibb www.reyataz.com (800) 321–1335 AWP:

$1,306.20 / month for 300 mg capsules; $1,318.60 / month for 200 mg capsules

HIV DRUG GUIDE

2013

Dizziness and lightheadedness, nausea, and possible jaundice (yellowing of the skin or eyes) which, although not related to liver damage, should be reported to your medical provider right away. Other side effects may include rash, kidney stones, gall stones, and elevated liver enzymes, a sign of liver damage (more common in people with hepatitis B or C). Reyataz should not be taken by treatment-experienced patients on hemodialysis because its levels are significantly decreased. Reyataz has been shown not to increase lipid levels, but higher lipid levels may be seen (unlikely) if it is boosted with Norvir. See page 57 for potential drug class side effects.

Potential drug interactions

See package insert for the most complete list of interactions. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Medications used to treat acid reflux (GERD) and heartburn, like proton pump inhibitors (PPIs) and H2-receptor antagonists (H2RAs),

Doctor’s comments

Reyataz (atazanavir) allows for a number of different dosing options. It is most often taken with ritonavir boosting, but it is the only PI in common use these days that may be taken unboosted. There are important drug interactions. If taken with tenofovir, either alone or in Truvada, it must be boosted with ritonavir. If taken with efavirenz (Sustiva), higher doses of Reyataz are needed. Reyataz requires the normal acidic stomach environment for absorption. Drugs which interfere with acid production, particularly those for acid reflux, cannot be taken with Reyataz. Antacids and H2 blockers may be taken, but dosing needs to be separated by a significant amount of time and this leads to complicated dosing regimens. The most common side effect of Reyataz is elevated bilirubin, usually a low level and benign. In some patients, elevated bilirubin causes skin to turn yellow. At low levels, people may just appear flushed, but at higher levels jaundice can be disturbing. In rare cases, bilirubin levels become so high that the drug must be stopped. — Howard A. Grossman, MD

Activist’s comments

I voted for approval of this “lipid friendly” PI when I was a member of the FDA Anitiviral Advisory Committee. This is a decent PI as it does not create cross-resistance to other PIs, it’s once-daily, and it is a more lipid-friendly PI without the Norvir boost. Since the drug lowers the levels of tenofovir, any fixed dose combos must be taken with a booster to increase the levels of Reyataz, but that’s not an issue if you decide to use the boost. I know several people who are quite happy with Reyataz unboosted, but they don’t have a lot of drug resistance mutations. Oh, and if you need to take medications to reduce heartburn, you need to take the drugs separately. It’s complicated. — Matt Sharp

can lower the levels of Reyataz. Treatment-experienced people cannot take Reyataz with PPIs. Treatment-naïve people can take a PPI in a dose comparable to Prilosec OTC 12 hours before Reyataz/Norvir. H2RAs like Pepcid may be taken (no more than 20 mg twice a day if treatment-experienced or 40 mg twice a day if treatmentnaïve, or equivalent doses) at the same time as Reyataz/ Norvir with food or at least 10 hours later. If taking with Viread or Truvada and an H2RA, you must take the 400 mg Reyataz/100 mg Norvir dose with food. When taking Reyataz without Norvir, dose can be taken at least two hours before and at least 10 hours after an H2RA. Reyataz should be taken two hours before or one hour after antacids (Rolaids, Tums, etc.). Do not take with alfuzosin, Camptosar, Crixivan, midazolam, pimozide, Priftin, triazolam, Victrelis or St. John’s wort. Do not use Advicor, Altoprev, Livalo, lovastatin, Simcor, simvastatin, or Vytorin. Alternatives are atorvastatin, Crestor, fluvastatin, and pravastatin, but should be used with caution and started at the lowest dose possible; monitor closely for increased side effects. Must be taken two hours before or one hour after Videx EC (unless taking Videx EC with Viread). Treatment-naïve people should take 400 mg Reyataz/Norvir (100 mg) when taking with Sustiva, but treatment-experienced people should not take Reyataz with Sustiva. Viread decreases the levels of Reyataz and Reyataz increases Viread levels, monitor for adverse events. Reyataz can be taken unboosted with Epzicom if Norvir is not indicated or tolerated. Use the heart medications bepridil, Cordarone, quinidine, and lidocaine cautiously. Monitoring may be required when used with warfarin. Reyataz increases levels of fluticasone in Advair, Flonase, and Flovent; monitor for signs of Cushing’s syndrome, including rounded face. Effectiveness of birth control pills may be decreased; consider using other contraception. Oral contraception should contain no more than 30 mcg of ethinyl estradiol if taking Reyataz without Norvir and at least 30 mcg if taken with Norvir. Use caution when using itraconazole or ketoconazole. Voriconazole is not recommended. Monitor for Reyataz side effects when taking with Noxafil. Reducing dose and frequency of rifabutin to 150 mg every other day or three times a week is recommended. Use caution with carbamazepine, phenobarbital, and phenytoin. Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Calcium channel blockers should be monitored. A lower dose of trazodone is recommended. Use with caution with bosentan, salmeterol, and immunosuppressants, and use lower dose of colchicine. Use with Norvir when taking buprenorphine. Monitor before sedation. Reyataz can decrease the effects of Malarone. Incivek can be used with boosted Reyataz.

More information

Norvir-boosted Reyataz is a recommended PI by DHHS treatment guidelines for people starting HIV therapy for the first time, and has also been elevated from an “alternative” to a “preferred” boosted PI for pregnancy. It is being studied in combination with the booster drug cobicistat. See package insert for details of potential side effects and interactions.

March+April 2013 | positivelyaware.com/reyataz

Viracept

nelfinavir, or NFV PI: ProTease Inhibitor

Potential side effects and toxicity

Most common include diarrhea, stomach discomfort, nausea, gas, weakness, and rash. See page 57 for potential drug class side effects.

Potential drug interactions

See package insert for the most complete list of interactions. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Viracept increases levels of Invirase and Crixivan, so dose adjustments may be needed. Do not take with alfuzosin, Revatio, midazolam (oral Versed), Cordarone (amiodarone), triazolam (Halcion), rifampin, Priftin (rifampetine), Prilosec OTC (omeprazole), garlic supplements, or the herb St. John’s wort. Do not use Advicor, Altoprev, Livalo, lovastatin (Mevacor), Simcor, simvastatin (Zocor), or Vytorin for the treatment of high cholesterol. Cholesterol-lowering alternatives are atorvastatin (Lipitor), Crestor, fluvastatin, and pravastatin (Pravacol), but should be used with caution and started at the lowest dose possible; monitor closely for increased side effects from these medications. Viracept may decrease levels of methadone, which may need to be increased, but withdrawal rarely occurs. Use calcium channel blockers with caution. Blood levels of Viracept are reduced by rifampin and may be reduced by carbamazepine (Tegretol), phenobarbital, and phenytoin (Dilantin), so it is important to inform your doctor if you are taking any of these medications. Mycobutin (rifabutin) dose must be decreased when used with Viracept. Prescriber may need to adjust doses of any of these drugs accordingly. Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Increases levels of fluticasone (found in Advair, Flonase, and Flovent); use only if the benefits outweigh the risks,

Doctor’s comments

When Viracept (nelfinavir) first appeared it was welcomed as being far more tolerable than other PIs and with a far more convenient dosing schedule of twice a day. Viracept is the only PI of which the drug level cannot be boosted by ritonavir. It required a lot of pills at first, but a larger-dose pill was approved later. Viracept became a very popular drug until it was discovered that it was less effective than boosted PIs like Kaletra and a large number of patients began to fail on the drug with rebound of viral loads. The drug was heavily marketed to prison communities and its use persisted in prisons for much longer, but Viracept is rarely used today. — Howard A. Grossman, MD

and monitor for signs of Cushing’s syndrome (increased fat in the abdomen, fatty hump between the shoulders, rounded face, red/purple stretch marks on the skin, bone loss, possible high blood pressure, and sometimes diabetes). Effectiveness of birth control pills may be decreased; consider the use of alternative or additional methods of contraception. Also, increased levels of trazodone can occur and this combination should be used with caution. A lower dose of trazodone is recommended. Use with caution with bosentan, salmeterol, immunosuppressants (including transplant drugs), and colchicine (lower colchicine dose).

More information

Rarely used, Viracept is the only protease inhibitor that is never used with Norvir. Do not leave the pharmacy without anti-diarrhea meds such as Immodium, or Tums or other calcium products. Taking a 500 mg calcium supplement with doses hugely decreases diarrhea. Also try Solgar oat bran tablets, psyllium husk fiber bars, and pancreatic enzymes (all with meals). As an extra precaution, take a change of clothes with you every day for the first several weeks—stick it out; most often, symptoms improve after two or three weeks. People using Viracept can crush adult tablets or dissolve tablets in a small amount of water. Mixing Viracept with acidic food or juice (e.g., orange/apple juice or apple sauce) is not recommended, due to resulting bitter taste. To get the full benefit of Viracept by increasing its level in the body, it must be taken with a meal. No longer a preferred PI in pregnancy, Viracept is still okay to use if the preferred and alternative PIs (Kaletra, Prezista, and Reyataz) are not an option. It has been used extensively in pregnancy in the past, and it is well tolerated during pregnancy. In 2007, Viracept manufactured in Europe was recalled from the market because of high levels of ethyl methane mesylate (EMS). Viracept manufactured in United States was found to have lower levels of EMS than the European product. However, the FDA recommended that pregnant women not be treated with Viracept and that pediatric patients not be started on Viracept. By early 2008, Viracept manufactured both in Europe and the U.S. was found to meet safety standards, and the FDA and European Medicines Agency lifted their warnings about safety. See package insert for more complete information on potential side effects and interactions.

STANDARD DOSE:

1,250 mg taken as either two 625 mg tablets or five 250 mg tablets twice daily with food. Take missed dose as soon as possible, unless it is closer in time to your next dose. Do not double up on your next dose. manufacturer:

ViiV Healthcare

www.viivhealthcare.com (877) 844-8872 AWP:

$965.40 / month for 250 mg and 625 mg tablets

Activist’s comments

I used to joke that Agouron, the company that made this protease inhibitor, should co-package underwear with the prescription as it is notorious for causing daily diarrhea. I remember when activists had high hopes for this fourth PI because the first three had failed to work. Viracept is no longer recommended or used by anyone that I know. — Matt Sharp

March+April 2013 | positivelyaware.com/viracept

HIV DRUG GUIDE

2013

Isentress

raltegravir, or RAL INSTI: Integrase inhibitor (integrase strand transfer inhibitor)

Potential side effects and toxicity

STANDARD DOSE:

One 400 mg film-coated tablet twice a day, with or without food, with no dietary restrictions. Can be taken by children two years or older. Dosing is based on weight for children 2–11 years old. Take a missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. A new pediatric formulation is now available in the form of 25 mg and 100 mg scored chewable tablets (which can also be swallowed), taken with or without food. The chewable tablets are not bioequivalent to the film-coated tablets; therefore, do not substitute chewable tablets for film-coated tablets. manufacturer:

Merck and Co.

www.isentress.com (800) 622–4477 AWP:

$1,228.69 / month

Very tolerable, but most common are diarrhea, insomnia, nausea, headache, and fatigue. The side effect profile in children is comparable to adults. Less common are abdominal pain, vomiting, weakness, dizziness, and lipodystrophy. May cause elevated levels of a muscle enzyme (creatine kinase). Contact your health care

Doctor’s comments

Isentress (raltegravir) is the first approved integrase inhibitor, providing a new weapon for anti-HIV attack. Integrase inhibitors work at an important point in the life cycle of HIV, blocking the integration, or incorporation, of viral DNA into the host DNA. Many patients who have become resistant to anti-HIV drugs are still sensitive to drugs active against this new target. The drug is extremely well-tolerated, although in headto-head trials with ritonavir-boosted elvitegravir, the participants on Isentress had a higher rate of elevated liver enzymes. In studies, it was the first anti-HIV drug to be shown more effective in combination with Truvada than the industry leader, Atripla. Viral suppression was superior and the side effect profile better. Isentress and Truvada are a recommended first-line therapy in the DHHS guidelines. The only thing limiting more widespread use of the drug is the need for twice-daily dosing. In clinical trials, once-daily dosing of Isentress was not as effective as twice-daily and this was even more pronounced in people with high viral loads. It is an interesting side note that while a decade ago there was widespread skepticism about once-a-day dosing of medications, twice-daily being considered “just fine,” now, the pendulum has swung and twice-daily dosing seems somehow intolerable. The truth is that most people are quite comfortable taking medications twice a day. Isentress/Truvada is such an effective combination and so well tolerated that it might be worth breaking the once-daily paradigm, especially for those with a virus resistant to NNRTIs or for people who are intolerant of other drugs. There appears to be cross-resistance between Isentress and elvitegravir, including Stribild. — Howard A. Grossman, MD

Activist’s comments

HIV DRUG GUIDE

2013

I was the second person in the Isentress expanded access program in 2006, and it was like pulling teeth to get enrolled. But the drug was critical for many who had been waiting years for a new drug class. And adding it to another new drug, especially Prezista, provided a powerful lifesaver for many. For the first time in 20 years of taking HIV meds, I was able to bring my viral load to undetectable, and it has stayed stable ever since. The drug is safe, forgiving if doses are missed, and potent. Now, other companies are developing me-too drugs, and second generation meds for people who may have developed resistance to Isentress, which is possible, especially if not taken according to the twice-daily regimen. — Matt Sharp

provider if you experience unexplained muscle pain, tenderness, or weakness. May cause anemia, neutropenia, and gastritis. Increases in ALT, AST, and total bilirubin, all signs of liver toxicity, seen in around 8% of people taking Isentress, especially those co-infected with hepatitis B or C. Although rarely seen, side effects can include severe and potentially fatal skin and hypersensitivity (allergic) reactions and cerebellar ataxia (sudden, uncoordinated movement due to disease or injury of the brain). Seek medical attention and immediately stop taking Isentress and your other HIV medications if you develop a rash associated with any of the following symptoms: fever, general ill feeling, extreme tiredness, muscle or joint aches, blisters, oral lesions, swelling of the eyes, lips, mouth, or face, difficulty breathing, and/or signs and symptoms of liver problems (such as yellowing of the skin or whites of the eyes, dark or tea-colored urine, pale stools/bowel movements, nausea, vomiting, loss of appetite, or pain, aching, or sensitivity on the right side below the ribs). Chewable tablets contain phenylalanine, which can be harmful to patients with phenylketonuria. See page 57 for potential drug class side effects.

Potential drug interactions

Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Reyataz and Reyataz/Norvir increase blood levels of Isentress, but no dose adjustment is recommended. Use caution with rifampin— increase dose of Isentress to 800 mg twice a day. Remember to decrease the Isentress dose back to 400 mg twice a day when you finish taking rifampin. There is no need to increase the Isentress dose with rifabutrin. There are no data on dosing of the new chewable tablets with rifampin. Prilosec can increase concentrations of Isentress, but no dose adjustment is recommended. There is no interaction with methadone. Isentress can be used with either Incivek or Victrelis.

More information

The data are in accord with the advocate view that advanced patients are having dramatic results and almost no side effects. The 156-week data in ART-naïve and 96-week data in ART-experienced patients show that Isentress continues to be effective with great tolerability. DHHS guidelines note drawbacks with Isentress: twice-a-day dosing and a lower barrier to drug resistance than with boosted PIs. Greater tolerability, which results in greater adherence, however, may help overcome those issues. Adherence is important because of the drug’s short half-life and its low genetic barrier to drug resistance (meaning that it may only take very few missed doses for this medication to stop working). The guidelines state that before prescribing Isentress, providers may want to order a resistance test that can measure INSTI resistance (standard tests cannot). If resistance to Isentress develops, the new integrase inhibitor elvitegravir (part of the Stribild tablet) will likely not work, however the investigational INSTI dolutegravir, part of the upcoming STR “572-Trii,” may still be effective. See package insert for more complete information on potential side effects and interactions.

