Table of Contents: AIDS Community Research Initiative of America

2003

ACRIA - Fall 2003 / Winter 2004 - Vol. 12, No.4 / Vol. 13, No. 1

This issue of ACRIA Update was a collaborative effort, researched and written by:

James Learned, ACRIA's Director of Treatment Education and Editor of ACRIA Update; Mark Milano, treatment educator at ACRIA and longtime AIDS treatment activist; and Donna M. Kaminski, ACRIA's Associate Director of Treatment Education.
Special thanks to Tim Horn for his editorial review of some of the contents of this issue.

Drugs! Drugs! Drugs!: An Overview of the Approved Anti-HIV Medications: This double issue of ACRIA Update includes discussions of each of the currently approved anti-HIV medications (antiretrovirals). Depending on whether you count new formulations of existing drugs, there are now between nineteen and twenty-one antiretrovirals available in the U.S., including four that were approved in 2003 alone.
Nucleoside and Nucleotide Reverse Transcriptase Inhibitors: The NRTIs are also called nucleoside/nucleotide analogs or "nukes" for short. Once HIV has entered a cell, usually a CD4 cell, it uses an enzyme called reverse transcriptase to change its genetic material, RNA, into DNA. The viral DNA is then integrated into the human DNA in the nucleus of the cell. This programs the cell to make new copies of HIV. Once the cell is activated, the DNA in the nucleus creates pieces of HIV.
Retrovir: Retrovir (AZT, azidothymidine, ZDV, zidovudine) has been studied more than any other antiretroviral used for the treatment of HIV. It was the first anti-HIV drug approved by the FDA (March 1987) and has been used in clinical trials of almost every new antiretroviral since that time.
Videx: Videx, Videx EC (ddI, didanosine, dideoxyinosine) - Videx was the second anti-HIV drug approved by the FDA. Its approval in October 1991 was unique in that it was the first time that a drug was approved based on surrogate markers such as lab results (in this case, increased CD4 cells) rather than on clinical endpoints such as disease progression or survival.
Hivid: Hivid (ddC, zalcitabine, dideoxycytidine) is rarely used anymore, but, as with most new drugs, its approval by the FDA in June 1992 was eagerly anticipated. Now, its three-times-a-day dosing, poor showing in clinical trials, multiple drug interactions, and potentially serious side effects combine to make it the least prescribed nucleoside analog.
Zerit: Zerit, Zerit XR (d4T, stavudine) - Zerit became the fourth drug available for the treatment of HIV when it was approved by the FDA in June 1994. The drug's initial approval was only for people with advanced HIV disease who no longer responded to or who couldn't tolerate the three drugs available at the time - Retrovir (AZT), Hivid (ddC) and Videx (ddI).
Epivir: Epivir (3TC, lamivudine) is a powerful drug with minimal side effects, an easy dosing schedule, and few drug interactions. It may be one of the most useful nucleoside analogs available, particularly if it's used strategically. By the time it received accelerated approval from the FDA in November 1995, close to 30,000 people had already received Epivir through the largest expanded access program ever.
Ziagen: Ziagen (abacavir sulfate, ABC), approved by the FDA in December 1998, was the first new NRTI to become available in the era of Highly Active AntiRetroviral Therapy (HAART). As such, it had to compete for a special place in combination therapy. Initial studies of Ziagen had shown it to be as powerful as a protease inhibitor at lowering viral load when taken alone, so the drug's manufacturer, GlaxoSmithKline, positioned (and priced) it as an alternative to a protease inhibitor or non-nucleoside as part of a three-drug combination.
Viread: Viread (tenofovir disoproxil fumarate, TDF) was approved by the FDA in October 2001 and is still the only nucleotide analog available. Nucleotide analogs work like nucleoside analogs (Retrovir [AZT], Videx [ddI], Zerit [d4T], etc.)
Emtriva: Emtriva (emtricitabine, FTC), the most recently approved nucleoside analog, probably caused less excitement when it was approved in July 2003 than any antiretroviral so far. Many people viewed it simply as a "me-too" drug because its chemical structure and activity are so similar to Epivir (3TC).
Combivir: Combivir is a formulation of two drugs - Retrovir (AZT) and Epivir (3TC) - into one tablet. The two have long been used together, originally as a two-drug combination, and then as the backbone of many three-drug regimens. Retrovir has been available separately since 1987 and Epivir since 1995.
Trizivir: Trizivir is not a single drug, but a formulation of three drugs into one tablet. All three drugs - Retrovir (AZT), Epivir (3TC), and Ziagen (abacavir) - continue to be available separately.
