Buyers' Club Crisis by John S. James
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The first AIDS "buyers' clubs" were started almost ten years ago
to obtain potential treatments which were legal but not readily available.
Throughout their history these groups have repeatedly provided the first access
to lifesaving treatments before they are approved in the U.S. -- and despite
important improvements in the drug-approval process, the clubs still continue to
do so (by making available NTZ, for example, or albendazole, before workable
formal mechanisms were ready; earlier examples included clarithromycin, ddC,
and thalidomide). The Economics of AIDS Treatment OrganizationsThe original buyers' clubs (which still exist today, after almost ten years)
are part of a second wave of AIDS organizations, which challenged the
everybody-dies orientation of the early AIDS era. Other organizations in this
second wave include Project Inform, AIDS Treatment News, and treatment
committees in some ACT UP chapters and other activist groups.
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Fewer AIDS Deaths: by John S. James
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The most important benefit of AIDS treatment is saving lives, but this is
often hard to measure. While large clinical trials offer the most authoritative
proof that a treatment is working, "survival endpoint" trials often
take years, and present major ethical and practical problems, since no one
wants to be assigned to the group which spends months or years receiving a
treatment that results in more deaths. Also, clinical trials often test drugs
under artificial conditions, such as with a non-representative patient group to
get cleaner, more homogeneous data -- or with a design more focused on what a
company needs to get its new drug approved than on the practical information
doctors and patients need to know.
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FDA Advisory Committee by Mark Mascolini |
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The FDA's Antiviral Drugs Advisory Committee split evenly on whether to
recommend accelerated approval of delavirdine, the non-nucleoside reverse
transcriptase inhibitor developed by Pharmacia & Upjohn. After reviewing
data from three clinical trials at a November 22 hearing, four committee
members recommended approval despite delavirdine's variable effects on CD4
count and viral load when combined with AZT, ddI, or both. They argued that the
drug seems safe (rash is the only notable side effect) and that it may prove
useful for people who have failed or cannot tolerate most other drugs for HIV.
But another four members of the committee remained unconvinced that delavirdine's impact on CD4 cells and circulating virus would translate into slower HIV disease progression. Indeed, in the one study that evaluated delavirdine's effect on rates of opportunistic diseases or death, delavirdine plus ddI was no better than ddI alone. Now the FDA must decide whether to approve delavirdine pending the results of an ongoing trial that may confirm a benefit, or whether to deny approval. After the hearing, Dr. Donald Batts of Pharmacia & Upjohn expressed confidence about winning accelerated approval and pledged to work with the FDA toward that end. The study that assessed the effects of delavirdine on disease progression compared the standard dose of ddI plus 400 mg of delavirdine three times daily against ddI plus placebo in almost 1200 people with an average CD4 count of 135. All had taken AZT before and about 25% had taken ddI. An independent panel that looks at results as they come in decided to end the trial early because it judged that there would be no difference between the two groups in rates of disease progression or death. At that point there were 66 deaths in the ddI/delavirdine group and 61 deaths in the ddI/placebo group. There were fewer cases of herpes zoster (shingles) and parasitic infections in the ddI/delavirdine group than in the ddI/placebo group. But there was no major difference between the groups in overall rates of opportunistic diseases. Although CD4 counts were substantially higher and viral load drops greater in the combination group in the first 8 to 12 weeks of the study, those differences disappeared. Another trial found that CD4 and viral load improvements were sustained for a year or more among people with less advanced disease who were taking delavirdine plus AZT. This study compared AZT plus placebo with AZT plus one of three doses of delavirdine: 200, 300, or 400 mg three times daily. There were about 180 individuals in each of the four study groups, and their average CD4 count was between 325 and 340. About 60% had not taken AZT before, while the rest had taken it for fewer than 6 months. After 52 weeks of study, people taking either the 300- or 400-mg doses of delavirdine plus AZT sustained 20 to 30 CD4 cell increases, and this improvement was significantly better than the results in the other two groups. The level of circulating HIV stayed about a half-log (3-fold) below starting levels in the 300 and 400 mg groups for 52 weeks, and this decrease in viral load was again significantly better than the decrease in the other two groups. An analyst from the