March+April 2013 | positivelyaware.com/isentress

dolutegravir, or DTG

(brand name not yet established)

dolutegravir

INSTI: Integrase inhibitor (integrase strand transfer inhibitor)

Potential side effects and toxicity

Seen in clinical studies: nausea, diarrhea, headache, dizziness, fatigue, weakness, and upset stomach or indigestion. Associated with a small increase in creatinine (sign of kidney toxicity) resulting from the anticipated inhibition of creatinine secretion without affecting actual glomerular filtration rate (kidney test). Available data limited due to investigational drug status.

Potential drug interactions

Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Reyataz increases dolutegravir levels while Prezista, Lexiva, Aptivus, Sustiva, and rifabutin have been shown to decrease it by anywhere from 30–75%, and Intelence decreases it by 88%. This interaction can be counteracted by the addition of Kaletra or ritonavir-boosted Prezista. Antacids need to be separated from dolutegravir by at least two hours. Non-antacid acid reflux/heartburn medications are okay to use as no change in dolutegravir levels was seen with omeprazole. More drug interactions are anticipated, but data are limited right now due to investigational drug status.

Doctor’s comments

Dolutegravir is an investigational second-generation integrase inhibitor. Results from the 96-week comparison with efavirenz (Sustiva), SPRING-1, showed dolutegravir 50 mg to be effective at reducing HIV viral load and raising CD4 counts in integrase-naïve patients. In a Phase 3 trial (SINGLE), dolutegravir combined with abacavir and lamivudine was actually superior to Atripla (a fixed-dose combination of dolutegravir/abacavir/lamivudine is under review). The dolutegravir arm was better tolerated with far fewer dropouts. Effectiveness was maintained in both high and low viral load groups. It appears that dolutegravir will be effective even in patients who have developed resistance to Isentress (raltegravir) and elvitegravir (which appear to have cross resistance with one another). Dosing will probably be once-a-day in treatment-naïve patients and twicea-day in experienced patients. ViiV submitted the drug for approval in the U.S., Canada, and the EU in December 2012. — Howard A. Grossman, MD

Activist’s comments

Still in the oven, this new drug may be effective for people who may have developed resistance to Isentress or elvitegravir. Dosing has not been established, but so far it may be a twice-daily dose for treatment-experienced individuals, though oncedaily for people naïve to HIV treatment. In the war for HIV drug market dominance, ViiV plans to coformulate the drug in a single dose tablet with two older drugs, abacavir and lamivudine, which may bring those drugs out of the so-called HIV drug graveyard. — Matt Sharp

More information

Still in clinical study, but available through expanded access (free medication for eligible individuals in great need). Approval is expected later this year. Dolutegravir is a second-generation INSTI, meaning that it can work in many individuals whose virus has developed resistance to Isentress and elvitegravir (part of Stribild), but it will need to be dosed twice daily in these individuals. Based on current data, dolutegravir appears to be an exciting addition to current antiretrovirals. Will likely be co-formulated as one pill once daily with Epzicom for treatment-naïve patients (see the “572-Trii” page). It has fewer drug interactions than Stribild and appears to be well tolerated; most patients stayed on treatment despite reports of more than 10% experiencing nausea and diarrhea. The ongoing SINGLE study, in patients who are treatment-naïve (meaning that they have never been on HIV medications before), demonstrated superiority of dolutegravir/Epzicom compared to the single tablet regimen Atripla. At 48 weeks, 88% of study participants on the dolutegravir regimen were virologically suppressed (undetectable) vs. 81% of participants on Atripla. Differences in the slightly better outcomes for dolutegravir were mostly driven by a higher rate of discontinuation due to side effects in the Atripla group. It is being studied at a twice-daily dose with an optimized background regimen (the best regimen a medical provider can create for an individual) in people with current or a history of treatment failure with an INSTI (basically, those for whom Isentress no longer works, but also those who experienced virologic failure on elvitegravir). The SPRING-1 four-arm dose-ranging study looked at people who are ART naïve. At week 96, 88% of patients on dolutegravir 50 mg were able to achieve an undetectable viral load (less than 50 copies/mL) vs. 72% for Sustiva (taken with either Truvada or Epzicom). Responses in the dolutegravir 10 mg and 25 mg arms were 79% and 78%, respectively. Based on this dose-ranging study, the dose selected for larger studies in treatment-naïve patients was 50 mg (tablet or capsule). The SPRING-2 study, again in treatment-naïve patients, compared dolutegravir to Isentress, each with either Truvada or Epzicom. At week 48, once-daily dolutegravir was found to be non-inferior to twice-daily Isentress with 88% vs. 85% of patients respectively with undetectable viral loads. In the VIKING-3 Phase 3 (advanced) study, dolutegravir was added to a failing therapy in people with multi-class HIV drug resistance (including integrase inhibitor resistance) for seven days, and then continued on dolutegravir with their background regimen optimized. Despite this resistance profile, at 24 weeks (still early results) 63% of patients who had dolutegravir added to their failing regimen were able to achieve an undetectable viral load. This is a large study, with 183 individuals. Data from the SAILING study investigating once-daily dolutegravir in treatment-experienced patients with no previous exposure to integrase inhibitors is due to be presented at upcoming scientific meetings. A pediatric sprinkle formulation of dolutegravir is also being studied. See package insert, when available, for more complete information on potential side effects and interactions.

March+April 2013 | positivelyaware.com/dolutegravir

Investigational drug at press time; photo unavailable.

STANDARD DOSE:

One 50 mg tablet once a day for people on HIV therapy for the first time used in research. Twice-daily dosing in people who have viral resistance to Isentress and elvitegravir. Expected to have no food restrictions. Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. manufacturer:

ViiV Healthcare

www.viivhealthcare.com (877) 844-8872 AWP:

TBD: Drug not yet approved at press time. Available through expanded access program; www.dolutegravir-eap.com

HIV DRUG GUIDE

2013

elvitegravir

(brand name not yet established)

elvitegravir, or EVG

INSTI: Integrase inhibitor (integrase strand transfer inhibitor)

Potential side effects and toxicity

Investigational drug at press time; photo unavailable.

STANDARD DOSE:

150 mg once a day boosted with 150 mg cobicistat used in research. Take with food. Take missed dose as soon as possible, unless it is closer in time to your next dose. Do not double up on your next dose. Use is limited to people with creatinine clearance of greater than 70 mL/min.

Most common side effects are nausea, diarrhea, abnormal dreams, and headaches. Others may include upper respiratory tract infection, bronchitis, back pain, sinusitis, joint pain, and urinary tract infection. The incidence of these side effects were the same as seen with Isentress in one clinical study (3% to 6%), with the exception of diarrhea, seen more often (12% vs. 7%). Laboratory abnormalities indicating potential liver damage (GGT, ALT, and AST elevations) were lower with elvitegravir (3% vs. 6%, 2% vs. 5%, and 1% vs. 5%, respectively for elvitegravir and Isentress). Decreases in kidney function have also been seen and kidney function should be monitored closely. Liver enzymes can also be elevated as elvitegravir and cobicistat are processed through the liver (but the incidence is not higher than with PIs or NNRTIs). Available data are limited due to investigational drug status. See page 57 for potential drug class side effects.

Potential drug interactions

See package insert for most complete list of interactions. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Elvitegravir is metabolized primarily by the enzyme CYP450-3A (known as the P450

manufacturer:

Gilead Sciences, Inc. www.gilead.com (800) GILEAD-5 (445–3235) AWP:

TBD; drug not yet approved at press time.

Doctor’s comments

pathway) and any medications that affect this enzyme may affect the levels of elvitegravir.

More information

Not yet approved, but part of the single tablet, once daily regimen Stribild approved by the FDA last year. As part of Stribild, it was compared with Atripla and boosted Reyataz plus Truvada in patients who had never had HIV treatment. In both studies it was shown to be noninferior (no better, no worse) to the other regimen. The 96-week data from Study 145 (comparing elvitegravir to Isentress), presented at the 2012 International AIDS Conference, showed elvitegravir was non-inferior to Isentress, the only INSTI on the market at press time, in treatment-experienced people (this group, on average, does not respond as well as people taking HIV therapy for the first time). At 96 weeks of therapy, 48% of patients in the elvitegravir group and 45% of patients in the Isentress group achieved an undetectable viral load of less than 50 copies per mL. At 96 weeks there was an increase in CD4+ T-cell count of 205 cells for elvitegravir and 198 cells for Isentress. Of patients in each group, 7% developed integrase resistance mutations. Providers may want to order a resistance test that can measure INSTI resistance (standard tests cannot) prior to initiating an elvitegravir-containing regimen. See package insert, when available, for more complete information on potential side effects and interactions.

Elvitegravir, another integrase inhibitor, has not been approved as a stand-alone drug, and so is still investigational. It has been approved, though, as part of the so-called “quad pill,” Stribild, in combination with cobicistat, tenofovir DF, and emtricitabine. Integrase inhibitors work at an important point in the life cycle of HIV, blocking the integration of viral DNA into the host DNA. Many patients who have become resistant to anti-HIV drugs are still sensitive to drugs active against this new target. Elvitegravir is under review for approval as a stand-alone drug for use with other antivirals. Elvitegravir requires boosting in order to achieve adequate blood levels, either with ritonavir or with cobisistat, and can then be given once daily. In a head-to-head trial, elvitegravir/ritonavir was non-inferior to Isentress in experienced patients. Major side effects in studies have included nausea and diarrhea. It is not clear if this is from elvitegravir itself or from the drugs used to boost its levels. There appears to be cross-resistance between Isentress and elvitegravir. —Howard A. Grossman, MD

Activist’s comments

HIV DRUG GUIDE

2013

Gilead’s attempt at market dominance simply had to include an integrase inhibitor since they are the latest thing, so they really surprised no one when their quad pill (Stribild) containing elvitegravir, their own integrase inhibitor, reached approval. They want to bring the single agent to the market and final approval is expected soon. This drug holds similar virus mutation patterns as Isentress, so people who are resistant will need to wait until dolutegravir is approved. —Matt Sharp

March+April 2013 | positivelyaware.com/elvitegravir

Fuzeon

enfuvirtide, T-20, or ENF entry inhibitor: Fusion inhibitor

Potential side effects and toxicity

The most common are injection site reactions (ISRs), which occur in virtually all patients. The severity of reaction is variable, and for most is mild to moderate. Symptoms could include itching, swelling, redness, pain or tenderness, and hardened skin or bumps. Bumps, termed “nodules,” seem to occur more frequently and severely in areas of high muscle mass (most notably the center of the stomach—the abs—and the thighs). They will hurt with movement. Other side effects may

Doctor’s comments

Enfuvirtide is a fusion inhibitor, a drug that blocks viral entry into the cell by preventing the virus from fusing with the cell membrane. It was a major breakthrough when it first became available. It was approved in 2003 and at that time, there were many patients who had used up all available treatment options, had high-level drug resistance, and were getting ill. Fuzeon helped many to suppress HIV enough to continue on until new drugs were available. As with all anti-HIV medications, it must be taken in combination with other antivirals. While it is highly effective, Fuzeon is not an easy drug to use. A subcutaneous injection of it must be given twice daily. It is a delicate molecule and must be reconstituted and prepared carefully each day. Injections can be painful and many patients experience an injection site reaction with swelling, pain, and redness. To treat this, the daily injection routines often include massaging the area, applying cold or heat and other techniques to minimize pain and swelling, and carefully rotating injection sites, all of which can be very time-consuming. The only other significant toxicity with the drug was an indication of increased bacterial pneumonia in early studies. With the advent of many new effective drugs targeting resistant virus and new viral targets, the use of Fuzeon has declined dramatically, but it still remains a useful tool for the most experienced and drug-resistant patients. —Howard A. Grossman, MD

Activist’s comments

Once the pre-eminent salvage therapy, this drug has really lost its appeal for many reasons. It came along when there was a desperate need for new drug classes for people who had used all their treatment options. But the only injectable antiretroviral drug has had problems, not only due to the painful twicedaily injection site reactions, but due to its high cost—the highest of any HIV drug in history. It also required mixing the refrigerated drug vials. But innovative drug development eventually brought oral integrase inhibitors onto the scene, and people no longer needed to subject themselves to the Fuzeon ordeal. The nail in the coffin is the fact that its maker Roche has gone entirely out of the HIV drug business, yet there are still a handful of people who need it and have had success with it, despite the needles. — Matt Sharp

include diarrhea, nausea, and fatigue, but these are more likely due to the other HIV medications taken along with Fuzeon. Hypersensitivity (allergic-like) reactions are possible. Results of a post-marketing observational study were added to Fuzeon’s drug label showing a higher incidence of pneumonia in people taking Fuzeon. Risk factors for pneumonia included a low CD4+ T-cell count or high viral load when starting therapy, intravenous drug use, smoking, and a previous history of lung disease. It is unclear if this was related to the use of Fuzeon, so report cough, fever, or trouble breathing to your health care provider immediately. See page 57 for potential drug class side effects.

Potential drug interactions

To date, no interactions that are clinically significant have been found.

More information

With other powerful, newer drugs on the market, the twice-daily injectable Fuzeon is truly a medicine of last resort. Fuzeon is intended for treatment-experienced patients. Store kit at room temperature. Preparing and injecting Fuzeon can be complicated, so ask your health care provider to teach you how to do it. First, the drug needs to be dissolved with sterile water (provided in the kit), which may take up to 45 minutes. Never shake the vial with the Fuzeon, it will foam. Instead, roll it gently in your hands. To save time, you can prepare the two daily doses at the same time. You should store your second dose in the refrigerator, but it must be used within 24 hours of mixing it (allow it to warm to room temperature before using). Before injecting, it is important to make sure that the Fuzeon powder is completely dissolved. To minimize injection site reactions, inject where you can pinch an inch (upper arm, stomach, or thigh). If not, then be sure to use half the length of the needle. Inject slowly and apply a gentle massage after injection. Try using vibrating devices after injections. Using insulin syringes to inject instead of the ones in the kit may help decrease the injection site reactions. Taking a shower before injecting helps warm and soften the skin and may also help reduce injection site reactions. Some patients use Arnica cream to decrease the inflammation. Follow proper hygiene instructions to avoid infection. ISR may worsen when injection is repeated in the same spot or given deeper than intended, for example, into the muscle. Always rotate injection sites frequently. Never inject into moles, scars, bruises, nodules, or the navel. Fuzeon can be taken at the same time as other anti-HIV drugs. Fuzeon is the only anti-HIV compound on the market called a fusion inhibitor. Fusion inhibitors block fusion of HIV with a cell before the virus enters the cell and begins its replication process. Fusion inhibitors are a type of entry inhibitor (see Selzentry). See package insert for more complete information on potential side effects and interactions.

March+April 2013 | positivelyaware.com/fuzeon

STANDARD DOSE:

One subcutaneous (under the skin, like insulin) injection of 90 mg (1 mL) twice daily (every 12 hours) into the upper arm, thigh, or abdomen. Take with or without food, with no dietary restrictions. Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Each injection should be given in a different location from the previous one and at a site where there is no current injection site reaction from a previous dose. It is also approved for children 6 years or older. The dose for children is based on weight. manufacturer:

Genentech

www.genentech.com www.fuzeon.com (877) 4–FUZEON (438–9366) AWP:

$3,346.19 / month for 90 mg kit

HIV DRUG GUIDE

2013

Selzentry

maraviroc, or MVC entry inhibitor: CCR5 antagonist

Potential side effects and toxicity

STANDARD DOSE:

Available in 150 mg and 300 mg tablets. Can be taken with or without food, with no dietary restrictions. Take missed dose as soon as possible, unless it is closer in time to your next dose. Do not double up on your next dose. The recommended dose varies, depending on other medications the patient is taking: your doctor or pharmacist can determine which medications will affect Selzentry levels and recommend the appropriate dose for you. Before you start Selzentry, you will need a specific blood test (tropism assay, Trofile or Trofile ES) to determine if this medication will work for you. The results for a Trofile test may take up to a month. Selzentry only works for those people with CCR5-tropic virus.

