2003 was a year of abundance - as far as new HIV drug approvals go. Five new drugs entered the marketplace - making a total of 21 approved antiretrovirals in the U.S. - and a consensus is forming about which among the bewildering number of potential combinations are safe and reliable - and which should be avoided. Yet despite the best of care with all of our medicines and strategies, people continued to fall to AIDS last year - including several good friends of this publication.
The SAVE ADAP Committee of the AIDS Treatment Activists Coalition thanks everyone who worked hard this past year advocating for adequate funding for the AIDS Drug Assistance Program. While we have fallen far short of getting the money needed, we have succeeded in educating Congress about the importance of this lifesaving program. Your calls, letters, emails, and meetings with your elected officials have played a major role in this success.
A recent action by your company has shaken the HIV/AIDS community to its very core, threatening to transform and erode a productive relationship that has evolved between us in combatting this epidemic. The AIDS Treatment Activists Coalition (ATAC) is a national coalition of AIDS activists, many living with HIV/AIDS, working together to end the AIDS epidemic by advancing research on HIV/AIDS.
As the New Year began, Roche and Trimeris announced that they had decided to halt further development of their experimental entry inhibitor, T-1249. The drug was a follow-on to T-20 (enfuvirtide, Fuzeon), the first-of-its-kind fusion inhibitor that received FDA marketing approval in March of 2003. Since then, and despite high expectations, sales of T-20 have been disappointing due to its steep price and difficulty of administration. The $20,000-a-year drug must be injected under the skin two times a day. Some patients begin taking Fuzeon, then stop after a month or two due to fatigue with preparing and administering the drug. Yet many others adapt to the routine without difficulty and enjoy sustained results; there seems to be no argument about the ability of Fuzeon to suppress HIV for those willing to stick with it.
If the daily grind of subcutaneous injection of T-20 (Fuzeon) has got you down, why not let your T-cells make their own — with gene therapy? Dorothee von Laer and Marc Egelhofer from Georg-Speyer-Haus in Germany and colleagues recently reported on progress in constructing a vehicle for an artificial gene called C36 that produces a peptide with the same fusion-blocking sequence of T-20 (Fuzeon). The idea is to inject the gene, deliver it to blood cells, and let the cells manufacture a new protective weapon against HIV to place on their outer envelopes.
Most of the programs that serve the needs of communities affected by HIV/AIDS and ensure their human rights were the result of community mobilization and agitation. Whether we are gay men and drug users in the United States, heterosexual men and women in South Africa, or sex workers in India, most of the advances in our lives have come from going to our leaders and demanding change.
Advocacy is a strange thing in Russia. There is no equivalent term in Russian — and there seems to be no equivalent concept. People have always hoped to solve their problems on a personal level: "The Czar/Party Secretary/Boss/President is fair, he just doesn't know about my trouble. If I can make it clear to him, he will do something, for sure." Yeah, right.
This space reviews early laboratory findings from the Journal of Virology that shows scientists at work uncovering new ways to think about - and ultimately beat the virus.
PowerPoint presentations are the central spectacle at any scientific conference. In cool, darkened rooms, slide after slide marches from background to methods to results with inexorable logic. But PowerPoint has come under criticism lately for a tendency of the form to abbreviate truth, gloss over details, create an impression of analysis where there is none, and facilitate spin. The leading critic of Microsoft's ubiquitous presentation software, Edward Tufte, author of several books on representing complex quantitative data, points to the role of PowerPoint misdirection in the catastrophic failure of the Columbia space shuttle. During a critical post-launch meeting the potential for serious wing damage at takeoff was masked by a bland slide title disguising the alarming reality nested within dumbed-down bullet points below.
Gary Karch, Michigan Positive Action Coalition (MI-POZ)
The country's first major winter snowstorm left air traffic centers from LaGuardia to O'Hare temporarily paralyzed the first weekend in December 2003. Despite the deep freeze, approximately two dozen HIV/AIDS advocates from across the country battled long lines at airport terminals, waited all night for rescheduled flights, went on wild bus rides and tromped through snow drifts on New York City streets to reach the offices of Gay Men's Health Crisis to attend the first-ever strategy planning meeting of the AIDS Treatment Activists Coalition (ATAC).
GMHC Treatment Issues: November - Volume 17, Number 11
Most people today appreciate the value of antiretroviral therapy, if not its price. This is because the price of expensive anti-HIV medications in the U.S. is largely, and thankfully, invisible. Although uninsured or underinsured people with HIV may have to pay for their drugs out of pocket, the cost of pharmaceuticals for most HIV positive Americans is borne by private insurance or by the government through Medicaid or a state AIDS Drug Assistance Program (ADAP).
