Like a tsunami propagating across oceans, political shockwaves reverberated across continents as news broke in December 2004 about a U.S. government official's alleged cover-up of faulty data from an African AIDS trial of single-dose nevirapine to prevent mother-to-child transmission of HIV. The accusation, made by a disgruntled employee turned whistleblower at the National Institutes of Health (NIH), was quickly trumpeted by political figures as evidence that Africans had been made unknowing guinea pigs in a vast experiment with an unproven and unsafe drug.
Results from a Thai study (PHPT-2) designed to evaluate whether greater mother-to-child transmission efficacy could be gained by adding single-dose nevirapine to standard zidovudine prophylaxis found that efficacy came with the risk of resistance. In the study, 1,844 women were enrolled and mother and infant pairs randomized to three arms: single 200mg nevirapine dose to the mother in labor and 6mg to the baby within 72 hours of birth (the nevirapine-nevirapine arm); nevirapine dose to the mother and placebo to the infant (nevirapine-placebo) and both mother and baby receiving placebo (placebo-placebo). Additionally all mothers received zidovudine from 28 weeks of gestation and infants one week of zidovudine and formula feeding. The study endpoint was HIV infection of the infant.
A cost effectiveness analysis published in the August 20, 2004, edition of AIDS reports that the efficacy of the single-dose nevirapine regimen for reducing mother-to-child transmission in a field setting is much lower than desired and despite the low cost of the drug itself, requires significant financial resources to implement successfully.
The election of George W. Bush to a second term as President of the United States, combined with an increase in the Republican majority in both houses of Congress and an increase in the conservative faction of the majority, is likely to continue ominous conditions for HIV/AIDS service organizations and for national HIV/AIDS public policy. While the specific details of any negative impact cannot be ascertained fully at this time, there is a nearly universal consensus within the HIV/AIDS community that the fight against AIDS will be threatened seriously, domestically and globally, by a second Bush term in office. The very real difficulties, attacks, and outright setbacks that were experienced in the first term give credence to the concerns over what will happen over the next 2 – 4 years.
The Elizabeth Glaser Pediatric AIDS Foundation supports providing the safest, most effective regimen of drugs to prevent mother-to-child transmission in all instances. In the United States and other developed world settings, mother-to-child transmission has been dramatically reduced through aggressive prevention and treatment programs that are widely available. In the developing world, due to poor infrastructure and the high cost of other regimens, nevirapine, administered as one dose to the mother at the onset of labor and one dose to the child within 72 hours of birth, is frequently the only option feasible and available.
The issue of resistance to nevirapine and its impact on subsequent use in HIV infected women has been debated. Several important facts need to be considered.
Over a year ago, sharing a cab on the way to the airport after a meeting at the NIH (National Institutes of Health), I had a conversation with two AIDS researchers about the Good Clinical Practice (GCP) guidelines for conducting clinical research. As soon as I got home I looked up the guidelines and was struck by the fact that, while these were supposed to be "universal" guidelines, they were obviously drawn up with the resource-rich world in mind. It seemed unlikely that the authors had asked anyone in Africa, Asia, Latin America, or the Caribbean what they thought about these standards. I also recall hearing what these researchers thought were the "right" and "wrong" lessons to be learned from the HIVNET 012 trial (this was several years ago, shortly after questions about the study were first raised).
GMHC Treatment Issues: September / October - Volume 18, Number 9&10
In nearly every corner of the globe, HIV treatment advocates are working for people living with HIV/AIDS, helping them to get the care they need and the respect they deserve; helping them to get the most out of whatever medications are available; to understand what is happening with the virus in their bodies and to learn what they can do to maintain and improve their health. In the U.S. the job may involve getting a client who needs an unaffordable drug for their salvage regimen admitted to a patient assistance program. In one part of Kenya, it may be getting a client access to free tuberculosis treatment and drugs to prevent pneumonia in the hope that serious illness can be forestalled until antiretroviral (ARV) drugs finally become available.
Not too long ago, I met my new doctor. As he went over my lab numbers he immediately started discussing medication. I stopped him and proposed waiting until I had permanent housing. Reluctantly, he agreed and we decided to meet again in a month. It seemed we were off to a good doctor/patient relationship.