Most common include cough, fever, cold, rash, muscle and joint pain, stomach pain, and dizziness. Other potential side effects may include liver toxicity and an allergic reaction may happen before the liver problems. It is recommended that Selzentry be stopped and your doctor contacted right away if you develop a rash, yellowing of your eyes or skin, dark urine, vomiting, and upper stomach pain. Other rare side effects may include dizziness or fainting when standing up due to low blood pressure. Should not be used in people with severe or end-stage

Doctor’s comments

AWP:

Selzentry (maraviroc) is an entry inhibitor, blocking an important protein that HIV uses to enter cells. HIV can utilize two different proteins called CCR5 (or R5) and CXCR4 (or X4). In order to determine which protein is utilized a tropism assay (test) must be run prior to prescribing Selzentry. If the virus is R5 tropic then Selzentry should show antiviral activity. If the test shows dual-mixed or X4 tropic viruses, then it will not be effective. In the U.S. there is only one approved tropism assay and it is quite expensive and takes several weeks to get results. These are often barriers to prescribing Selzentry. Still, when used against R5 tropic viruses, it has proven very effective. It is approved for use in naïve and experienced patients. Dosing must be carefully determined. There are a multitude of important drug interactions which require different doses (see this page or the online interaction chart for details). Selzentry is not a preferred drug in the DHHS guidelines. It is considered an acceptable alternative, but the guidelines state that more definitive data is needed. The MOTIVATE trial showed good results in treatment-experienced patients taking Selzentry with a number of different protease inhibitors. Study A4001078 first reported at IAS 2012 found once-daily Selzentry with ritonavir-boosted Reyataz to be comparable to Truvada with boosted Reyataz in treatment-naïve patients. Selzentry should not be used in patients with endstage renal disease or severe renal impairment. — Howard A. Grossman, MD

$1,259.82 / month for 300 mg tablets

Activist’s comments

manufacturer:

ViiV Healthcare

www.viivhealthcare.com (877) 844-8872

HIV DRUG GUIDE

2013

Debatably one of the most intensive research efforts that turned out to be a market flop, Selzentry (maraviroc) delivered an exciting new target for HIV therapy in the CCR5 co-receptor of T-cells. Pfizer (the original maker) had worked desperately to bring this drug to the market, but the appeal was just not there, and the results so-so. The need for a tropism blood test to determine whether your virus had the right co-receptor to target was only part of the problem, but other drugs provided better results in the long run. One interesting aspect is that Selzentry improves CD4 cell numbers. Today, gene therapy research is also targeting the CCR5 co-receptor with some astounding results. Maybe [developer] Pfizer knew something we didn’t? — Matt Sharp

kidney disease who are taking medications that can affect the levels of Selzentry (check with your provider). Selzentry affects immune system cells and could possibly increase the risk of infections and cancer, although this has not been observed in studies with up to five years of follow-up. See page 57 for potential drug class side effects.

Potential drug interactions

See package insert for the most complete list. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Interactions with other medications and anti-HIV drugs include: 150 mg twice daily if taken with medications that increase the levels of Selzentry such as protease inhibitors (except for Aptivus) and Rescriptor; 300 mg twice daily if taken with Aptivus, Viramune, Fuzeon, and all of the NRTIs and medications that do not affect the levels of Selzentry; and 600 mg twice daily if taken with medications that decrease the levels of Selzentry such as Sustiva, Intelence, and some anti-convulsants such as phenobarbital, phenytoin, and carbamazepine. Dose change may be required if kidney function is less than 30 mL/min. Not recommended with Priftin or St. John’s wort. Dose adjustment needed for clarithromycin, Mycobutin, itraconazole, ketoconazole, midazolam, rifampin (use 600 mg twice-daily Selzentry dose), and voriconazole.

More information

Complex dosing, the need for a tropism test, and competition from newer drugs have dimmed some of the initial enthusiasm for this drug. The tropism test needed is now generally paid for by public health departments, Medicare, and private insurance coverage. ViiV may cover the payment for the Trofile test if someone is ADAP-eligible and insurance doesn’t cover the test. Viral tropism refers to the types of HIV that a person can have, CCR5 (R5) or CXCR4 (X4) (see Doctor’s Comments). As the name “CCR5 inhibitor” suggests, Selzentry inhibits (blocks) CCR5, shutting down this point of entry for the virus. Most people are infected with R5 virus, and then over time, X4 and mixed viruses may accumulate. Blocking R5 with Selzentry does not cause a shift to X4 or negatively affect disease progression or CD4 count in people whose virus can use either R5 or X4 (dual-tropic). Selzentry seems to have minimal impact on lipid levels. In the MERIT clinical trial, the initial analysis suggested that Selzentry was unable to match Sustiva’s viral loads of less than 50 copies (undetectable), but a re-analysis of the data showed the regimens to be comparable in achieving undetectable viral loads in treatment-naïve participants at 96 weeks, leading to FDA approval for this group. See package insert for more complete information on potential side effects and interactions.

March+April 2013 | positivelyaware.com/selzentry

efavirenz / emtricitabine / tenofovir DF, or EFV / FTC / TDF

Atripla

STR: SINGLE-TABLET REGIMEN—NNRTI and NRTIs

Potential side effects and toxicity

See the individual drugs contained in Atripla—Sustiva, Emtriva, and Viread (efavirenz, emtricitabine, and tenofovir DF). Atripla is well tolerated in most, but not all, individuals. Use with caution in individuals with depression or other psychiatric issues, especially if not under a psychiatrist’s care. Other side effects may include diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash. Kidney function should be assessed before initiating treatment and throughout therapy as determined by a provider. Women should not become pregnant on Atripla or for 12 weeks after discontinuation, because of the risk of birth defects (greatest in the first trimester). Dose cannot be adjusted for people with kidney problems. See page 57 for potential drug class side effects.

Potential drug interactions

See the individual drugs contained in Atripla: Sustiva, Emtriva, and Viread. Do not take Atripla with Combivir, Complera, Edurant, Emtriva, Epivir, Epivir-HBV, Epzicom, Hepsera, Intelence, Rescriptor, Stribild, Sustiva, Trizivir,

Doctor’s comments

Atripla was the first triple combination fixed dose pill approved. It quickly became the most widely prescribed antiviral regimen and the gold standard for initial treatment. It is the preferred treatment in almost all treatment guidelines. The combination is effective, well-tolerated, and safe. The limits to Atripla use are most often related to the side effects of the component drugs. Efavirenz (Sustiva) has central nervous system/psychiatric effects including somnolence and a feeling some have likened to being high. It can cause severe depression in some. Many patients also experience sleep disturbances, mostly from especially vivid dreams. Most people take the drug at bedtime so that they can sleep through the period of altered consciousness, but there are some people who can take it any time of day without an effect. Some patients also experience allergic reactions and Stevens-Johnson syndrome, an especially severe skin reaction that can be life threatening, has been reported in some cases. Tenofovir can have effects on the kidneys. — Howard A. Grossman, MD

Activist’s comments

Having been one of those people who had to gobble a handful of antiretroviral pills several times a day, I never dreamed there would be a once-a-day combo pill. It is quite a remarkable achievement in the history of HIV drug development, especially that it is a complete regimen in a once-daily pill. Despite Sustiva’s weird neuro-effects, dizziness, vivid dreams, etc., this STR is still a preferred regimen according to the antiretroviral guidelines. It may be outpaced eventually by integrase inhibitor-based fixed dose pills, but until then it will continue to be popular. — Matt Sharp

Truvada, Viramune, Viread, or “572-Trii” since these medications are already in Atripla or they have equivalent medications. Atripla should not be taken with Vascor, midazolam (oral Versed), pimozide, triazolam, voriconazole (Vfend), or St. John’s wort. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not, as there are many other drug interactions which are not listed here.

More information

Atripla was the first complete HIV treatment regimen in one pill, taken once daily, but now has head-to-head competition from Complera and Stribild. Atripla is one of four preferred regimens for treatment-naïve patients in the DHHS HIV treatment guidelines. Atripla is one of the most commonly prescribed medications for those taking HIV medicine for the first time due to the ease of taking one pill, once a day. Another benefit: the single tablet cuts the number of insurance co-pays. Approval of Complera and Stribild, however, made Atripla’s side effect profile harder to overlook. Sustiva (efavirenz) should not be taken during pregnancy. According to federal HIV perinatal guidelines, however, because the birth defect risk is limited to the first six weeks of pregnancy but pregnancy is rarely recognized before six weeks, the recommendation is that women in their first trimester be continued on efavirenz as long as viral load remains undetectable. The efavirenz in Atripla can cause a false positive for marijuana on certain drug tests. A more specific confirmatory test can be done. Atripla should not be used in patients under 12 years of age. Most treatmentexperienced people (those who’ve already been on HIV therapy) may not be able to use Atripla due to having developed drug resistance (when their medications may no longer work against the virus). Drug resistance most commonly occurs when people don’t take their HIV medicine as prescribed, but some may also be infected with a drug-resistant virus against which some of the medications in Atripla will not work. Because it is one dose once a day, it is important not to miss a dose. Be careful when stopping Atripla, so that you avoid the rapid development of HIV resistance to it—check with your doctor or pharmacist first. Use of tenofovir DF must be monitored in people with underlying kidney problems. In this combination product, the tenofovir and emtricitabine dose cannot be adjusted. Therefore, Atripla should not be used in people with severe kidney problems. Tenofovir DF and emtricitabine are also both used to treat hepatitis B. If you are co-infected with hepatitis B, when you stop Atripla your hepatitis B may be reactivated. If your HIV develops resistance to tenofovir and/or emtricitabine, it does not mean that your hepatitis B is also resistant to them and your provider may continue them even if your HIV regimen is being changed. Gilead and BMS are forever to be commended for working together to bring Atripla to market, the first collaboration of its kind. See package insert for more complete information on potential side effects and interactions.

March+April 2013 | positivelyaware.com/atripla

STANDARD DOSE:

One tablet (600 mg efavirenz / 200 mg emtricitabine / 300 mg tenofovir), once daily, preferably at bedtime, on an empty stomach for patients 12 years and older weighing at least 88 pounds. Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. Dose cannot be adjusted for people with kidney problems and Atripla should not be used in people with moderate or severe kidney or liver impairment. manufacturer:

Bristol-Myers Squibb www.bms.com (800) 321–1335 and

Gilead Sciences www.gilead.com (800) GILEAD-5 (445–3235) www.atripla.com AWP:

$2,253.88 / month

HIV DRUG GUIDE

2013

Complera

rilpivirine / emtricitabine / tenofovir DF, or RPV / FTC / TDF STR: SINGLE-TABLET REGIMEN—NNRTI and NRTIs

Potential side effects and toxicity

STANDARD DOSE:

One tablet (25 mg rilpivirine / 200 mg emtricitabine / 300 mg tenofovir) once daily, with a meal of at least 400 calories such as two slices of pizza; two slices of whole wheat toast with peanut butter, fresh fruit, and orange juice; a roast beef sandwich on a hard roll with mayo and cheese; two cups of spaghetti with marinara sauce and a slice of bread; or tortilla with chicken, rice, and beans. Take missed dose as soon as possible but no later than 12 hours after your regularly scheduled dose. Do not double up on your next dose. The dose of this fixed dose combination pill cannot be adjusted for people with kidney function of less than 50 mL/min— therefore, it should be used with caution in individuals with kidney problems. manufacturer:

Janssen Therapeutics

www.janssentherapeutics.com (877) JANSSEN (526-7736) and

Gilead Sciences

www.gilead.com (800) GILEAD-5 (445–3235) www.complera.com AWP:

$2,323.84 / month

HIV DRUG GUIDE

2013

See the individual drugs contained in Complera—Edurant and Truvada (rilpivirine / emtricitabine / tenofovir DF). Moderate to severe side effects are uncommon: insomnia, headache, nausea, dizziness, rash, abnormal dreams, and depressive disorders (depression, negative thoughts, suicidal thoughts or actions). See page 57 for potential drug class side effects.

Potential drug interactions

Do not take this drug with Atripla, Combivir, Edurant, Emtriva, Epivir, Epivir-HBV, Epzicom, Hepsera, Intelence, Rescriptor, Stribild, Sustiva, Trizivir, Truvada, Viramune, or Viread, since Complera contains these medications or has equivalent medication. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not as there are many other drug interactions which are not listed here. Antacids can be taken two hours before or four hours after a Complera dose. H2 receptor antagonists,

Doctor’s comments

Complera is the second approved fixed dose medication containing three drugs. Rilpivirine is an extremely well-tolerated NNRTI. Compared to efavirenz, it has very low levels of CNS/psychiatric side effects. In the registrational trial for rilpivirine, a combination of rilpivirine with tenofovir and emtricitabine performed as well as Atripla in patients with viral loads under 100,000 copies/mL but there were a greater number of failures in the rilpivirine arm with higher viral loads. This led to recommendations that rilpivirine and, by extension, Complera, not be used at viral loads greater than 100,000 copies/ mL. This fact may account for the slow uptake in use of Complera. More recent data has thrown this into question. Reports of the STaR trial documented that Complera was non-inferior to Atripla at viral loads up to 500,000. The label was changed in January 2012 and Complera is now approved for use in patients with viral loads up to 100,000 copies/mL. Patients who are taking Complera are very satisfied and for providers it is a simple drug to prescribe—having so few side effects means that there is less education necessary and less resistance from patients. Complera must be taken with at least 400 calories of solid food. This makes it not the best choice for some people with irregular schedules. — Howard A. Grossman, MD

Activist’s comments

The fight against Sustiva’s dominance continues. This combo-regimen pill may not be a breakthrough but more of a competition for market dominance, since Gilead co-owns both STR pills. Because of Edurant, people with higher viral loads may not benefit from the drug, but they also may not want the ever-present neurotoxicity associated with the efavirenz part of Atripla, so Complera is perhaps an attractive alternative. — Matt Sharp

such as Pepcid, Tagamet, and Zantac, can be taken 12 hours before or four hours after a Complera dose. Proton pump inhibitors (PPIs) (Nexium, Prevacid, Prilosec, etc.) can’t be taken with Complera. Do not take Complera with carbamazepine, oxcarbazepine, phenobarbital, or phenytoin; rifabutin, rifampin, or Priftin; or the herb St. John’s wort (other herbs have not been studied with Complera, but use caution if planning to take any herbs). Do not take with more than one dose of the injectable steroid dexamethasone. Clinically monitor drug levels of fluconazole, Sporanox, Nizoral, Noxafil, and voriconazole; no dose adjustments are needed. Use azithromycin when possible instead of the antibiotics clarithromycin (Biaxin), erythromycin, and Ketek. These agents will increase rilpivirine levels, which can increase the risk for side effects. Methadone levels may be reduced slightly but no dose adjustments are necessary; still, it is recommended to monitor for withdrawal. Early data shows that Complera may be taken with Incivek without any dose adjustments.

More information

Complera is FDA-approved for people starting therapy for the first time who have viral loads of 100,000 copies/mL or less. According to DHHS HIV treatment guidelines, Complera is an alternative therapy for people who cannot take Atripla and are starting HIV therapy for the first time. In the STaR study, Complera was more tolerable than Atripla and did not have the same cholesterol elevations. Nervous system and psychiatric events were the most common side effects but higher in the Atripla group. In the SPIRIT study, 317 participants switched from a Norvir-boosted protease inhibitor regimen and most maintained undetectable viral load at one year after the switch to Complera. Concerns about switching from Atripla to Complera were eased when decreases in Complera levels were only seen in the first few weeks of a 12-week study, and participants maintained their undetectable viral loads. Complera must be taken with a meal of at least 400 calories, including some fat. Nutritional drinks, even high-calorie protein shakes or products like Ensure, are not enough for proper absorption, and do not constitute a meal. Taken with a protein shake, rilpivirine levels were still half of what they are with a meal. Rilpivirine, emtricitabine, and tenofovir all have long half-lives (time it takes a drug in the body to be reduced by half), making them a great combination. Complera pills are smaller in size than Atripla. Check for hepatitis B before starting therapy (see Truvada). Some government programs may not pay for Complera but require that patients take its separate components. Kudos to Janssen Therapeutics, developer of Edurant, and Gilead for collaborating on Complera. See package insert for more complete information on potential side effects and drug interactions.