You can be a "blipper" and still be chipper, suggests a study in the Noember 2003 issue of the Journal of Virology by Michele Di Mascio and her colleagues from the Los Alamos National Laboratory and the Aaron Diamond AIDS Research Center in New York. Blips are usually thought of as occasional, transient, episodes of low-level HIV RNA viremia in someone who is adherent to their antiretroviral therapy and otherwise enjoys a well-suppressed viral load.
HIV treatment activists met with officials and staff of the federal Food and Drug Administration (FDA) on November 14, 2003 in Rockville, Maryland. The FDA hosted the meeting to update the community on several recent drug approvals and to address several questions that activists had been asking about the future of drug approval for HIV in the U.S.
In 1994, Carlton Hogan testified before an FDA Antiviral Advisory Committee about the risks of letting drugs loose in the population without a rigorous method to detect and report late emerging toxicity. In 2003, AIDS activists met with FDA and repeated many of the concerns that Hogan outlined: the need for post-marketing follow-up, the failure of drug companies to live up to commitments made to study drugs after they are approved, the inadequacy of penalties available to FDA for enforcing those commitments.
GMHC Treatment Issues: October - Volume 17, Number 10
The "S" in AIDS stands for "syndrome," which refers to a pattern of illness proceeding from the immune deficiency that develops in the years after a person becomes infected with HIV: the human immunodeficiency virus. Many people have pointed out the semantic illogic of "getting AIDS," that "you can't catch a syndrome," but, despite liberties taken with the name, the illnesses associated with HIV disease are real and deadly.
Over the past 50 years, and without any significant advances in the past 30 years, a number of fairly reliable medicines have been developed that effectively treat tuberculosis — as long as they are consistently and correctly taken.
As if it weren’t bad enough that tuberculosis affects a third of the world's population, 99.5% of those cases, or roughly 1.8 billion people, exhibit no outward symptoms of infection. They have a latent form of the disease. It sounds almost benign, but the reality is that the bacterium that causes the active disease — Mycobacterium tuberculosis or M.Tb persists in their lungs, cleverly concealed and notoriously hard to detect.
Susan Goldstein and colleagues from the Centers for Disease Control (CDC) have projectedthat if everyone born in 2000 were considered as a single cohort, and none were vaccinated for HBV, over their lifetimes they would experience 64.8 million HBV infections resulting in 9.7 million chronic infections. In this imaginary cohort there would be 1.4 million deaths from chronic infection and 65,000 deaths due to acute hepatitis B. Perinatal infection would contribute 21 percent of these deaths, infections occurring between birth and age 5 would account for 48 percent, and infections acquired after the age of 5 would lead to 31 percent of the deaths. They estimate that HBV infection would be responsible for 1.3 percent of the deaths of all people born in 2000.
The perils of prophylaxing against one disease only to introduce drug-resistant strains of another bug were the topic of a poster at the annual conference of the Infectious Disease Society of America (IDSA) in San Diego.
The enormously productive EuroSIDA study has reported on the prevalence of HCV in the cohort and on the effect that hepatitis C infection has on response to HAART. At the 9th European AIDS Conference in Warsaw, Poland, Jurgen Rockstroh, from Bonn, presented an evaluation of 4,957 members (50.6%) of the large cohort who have had an HCV antibody test. About a third (1685) were HCV positive.
I've been an HIV/AIDS activist for the past ten years. Although I knew that I was going to die of AIDS, no one specified exactly what that really meant in terms of the opportunistic infection that would take me. In my life as a person living with HIV, the nearest that I came to actually dying was when I had tuberculosis. And if I had died of tuberculosis, I would have been one of the AIDS statistics. Everybody, because they know I am HIV-positive, would have said I died of AIDS. Now technically, that would probably be true, because the underlying cause would have been HIV. But the fact that I took the TB medicines and got well shows that something is missing — that in our fight against AIDS, we are not looking at the individual opportunistic infections that can be cured.
GMHC Treatment Issues: September - Volume 17, Number 9
We’ve heard a lot about HIV entry inhibitors in 2003. The new injectable fusion blocker Fuzeon (T-20, enfuvirtide) is the first member of this new class of HIV drugs to hit the market, and several oral drugs intended to block HIV entry into cells at other steps are just starting clinical trials. As a class, the entry inhibitors are designed to keep HIV from merging with a new cell in someone who is already infected. But before HIV can put down roots and start infecting those billions of immune cells, at least one viral particle must make its way past the body’s skin or mucosa — barriers that are supposed to keep the outside out, and the inside in.