NNRTIs: Non-Nucleoside Reverse Transcriptase Inhibitors: The NNRTIs are also called non-nucleosides or "non-nukes" for short. These drugs interfere with HIV's reproduction process at the same point as the NRTIs but in a different way. The NNRTIs attach themselves to the reverse transcriptase enzyme, changing its shape and preventing it from functioning properly. Reverse transcriptase can't translate HIV RNA into DNA. If there's no viral DNA to integrate into the nucleus of the cell, HIV reproduction is slowed down.
Viramune: Viramune (nevirapine, NVP) was the first non-nucleoside reverse transcriptase inhibitor (NNRTI) approved by the FDA, but has taken a back seat to Sustiva (efavirenz) due to the latter NNRTI's impressive results in clinical trials. New data could change that, as we find that Viramune's "poor cousin" status may more likely be the result of unfortunate research decisions rather than a lack of strength.
Rescriptor: Rescriptor (delavirdine, DLV) received FDA approval in April 1997, becoming the second non-nucleoside reverse transcriptase inhibitor (NNRTI) available. Mixed results from clinical trials and a difficult dosing schedule (two pills three times a day) combine to make it one of the least-prescribed antiretrovirals.
Sustiva: Sustiva (efavirenz, EFV) - Its FDA approval in September 1998 made Sustiva the third available NNRTI. Since then, it has become one of the most popular antiretrovirals and is often recommended for a person's first regimen because of its effectiveness and once-a-day dosing. While its nervous system side effects can be a problem, many people have found them to be temporary or at least manageable.
PIs: Protease Inhibitors: The protease inhibitors, or PIs, work at a later stage in the HIV life cycle than the NRTIs and NNRTIs. Once HIV's genetic material has been changed from RNA to DNA and is integrated into the DNA in the cell's nucleus, the cell produces a long chain of genetic material (proteins and enzymes). HIV's protease enzyme acts like a pair of scissors, cutting the chain into smaller pieces which then come together to form new copies of the virus.
Invirase and Fortovase: Invirase and Fortovase (saquinavir mesylate, SQV) are different versions of the same drug. Invirase caused a big splash in December 1995 when it became the first protease inhibitor approved by the FDA - the first in a whole new class of antiretrovirals. Unfortunately, Invirase isn't absorbed by the body as well as other anti-HIV drugs, so a more readily-absorbed formulation called Fortovase was eventually released in November 1997.
Norvir: Norvir (ritonavir, RTV) is one of the strongest but least prescribed protease inhibitors on the market today. In several studies, Norvir has shown a strong reduction in viral load and an increase in CD4 cells, especially when taken with one or two other anti-HIV medications.
Crixivan: Crixivan (indinavir sulfate, IDV was approved by the FDA in March 1996, just two weeks after Norvir (ritonavir). Crixivan's ability to lower viral load to undetectable levels in most people who used it in a three-drug combination made it the "gold standard" of the day. As more drugs with less severe food restrictions and fewer doses per day have become available, Crixivan's popularity has waned.
Viracept: Viracept (nelfinavir mesylate, NFV) has enjoyed wide use since its FDA approval in March 1997. By 1999, it was the most frequently prescribed protease inhibitor (PI) on the U.S. market and today is second only to Kaletra (lopinavir/ritonavir).
Agenerase and Lexiva: Agenerase (amprenavir) and Lexiva (fosamprenavir calcium) are different versions of the same drug. Agenerase was the fifth protease inhibitor to hit the market when the FDA approved it in April 1999. Agenerase's lackluster performance in clinical trials and its high pill count have made it one of the least-prescribed protease inhibitors.
Kaletra: Kaletra (lopinavir/ritonavir, LPV) is one of the strongest and most prescribed protease inhibitors on the U.S. market today. Its approval by the FDA in September 2000 marked the first time that a protease inhibitor (PI) was designed and approved as a boosted drug - the capsules contain the active drug, lopinavir, along with a small amount of Norvir (ritonavir).
Reyataz: Reyataz (atazanavir sulfate, ATV) was approved by the FDA in June 2003 as the first protease inhibitor (PI) to be taken once a day. For people who are just starting treatment, studies showed that Reyataz lowers viral load almost as well as Sustiva (efavirenz), a strong non-nucleoside, and almost as well as (although not better than) Viracept (nelfinavir), a relatively weak PI.
Entry Inhibitors: Entry inhibitors work at HIV's first point of contact with a human cell. This occurs at an earlier stage in the HIV lifecycle than the other antiretrovirals. To successfully infect a cell, HIV needs to attach to and enter the cell through a series of steps.
Fuzeon: Fuzeon (enfuvirtide, T-20) ushered in a new class of anti-HIV drugs (fusion inhibitors) when it received FDA approval in March 2003. For people whose HIV had become resistant to many drugs from the other classes, it offered new hope of bringing viral loads down below detection, but it came with two major obstacles.
Glossary of Terms
ACRIA News - ACRIA Trials - Contributions - Masthead