March+April 2013 | positivelyaware.com/complera

elvitegravir / cobicistat / emtricitabine / tenofovir DF, or EVG / COBI / FTC / TDF

Stribild

STR: SINGLE-TABLET REGIMEN—Boosted integrase inhibitor and NRTIs

Potential side effects and toxicity

See the individual drugs contained in Stribild: elvitegravir, Emtriva (emtricitabine), Viread (tenofovir DF), and cobicistat. Most common are nausea and diarrhea. Abnormal dreams, headaches, and fatigue have also been seen. Others include changes in kidney function tests (see cobicistat page for more, and reassuring, information), bone problems, and elevated liver function

Doctor’s comments

Stribild is the third fixed dose combination pill approved. It is known more colloquially as the “quad.” While there are indeed four drugs in it, this is a bit of a misnomer since only three of them are antiviral drugs. The fourth, cobicistat, is a pharmacologic boosting drug that raises blood concentrations of elvitegravir to acceptable levels. Stribild has proven quite effective and tolerable. It has demonstrated comparable efficacy to Atripla and to atazanavir/ ritonavir/Truvada. Cobicistat is a molecule similar to ritonavir and its availability creates new possibilities for an alternative to ritonavir. The main side effects with Stribild were diarrhea and nausea, both of which are common with ritonavir. It does seem to not have the same lipid effects as ritonavir; in fact lipid levels were higher in the Atripla arm compared to the Stribild arm. The full range of drug interactions with cobicistat are not yet clear. There are complex interactions with oral contraceptives. Cobicistat causes a decrease in creatinine secretion in the urine and a rise in blood levels. This rise does not appear to have any clinical significance, but clinicians must be aware of the chance of the laboratory abnormality so that it is not confused with kidney toxicity. The usual cautions with tenofovir apply to Stribild with monitoring of renal function necessary, so the rise in creatinine alone cannot be used to measure this. Bone loss is also a potential side effect related to tenofovir. Given the tolerability of other drug combinations in the class and the very high price of Stribild, as well as side effects not that much different from Norvir and cross-resistance with Isentress, it is unclear to me where Stribild will fit in the armamentarium, but it is always useful to have another alternative. — Howard A. Grossman, MD

Activist’s comments

The once-daily power pill affectionately known as the “Quad” has not turned out to be the smash seller Gilead had hoped, but it has not been out there for six months yet, so hold on to your hats. The first antiretroviral drug containing four drugs from three different classes is quite a remarkable achievement. Despite the fact that the drugs in the combo are all their own, Gilead has to be commended for thinking outside of the box, or on behalf of the consumer for a change. The price remains exorbitant and unacceptable and is creating fodder for newly formed ACT UP chapters. Activists also mocked the Stribild name as “strive to build profit.” — Matt Sharp

tests. See page 57 for potential drug class side effects.

Potential drug interactions

See package insert for the most complete list. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Do not take with Atripla, cobicistat, Combivir, Complera, elvitegravir, Emtriva, Epivir, Epivir-HBV, Epzicom, Hepsera, Norvir, “572-Trii,” Trizivir, Truvada, or Viread, since these medications are already in Stribild or it has equivalent medications. Do not take at the same time with antacids. Separate by at least 2 hours from antacids and vitamins/supplements containing aluminum or magnesium. Elvitegravir induces CYP2C9 (it revs up the activity of this enzyme in the liver), which can decrease blood levels of many medications, including some for diabetes and depression. Cobicistat is a potent CYP3A4 inhibitor (it slows down the activity of this enzyme), and is expected to have many drug interactions, similar to those seen with Norvir. Do not take with Advicor, alfuzosin, Altoprev, ergotamine, Livalo, lovastatin, methylergonovine, midazolam, pimozide, Revatio, rifabutin, Rifadin, rifampin, Simcor, simvastin, triazolam, voriconazole, Vytorin, garlic supplements, or St. John’s wort. Cholesterol-lowering alternatives are atorvastatin, Crestor, fluvastatin, and pravastatin, but should be used with caution and started at the lowest dose possible; monitor closely for increased side effects from these medications. Titrate dose of antidepressants. No dose adjustments needed with proton pump inhibitors. Use with caution and therapeutic monitoring of antiarrhythmic drugs. Increases levels of fluticasone (found in Advair, Flonase, and Flovent); monitor for signs of Cushing’s syndrome (such as rounded face). A lower dose of trazodone is recommended. Methadone may need to be increased. Use caution with anti-convulsants carbamazepine, phenobarbital, and phenytoin, and calcium channel blockers. Cialis, Levitra, and Viagra levels are increased; doses should not exceed 10 mg Cialis or 2.5 mg Levitra per 72 hours, or 25 mg Viagra per 48 hours. Effectiveness of birth control pills may be decreased; consider the use of alternative or additional contraception. Clarithromycin levels can increase. Use with caution with bosentan, salmeterol, and immunosuppressants; lower colchicine dose. Incivek or Victrelis with Stribild can potentially reduce the effectiveness of both drugs— combined use is not recommended.

STANDARD DOSE:

One tablet (150 mg elvitegravir / 150 mg cobicistat / 200 mg emtricitabine / 300 mg tenofovir) once daily with food. Take missed dose as soon as possible, unless it is closer in time to your next dose. Do not double up on your next dose. Dose cannot be adjusted for people with kidney problems, therefore it should not be started in individuals with estimated creatinine clearance less than 70 mL per min. and should be discontinued if CrCl decreases to 50 or less. manufacturer:

Gilead Sciences www.gilead.com (800) GILEAD-5 (445-3235) AWP:

$2,810.96 / month

More information

Stribild was approved by the FDA in August 2012 for HIV treatment-naïve people, and the guidelines quickly added it to its list of alternative regimens while citing limitations. One doctor newsletter noted the addition “reflects the value of single tablet regimens in general and increasing enthusiasm for integrase inhibitors in particular.” Not recommended for people with severe liver impairment. Stribild is available through all state ADAPs. Insurance companies may require prior authorization. See page 70. See package insert for more complete details about potential side effects and drug interactions.

March+April 2013 | positivelyaware.com/stribild

HIV DRUG GUIDE

2013

“572-Trii”

(brand name not yet established)

dolutegravir / abacavir / lamivudine, or DTG / ABC / 3TC STR: SINGLE-TABLET REGIMEN—INSTI and NRTIs

Potential side effects and toxicity

See the individual drugs contained in “572-Trii”: dolutegravir, Ziagen, and Epivir. Available data are limited due to investigational drug status. Investigational drug at press time; photo unavailable.

STANDARD DOSE:

One tablet (50 mg dolutegravir / 600 mg abacavir / 300 mg lamivudine) once a day for people on HIV therapy for the first time used in research. Twice-daily dosing in people who have viral resistance to Isentress and elvitegravir. Take missed dose as soon as possible, unless it is closer to the time of your next dose. Do not double up on your next dose. manufacturer:

ViiV Healthcare

www.viivhealthcare.com (877) 844-8872 AWP:

TBD; investigational drug at press time.

Potential drug interactions

See the individual drugs contained in “572-Trii”: dolutegravir, Ziagen, and Epivir. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Dolutegravir has no effect on midazolam, tenofovir, rilpivirine, methadone, and oral contraceptives. Reyataz increases dolutegravir levels while Prezista, Lexiva, Aptivus Sustiva, and rifabutin have been shown to decrease it by anywhere from 30-75%, and Intelence decreases it by 88%. This interaction can counteracted by the addition of Kaletra or ritonavir-boosted Prezista. Antacids need to be separated from dolutegravir by at least two hours. This is due to what is called metal cation chelation (meaning that magnesium, aluminum and calcium in antacids bind to dolutegravir and keep it from being absorbed). Non-antacid acid reflux/heartburn medications are okay to use as no change in dolutegravir levels was seen with omeprazole. More drug interactions are anticipated, but data are limited right now due to investigational drug status.

More information

The single tablet regimen (“572-Trii”) containing

dolutegravir, abacavir, and lamivudine is currently being studied. “572-Trii” is pronounced “572-try.” See the individual drugs contained in “572-Trii”—dolutegravir, Ziagen, and Epivir—for more information. Dolutegravir is a second-generation INSTI, meaning that it can work in many individuals whose virus has developed resistance to Isentress and elvitegravir, but it will need to be dosed twice daily in these individuals. Based on the current data, “572-Trii” appears to be an exciting addition to the current antiretrovirals. It gives us another single tablet complete regimen. There will be twice-daily dosing for patients with INSTI drug resistance. It will have fewer drug interactions than Stribild and appears to be well tolerated; most patients stayed on treatment despite reports of more than 10% experiencing nausea and diarrhea. Does not require use with a booster medication as does elvitegravir (see elvitegravir). The ongoing SINGLE study, in patients who are treatment-naïve (meaning that they have never been on HIV medications before), demonstrated superiority of dolutegravir/Epzicom compared to the single tablet regimen Atripla. At 48 weeks, 88% of study participants on the dolutegravir regimen were virologically suppressed (less than 50 copies/mL) vs. 81% of participants on Atripla. Differences in the slightly better outcomes for dolutegravir were mostly driven by a higher rate of discontinuation due to side effects in the Atripla group. Dolutegravir is expected to receive FDA approval this year (see dolutegravir page). See package insert, when available, for more complete information on potential side effects and interactions.

Doctor’s comments

Dolutegravir is an investigational second-generation integrase inhibitor found in “572-Trii” along with abacavir/lamivudine. Results from the 96-week comparison with efavirenz, SPRING-1, showed dolutegravir 50 mg to be effective at reducing HIV viral load and raising CD4 counts in integrase-naïve patients. In the Phase 3 trial SINGLE, “572-Trii” was actually found to be superior to Atripla. It has completed several Phase 3 trials and FDA evaluation is most likely imminent. — Howard A. Grossman, MD

Activist’s comments

HIV DRUG GUIDE

2013

In the spirit of fixed-dose combo pills, another new drug is on its way to a pharmacy near you (assuming FDA approval and all the access hurdles are jumped). ViiV wants to be in direct competition with Gilead’s Stribild, which is a combination of their new integrase inhibitor, and background nukes, plus their own booster. ViiV will attempt a similar approach with their new “572-Trii” using their own drugs dolutegravir, abacavir, and lamivudine. I’m scratching my head over why people would want to use “572-Trii” due to abacavir, but one advantage is that there is no booster required and it may work for those who have used up Isentress. This is the new way of drug company wars—competing for the treatment naïve population, potency, and once-daily dosing. But a lot is still unknown, as dolutegravir is not even approved yet. — Matt Sharp

March+April 2013 | positivelyaware.com/trii

cobicistat (formerly GS-9350), or COBI

(brand name not yet established)

cobicistat

PKE: pharmacokinetic enhancer/booster

Potential side effects and toxicity

Seen in clinical studies: diarrhea, nausea, lipid elevations (increases in cholesterol and triglycerides), creatine kinase, hematuria (red blood cells in the urine), increased serum creatinine (SCr), and decreased estimated glomerular filtration rate (e-GFR)—the last two are signs of possible kidney malfunction. The SCr increase occurred within weeks of starting cobicistat and was reversible with kidney function returning to normal within a few days after stopping cobicistat. The decreased e-GFR appears to not impact health. Available data are limited due to investigational drug status.

Potential drug interactions

It is very important that you let your provider/pharmacist know of any/all medications/herbals/supplements, prescription or not, that you take before starting on a regimen that contains cobicistat (Stribild is the only one right now but others are coming soon). Antacids need to be separated from cobicistat by at least two hours.

Doctor’s comments

Cobicistat is a pharmacokinetic enhancer that can boost the levels of many HIV drugs. Previously, the only drug used for this consistently has been ritonavir (with small numbers of providers using azole antifungals and Rescriptor for this purpose). Cobicistat has been approved for use as part of the single-tablet regimen Stribild, but it has not yet been approved for use as a stand-alone agent. Cobicistat is similar to ritonavir. The main side effects appear to be nausea and diarrhea. The effects on lipids are not yet completely clear. In the head-to-head trial of Stribild vs. Atripla, lipid levels were higher in the Atripla arm. Cobicistat can cause a decrease in secretion of creatinine by the kidneys and a rise in blood levels. This does not appear to be clinically significant at all. If cobicistat is approved for use on its own, we can expect to see it combined with several other drugs and fixed dose combinations are in development. — Howard A. Grossman, MD

Activist’s comments

This pharmacokinetic enhancer works by inhibiting the CYP3A4 enzyme in the liver that breaks down many HIV drugs that use the same enzyme. In doing so, cobicistat boosts the effectiveness of the HIV drugs. Activists have been pushing for years for anyone to develop a safer, more tolerable PK enhancer to compete with Norvir—the former protease inhibitor-cum-booster that has significant side effects and the horrid reputation of having its price raised by 400%. But when Gilead added cobicistat to its repertoire, it turns out it might not be as friendly a drug after all because it still has a poor gastrointestinal side effects profile. Time will tell, however, as it is currently a quarter of Stribild (formerly known as “the Quad”) and may reach approval as a standalone booster this year and in other fixed dose combinations in the future. — Matt Sharp

Cobicistat may increase levels of certain calcium channel blockers, beta-blockers, HMG-CoA reductase inhibitors (statins), antiarrhythmics, sedative-hypnotics, erectile dysfunction agents, inhaled corticosteroids, and norgestimate. It increases serum levels of elvitegravir and several protease inhibitors, including Reyataz and Prezista. Azole antifungals (such as itraconazole) and clarithromycin may increase serum cobicistat concentrations (and cobicistat may simultaneously increase serum levels of clarithromycin when co-administered). Rifabutin and some antiepileptic medications (e.g., carbamazepine and phenytoin) may decrease cobicistat levels. The drug interaction profile is expected to be as extensive as Norvir’s because cobicistat is metabolized by CYP3A, and, to a minor extent, CYP2D6, as well as inhibiting cellular transporters p-glycoprotein, BCRP, OATP1B1, and OATP1B3.

More information

Stribild, which contains cobicistat, was FDA approved in August 2012. Stand-alone cobicistat is expected to be approved in 2013. It is being studied in combination with Prezista and Reyataz in place of Norvir and it is also in studies comparing it to Norvir as a booster. Gilead is in collaboration with Janssen and Bristol-Myers Squibb to co-formulate single tablets containing Prezista/cobicistat, Prezista/cobicistat/emtricitabine/GS-7340 (or TAF), and Reyataz/cobicistat. It does not seem to be able to boost Aptivus. Levels of both Aptivus and cobicistat were lowered when the two drugs were combined. Cobicistat is not an HIV medication, but a drug used to boost levels of HIV protease inhibitors, as Norvir does now, allowing for fewer pills and (usually) once-daily dosing. Norvir can be difficult to tolerate, and its manufacturer angered the HIV community by raising its price 400% one year to make up for its widely used smaller booster dose. (Norvir was initially used in higher doses to fight HIV, but is now only used as a booster.) As an alternative to Norvir, COBI’s development has created a lot of excitement. Unfortunately, it has the increased cholesterol and triglycerides of Norvir, along with some of the stomach upset. There is also the potential negative impact on the kidneys, although further findings have been reassuring. The 10% increase in creatinine levels that was seen initially did not continue to increase out to 48 weeks, and was reversible upon stopping cobicistat. Results from Gilead’s 114 study (atazanavir/emtricitabine/ tenofovir/cobicistat vs. atazanavir/emtricitabine/tenofovir/ritonavir) showed that 85% of patients taking the cobicistat formulation achieved undetectable viral load of less than 50 copies/mL, compared to 87% of patients taking Norvir. There was similar safety and tolerability. See package insert when available for more complete information on potential side effects and interactions.