For many years in the early part of the U.S. epidemic, there was a general denial that women were at risk for getting AIDS from sex. Even when it was clear that women were being infected, the risk was not taken seriously. Now, half of new HIV infections occur in women. How did you, as an epidemiologist, go about understanding what you were seeing when this new disease first appeared?
Do women in the U.S. really need a microbicide? Good question. It seems to me that most of us — whether in Vietnam or in Texas — could use some form of protection that would allow us to control our risk for HIV and other STIs without depending upon a partner. This being the case, an ideal microbicide — one a woman could use ahead of time; that provided near 100 percent protection and was not apparent to her partner — would be welcomed. As one woman said to me, “I want something I do not have to ask him if we can use. I am always scared that he is going to say no and then what am I going to do?” Many women are afraid that their partner will refuse to wear a condom. Others are afraid that they will be harmed either physically or emotionally if they insist on using condoms. In some relationships, simply suggesting the use of a condom can cause suspicion, rejection and even violence. A good microbicide would help alleviate some of these women’s fears and hopefully reduce their risk of getting HIV.
The Global Campaign for Microbicides is a broad-based, international coalition initiated in 1998 to build support among policy makers, opinion leaders, and the general public for increased investment into microbicides and other user-controlled HIV prevention methods. The Campaign uses advocacy, policy analysis, and social science research to accelerate product development, facilitate widespread access and use, and protect the needs and interests of users, especially women worldwide.
The Global Campaign for Microbicides in North America is involved with groups in several U.S. and Canadian cities. Primarily these are collaborations with family planning, women’s health, and AIDS organizations, with the local groups undertaking to serve the dual purpose of local community education and legislative advocacy. The work of these independent groups is extremely varied, and reflects both the geographic diversity and the specific backgrounds and interests of the individuals pushing the efforts forward. Here are some snapshots of microbicide advocacy in the U.S.
At the 43rd Annual ICAAC Conference in Chicago, Joseph Gathe, a clinical investigator and HIV clinician at a large inner city clinic in Houston, Texas, presented a poster reporting 24-week results from a controversial pilot study that employed only one antiretroviral to treat HIV-infected patients starting their first regimen. The 30 patients in the study were treated with the twice-a-day protease inhibitor Kaletra, a co-formulation of lopinavir with low-dose ritonavir added for pharmacokinetic enhancement. At week 24 of the 48-week study, the one-drug strategy had produced virologic efficacy comparable to that seen with standard triple-drug HAART.
In August 2003, the U.S. Food and Drug Administration’s (FDA) Antiviral Drugs Advisory Committee met to discuss clinical trial designs for topical microbicides. The FDA has received several sponsor applications to conduct trials of candidate microbicides with an eye to approval. From the agency’s standpoint, two anxieties hung over the discussion. The first was the sobering lesson of the COL1492 study of nonoxynol-9, which turned out to actually increase HIV risk. The second was agency skepticism, and palpable fear, about releasing a product that might be less effective than what is considered the U.S. gold standard: condoms.
GMHC Treatment Issues: July / August - Volume 17, Number 7-8
The accessibility of quality HIV care, with and without antiretroviral therapy (ART), varies widely across the globe. As drug prices have fallen in resource-poor areas, dozens of small pilot programs are now proving that that therapy is effective, feasible and subject to problems familiar in the rich countries. Meanwhile, in the U.S., several hundred thousand people are estimated to have HIV and not know it or want to deal with it. Many of these people have limited access to care and may finally enter the system only after symptoms develop. Barriers to care, such as stigma, lack of knowledge, and lack of money, cut across hemispheres and time zones.
Seventeen abstracts described clinical outcomes, adherence, and costs of treating 2442 adult patients in 10 African countries. In addition to these, a number of other papers discussed treatment experiences in Asia and Latin America. Most studies were retrospective chart reviews; no randomized treatment trials were reported. Numbers refer to published abstracts; full references at end of article.
There are many real and perceived barriers to expanding treatment to large numbers of people in the developing world. Among those most often referred to are lack of political will, the high price of ARVs; the lack of trained staff and other elements of healthcare infrastructure; the complexity of treatment protocols and laboratory monitoring.
Hepatitis C infection is prevalent among injection drug users around the world, and in the United States, as many as 90 percent of the people who acquired HIV from injection drug use also have hepatitis C virus (HCV). Overall, 16–25 percent of people with HIV in the U.S. are also coinfected with HCV.
The person writing this letter has some experience gained in prevention activities against the spread of HIV/AIDS in India during the last eight years. Initially the Government and funding agencies came along in a big way addressing the issue of HIV through prevention projects. During the course of implementing these top down projects, myself and my organization felt some severe inadequacies starting with the conceptualization, to the implementation and down to preparations on the ground. In short, in project lingo, these are lessens learned.