ACRIA - Summer 2003 - Vol. 12, No.3

Starting, Switching, Stopping: Personal Perspectives on Making Treatment Decisions: James Learned; For this issue of ACRIA Update, we wanted to explore the different ways that people make decisions to start, switch, or stop antiretroviral treatment. We invited individuals to share their personal experiences and deeply appreciate the contributors' willingness to offer their stories so thoughtfully and honestly.
My Sordid Antiviral Past: Carlton Hogan; In retrospect, I probably started AZT too early, although I have survived when many people I knew with higher T-cell counts back then are gone. Who knows why? From 1985 to 1988, I had a pretty severe case of what used to be called ARC (AIDS-Related Complex) - swollen glands, night sweats, shingles, etc.
Crossing the Line: Jennifer McGaugh; In one of the most difficult decisions I've ever made, I started taking HIV medications recently. I crossed a line I said I'd never cross. I remember a conversation I had 13 years ago with a former roommate named Brian.
Letting Someone Else Drive: Christopher Murray; Like many HIV community activists, I became involved after my own diagnosis. My work in the field has become my profession, training people with HIV to become community advocates and represent themselves and others with HIV on local advisory boards and planning groups.
Hangin In: Sue Gibson; I began taking antiretrovirals shortly after I tested positive in 1989. My thinking was, "I don't know what happens to people who take AZT (which was already becoming controversial among people with AIDS), but I do know what happens to people who don't!" So I carried AZT around in my pocket and took too much too often, as we did in those days.
Just Point Me in the Right Direction: Ellen Hahn; I've always been healthy. I thought hospitals were places to visit other people and was convinced that doctors were merely human. I did not know the difference between vitamins, minerals, enzymes and amino acids; nor did I care.
Heart to HAART: Devan Nambiar; I miss the fiery sun, the torrential rains, and the lush greenery in Kerala, South India. I miss the erotic temple sculptures of Khajuraho, local foods (idly, dosa, and chai), Ayurvedic massages, and sunsets by the Ganges River.
Had A Great Time, Wish I Was There: Jim Pickett; It's been over a year since I've returned from a two-year holiday from drugs. The break in the war arose through a unilateral decision. I'd had enough.
Finding the Right Fit: Shelley Singer; It was September 1997 and I was a singer, karaoke host, and wife of the owner of the hottest karaoke bar in the San Fernando Valley. I'd been suffering from a deep pain in my chest, making it impossible to swallow. A doctor told me I probably had an ulcer and to see him again in two weeks.
Taking Control: Eric Goldman; I was diagnosed HIV-positive on October 14, 1999, with T-cells around 170 and a viral load around 70,000. About ten weeks later, my Dad was diagnosed with pancreatic cancer. Although he never knew it, he and I began our experiences with meds at about the same time.
Happy Holidays?: Nancy Soto; The city was decorated with holiday glitter. Everywhere you looked there were people smiling and festivities in the air. Christmas was three days away, and I was given the worst news anyone could ever hear. You are HIV-positive.
ACRIA News - ACRIA Studies In Progress - Stop The Presses! - NATAF 2003 - Contributions - Masthead