March+April 2013 | positivelyaware.com/cobicistat

Investigational drug at press time; photo unavailable.

STANDARD DOSE:

150 mg once a day used in research. Cobicistat is not an HIV drug, but is used to increase the levels of elvitegravir (investigational INSTI, see elvitegravir page) and, possibly, HIV protease inhibitors, which will allow for lower and fewer doses of these medications while maintaining their effectiveness. Take missed dose as soon as possible, unless it is closer in time to your next dose. Do not double up on your next dose. manufacturer:

Gilead Sciences www.gilead.com (800) GILEAD-5 (445-3235) AWP:

TBD; drug not yet approved at press time.

HIV DRUG GUIDE

2013

Egrifta (tesamorelin) for HIV-RELATED EXCESS BELLY FAT STANDARD DOSE:

2 mg via subcutaneous (under the skin) injection once daily in the abdomen, rotating injection sites and avoiding scar tissue, bruises, and the navel. Each dose necessitates mixing two 1-mg vials (requiring refrigeration) of Egrifta with one vial of sterile water (stored at room temperature) or one 2-mg vial with one vial of sterile water. The vial should be rolled gently between the hands for 30 seconds to ensure reconstitution into a clear, colorless solution. Once mixed, Egrifta should be administered right away. manufacturer:

EMD Serono, Inc. egrifta.com 877-714-AXIS (2947)

A potential complication of HIV, antiretroviral therapy, or both may be the redistribution of adipose (fat) tissue, otherwise known as lipodystrophy; reports of prevalence in the U.S. vary widely, anywhere from 2â&#x20AC;&#x201C;60% of all HIV-positive patients. Lipohypertrophy (a form of lipodystrophy) is the accumulation of excess visceral adipose tissue (VATâ&#x20AC;&#x201D;deep belly fat surrounding the liver, stomach, and other abdominal organs). In 2010, Egrifta became the first FDA-approved medication to reduce VAT. Egrifta is an analogue of growth hormone releasing factor (GRF) that acts on pituitary cells in the brain to stimulate our own growth hormone production. The effect of this agent appears to be within the first three to six months of initiation. Two Phase 3 clinical trials compared Egrifta to placebo (fake pill); both trials found that Egrifta significantly lowered VAT at both 26 and 52 weeks. Adverse events were more commonly seen in the Egrifta arm compared to placebo. It is important to note that changes in VAT observed with Egrifta are reversed once the drug is discontinued. Egrifta should not be administered in patients who have pituitary gland tumor(s), pituitary gland surgery, or other problems related to their pituitary

gland; active cancer; hypersensitivity to either tesamorelin and/or mannitol; or who are pregnant. Egrifta should be used with caution in patients who have neoplasms (abnormal growth of tissue such as a tumor), elevated insulin-like growth factor 1 (IGF-1), fluid retention, diabetes, or pre-diabetes. The most common side effects include: joint pain, pain in legs and arm, swelling in legs, muscle soreness, tingling, numbness and prickling, nausea, vomiting, rash, and itching. Other warnings include hypersensitivity reactions, injection site reactions, and acute critical illness. Despite initial thoughts that Egrifta may have significant drug-drug interactions with medications that need CYP450 (an enzyme in the liver) to be activated, a study in healthy volunteers proved otherwise. However, it has not been studied with medications that use other enzymes in the liver, therefore, response to medications that need the liver to be activated should be monitored for response and adverse reactions. Long-term safety data is unknown. There have been previous reports of an increased risk of cancer with elevated IFG-1 levels. Other long-term concerns include development of retinopathy.

awp:

$23,900 annually, or $1,964 for 30 days

Fulyzaq (crofelemer)

photo unavailable at press time.

for HIV/AIDS-Associated Diarrhea STANDARD DOSE:

One 125 mg delayedrelease tablet taken orally twice a day, with or without food. The tablet should be swallowed whole and should not be crushed or chewed. manufacturer:

Salix Pharmaceuticals www.fulyzaq.com (919) 862-1000 AWP:

Unavailable at press time. 56

In December 2012, the FDA approved Fulyzaq

(crofelemer) as the first anti-diarrheal indicated for the symptomatic relief of non-infectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy. Currently, what is typically recommended is for the patient to take medication(s) with food and/ or use Imodium for symptomatic diarrhea. Fulyzaq approval was based on a randomized trial of 374 HIV-positive patients taking Fulyzaq or a sugar pill twice daily. Through 20 weeks, 17.6% of patients taking Fulyzaq had two or less watery bowel movements per week compared to only 8% of patients who took the sugar pill. Fulyzaq was less effective in African Americans in clinical studies. At this time, there are no patients who should

avoid taking Fulyzaq. If a patient is complaining of diarrhea, an infectious cause should be ruled out prior to initiating Fulyzaq. Some of the most common side effects included bronchitis, cough, flatulence, and increased bilirubin. Fulyzaq may cause fetal harm, based on animal data. Fulyzaq has not been studied in patients younger than 18 years old and its use in this population cannot be recommended at this time. Fulyzaq has the potential to inhibit CYP450 liver enzyme 3A. There were no clinically relevant drug-drug interactions seen between Fulyzaq and Viracept (nelfinavir), zidovudine, or lamivudine.

March+April 2013 | positivelyaware.com

DRUG CLASS Side Effects Updated by Renata Smith, Pharmd, and EniD Vázquez

o learn all the details about each drug’s potential side effects, see the drug’s page or get out

a magnifying glass and read that tiny print in the Patient Information insert that comes with your medications. Remember that side effects may or may not occur. Some are more common than others, and individuals react differently to the same drug. A drug regimen cannot be chosen solely on the basis of potential side effects. Pay attention to any changes that you notice with your body and discuss any symptoms, however minor, with your health care providers, including your pharmacist, since small reactions may become serious. There may also be management techniques for the side effect. Listed below are the most common side effects for each class of drugs as well as for therapy as a whole. Remember, not every drug in each class will have every side effect. ART There are potential side effects (good and bad) associated with HIV therapy itself. Good: Taking ART (antiretroviral therapy) can make people less likely to transmit HIV if they have an undetectable viral load (less than 50 copies/mL), according to DHHS HIV treatment guidelines updated last year. There should be no other sexually transmitted infection present among sex partners, HIV-positive or not, as it would increase risk of transmission. Of note, HIV can be undetectable in blood levels but detectable in genital fluids, thereby increasing risk of transmission. For more details, go to www.aidsinfo. nih.gov. Bad: Immune Reconstitution Inflammatory Syndrome (IRIS) may occur as the immune system regains strength; signs and symptoms of inflammation from previous infections may occur soon after ART is initiated. Report symptoms of illnesses such as shingles and tuberculosis (TB) to a health care provider right away. NRTIs: Nucleoside Reverse Transcriptase Inhibitors Combivir, Emtriva, Epivir, Epzicom, Retrovir, Trizivir, Truvada, Videx EC, Viread, Zerit, and Ziagen Rare but potentially serious side effects with all NRTIs: Enlarged, fatty liver and lactic acidosis (accumulation of lactate in the blood and abnormal acidbase balance). Lactic acidosis may cause persistent fatigue, abdominal pain or distension, nausea/vomiting, and difficulty breathing. NNRTIs: Non-Nucleoside Reverse Transcriptase Inhibitors Edurant, Intelence, Rescriptor, Sustiva, and Viramune Common with NNRTIs is rash.

PIs: Protease Inhibitors Aptivus, Crixivan, Invirase, Kaletra, Lexiva, Norvir, Prezista, Reyataz, and Viracept Seen with all PIs except Prezista and unboosted Reyataz (and sometimes boosted Reyataz as well): Increased levels of cholesterol and triglycerides, which may be associated with an increased risk of heart disease. Other possible side effects are lipodystrophy (body fat changes, including thinning of the face, arms, and legs, with or without fat accumulation in the stomach, breasts, and upper back), onset of new cases or worsening of diabetes (see your doctor promptly), and increased bleeding in hemophiliacs. Integrase inhibitors Isentress, dolutegravir, elvitegravir At press time, Isentress was the only standalone integrase inhibitor on the market, but Stribild, approved last year, contains elvitegravir. Dolutegravir and elvitegravir are expected to be FDA approved in 2013. No drug class side effects known to date. Entry inhibitors Fuzeon and Selzentry No drug class side effects known to date. STRs: Single-Tablet Regimens Atripla, Complera, Stribild A fourth STR, “572-Trii,” is expected to be approved next year. Because each pill contains a combination of medicines from different drug classes, the best thing to do is look up each drug in the pill. PKE: Pharmacokinetic Enhancer Cobicistat is currently the only PK booster that is not an anti-HIV drug (Norvir is a booster but is also an HIV protease inhibitor—see above). Though cobicistat has not been FDA approved on its own, it is an ingredient in Stribild, which has been approved. No drug class side effects known to date.

March+April 2013 | positivelyaware.com

HIV DRUG GUIDE

2013

The

one

for me

Patient model. Pill shown is not actual size.

What is COMPLERA? COMPLERA is a prescription HIV medicine that is used as a complete regimen to treat HIV-1 in adults who have never taken HIV medicines before and who have an amount of HIV in their blood (this is called “viral load”) that is no more than 100,000 copies/mL. COMPLERA contains 3 medicines – rilpivirine, emtricitabine and tenofovir disoproxil fumarate. It is not known if COMPLERA is safe and effective in children under the age of 18 years. ®

COMPLERA® does not cure HIV-1 infection or AIDS. To control HIV-1 infection and decrease HIV-related illnesses you must keep taking COMPLERA. Avoid doing things that can spread HIV-1 to others: always practice safer sex and use condoms to lower the chance of sexual contact with body fluids; never reuse or share needles or other items that have body fluids on them, do not share personal items that may contain bodily fluids. Ask your healthcare provider if you have questions about how to reduce the risk of passing HIV-1 to others.

IMPORTANT SAFETY INFORMATION What is the most important information you should know about COMPLERA? COMPLERA® can cause serious side effects: • Build-up of an acid in your blood (lactic acidosis), which is a serious medical emergency. Symptoms of lactic acidosis include feeling very weak or tired, unusual (not normal) muscle pain, trouble breathing, stomach pain with nausea or vomiting, feeling cold, especially in your arms and legs, feeling dizzy or lightheaded, and/or a fast or irregular heartbeat. • Serious liver problems. The liver may become large (hepatomegaly) and fatty (steatosis). Symptoms of liver problems include your skin or the white part of your eyes turns yellow (jaundice), dark “tea-colored” urine, light-colored bowel movements (stools), loss of appetite for several days or longer, nausea, and/or stomach pain. • You may be more likely to get lactic acidosis or serious liver problems if you are female, very overweight (obese), or have been taking COMPLERA for a long time. In some cases, these serious conditions have led to death. Call your healthcare provider right away if you have any symptoms of these conditions. • Worsening of hepatitis B (HBV) infection. If you also have HBV and stop taking COMPLERA, your hepatitis may suddenly get worse. Do not stop taking COMPLERA without first talking to your healthcare provider, as they will need to monitor your health. COMPLERA is not approved for the treatment of HBV.

Who should not take COMPLERA? Do not take COMPLERA if you have ever taken other anti-HIV medicines. COMPLERA may change the effect of other medicines and may cause serious side effects. Your healthcare provider may change your other medicines or change their doses. Do not take COMPLERA if you also take these medicines: • anti-seizure medicines: carbamazepine (Carbatrol, Equetro, Tegretol, Tegretol-XR, Teril, Epitol); oxcarbazepine (Tileptal), phenobarbital (Luminal), phenytoin (Dilantin, Dilantin-125, Phenytek) • anti-tuberculosis medicines: rifabutin (Mycobutin), rifampin (Rifater, Rifamate, Rimactane, Rifadin) and rifapentine (Priftin) • proton pump inhibitors for stomach or intestinal problems: esomeprazole (Nexium, Vimovo), lansoprazole (Prevacid), dexlansoprazole (Dexilant), omeprazole (Prilosec), pantoprazole sodium (Protonix), rabeprazole (Aciphex) • more than 1 dose of the steroid medicine dexamethasone or dexamethasone sodium phosphate • St. John’s wort (Hypericum perforatum) If you are taking COMPLERA you should not take other HIV medicines or other medicines containing tenofovir (Viread, Truvada, Stribild or Atripla); other medicines containing emtricitabine or lamivudine (Emtriva, Combivir, Epivir, Epivir-HBV, Epzicom, Trizivir, Atripla, Stribild or Truvada); rilpivirine (Edurant) or adefovir (Hepsera). In addition, tell your healthcare provider if you are taking the following medications because they may interfere with how COMPLERA works and may cause side effects: • certain antacid medicines containing aluminum, magnesium hydroxide, or calcium carbonate (examples: Rolaids, TUMS). These medicines must be taken at least 2 hours before or 4 hours after COMPLERA. • medicines to block stomach acid including cimetidine (Tagamet), famotidine (Pepcid), nizatidine (Axid), or ranitidine HCL (Zantac). These medicines must be taken at least 12 hours before or 4 hours after COMPLERA. • any of these medicines: clarithromycin (Biaxin); erythromycin (E-Mycin, Eryc, Ery-Tab, PCE, Pediazole, Iloson), fluconazole (Difulcan), itraconazole (Sporanox), ketoconazole (Nizoral) methadone (Dolophine); posaconazole (Noxifil), telithromycin (Ketek) or voriconazole (Vfend). • medicines that are eliminated by the kidneys like acyclovir (Zovirax), cidofovir (Vistide), ganciclovir (Cytovene IV, Vitrasert), valacyclovir (Valtrex) and valganciclovir (Valcyte).

COMPLERA.

A complete HIV treatment in only 1 pill a day. COMPLERA is for adults who have never taken HIV-1 medicines before and have no more than 100,000 copies/mL of virus in their blood.

Ask your healthcare provider if it’s the one for you.

These are not all the medicines that may cause problems if you take COMPLERA. Tell your healthcare provider about all prescription and nonprescription medicines, vitamins, or herbal supplements you are taking or plan to take.

The most common side effects reported with COMPLERA are trouble sleeping (insomnia), abnormal dreams, headache, dizziness, diarrhea, nausea, rash, tiredness, and depression. Some side effects also reported include vomiting, stomach pain or discomfort, skin discoloration (small spots or freckles) and pain.

Before taking COMPLERA, tell your healthcare provider if you: • Have liver problems, including hepatitis B or C virus infection, or have abnormal liver tests • Have kidney problems • Have ever had a mental health problem • Have bone problems • Are pregnant or planning to become pregnant. It is not known if COMPLERA can harm your unborn child • Are breastfeeding: Women with HIV should not breastfeed because they can pass HIV through their milk to the baby. Also, COMPLERA may pass through breast milk and could cause harm to the baby

This is not a complete list of side effects. Tell your healthcare provider or pharmacist if you notice any side effects while taking COMPLERA, and call your healthcare provider for medical advice about side effects.

COMPLERA can cause additional serious side effects: • New or worsening kidney problems, including kidney failure. If you have had kidney problems, or take other medicines that may cause kidney problems, your healthcare provider may need to do regular blood tests. • Depression or mood changes. Tell your healthcare provider right away if you have any of the following symptoms: feeling sad or hopeless, feeling anxious or restless, have thoughts of hurting yourself (suicide) or have tried to hurt yourself. • Changes in liver enzymes: People who have had hepatitis B or C, or who have had changes in their liver function tests in the past may have an increased risk for liver problems while taking COMPLERA. Some people without prior liver disease may also be at risk. Your healthcare provider may need to check your liver enzymes before and during treatment with COMPLERA. • Bone problems can happen in some people who take COMPLERA. Bone problems include bone pain, softening or thinning (which may lead to fractures). Your healthcare provider may need to do additional tests to check your bones. • Changes in body fat can happen in people taking HIV medicine. • Changes in your immune system. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your healthcare provider if you start having new symptoms after starting COMPLERA.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit http://www.fda.gov/medwatch or call 1-800-FDA-1088. Additional Information about taking COMPLERA: • Always take COMPLERA exactly as your healthcare provider tells you to take it. • Take COMPLERA with a meal. Taking COMPLERA with a meal is important to help

get the right amount of medicine in your body. (A protein drink does not replace a meal). Stay under the care of your healthcare provider during treatment with COMPLERA and see your healthcare provider regularly. Please see Brief Summary of full Prescribing Information with important warnings on the following pages.