First, Viread is turning out to have more pharmacological interactions than were understood at first. An interaction with Videx EC (ddI) has been recognized to raise ddI levels and a letter from Bristol-Myers Squib (BMS) recommends separating Viread dosing by two hours before or one hour after taking ddI. Some doctors have reduced dosing of Videx EC from 400mg to 250mg once-a-day taken simultaneously with Viread, but, so far, there is no clinical trial data to validate this approach.
An announcement has been made. Is that enough to finally stop the river of death in South Africa? After years of refusal, the government there has asked that a plan be developed to bring antiretroviral drugs to several million of its citizens who will surely die if their HIV disease continues untreated. At a pace of over 1000 deaths per day in a country twice the size of Texas, the mortality rate in South Africa has not yet peaked, and hundreds of thousands more will surely die before the plan is written, the implementation rolled out, and the drugs begin to flow to hospitals and clinics.
I think we're blessed to live in the State of California, which is somewhat of a freestanding republic in and of itself. In 1996, the people of California voted to allow physicians to talk to their patients about the medicinal use of cannabis. Then, through the work of Senator John Vasconcellos, one of our state senators, appropriations were made to the University of California that established the Center for Medicinal Cannabis Research (www.cmcr.ucsd.edu). And that Center has had funds for the past three years that allows it to support clinical trials to investigate the use of marijuana for medicinal purposes.
Since the beginning of the AIDS crisis, a number of "alternative" medical treatments have been proposed and used with unknown success, such as herbal compounds, nutritional supplements, traditional Chinese medicine, as well as physical manipulation techniques and spiritual approaches. Although these methods have all been lumped together under the generic category "Alternative or Complementary Health Care," they differ substantially in philosophy, modality, cost, and other important ways.
The Foundation for Integrative AIDS Research (FIAR) is a not-for-profit organization formed in October, 2001, to sponsor and stimulate interest in clinical trials of herbal and nutritional treatments for people with HIV, AIDS and chronic hepatitis. The goal is to show whether or not these treatments can lessen symptoms, delay the use of Western drugs, reduce side effects, and are safe. FIAR is working to develop studies in developing nations where indigenous treatments are used and Western drugs are largely unavailable. FIAR also seeks to help bring affordable Western drugs, education and prevention to such under-served areas.
Atazanavir has been developed as a once-a-day (QD) protease inhibitor to treat HIV infection in combination with other antiretrovirals. Its approved dosage will be 400mg QD, taken with food. The convenience of QD dosing is expected to enhance regimen adherence and contribute to treatment effectiveness.
The longer the AIDS plague continues, the more important it becomes to integrate and multiply the opportunities for access to complementary therapies in the lives of our communities. Whether through traditional healing practices received from ancestors, or through desperation and the need for alternative options, more and more individuals are using complementary therapies to support and enhance the quality of their lives. The increasing complexity of HIV medical management and its side effects, the increasing limits on access to care, and the growing toll of untreated mental health conditions compel us to recognize and institutionalize effective complementary therapies into all of our helping organizations.
For most people, HIV infection, if not treated, causes a long, slow decline in immune capacity to a point when they become susceptible to dangerous opportunistic infections. In some, this decline can happen within a few years; for a few, it hasn't happened yet after 20 years.
Julian Meldrum - With commentary by Dr. Vijay Anthony Prabhu and Dr. Desmond Martin
Fixed-dose combination antiretrovirals (FDC ARVs) are products that combine two or more active drugs in one tablet or capsule. In many countries, they now offer the cheapest available route to a complete and effective ARV regimen. There are many potential advantages of using FDCs. The most obvious are the simplification of what is supplied to and taken by individual patients and reduced potential for inappropriate sharing of drugs.
May 13, 2003, an FDA advisory committee met outside of Washington, D.C. to consider the approval of a new protease inhibitor, atazanavir (ATV). The drug was mostly well received by the committee; efficacy in treatment naive patients was applauded and a recommendation for approval voted unanimously.
Last December Gilead Sciences announced a plan to make their nucleotide reverse transcriptase inhibitor Viread (tenofovir) available to clinics and treatment programs in the developing world at an affordable price. Joe Steele, the architect of Gilead's plan, recently answered questions about the logistics and motivation for the program.
"Goodbye, America — The place where I'll never ever be," goes the song, testifying to the fact that the "good life" the U.S. and the West symbolize remain out of reach for most people in the region. I couldn't help thinking that this song was an appropriate coda to a meeting that stressed the stunning lack of access to basic HIV treatments and diagnostics and the unwillingness of the West to intervene on any appropriate scale to assist these countries on the doorstep to Europe in confronting an epidemic that is exploding all around them.