ACRIA - Spring 2003 - Vol. 12, No.2

More Than The Virus: OIs, Metabolic Complications & AIDS-Related Cancers: J Daniel Stricker, Editor in Chief; Much of the focus of HIV research and treatment is on suppression of the human immunodeficiency virus itself. Unfortunately, it's not just about the virus, damn it.
Opportunistic Infections: They're Still Here: Tim Horn; When I first got involved in HIV/AIDS treatment education and advocacy work about ten years ago, more than 40,000 people were dying of AIDS every year in this country, compared to the 16,000 or so deaths reported annually today.
Personal Perspective: Pacing Myself: Cathy Olufs; As a community scholarship recipient to this year's Conference on Retroviruses and Opportunistic Infections, I looked ahead to the frigid mid-winter trip to Boston with both anticipation and a strong sense of anxiety. Anticipation at the chance to see many of my community activist friends from around the world, and anxiety at the deluge of scientific data that I would be challenged to sort through and make sense of.
Metabolic Complications: A Look at the IAS Guidelines: Heidi Nass; It seems like the longer HIV/AIDS is around, the more complicated it gets. Truthfully, science is still learning exactly how HIV (not to mention the immune system!) works. Then there are the treatments for HIV. They work for a lot of people, but they have to be used in just the right combinations, in just the right way�and they bring with them a whole other set of complications that have to be sorted out from the effects of HIV.
Personal Perspective: Stay There: Laura McTighe; When I got back from the 10th Conference on Retroviruses and Opportunistic Infections in February, my friend and colleague John Bell asked me, "So how did it go?" I told him it was great, but that I had understood less than half of the information presented at the conference.
AIDS-Related Cancers: An Update: Jeffrey T. Schouten, MD; The "modern era" of antiretroviral therapy has resulted in a significant decrease in the number of people who develop AIDS-related cancers. Obviously, this is great news for people living with HIV. But it has presented a challenge to the conduct of clinical trials for the treatment of AIDS-related cancers since fewer people are available to participate in these trials.
Resources
Personal Perspective: Attending a Scientific Conference When You're Not a Scientist: Dan Dunable; Like many treatment educators working in the HIV/AIDS community, I wasn't trained in medicine, but learned about antiretroviral therapies, opportunistic infections, and other aspects of the disease by educating myself for my own health.

ACRIA - Winter 2002/2003 - Vol. 12, No.1

Drugs in Development: New Promise: Even with sixteen antiretrovirals approved in the United States for the treatment of HIV, new drugs and combinations are urgently needed. Most current regimens involve difficult dosing schedules, lots of pills, and short- and long-term side effects.
The HIV Life Cycle: Written & Illustrated by David Pieribone; Understanding how the human immunodeficiency virus (HIV) works inside the human cell gives scientists important clues about how to attack it at its most vulnerable points. Knowing the secrets of how the virus functions and reproduces itself - a process called its life cycle - can help scientists design new drugs that are more effective at suppressing HIV and have fewer side effects.
Anti-HIV Candidates in the Pipeline: Liz Highleyman; In the past year or so, the HIV drug pipeline seemed to slow to a trickle, with only one new approval, tenofovir (Viread). But the future is beginning to look brighter.
Drug Name Confusion: Liz Highleyman
The Drug Development Process: Liz Highleyman; It usually takes ten or more years for a promising candidate to wind its way through the drug development process (although activists have succeeded in speeding up development of medications for HIV and other life-threatening diseases). According to the Food and Drug Administration (FDA), only one in 1,000 compounds makes it from the laboratory to clinical trials in humans, and only one in five that enters human trials is ever approved.
What Ever Happened To . . .?: Liz Highleyman
Once-A-Day Dosing: Balancing Convenience and Effectiveness: Theo Smart; The era of once-a-day anti-HIV therapy is upon us with five antiretrovirals approved for once-a-day use and more on the way. It is now possible to construct a first- and even second-line once-a-day anti-HIV regimen.
New and Improved? Next Generation Drugs in Existing Classes: Mark Milano; There's lots of talk these days about new targets for antiretrovirals - fusion, integrase, zinc fingers, and other approaches. Drugs using current targets (the reverse transcriptase and protease enzymes) have plenty of problems, including difficult dosing, short- and long-term side effects, resistance - the list goes on. The following are brief descriptions of some of the new drugs in development from currently approved classes.
FDA-Approved Antiretrovirals for the Treatment of HIV: Mark Milano
Entry Inhibitors: The Bouncers at the Door: Donna M. Kaminski; There is good news on the horizon for people whose HIV is resistant to many currently approved antiretrovirals - the development of a new class of anti-HIV drugs called entry inhibitors. Entry inhibitors have shown promising results for people with few treatment options.
Personal Perspective - The Constant Survival Battle and T-20: Matt Sharp; In 1988 I tested HIV positive at an anonymous clinic in Oklahoma City. One year later, in the turbulent and desperate years of the AIDS epidemic when street demonstrations were as common as the funerals of many of my friends, I first began taking anti-HIV drugs.
ACRIA News - ACRIA Trials - Contributions - Masthead