Treatment advocates from across the globe have challenged national governments and multi-lateral agencies to demonstrate greater political will and commitment in their response to the dual epidemics of tuberculosis (TB) and HIV.
There is a growing need for new anti-HIV medications for people who have developed resistance to available drugs in every class of therapy and are no longer able to construct a suppressive regimen. These so-called salvage patients are part of an expanding population who, whether because of improper prescribing, inadequate pharmacokinetics, or poor adherence, find themselves chronically awaiting the next ARV to enter the marketplace. It is now understood that simply adding the latest drug down the pipeline to a failing regimen — a practice called serial monotherapy — will quickly result in resistance to the newcomer as well, and that unless at least two new active ARV agents are added to a salvage regimen, the chain of virologic failure due to resistance can not be broken.
As I watched the election returns, I felt a profound sense of despair and hopelessness. If the accusations of voter fraud were not true, the American people had chosen to re-elect one of the worst administrations in history, in spite of the debacle of the last four years. How could this have happened? What were they thinking?
GMHC Treatment Issues: July / August - Volume 18, Number 7&8
Good evening, ladies, gentlemen and friends. Welcome to Bangkok. Sorry if I am a little nervous, but I am not used to speaking on stage; I am more experienced with speaking on the street. First I would like to say thank you to the people who supported my invitation to speak, and thank you to the International AIDS Society, because it means a lot to me, to speak from the perspective of a drug user living with HIV.
It's become conventional wisdom that the International AIDS Conference (IAC) is no longer the place to find cutting-edge research on HIV science. And although Track A, the basic science track at the conference, had fewer posters and presentations than the tracks for clinical research, prevention, social issues and policy, a respectable 618 basic science presentations were submitted and 439 accepted to the 2004 IAC in Bangkok. Here's selection of abstracts covering one aspect of HIV basic research of emerging importance.
A Canadian company, Anormed Inc., is carving out a specialty niche for itself as a developer of drugs that bind to chemokine receptors, such as CCR5 and CXCR4. They were the first to put an X4 blocking drug into people with HIV and proved that the concept was viable. Unfortunately, the company's first X4 drug candidate, AMD3100, produced heart rhythm abnormalities in several patients during Phase I testing and only demonstrated limited efficacy at achievable concentrations. Undaunted, Anormed has come back with a new, structurally different candidate, called AMD070, an orally available drug that has now been tested in healthy subjects and was shown to be available in the blood at concentrations thought sufficient to suppress HIV.
The success of any government's health care system depends on whether health care is affordable, accessible, promotes quality, offers maximum coverage for its citizens, supports innovation, and provides access to the newest technology. It is by these standards that Americans, especially people living with HIV/AIDS, should judge the 2004 candidate's campaign proposals. The following outlines the plans offered by the President Bush and Senator Kerry.
With conventional CD4 T-cell counts and viral load tests all but unaffordable for routine use in resource-poor settings where low-cost antiretroviral medications are now being offered, there has been a disorganized scramble to come up with alternative ways to monitor therapy. One approach has been to simplify or modify existing technology to squeeze out greater efficiency. Researchers have been experimenting with generic versions of expensive reagents and test materials and using them in smaller quantities to attain significant savings. A major maker of laboratory-based cell counting equipment now offers a rugged, battery powered unit that can be taken into the field to perform CD4 tests. Less successful have been attempts to substitute the easily obtained total lymphocyte count (TLC) for the far more specific CD4 count.
I'm tired from "tops" who believe they can't contract HIV. I'm tired from "bottoms" who c ontinue to roll the dice. I'm tired from irresponsible HIV-positive barebackers. I'm tired from irresponsible HIV-negative barebackers. I'm tired of the belief that barebackers are always gay men. I'm tired, because it ain't true. I'm tired of condoms. I'm tired for everyone waiting for the results to come back from an HIV test. I'm tired.
GMHC Treatment Issues: May / June - Volume 18, Number 5&6
Stephen Lewis, UN Special Envoy for HIV/AIDS in Africa
There is one factor more than any other that drives me crazy in doing the Envoy job: it's the ferocious assault of the virus on women. We're paying a dreadful and inconsolable price for the refusal of the international community, every member of the community without exception, to embrace gender equality. And in so many parts of the world, gender inequality and AIDS is a preordained equation of death.