GMHC Treatment Issues: April - Volume 17, Number 4
Much of your research has focused on the systems through which people receive medical care and how those systems affect the actual outcomes of care in terms of, say, fewer hospital days or improved quality of life. In a broad sense, this kind of research is part of a trend to patient-centered care, in which those being treated are considered an integral part of the health care system.
The 10th Annual Retrovirus Conference held recently in Boston featured several presentations on novel ways to look at HIV pathogenesis (how the virus causes disease) and how the virus might evade attacks by each of the three main immune defense systems: cell-mediated, humoral and innate immunity.
The powerful antiretroviral (ARV) drugs taken by people with HIV and AIDS caused a revolution in treating the disease after death rates plummeted when effective combination therapy was widely introduced in 1996. But almost immediately, clinicians began to worry about increasing blood levels of cholesterol and triglycerides seen in patients receiving the drugs.
Roche has announced that the wholesale acquisition cost (WAC) of Fuzeon will be about $20,000. A more commonly quoted price is the average wholesale price (AWP), which typically runs about 25 percent higher than the WAC. The price paid by ADAPs and Medicaid is likely to be less than WAC. People who can afford to simply write a check will pay the highest price for Fuzeon. On launch day, a Chronimed employee quoted a cash-and-carry price of $2,200 a month, or $26,400 a year for the drug.
Over a few days in early March, 2003, dozens of flights touched down in Cape Town, South Africa unloading AIDS activists from around the world. Nearly 125 participants from 67 countries came to attend the International Treatment Preparedness Summit, an event "organized by an ad-hoc coalition of treatment activists from around the globe" and sponsored by over a dozen donor organizations.
New York City recently published a new generation of AIDS statistics that marries its traditional AIDS reporting with new data drawn from HIV reporting that began in mid-2000. The result is a picture of AIDS in New York that is shocking.
GMHC Treatment Issues: March - Volume 17, Number 3
On March 13, 2003, the U.S. Food and Drug Administration granted Trimeris, Inc. approval to sell T-20, brand name Fuzeon, generic name enfuvirtide, the first of a new class of HIV drugs called fusion inhibitors. GMHC Treatment Issues has been tracking the development of T-20 since 1996.
Fuzeon was approved in the U.S. primarily on the basis of 24-week efficacy and safety data from two large clinical trials called TORO 1 and TORO 2 (T-20 versus Optimized Regimen Only, 1 and 2)
T-20 is the first drug of a new class of HIV inhibitors that perform entry inhibition. More specifically, T-20 is one of a subset of entry blockers called fusion inhibitors. It acts by preventing the envelope of HIV from fusing to its target's cellular membrane.
Seven minutes from Sangster International Airport in Montego Bay, Jamaica, there is a somewhat run-down house perched on a hill with a breathtaking view of the luxury beachfront hotels below and of the cruise ships docked across the bay.
A four-day International Treatment Preparedness Summit kicked off here on Thursday, March 13, with over 120 treatment activists drawn from 67 countries in attendance.
There's been a shakeup in the government's efforts to test a vaccine for HIV. First, the National Institutes of Health (NIH) cancelled plans by its HIV Vaccine Trials Network (HVTN) to launch a large, international study of an HIV vaccine next year. The reason? Disappointing smaller studies with a canarypox-based vaccine combination gave little reason to think it would do any better in an 11,000 person, eighty million dollar trial.
GMHC Treatment Issues: January/February - Volume 17, Number 1-2
Well, the President's budget for the coming fiscal year arrived on Capitol Hill at the beginning of February and except for an unexpected spasm of largesse for global AIDS efforts, the news looks bleak for domestic HIV programs, as well as Medicaid, which provides healthcare to thousands of people with HIV/AIDS.
Boehringer Ingelheim announced the start of two large Phase III trials of tipranavir, a new kind of protease inhibitor (PI) that binds to the enzyme in a different way than currently available PIs. The U.S. study, dubbed RESIST 1, is aimed at people who have developed resistance to existing protease inhibitors and is one leg of the largest clinical research program ever launched for this highly treatment-experienced population.
On Valentine's, Roche invited state ADAP (AIDS Drug Assistance Program) directors and community activists to a meeting about Fuzeon (T-20, enfuvirtide) pricing at its manufacturing plant in Boulder, Colorado. Unfortunately, only the directors of four ADAPs were able to attend, although these represented the country's largest programs.
This information is designed to support, not replace, the relationship that exists between you and your doctor.