Learn more at www.COMPLERA.com

Patient Information

•

COMPLERA (kom-PLEH-rah) (emtricitabine, rilpivirine, tenofovir disoproxil fumarate) tablets ®

Brief summary of full Prescribing Information. For more information, please see the full Prescribing Information including Patient Information. What is COMPLERA? •

COMPLERA is a prescription HIV (Human Immunodeficiency Virus) medicine that is used to treat HIV-1 in adults – who have never taken HIV medicines before, and – who have an amount of HIV in their blood (this is called ‘viral load’) that is no more than 100,000 copies/mL. Your healthcare provider will measure your viral load.

(HIV is the virus that causes AIDS (Acquired Immunodeficiency Syndrome)). •

COMPLERA contains 3 medicines – rilpivirine, emtricitabine, tenofovir disoproxil fumarate – combined in one tablet. It is a complete regimen to treat HIV-1 infection and should not be used with other HIV medicines.

•

It is not known if COMPLERA is safe and effective in children under the age of 18 years old.

•

COMPLERA does not cure HIV infection or AIDS. You must stay on continuous therapy to control HIV infection and decrease HIV-related illnesses.

•

Ask your healthcare provider if you have any questions about how to prevent passing HIV to other people. Do not share or re-use needles or other injection equipment, and do not share personal items that can have blood or body fluids on them, like toothbrushes and razor blades. Always practice safer sex by using a latex or polyurethane condom to lower the chance of sexual contact with semen, vaginal fluids or blood.

Who should not take COMPLERA? Do not take COMPLERA if: • your HIV infection has been previously treated with HIV medicines. •

you are taking any of the following medicines: – anti-seizure medicines: carbamazepine (Carbatrol, Equetro, Tegretol, Tegretol-XR, Teril, Epitol); oxcarbazepine (Trileptal); phenobarbital (Luminal); phenytoin (Dilantin, Dilantin-125, Phenytek) – anti-tuberculosis (anti-TB) medicines: rifabutin (Mycobutin); rifampin (Rifater, Rifamate, Rimactane, Rifadin); rifapentine (Priftin) – proton pump inhibitor (PPI) medicine for certain stomach or intestinal problems: esomeprazole (Nexium, Vimovo); lansoprazole (Prevacid); dexlansoprazole (Dexilant); omeprazole (Prilosec, Zegerid); pantoprazole sodium (Protonix); rabeprazole (Aciphex) – more than 1 dose of the steroid medicine dexamethasone or dexamethasone sodium phosphate – St. John’s wort (Hypericum perforatum)

•

If you take COMPLERA, you should not take: – Other medicines that contain tenofovir (Atripla, Stribild, Truvada, Viread)

What is the most important information I should know about COMPLERA? COMPLERA can cause serious side effects, including: • Build-up of lactic acid in your blood (lactic acidosis). Lactic acidosis can happen in some people who take COMPLERA or similar (nucleoside analogs) medicines. Lactic acidosis is a serious medical emergency that can lead to death. Lactic acidosis can be hard to identify early, because the symptoms could seem like symptoms of other health problems. Call your healthcare provider right away if you get any of the following symptoms which could be signs of lactic acidosis: – feel very weak or tired – have unusual (not normal) muscle pain – have trouble breathing – have stomach pain with nausea (feeling sick to your stomach) or vomiting – feel cold, especially in your arms and legs

– Other medicines that contain emtricitabine or lamivudine (Combivir, Emtriva, Epivir or Eprivir-HBV, Epzicom, Trizivir, Atripla, Truvada, Stribild) – rilpivirine (Edurant) – adefovir (Hepsera) What should I tell my healthcare provider before taking COMPLERA? Before you take COMPLERA, tell your healthcare provider if you: • have or had liver problems, including hepatitis B or C virus infection, kidney problems, mental health problem or bone problems •

– feel dizzy or lightheaded Severe liver problems. Severe liver problems can happen in people who take COMPLERA. In some cases, these liver problems can lead to death. Your liver may become large (hepatomegaly) and you may develop fat in your liver (steatosis). Call your healthcare provider right away if you get any of the following symptoms of liver problems:

•

– your skin or the white part of your eyes turns yellow (jaundice) – dark “tea-colored” urine – light-colored bowel movements (stools)

are breast-feeding or plan to breast-feed. You should not breastfeed if you have HIV because of the risk of passing HIV to your baby. Do not breastfeed if you are taking COMPLERA. At least two of the medicines contained in COMPLERA can be passed to your baby in your breast milk. We do not know whether this could harm your baby. Talk to your healthcare provider about the best way to feed your baby.

– loss of appetite for several days or longer

Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements.

– nausea

•

– stomach pain •

are pregnant or plan to become pregnant. It is not known if COMPLERA can harm your unborn child. Pregnancy Registry. There is a pregnancy registry for women who take antiviral medicines during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk to your healthcare provider about how you can take part in this registry.

– have a fast or irregular heartbeat •

Worsening of Hepatitis B infection. If you have hepatitis B virus (HBV) infection and take COMPLERA, your HBV may get worse (flare-up) if you stop taking COMPLERA. A “flare-up” is when your HBV infection suddenly returns in a worse way than before. COMPLERA is not approved for the treatment of HBV, so you must discuss your HBV with your healthcare provider. – Do not let your COMPLERA run out. Refill your prescription or talk to your healthcare provider before your COMPLERA is all gone. – Do not stop taking COMPLERA without first talking to your healthcare provider. – If you stop taking COMPLERA, your healthcare provider will need to check your health often and do blood tests regularly to check your HBV infection. Tell your healthcare provider about any new or unusual symptoms you may have after you stop taking COMPLERA.

You may be more likely to get lactic acidosis or severe liver problems if you are female, very overweight (obese), or have been taking COMPLERA for a long time.

COMPLERA may affect the way other medicines work, and other medicines may affect how COMPLERA works, and may cause serious side effects. If you take certain medicines with COMPLERA, the amount of COMPLERA in your body may be too low and it may not work to help control your HIV infection. The HIV virus in your body may become resistant to COMPLERA or other HIV medicines that are like it.

Especially tell your healthcare provider if you take: • an antacid medicine that contains aluminum, magnesium hydroxide, or calcium carbonate. If you take an antacid during treatment with COMPLERA, take the antacid at least 2 hours before or at least 4 hours after you take COMPLERA. •

•

a medicine to block the acid in your stomach, including cimetidine (Tagamet), famotidine (Pepcid), nizatidine (Axid), or ranitidine hydrochloride (Zantac). If you take one of these medicines during treatment with COMPLERA, take the acid blocker at least 12 hours before or at least 4 hours after you take COMPLERA. any of these medicines (if taken by mouth or injection): – clarithromycin (Biaxin) – erythromycin (E-Mycin, Eryc, Ery-Tab, PCE, Pediazole, Iloson) – fluconazole (Diflucan)

•

trouble sleeping (insomnia)

•

abnormal dreams

•

headache

•

dizziness

•

diarrhea

•

nausea

•

rash

•

tiredness

•

depression

Additional common side effects include: •

– itraconazole (Sporanox)

vomiting

•

– ketoconazole (Nizoral)

stomach pain or discomfort

•

– methadone (Dolophine)

skin discoloration (small spots or freckles)

•

pain

– posaconazole (Noxafil) – telithromycin (Ketek) – voriconazole (Vfend) •

The most common side effects of COMPLERA include:

medicines that are eliminated by the kidney, including acyclovir (Zovirax), cidofovir (Vistide), ganciclovir (Cytovene IV, Vitrasert), valacyclovir (Valtrex), and valganciclovir (Valcyte)

Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of COMPLERA. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 (1-800-332-1088).

What are the possible side effects of COMPLERA?

How should I take COMPLERA?

COMPLERA can cause serious side effects, including: • See “What is the most important information I should know about COMPLERA?”

•

Stay under the care of your healthcare provider during treatment with COMPLERA.

•

Take COMPLERA exactly as your healthcare provider tells you to take it.

•

Always take COMPLERA with a meal. Taking COMPLERA with a meal is important to help get the right amount of medicine in your body. A protein drink does not replace a meal.

•

Do not change your dose or stop taking COMPLERA without first talking with your healthcare provider. See your healthcare provider regularly while taking COMPLERA.

•

If you miss a dose of COMPLERA within 12 hours of the time you usually take it, take your dose of COMPLERA with a meal as soon as possible. Then, take your next dose of COMPLERA at the regularly scheduled time. If you miss a dose of COMPLERA by more than 12 hours of the time you usually take it, wait and then take the next dose of COMPLERA at the regularly scheduled time.

•

Do not take more than your prescribed dose to make up for a missed dose.

•

New or worse kidney problems, including kidney failure, can happen in some people who take COMPLERA. Your healthcare provider should do blood tests to check your kidneys before starting treatment with COMPLERA. If you have had kidney problems in the past or need to take another medicine that can cause kidney problems, your healthcare provider may need to do blood tests to check your kidneys during your treatment with COMPLERA. Depression or mood changes. Tell your healthcare provider right away if you have any of the following symptoms: – feeling sad or hopeless – feeling anxious or restless – have thoughts of hurting yourself (suicide) or have tried to hurt yourself

•

Change in liver enzymes. People with a history of hepatitis B or C virus infection or who have certain liver enzyme changes may have an increased risk of developing new or worsening liver problems during treatment with COMPLERA. Liver problems can also happen during treatment with COMPLERA in people without a history of liver disease. Your healthcare provider may need to do tests to check your liver enzymes before and during treatment with COMPLERA.

•

Bone problems can happen in some people who take COMPLERA. Bone problems include bone pain, softening or thinning (which may lead to fractures). Your healthcare provider may need to do additional tests to check your bones.

•

Changes in body fat can happen in people taking HIV medicine. These changes may include increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the main part of your body (trunk). Loss of fat from the legs, arms and face may also happen. The cause and long term health effect of these conditions are not known.

•

Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking HIV medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your healthcare provider if you start having new symptoms after starting your HIV medicine.

This Brief Summary summarizes the most important information about COMPLERA. If you would like more information, talk with your healthcare provider. You can also ask your healthcare provider or pharmacist for information about COMPLERA that is written for health professionals, or call 1-800-445-3235 or go to www.COMPLERA.com Issued: January 2013

COMPLERA, the COMPLERA Logo, EMTRIVA, GILEAD, the GILEAD Logo, GSI, HEPSERA, STRIBILD, TRUVADA, and VIREAD are trademarks of Gilead Sciences, Inc., or its related companies. ATRIPLA is a trademark of Bristol-Myers Squibb & Gilead Sciences, LLC. All other marks referenced herein are the property of their respective owners. ©2013 Gilead Sciences, Inc. All rights reserved. CON15582 02/13

Keeping standards Current DHHS treatment guidelines for first time therapy* A regimen should be individualized on the basis of virologic efficacy (suppression of viral load to less than 50 copies per mL), toxicity, pill burden, dosing frequency, drug-drug interaction potential, drug resistance testing results, and co-morbid conditions (such as kidney disease, hepatitis B or C, etc.). See details about the strength of the recommendations in the DHHS documents online.

Patients new to antiretroviral therapy DRUG Class

should start on one of three types of combination regimens:

Abbreviations:

INSTI: integrase strand transfer inhibitor NNRTI: non-nucleoside reverse transcriptase inhibitor NRTI: nucleos(t)ide reverse transcriptase inhibitor PI: protease inhibitor

generic name

NNRTI-based regimen

INSTI-based regimen

(preferably boosted)

Preferred regimens NNRTI-based

Atripla (EFV 1/FTC/TDF)3

PI-based

boosted Prezista (DRV/r) (once daily) + Truvada (FTC/TDF)3 boosted Reyataz (ATV/r) + Truvada (FTC/TDF)3

Abbreviations:

3TC: lamivudine ABC: abacavir ATV: atazanavir COBI: cobicistat ddI: didanosine DRV: darunavir EFV: efavirenz EVG: elvitegravir FPV: fosamprenavir FTC: emtricitabine LPV: lopinavir MVC: maraviroc NVP: nevirapine RAL: raltegravir RPV: rilpivirine r: low dose ritonavir SQV: saquinavir TDF: tenofovir DF ZDV: zidovudine (or AZT)

PI-based regimen

INSTI-based

Isentress (RAL) + Truvada (FTC/TDF)3

Preferred for pregnant women PI-based

Kaletra (LPV/r) (twice daily) + Combivir (3TC/ZDV)3 boosted Reyataz (ATV/r) (once daily) + Combivir (3TC/ZDV)3

Alternative regimens Based on personal characteristics and needs, in some instances, an alternative regimen may actually be a preferred regimen for an individual. NNRTI-based

Complera (RPV/FTC/TDF)3 Edurant (RPV) + Epzicom (ABC/3TC)3, 4 Sustiva (EFV 1) + Epzicom (ABC/3TC)3, 4

PI-based

Kaletra (LPV/r) (once or twice daily) + Epzicom (ABC/3TC)3, 4 or Truvada (FTC/TDF)3 boosted Lexiva (FPV/r) (once or twice daily) + Epzicom (ABC/3TC)3, 4 or Truvada (FTC/TDF)3 boosted Prezista (DRV/r) + Epzicom (ABC/3TC)3, 4 boosted Reyataz (ATV/r) + Epzicom (ABC/3TC)3, 4

HIV DRUG GUIDE

2013

INSTI-based

Isentress (RAL) + Epzicom (ABC/3TC)3, 4 Stribild (EVG/COBI/FTC/TDF)

March+April 2013 | positivelyaware.com

Other antiretroviral regimens Regimens that may be selected for some patients but are less satisfactory than preferred or alternative regimens. NNRTI-based

Edurant (RPV) + Combivir (3TC/ZDV)3 Sustiva (EFV 1) + Combivir (3TC/ZDC)3 Viramune (NVP2) + Combivir (3TC/ZDV)3 or Epzicom (ABC/3TC)3, 4 or Truvada (FTC/TDF)3

PI-based

boosted Invirase (SQV/r) + Combivir (3TC/ZDV)3 or Epzicom (ABC/3TC)3, 4 or Truvada (FTC/TDF)3

These combinations are among those available as co-formulated fixed dose combinations:

EFV/FTC/TDF (Atripla) 3TC/ZDV (Combivir)

Kaletra (LPV/r) + Combivir (3TC/ZDV)3 RPV/FTC/TDF (Complera)

boosted Lexiva (FPV/r) + Combivir (3TC/ZDV)3 boosted Prezista (DRV/r) + Combivir (3TC/ZDV)

boosted Reyataz (ATV/r) + Combivir (3TC/ZDV)3

ABC/3TC (Epzicom)

Reyataz (ATV) + Combivir (3TC/ZDV)3 or Epzicom (ABC/3TC)3, 4

LPV/r (Kaletra) INSTI-based

Isentress (RAL) + Combivir (3TC/ZDV)3

CCR5 antagonistbased regimen

Selzentry (MVC) + Combivir (3TC/ZDV) or Epzicom (ABC/3TC) Truvada (FTC/TDF)3 5

3, 4

EVG/COBI/FTC/TDF (Stribild) FTC/TDF (Truvada)

1. Except during first trimester of pregnancy or in women with high pregnancy potential. 2. Nevirapine (Viramune) should not be initiated in women with CD4+ T-cell count greater than 250 cells/mm3 or in men with CD4+ T-cell count greater than 400 cells/mm3. 3. Emtriva (emtricitabine) and lamivudine (Epivir) are interchangeable. 4. ABC should not be used in people who test positive for HLA-B*5701. 5. MVC may be considered in people who have only CCR5-tropic HIV.

Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Section accessed February 6, 2013; Tables 5a and 5b.

** Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission.

Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/PerinatalGL.pdf. Accessed February 6, 2013; Table 5.

March+April 2013 | positivelyaware.com

HIV DRUG GUIDE

2013

A n n i v e r s a ry pa r t n e r s $100,000 AND ABOVE

$50,000 AND ABOVE

$25,000 AND ABOVE

The Lloyd A. F ry Foundation

Being there for one another. In June 1987, a small group of people living with HIV at the height of the epidemic were drawn together by their desire to share experiences, exchange ideas and information, and offer support to one another. This was the beginning of Test Positive Aware Network, publisher of Positively Aware. As TPAN finishes commemorating its 25th anniversary, we are one of Chicago’s oldest agencies devoted exclusively to HIV-related services. TPAN offers a variety of peer-led programs and services which are continually adapted to meet the changing needs of the community.

AIDS Foundation of Chicago BlueCross BlueShield of Illinois John Ceriale Cheetah Gyms The Gibbs Family Foundation Gilead Sciences, Inc. Macy’s MillerCoors Steamworks

PUBLISHER OF

We thank our anniversary partners who’ve been there for us, so that we can be here for you.

$10,000 AND ABOVE

5 5 3 7 N . B r oa d way S t. | C h i c ag o , IL 6 0 6 4 0 | 7 7 3 - 9 8 9 - 9 4 0 0 | w w w.t pa n . c o m

Treating Hepatitis B and C By Liz Highleyman

Hepatitis B

reatment for chronic hepatitis B virus

Photo: ISTOCKPHOTO.COM/ pixologicstudio Photo:

(HBV) infection has not advanced as fast as HIV and hepatitis C therapy in recent years, but approval of new drugs has led to higher response rates. Nucleoside/nucleotide analogs are the mainstay of hepatitis B treatment. FDA-approved options include Baraclude (entecavir), Epivir (lamivudine or 3TC), Hepsera (adefovir dipivoxil), Tyzeka (telbivudine), and Viread (tenofovir disoproxil fumarate). Emtriva (emtricitabine) is also active against HBV, but has not yet been approved for this purpose. These are all pills taken once daily. Conventional interferon and pegylated interferon alfa-2a (Pegasys) are also approved for treating hepatitis B. The more potent formulation, Pegasys, is injected once weekly. Not everyone with hepatitis B needs treatment, depending on the extent of liver damage and other factors. A complete cure, meaning HBV clearance and development of protective antibodies, is uncommon. But most people can achieve viral load suppression, which lowers their risk of developing liver cirrhosis and liver cancer. Treatment usually lasts for at least one year, and many people stay on nucleoside/nucleotide analogs for several years to maintain viral suppression. There are three ways to measure hepatitis B treatment response. Virologic response means suppression of viral replication, ideally reaching undetectable HBV DNA viral load in the blood. Biochemical response is normalization of the liver enzyme alanine aminotransferase, or ALT. Serological response refers to clearance of HBV antigens and development of antibodies (seroconversion). U.S. and European treatment guidelines recommend Baraclude or Viread monotherapy for first-line hepatitis B treatment >>>

March+April 2013 | positivelyaware.com

>>> for HIV-negative people. These drugs offer the best overall response rates and a high barrier to resistance. There are two types of HBV, hepatitis B “e” antigen (HBeAg) negative and positive, the latter being harder to treat. In clinical trials, virologic response rates for Baraclude and Viread were 90% and 93%, respectively, for HBeAg-negative people, and 67% and 76% for HBeAg-positive people. Both drugs are generally safe and well tolerated, though tenofovir can sometimes cause bone loss and kidney impairment. Combining nucleoside/nucleotide analogs does not significantly improve response for hepatitis B treatment-naïve people, but it may be beneficial for people with drug-resistant HBV. Lamivudine, which is available in a generic formulation, is the least expensive treatment, but drug resistance is common. Pegylated interferon promotes HBeAg seroconversion, and combining interferon with nucleoside/nucleotide analogs improves effectiveness. But interferon can cause difficult side effects, and combining it with Tyzeka can cause peripheral neuropathy. Viread, Epivir, and Emtriva are active against both HBV and HIV. Guidelines recommend that people with HIV and HBV co-infection should include dually active drugs in their antiretroviral regimen. HIV/HBV co-infection should be managed by clinicians who have experience treating both diseases, since using these medications incorrectly can lead to drug resistance in one or both viruses. Hepatitis B can be prevented by a three-dose vaccine. This is now included in routine infant vaccinations and is recommended for many adults, including gay men, pregnant women, and people with HIV or hepatitis C.

Hepatitis C reatment for hepatitis C virus

HIV DRUG GUIDE

2013

(HCV) infection has advanced dramatically in the past few years as direct-acting antiviral agents, or DAAs, have improved cure rates and shortened treatment duration. The main measure of hepatitis C treatment success is virologic response, or reduction of HCV RNA. Viral load is typically measured after four weeks on treatment (rapid virologic response, or RVR), after 12 weeks (early virologic response, or EVR), at the end of treatment, and after finishing treatment. Sustained virologic response (SVR), or continued undetectable HCV viral load 24 weeks after completing treatment, is traditionally considered a cure. The FDA recently said SVR at 12 weeks post-treatment can also be considered a cure. Sustained response can halt liver disease progression and lowers the risk of developing cirrhosis and liver cancer. Not everyone with hepatitis C needs treatment,

Computer-generated image of hepatitis B virus.

but it is recommended for people with at least moderate liver damage, usually determined by a liver biopsy. Treatment during acute infection (the first six months after infection) has a very high success rate, but most people do not realize they are infected this soon. Overall, about 25% of people clear HCV spontaneously without treatment, but the proportion is lower among people with HIV. The previous standard of care for chronic hepatitis C was pegylated interferon alfa-2a (Pegasys) or alfa-2B (PegIntron) injected once weekly plus a weight-adjusted oral dose of ribavirin. Treatment duration is 48 weeks for people with difficult-totreat HCV genotypes 1 or 4 and 24 weeks for those with genotypes 2 or 3. The overall SVR rate for HCV mono-infected people is about 75% for genotypes 2 or 3, but less than 50% for genotype 1. For the most difficult-to-treat groups of patients, response rates can be as low as 5%. Several factors influence how well interferonbased therapy works. In addition to HCV genotype, high pre-treatment HCV viral load, advanced liver fibrosis or cirrhosis, insulin resistance, and HIV co-infection are associated with poorer response. People trying treatment again after previous nonresponse do not do as well as those being treated for the first time. People of African descent generally do not respond as well as white patients. In 2009, researchers discovered that the latter two factors are largely attributable to variations in the IL28B gene. People with the favorable “CC” gene

March+April 2013 | positivelyaware.com

Photo: ISTOCKPHOTO.COM

Treatment during the first six months after HCV infection has a very high success rate, but most people don’t realize they are infected this soon.

pattern respond best to interferon, people with the “TT” pattern have the lowest response rates, and people with the “CT” pattern are in between. Pegylated interferon causes notorious side effects, including flu-like symptoms (fever, chills, fatigue, muscle aches), depression, and low white blood cell count. Ribavirin can cause anemia due to red blood cell destruction. These side effects may be severe enough that people avoid going on treatment, stop treatment prematurely, or lower their drug doses. The current standard of care for hepatitis C combines direct acting antivirals with the previous standard of care, pegylated interferon plus ribavirin. DAAs work by targeting different steps of the viral lifecycle. Polymerase inhibitors, which interfere with copying viral genetic material, and protease inhibitors, which block construction of new viral particles, are familiar from HIV treatment. NS5A replication complex inhibitors target an HCV enzyme that works in conjunction with polymerase. In 2011, the FDA approved the first two DAAs for genotype 1 chronic hepatitis C, the protease inhibitors Incivek (telaprevir, developed by Vertex) and Victrelis (boceprevir, developed by Merck). In pivotal clinical trials, adding one of these drugs to pegylated interferon/ribavirin raised overall treatment response rates significantly, both for HIV-negative and HIV-positive patients. Both drugs are taken three times daily with pegylated interferon/ribavirin (Incivek for 12 weeks, Victrelis for 28 or 36 weeks), followed by continued

treatment with pegylated interferon/ribavirin alone. Treatment-naïve people with good early viral suppression can stop treatment sooner (at 24 or 28 weeks), while others continue treatment through week 48. In Phase 3 clinical trials of HIV-negative people, Incivek SVR rates were 79% for previously untreated people, 86% for prior relapsers, and 32% for prior null responders (those who previously had little or no decrease in HCV viral load). Victrelis SVR rates were 90% for previously untreated people and 66% for prior relapsers and partial non-responders (null responders were excluded). So-called difficult-to-treat patient groups do not respond as well to hepatitis C therapy but may have a more urgent need for treatment. People with liver cirrhosis can be successfully treated with triple therapy including Incivek or Victrelis, but they have a higher frequency of side effects; studies of liver transplant recipients are underway. HIV/HCV coinfected people using Incivek or Victrelis can achieve response rates close to those of HCV mono-infected people with similar side effects. However, due to drug-drug interactions, these DAAs should not be combined with certain antiretrovirals. Not surprisingly, adding another drug to the mix can increase adverse events. The most notable side effect of Incivek is skin rash, while Victrelis can cause anemia. The tradeoff is shorter treatment duration and a better chance of achieving a cure.

Overall, about 25% of people clear HCV spontaneously without treatment, but the proportion is lower among people with HIV.

HCV drugs in the pipeline

everal new HCV protease inhibitors are now in clinical trials including asunaprevir (BMS-650032, developed by Bristol-Myers Squibb), danoprevir (RG7227, Roche/Genentech), faldaprevir (BI 201335, Boehringer Ingelheim), simeprevir (TMC435, Janssen), sovaprevir (ACH-1625, Achillion), vaniprevir (MK-7009, Merck), ABT-450 (Abbott), and GS-9256 (Gilead Sciences). Experimental polymerase inhibitors

include the nucleoside/nucleotide analogs mericitabine (RG7128), sofosbuvir (GS-7977), and VX-135 (Vertex). Non-nucleoside polymerase inhibitors include setrobuvir (ANA598, Roche), tegobuvir (GS9190), ABT-333, BI 207127, BMS-791325, and VX-222. NS5A replication complex inhibitors

under development include daclatasvir (BMS790052), ABT-267, and GS-5885. Other therapies under study for hepatitis C include the cyclophilin inhibitor alisporivir and pegylated interferon lambda, a new type of interferon that works as well as pegylated interferon alfa but with fewer side effects. Several experimental DAAs are taken once daily with treatment durations as short as eight weeks.

March+April 2013 | positivelyaware.com

HIV DRUG GUIDE

2013

hepatitis C treatment has improved markedly with the advent of direct-acting drugs.

HIV DRUG GUIDE

2013

>>> In general, the new drugs are better tolerated than current standard-of-care treatment. For many of these drugs, the IL28B gene pattern does not matter as much as it does for interferon. However, HCV subtype has emerged as an important factor, with subtype 1b being easier to treat than 1a. Several DAA candidates have demonstrated good outcomes in combination with pegylated interferon alfa and ribavirin in Phase 2 clinical trials and are now moving into Phase 3 testing. Many people with hepatitis C are waiting for alloral, interferon-free regimens, several of which (with or without ribavirin) are currently in Phase 2 or Phase 3 clinical trials. Like antiretroviral therapy for HIV, combining medications from different classes improves effectiveness and lowers the risk of drug resistance. Regimens that combine an HCV protease inhibitor and a NS5A inhibitor appear especially potent. For example, a 12-week regimen of sofosbuvir plus daclatasvir cured 90% to 100% of treatment-naïve people with HCV genotypes 1, 2, or 3. A 12-week triple regimen of sofosbuvir, GS-5885, and ribavirin has so far produced 100% sustained response at four weeks post-treatment in an one study, while another is looking at sofosbuvir/GS-5885 in a co-formulated pill without ribavirin. Daclatasvir plus asunaprevir for 12 weeks cured

about 80% of people with HCV subtype 1b, rising to 100% when ribavirin was added. The first two drugs plus BMS-791325 cured more than 90% of people with both HCV subtypes. Almost all genotype 1b patients—even null responders—were cured with a four-drug, oral regimen of ABT-450, ABT-333, ABT-267, and ribavirin taken for only eight weeks, as well as various three-drug combinations taken for 12 weeks. Faldaprevir, BI-207127, and ribavirin for 28 weeks cured 80% of genotype 1b patients, with a cure rate almost as high for those with cirrhosis. In summary, hepatitis C treatment has improved markedly with the advent of direct-acting drugs. People who do not respond to or cannot tolerate interferon have the most to gain from the new DAAs. Interferon-free combinations are now entering late stages of testing and some experts predict that the first such regimens may be available in two to three years. Some people will likely continue to need pegylated interferon for the foreseeable future, but adding DAAs will shorten treatment and increase the likelihood of a cure. LIZ HIGHLEYMAN (liz@hivandhepatitis.com) is a

San Francisco-based medical journalist specializing in HIV and viral hepatitis, and is editor-in-chief of HIVandHepatitis.com.

Are you Aware? Get Positively Aware. ❑ 1-year subscription: $30 donation.

Six bi-monthly issues every year. Subscriptions are mailed free of charge within the U.S. to those who are HIV-positive.

❑ Bulk copies (U.S. only):

Available free of charge; however, a donation is requested to cover shipping. No international bulk orders. Minimum order 10 copies, shipped via UPS (No P.O. Box addresses): ______ copies

❑ Back issues: $3 per copy. Enclosed is my payment. ______ copies: January+February 2013 ______ copies: November+December 2012

Bill to: Card Number Expiration date

security code

Name on Card Signature (required)

Charge my:

❑ Visa ❑ MasterCard ❑ American Express

total amount: $___________

______ copies: September+October 2012

Charges will appear on your credit card statement as TPA Network. Test Positive Aware Network (TPAN) is a not-for-profit organization dedicated to providing support and information to all people affected by HIV.

______ copies: July+August 2012

Ship to:

______ copies: May+June 2012

❑ Sign me up for the E-News, PA’s weekly email newsletter:

Name Agency (if applicable)

email address

Address

❑ Enclosed is my donation of:

❑ $25 ❑ $50

❑ $100 ❑ $250 ❑ $500 ❑ $_______

Your contribution helps provide subscriptions to people who can’t afford them. All donations are tax-deductible to the full extent allowed by law.

City State

Phone

e-mail

Mail to:

Positively Aware

5537 N. Broadway St. Chicago, IL 60640

Zip

Hey, have you heard the news? For eligible patients, Merck covers up to $400 on out-of-pocket costs, for each of up to 12 prescriptions.

Savings Coupon for ISENTRESS: eligibility restrictions, terms, and conditions apply.a To find out more visit isentress.com. 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.

a For

eligible privately insured patients. Restrictions apply. Please see full Terms and Conditions on isentress.com.

Model

DON’t break the bank

HIV co-pay & pati

Assistance programs can help pay for meds By Jeff Berry

Treatment for HIV is effective yet costly, but it doesn’t have to break the bank. Following are ways to help pay for not only your HIV meds, but other drugs commonly used by people with HIV.