What is the situation for access to antiretroviral (ARV) drugs in India now?In April, the government started giving free ARV drugs in six high prevalence states in India, but only a few people are getting them so far. They are focusing on high prevalence states, but we need access everywhere. A few people are getting treatment, but they still don't have monitoring or education and the government workers are still not comfortable working with people with HIV.
This year's Keystone Symposia on Molecular Mechanisms of HIV Pathogenesis (X7) and HIV Vaccine Development (X8) was held in British Columbia's Whistler Resort, Canada, from 12 – 18 April 2004. This highly specialised and relatively small annual meeting is often not attended by community activists or press. The focus on basic science means that much of what is presented and discussed has little, if any, direct implications for clinical practice. However, the meeting attracts some of the world's experts on HIV immunology and pathogenesis as a forum to exchange and discuss ideas and data. From year to year, the feeling of these meetings can shift from optimism and excitement, to a mundane business-as-usual mood, to an urgent knuckle-down and crack-on intensity. This year's meeting was somewhere between the latter two.
An examination of three GMHC clients, whose regimens typify the needs of people with HIV, shows that the discount card program is not comprehensive, lacks choice, and offers uneven savings.
In the first part of December 2003, the HIV/AIDS treatment community was shocked to hear that Abbott Laboratories was raising the price of its HIV drug, Norvir, five-fold. The price per 100mg pill would increase from $2.14 to $10.71 (average wholesale prices; $1.71 to $8.57, wholesale acquisition cost).
The FDA has granted a fast-track approval to Gilead's new co-formulated FTC/tenofovir pill. It should be approved by September 12. This is sooner than had been expected but the company says it has sufficient manufacturing capacity to begin shipping soon after that date. The FDA speeded up approval after prodding by treatment activists and a recognition that seemingly small advances, such as co-formulation, are worthy of accelerated approval, because it can mean a big difference in treatment outcomes for people due to the improved adherence that comes with simpler regimens. GlaxoSmithKline (GSK) expects to add a third co-formulated pill to its line-up with a 3TC/abacavir combo that will likely be approved in August. GSK pioneered the combo concept for HIV drugs with their AZT/3TC pill, Combivir, approved in 1997, and followed it with Trizivir (abacavir/AZT/3TC) in 2000.
In 1884, German Chancellor Otto von Bismarck called together the major western powers of the world to apportion control of Africa amongst them. At the time of the conference, 80 percent of Africa was still under traditional and local rule.
GMHC Treatment Issues: March / April - Volume 18, Number 3&4
If you think about it, it's nothing short of amazing that some of us have made it this far. We have endured despite the threat of death, despite the symptoms and the stigma and all of the sheer indignities of HIV. We have fought back the fear and the depression, the sense of vulnerability, the discouragement — and the discouragers.
More and more AIDS service organizations (ASOs) are hearing an increasing demand from clients for help in preparing to enter the job market. Counselors at GMHC report a growing number of calls from people interested in "testing the waters" for a return to work. But there's more to helping people get ready for work than simply referring them to a resume writing class or to the State's vocational rehab office. Few ASOs are set up to offer the kind of sustained, multi-dimensional vocational rehabilitation support that people with a complex illness like HIV require.
Project KEEP was a three-year demonstration project to identify and develop service strategies for overcoming barriers to obtaining and maintaining employment for persons living with HIV/AIDS. After an initial community consultation and design phase to identify real and perceived barriers, comprehensive employment support services were provided to unemployed adults living with HIV/AIDS during a two-and-a-half year period.
"Making a Plan" (MAP) is a career counseling program for closed groups of eight to twelve clients who attend a two-hour session weekly for eight weeks. The MAP group counseling program began as a project of the Positive Resource Center (PRC), a San Francisco agency offering employment services exclusively for people living with HIV/AIDS.