FDA pointed out that CD4 improvements in the two higher-dose combination arms versus the low-dose combination arm and the AZT-alone arm did not begin to emerge until week 24 of the study and did not become significant until week 40. The FDA noted that there was no CD4 difference until 20% of the study participants had dropped out, and that the dropouts as a group were doing worse when they left the study than those who stayed in. As a result, the FDA told the advisory committee it found the CD4 improvement "suggestive but not convincing" and said that finding should be confirmed in another trial. Because of the tight hearing schedule, the company did not have a chance to challenge the FDA conclusion. But Pharmacia & Upjohn's William Freimuth, M.D., later argued that the year-long CD4 response in the two higher-dose delavirdine groups matches the long viral load response in those groups and so is more than "suggestive." Dr. Freimuth also said the company can demonstrate that most of the dropouts in the study who had been taking delavirdine were doing nearly as well as those who stayed in the study -- and substantially better than dropouts who were taking only AZT. Preliminary results from an ongoing study, ACTG 261, suggested that delavirdine plus AZT and ddI may boost CD4 counts more than AZT/ddI, AZT/delavirdine, or ddI/delavirdine after 40 weeks of treatment. But this improvement was not great in a strict data analysis in which results are figured according to original treatment assignments, even if study participants switch to another group at some point. (Experts believe this kind of analysis is the most reliable.) Further data from this study, two thirds of whose participants were drug naive, should be available in mid-January. In the ddI/delavirdine study, nearly half of the persons taking that combination had some skin rash as a result of one or both drugs, and over 40% of those taking AZT/delavirdine had rash. Thirty-one of 296 people taking ddI/delavirdine left the study because of rash, and 7 of 122 taking AZT/delavirdine did so. The rash emerges in the first weeks of therapy, and Dr. Batts said that 85% of those who get rash can keep taking delavirdine at full dose if they also take an over-the-counter antihistamine. But people taking delavirdine should not take nonsedating antihistamines such as terfenadine and astemizole. Other drugs that should not be taken with delavirdine are rifampin, rifabutin, cisapride, triazolam, alprazolam, and midazolam. Delavirdine doubles levels of clarithromycin in the blood. If treatment includes both delavirdine and ddI, the drugs are better absorbed if they are taken an hour apart. An important and only partly resolved question is the effect of delavirdine on protease inhibitors. So far, studies in healthy people without HIV infection found that delavirdine increases concentrations of saquinavir 4 to 5 times and doubles the concentration of indinavir. Possible interactions with ritonavir are less certain because volunteers took only half the recommended dose of ritonavir in the interaction studies. The company is now studying these combinations in people with HIV. The interaction between delavirdine and saquinavir seems enticing because low blood levels are a major problem with the current formulation of saquinavir. But this combination was associated with liver toxicity in the study with healthy volunteers, so it may prove crucial for anyone who takes the two drugs to have regular liver function tests. Some committee members suggested that the most likely role for delavirdine--if approved--may be for people who have used up other HIV drug options, especially those who have failed with indinavir or ritonavir. But committee chair Dr. Scott Hammer noted that using delavirdine only for advanced disease could bias evaluation of its potential worth. He urged rapid study of the drug in triple and even quadruple combinations to see if it can strengthen regimens when used earlier in infection. All committee members agreed that delavirdine should not be used alone, and some were dubious about combining it with only one other drug.
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Albendazole Free from Buyers' Club |
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Albendazole is a drug used in treating microsporidiosis; recently it has
been approved by the FDA for an unrelated use, so it is now available to U.S.
physicians. Some buyers' clubs carried this drug before it was available in the
U.S. There has never been a large demand (probably largely because
microsporidiosis is difficult to diagnose), but access has been important for
some people. AIDS Treatment Initiatives (see listing above), the buyers' club in Atlanta, will no longer be carrying albendazole, but has a limited supply of about 140 boxes of three 400 mg tablets each. Since this medicine expires in January 1997, the group will give it away to persons with a prescription for it. There is a standard $6 per order charge for shipping and handling. Mail or fax a request and prescription, including the doctor's name, address, and phone number, and the patient's name, shipping address, and phone number. AIDS Treatment Initiatives can be reached at 404/874-4845 phone, 404/874- 9320 fax.