Co-pay and Patient Assistance Programs Most pharmaceutical companies provide some level of assistance to individuals who are unable to afford their HIV medications by way of a patient assistance program, or PAP. These PAPs are typically for patients without insurance who don’t qualify for Medicare, Medicaid, or ADAP. Qualifications and criteria vary by program and are based on a percentage of Federal Poverty Level (FPL). Patients or providers should contact the program to see if they are eligible (see chart beginning on this page). Many companies also have co-pay assistance programs for those who have drug coverage through privately held insurance. These programs may cover all or part of the drug co-pay up to a specified amount. Certain restrictions and eligibility requirements apply (for example, recipients of ADAP, Medicare, and Medicaid are not eligible). By law, residents of Massachusetts are not eligible. Individuals can get the co-pay card directly from their provider, the manufacturer’s website, or by calling a

toll-free number. Once enrolled, bring the co-pay card to the pharmacy when filling your prescription. Some programs have a reimbursement process in case you are forced to pay the co-pay out of pocket if the pharmacy can’t or won’t accept the card. And some PAPs will make exceptions; for example, for a person on ADAP who has insurance but who has a high deductible, they may cover a certain percentage. Check with each program for details.

The Affordable Care Act Insurers are no longer able to deny coverage to children living with HIV/AIDS. Insurers also cannot impose lifetime caps on benefits for anyone. The Pre-existing Condition Insurance Plan helps those who have been locked out of the insurance market because of their health status, including those living with HIV/AIDS. Beginning in 2014, insurers won’t be able to deny coverage or impose annual limits on coverage. Low- and middleincome earners will be eligible for tax subsidies to help them buy coverage from state health insurance exchanges. Some states have refused to set up exchanges, so the federal government will do it for them. In states that haven’t refused it, Medicaid eligibility will expand to generally include those with incomes below 133% of the

The charts at right and on the following page give a brief description of many co-pay and patient assistance programs. If you need help, call the Project Inform Hotline at 800822-7422, or call the number or go to the website listed for each program. Also go to www. positivelyaware.com/copay as details of specific programs may change. 70

March+April 2013 | positivelyaware.com/copay

Drug

Company

Aptivus

Boehringer Ingelheim

Atripla

Bristol-Myers Squibb and Gilead Sciences

Combivir

ViiV Healthcare

Complera

Gilead Sciences and Janssen Therapeutics

Crixivan

Merck & Co.

Edurant

Janssen Therapeutics

Emtriva

Gilead Sciences

Epivir

ViiV Healthcare

Epzicom

ViiV Healthcare

Fuzeon

Genentech/Roche

Intelence

Janssen Therapeutics

Invirase

Genentech/Roche

Isentress

Merck & Co.

Kaletra

AbbVie, Inc.

Lexiva

ViiV Healthcare

Norvir

AbbVie, Inc.

Prezista

Janssen Therapeutics

Rescriptor

ViiV Healthcare

Retrovir

ViiV Healthcare

Reyataz

Bristol-Myers Squibb

Selzentry

ViiV Healthcare

Stribild

Gilead Sciences

Sustiva

Bristol-Myers Squibb

Trizivir

ViiV Healthcare

Truvada

Gilead Sciences

Videx EC

Bristol-Myers Squibb

Viracept

ViiV Healthcare

Viramune XR

Boehringer Ingelheim

Viread

Gilead Sciences

Zerit

Bristol-Myers Squibb

Ziagen

ViiV Healthcare

ent assistance programs (PAPs) Co-Pay Program

Patient Assistance

Details

None.

800-556-8317; pparx.com

Patient assistance program only.

866-784-3431 atripla.com

866-290-4767 atripla.com

Co-pay program covers up to $400 per month per prescription. Card available through provider.

877-844-8872 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $200 per month per prescription. Card available online or through provider. Must re-enroll and get new card for 2013.

877-505-6986 complera.com

800-226-2056 gilead.com/us_advancing_access

Co-pay program covers up to $400 per month per prescription. Card available through your provider.

None.

800-850-3430 merck.com/merckhelps

Patient assistance program only.

866-961-7169 edurant.com

800-652-6227 jjpaf.org

Co-pay: patient pays first $5, then rest of co-pay is covered; no cap. Card available through your provider or at janssentherapeutics.com.

877-505-6986 truvada.com

800-226-2056 gilead.com/us_advancing_access

Co-pay program covers up to $200 per month per prescription. Card available through provider.

877-844-8872 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $200 per month per prescription. Card available online or through provider. Must re-enroll and get new card for 2013.

877-844-8872 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $200 per month per prescription. Card available online or through provider. Must re-enroll and get new card for 2013.

None.

877-757-6243; fuzeon.com

Patient assistance program only. Also go to genentech.com.

866-961-7169 intelence.com

800-652-6227 intelence.com, or jjpaf.org

Co-pay: patient pays first $5, then rest of co-pay is covered; no cap. Card available through your provider or at janssentherapeutics.com.

None.

877-757-6243; genentech.com

Patient assistance program only.

866-350-9232 isentress.com

800-850-3430 isentress.com

Co-pay program covers up to $400 per month per prescription. Card available online or through provider.

800-441-4987 kaletra.com

800-222-6885 kaletra.com, or abbviepaf.org

Co-pay program covers up to $200 per month per prescription. Card available through provider. 30-day sample program available.

877-844-8872 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $200 per month per prescription. Card available online or through provider. Must re-enroll and get new card for 2013.

800-441-4987 norvir.com

800-222-6885 abbviepaf.org

Co-pay program covers up to $50 per month per prescription. Card available through provider.

866-961-7169 prezista.com

800-652-6227 jjpaf.org

Co-pay: patient pays first $5, then rest of co-pay is covered; no cap. Card available through your provider or at janssentherapeutics.com.

877-844-8872 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $200 per month per prescription. Card available online or through provider.

877-844-8872 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $200 per month per prescription. Card available online or through provider. Must re-enroll and get new card for 2013. For Retrovir only, not generic.

888-281-8981 reyataz.com

888-281-8981 bms.com

Co-pay program covers up to $200 per month per prescription. Card available online or through provider or by calling the toll-free number.

877-844-8872 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $200 per month per prescription. Card available online or through provider. Must re-enroll and get new card for 2013.

877-585-6986 stribild.com

800-226-2056 stribild.com

Co-pay program covers up to $400 per month per prescription. Card available through provider.

888-281-8981 sustiva.com

888-281-8981 bms.com

Co-pay program covers up to $200 per month per prescription. Card available through provider, or by calling toll-free number.

877-844-8872 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $200 per month per prescription. Card available online or through provider. Must re-enroll and get new card for 2013.

877-505-6986 truvada.com

800-226-2056 gilead.com/us_advancing_access

Co-pay program covers up to $200 per month per prescription. Card available through provider.

None.

bms.com

No company co-pay or patient assistance program for Videx. Available as generic.

877-844-8872 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $200 per month per prescription. Card available online or through provider. Must re-enroll and get new card for 2013.

877-411-8641 viramunexr.com

800-556-8317 needymeds.org

Co-pay program for Viramune XR only: Patient pays first $25, remainder of co-pay is covered; no cap. Get MasterCard debit card from provider. No co-pay or PAP for Viramune (IR); available as generic.

877-505-6986 truvada.com

800-226-2056 gilead.com/us_advancing_access

Co-pay program covers up to $200 per month per prescription. Card available through provider.

None.

bms.com

No company co-pay or patient assistance program for Zerit. Available as generic.

866-747-1170 mysupportcard.com

877-784-4842 viivhealthcareforyou.com

Co-pay program covers up to $200 per month per prescription. Card available online or through provider. Must re-enroll and get new card for 2013.

March+April 2013 | positivelyaware.com/copay

OTHER co-pay & p >>> Federal poverty line ($15,281 for an individual/$31,321 for a family of four). The Affordable Care Act also closes, over time, the Medicare Part D prescription drug benefit “donut hole.” Beneficiaries receive a 50% discount on covered brandname drugs while they are in the “donut hole,” with increased savings on prescription drugs while they are in the coverage gap until the gap is fully closed in 2020. In addition, AIDS Drug Assistance Program (ADAP) benefits are now considered as contributions toward Medicare Part D’s True Out of Pocket Spending Limit (“TrOOP”), so ADAP clients who are Medicare Part D enrollees should now be able to move through the donut hole much more quickly.

Welvista, Harbor Path, and the Common PAP Form Around one-third of all people receiving HIV treatment in the U.S. get their medications through AIDS Drug Assistance Programs (ADAPs). Welvista is a non-profit organization funded by the Heinz Family Philanthropies and seven pharmaceutical companies. The program facilitates access to HIV meds for those on ADAP waiting lists by streamlining paperwork and using a single mail-order pharmacy, rather than having to access multiple patient assistance programs. Go to www.welvista.org. Two other recent developments that will potentially ease access to PAPs are the Common PAP Form and HarborPath. The Department of Health and Human Services (DHHS), along with seven pharmaceutical companies, the National Alliance of State and Territorial AIDS Directors (NASTAD), and community stakeholders developed a common patient assistance program application that can be used by both providers and patients. Before, patients and advocates had to fill out different sets of paperwork for each company PAP—the new application should help simplify this process. Go to http://hab.hrsa.gov/ patientassistance to download the form. HarborPath is a non-profit organization that helps uninsured individuals living with HIV/AIDS gain access to brand-name prescription medicines at no cost, by providing case managers with a single “one-stop shop” online portal for PAP applications and medication fulfillment through a 72

mail-order pharmacy. Currently in its pilot phase in five states with two pharmaceutical companies on board, it hopes to expand in 2013, including adding medicines for hepatitis C. Go to www.harborpath.org.

Additional programs Co-pay and patient assistance programs are also available for drugs used to treat hepatitis B and C, and medications or treatments used for other HIV-related conditions such as lipodystrophy. This year for the first time we are including some of these in the co-pay and PAP chart (to the right). To learn more about patient assistance or co-pay programs for drugs used to treat certain opportunistic infections or other conditions such as high cholesterol and diabetes, talk to your provider, contact the manufacturer directly, or go to www.pparx. org and www.needymeds.org. Together Rx Access is a prescription savings program for uninsured individuals; call 800-966-0407, or enroll online at www.TogetherRxAccess.com. SurvivorRxPlan offers help in getting many medications not covered by ADAP, including alternative therapies and generics, even if you receive medicines through another discount program. It is available to individuals with incomes of up to $36,425, and higher based on family size. Go to www.SurvivorRxPlan.com.

Stay informed and up to date Keeping the lines of communication open between you and your health care provider, pharmacist, and case manager is essential when managing your health, so stay informed. In some cases, your health care provider may not be aware of all the programs available, so use the adjacent chart to check specific details. You can also go to www.positivelyaware.com/copay for the most current information, as details of specific programs may change. Special thanks to the Fair Pricing

Coalition for some of the information contained in this article. The Fair Pricing Coalition (FPC) regularly meets with drug companies on pricing and access issues. [Note: The author is a member of the Fair Pricing Coalition.] Go to www.fairpricing coalition.org. March+April 2013 | positivelyaware.com/copay

Hepatitis B Drug

Company

Baraclude

Bristol-Myers Squibb

Epivir-HBV Hepsera

ViiV Healthcare

Tyzeka

Novartis

Viread

Gilead Sciences

Hepatitis C Drug

Company

Copegus (ribavirin) Incivek

Genentech

Pegasys (peginterferon alfa-2a) PegIntron (peginterferon alfa-2b)

Genentech

Victrelis

Merck & Co.

Vertex Pharmaceuticals

Merck & Co.

Other Drug / ASSAY

Androgel (testosterone gel 1% & 1.62%) Used to treat adult males who have low or no testosterone. Egrifta

Injectable approved for treating HIV-related excess belly fat (lipohypertrophy).

Fulyzaq

Anti-diarrheal approved for use in those with HIV/AIDS and on antiretroviral therapy.

HLA-Aware

HLA-B*5701 test to determine if a person can start taking Ziagen, Epzicom, or Trizivir.

Procrit

Treats anemia due to zidovudine therapy.

Radiesse

Injectable facial filler approved for use in people with HIV to treat facial fat loss (lipoatrophy).

Sculptra

Injectable facial filler approved for use in people with HIV to treat facial fat loss (lipoatrophy).

Serostim

Injectable human growth hormone used for treating HIV-associated wasting in those on ART.

Testim (testosterone gel 1%) For adult males with low or no testosterone. Trofile Assay

A test used for determining the tropism of a person’s HIV to identify if a CCR5 antagonist (such as Selzentry) would be effective.

atient assistance programs (PAPs) Co-Pay Program

Patient Assistance

Details

855-898-0267

855-898-0267 bmspaf.org

Co-pay program covers $200 per month, per prescription. Ask operator to speak to someone about the Baraclude Co-pay Discount Benefits Program, and have card mailed to you.

888-825-5249

866-475-3678; gskforyou.com

Co-pay program covers $200 per month, per prescription.

None.

800-226-2056 gilead.com/us_advancing_access

PAP only, no co-pay program.

None.

800-277-2254 pparx.org

PAP only, no co-pay program. PAP is through Novartis Patient Assistance Foundation, Inc.

877-627-0415

800-226-2056 gilead.com/us_advancing_access

Co-pay program covers after first $50 and up to $200 per month for patients who are uninsured or pay their prescription costs in full.

Co-Pay Program

Patient Assistance

Details

None.

888-941-3331 pegasysaccesssolutions.com

PAP only, no co-pay program.

855-837-8394 incivek.com

Co-pay program covers up to 20% of total cost over the course of treatment, including co-pays, co-insurance, or deductibles for those who have commercial insurance or are paying cash.

None.

888-941-3331 pegasysaccesssolutions.com

PAP only, no co-pay program.

866-939-4372 pegintron.com merck-cares.com

866-363-6379 merckhelps.com

Co-pay program covers up to $200 per month, per prescription.

866-939-4372; victrelis.com

866-363-6379 merckhelps.com

Co-pay program covers up to 20% of total cost over the course of treatment, including co-pays, co-insurance, or deductibles for those who have commercial insurance or are paying cash.

Company

Co-Pay Program

Patient Assistance

Details

AbbVie, Inc.

800-441-4987 androgel.com

800-222-6885 abbviepaf.org; pparx.org

Co-pay: Patient pays first $10, then covers up to $50 per month. Card available through provider or you can print the card online.

EMD Serono

877-714-2947 egrifta.com

Co-pay program covers up to $500 of your co-pay or co-insurance, per prescription. AXIS Center provides education and support; go to website or call 877-714-2947.

Salix Pharmaceuticals

None at press time. fulyzaq.com

No PAP or co-pay program at this time. Check website for updates.

LabCorp/ViiV

None.

800-533-1037 viivhcdxresource.com

No co-pay program, PAP only. Covers entire cost of test for insured/uninsured. Test must be ordered by provider. Contact local ViiV rep, order online, or call.

Janssen

None.

800-652-6227 jjpaf.org

No co-pay program, PAP only.

Merz Aesthetics

None.

866-862-1211 radiesse-fl.com

No co-pay program. PAP is sliding scale based on patientâ&#x20AC;&#x2122;s annual income up to $80,000; reimbursement goes directly to physician.

Valeant Pharmaceuticals International

None.

866-310-7551 needymeds.org

No co-pay program. PAP provides two kits and one follow up kit. Free for those with an annual income below $22,340, and then on a sliding scale up to $61,940.

EMD Serono

877-714-2947 serostim.com

Co-pay program covers up to $200 of your co-pay or co-insurance per prescription discount, with a maximum of 12 prescription discounts per lifetime.

Auxilium

866-740-8252 testim.com

888-877-9192

Co-pay program covers up to $40 per month. Card available through provider or you can print the card online.

Monogram Biosciences

None.

877-436-6243 monogramvirology.com

Financial assistance to uninsured/underinsured; assists in prior authorization or if insurance reimbursement is denied. ViiV also has Tropism Access Program (TAP) for ADAP eligible; contact local ASO, ViiV rep, or state ADAP.

March+April 2013 | positivelyaware.com/copay

Committed to being a part of the solution With 600+ HIV-specialized pharmacies nationwide and in Puerto Rico, weâ&#x20AC;&#x2122;re dedicated to treating and stopping the spread of HIV/AIDS. Find a pharmacist and location near you at HIV.Walgreens.com.