Eric Ciasullo and Karen Escovitz National Working Positive Coalition (NWPC)
Isn't it just a few people living with HIV/AIDS that are able or want to transition to work? No. First, it is important to recognize that the vast majority of PLWHA are in their prime work-potential years. Second, increasing numbers of PLWHA are living longer lives and experiencing longer periods of time with minimal or manageable symptoms.
It's true that there's now a fairly comprehensive — but terribly complex and hard-to-grasp — set of federal and state laws and rules that encourage disabled SSDI and SSI recipients to try returning to work.
One of the more disabling side effects of antiretroviral therapy is loss of fat in the face known as facial wasting, or lipoatrophy. Fat loss in the cheeks and temples has been associated with the use of nucleoside reverse transcriptase inhibitors (NRTI) and most strongly with the use of Zerit. Many people who have enjoyed a dramatic recovery of health after starting therapy have found that the onset of facial wasting can be as identifying and stigmatizing as the wasting of AIDS.
Work is the single most normative experience for adults in our society. It is not a marginal or "special" issue. It is a central issue for most HIV-positive people just as it is for most other people. It is of critical importance for HIV-positive people who are not symptomatic, for those who are symptomatic but not disabled enough to qualify for disability benefits, for those who receive disability benefits but who want to do more with their lives, for those who cannot subsist on the pittance they receive from Social Security, for those whose futures are restored to them (whether temporarily or permanently) by successful treatment, and for those who want to make a positive contribution to their communities and to society.
GMHC Treatment Issues: January/February - Volume 18, Number 1&2
I vividly remember the moment I understood how complex the life cycle of HIV must be and how difficult it could become to find a cure. During a press briefing at the 1989 International Conference on AIDS in Montreal, Professor Jay Levy, of the University of California, San Francisco, was asked about the prospects for halting the devastation of AIDS.
Drug metabolism is highly complex and may be modulated by interactions between multiple enzymes and environmental factors. Although the CYP3A4 enzyme responsible for clearing many protease inhibitors from the system is best known, new enzymes and new interactions continue to come to light. And for every new metabolic player discovered there is the potential for genetic variability between individuals and populations to complicate treatment decisions.
Some of the most important talks at the 11th Annual Retrovirus Conference this year are now available as free webcasts. If you did not attend the conference or were unable to catch every session, you can access over 20 hours of plenary talks, mini-lectures and symposiums offered as video and audio accompanied by synchronized slides.
Over the past year and a half, HIV community members from around the globe have begun meeting to discuss how they can advance treatment literacy and increase PLWHA input into decisions by the research, education and care programs that affect them. Community advisory boards (CABs) have long been an important vehicle for representing the needs of people living with HIV to researchers and drug companies in the developed world.
Atze Das and colleagues from the University of Amsterdam reported in the Journal of Virology that they had successfully expressed small interfering RNAs (siRNA) targeted to the HIV Nef gene that blocked viral replication in long-term experiments. RNA interference is a recently discovered natural process where short (22 base pair) double strands of RNA can target complementary sequences of messenger RNA and prevent their translation into proteins.
The annual Retrovirus Conference, the most important scientific meeting of the year on HIV/AIDS, held this year in San Francisco from February 8-13, is not usually an occasion for social or political expression. In fact, the organizers actively discourage demonstrations and leafleting and reward any interruptions with banishment. This year's conference was remarkable for the manifestations of anger and protest at pharmaceutical maker Abbott Laboratories over a 400% increase in the price of their HIV drug, Norvir, announced in December of 2003.
Atazanavir (ATV, Reyataz) is the first once-a-day (QD) protease inhibitor (PI) to be marketed in the United States. The drug was approved in mid-2003 at a dose of 400mg QD, to be taken with food. The pivotal studies of atazanavir compared it to the two current standard-of-care drugs for first-line regimens, efavirenz (Sustiva) and ritonavir-boosted lopinavir (Kaletra).
Back in 1992, I co-authored a report about the AIDS research program at the National Institutes of Health (NIH) documenting redundancies and gaps in the effort and the lack of leadership in the program as a whole. Subsequently, Senators Edward Kennedy and Orrin Hatch with Representative Henry Waxman passed a bill substantially re-organizing the AIDS effort at NIH based on our report's recommendations.
This information is designed to support, not replace, the relationship that exists between you and your doctor.