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Books: Impure Science: AIDS, Activism, by Steven Epstein, |
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This book on AIDS treatment activism is based on the author's sociology
thesis at the University of California. A striking difference from most AIDS
activism books is that the author followed a methodology of analyzing both
mainstream and dissenting views in the same way; this differs from the usual
approach which tends to accept a mainstream world view as true, and then tries
to "explain" other opinions as various kinds of errors. (Many books
on treatment activism pick the authors' favorite heroes -- and often villains
as well -- typically chosen arbitrarily depending on whom the author happened
to talk to; the need to maintain these arbitrary white-hat/black-hat assignments
gets in the way of telling what people said and did, and why it was important.)
The strength of Impure Science is in telling what happened; its weakness (for
the general reader) is that it tends not to come to conclusions, leaving no
easy bottom line to take away. Part I of the book, "The Politics of Causation," looks at the questioning by Dr. Peter Duesberg and others about whether HIV causes AIDS. One looks in vain for Epstein's opinions about Duesberg and his views -- but does get a useful 135- page annotated chronology of the controversy. The longer and more important part II, "The Politics of Treatment," looks at many issues in AIDS treatment activism, for example in drug regulation, and in the design and methodology of clinical trials. Epstein sees CREDIBILITY STRUGGLES as central to the dynamic of science -- and is most interested in what it means, for good and/or for ill, when lay persons and groups develop their own expertise and enter into specialized policy realms previously left to certified experts. By making contemporary history accessible in an unbiased way, Impure Science will have lasting value for scholars, writers, policy experts, AIDS professionals and activists, and others with a deep interest in the subject. But it is probably too specialized to have much effect on the sound-bite world of general public discourse. For treatment activists, the practical bottom line that this reader has taken (or, perhaps, constructed) from the book is support for the view that the key factor influencing technical issues of AIDS research/development/treatment policy is the professional consensus (primarily of scientists and physicians, in academic, government, corporate, private, and other roles, but also including some other AIDS professionals, and lay experts to some extent). When treatment activists have an important concern, the best place to take it for action (if action is possible) is usually this professional consensus -- although of course there are also times to address other centers of influence, such as Congress, or the White House, or the FDA, or the public and the media.
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Buyers' Clubs List, |
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Each year AIDS Treatment News has published a list of AIDS buyers' clubs,
along with activist groups and PWA Coalition chapters, in one of our December
issues. This year we have listed the buyers' clubs separately, and provided
expanded information for them. Although AIDS buyers' clubs have existed for about ten years, there has never been an exact definition of what is and what is not a "buyers' club." Most buyers' clubs have 501(c)3 IRS status, meaning that they can receive tax-exempt contributions; but other groups organized as businesses have often been included in buyers' club lists (a matter debated for years but never resolved). Our listing below indicates groups which have 501(c)3 status (or are programs of larger 501(c)3 organizations). How did we decide which to include here? We started with our list from previous years, and also looked at lists kept by some buyers' clubs, and at community consensus or recommendations on which buyers' clubs or other businesses to list. Most of those below have been involved with AIDS (or sometimes other immune illnesses) for years. Some organizations which might qualify were not listed because we could not reach anyone by press time. If you believe we have omitted a group which should have been included (or included a group which should not have been), please let us know. We did not include cannabis buyers' clubs here, as we prefer to list them separately. Notes:
Buyers Clubs (U.S.)
Canada
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AIDS TREATMENT NEWS |
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What kinds of articles should we publish in the future? We would like to hear from you. Our printed reader survey is also online, at: http://www.immunet.org/atn
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