AIDS Treatment News
Editorial: by John S. James
The much increased credibility of viral load tests among
researchers and physicians (shown, for example, at the recent
international AIDS conference in Vancouver) creates both the
opportunity and the obligation to re-think FDA requirements
for clinical trials of new antiretroviral drugs. The current
system mandates serious mismanagement of clinical research,
because much, if not most, of the resources now spent on AIDS
clinical trials do not answer real-world questions that would
help doctors use these drugs with their patients. The
regulations and procedures which now require huge trials
designed around issues of the past must be reformulated to
instead require the kinds of trials that tell doctors and
patients what they need to know.
The current procedures are codified in the "accelerated approval" regulations published December 11, 1992. These regulations were a major advance over what they replaced, and were widely supported by almost everyone involved with AIDS treatment, including this writer. They allow a drug to be approved based on evidence from clinical trials which measure easily observed evidence of disease status (such as viral load and CD4 count) -- provided that the pharmaceutical company also agrees to complete, and has underway, the much larger, longer, and more difficult trials to confirm the drug's efficacy based on "clinical endpoints," meaning death or major disease progression.
The goal of this confirmation requirement -- to make sure that a new drug does more good than harm -- is easily understood, and widely influential. But now this requirement's real effects are very different, and seriously destructive. We need more flexibility, with different confirmatory trial requirements based on today's understanding and today's practical questions. The rest of this editorial will review some of the problems with the current system, and then look at what should replace it.
The Problems TodayToday a drug which has proven viral-load benefit must undergo at least one new trial to also prove that it reduces death or major illness, compared to some other treatment which is considered good enough to be ethical to use in a trial. For example, indinavir (brand name Crixivan(R), the Merck protease inhibitor) is now recruiting for its confirmatory trial, the government-run ACTG 320. This trial is controversial among activists, who argue that Merck should pay the entire bill to study its proprietary drug, leaving government funds for other research (Merck is contributing part of the expense). But the problems with this and most similar trials go much deeper than who pays the financial bill.
First, to prove for sure that a drug saves lives, people must die in a trial. (And paradoxically, it can turn out that the better the standard of care or other comparison arm, the more people must die overall to get statistical proof that the new drug is better.) Statistical proof of difference in death rate (or rate of major opportunistic infections) is hard to accumulate. And current trial design compounds the problem, by insisting on huge trials to prove this survival (or major disease progression) benefit from scratch -- as if we knew nothing in advance about the drug, or about HIV disease. Having to re-prove the treatment in one new trial alone (ignoring previous evidence) greatly increases the financial cost -- and also the number of deaths or serious illnesses required.
This sacrifice is needless, since it soon becomes evident from conversations with researchers that the real purpose for these trials is to provide some additional assurance that we are not walking into a rare (but potentially deadly) drug disaster. The tragedy is that we could address this safety issue much more efficiently by addressing it directly -- instead of seeking safety data by conducting a huge trial which uses death or major illness to re-prove a drug which has already been approved by the FDA, and usually is already widely accepted and widely used by the medical community.
The current system also has major ethical difficulties. For example, everyone agrees it would be unethical to conduct randomized trials which risk death or serious harm, unless the researchers have "equipoise", meaning that they really do not know which of the treatments being compared in the trial is best. But if there really is equipoise, it is unlikely that a pharmaceutical company will finance the trial. Companies will not spend millions of dollars for a major, clinical-endpoint study unless they are quite confident that their drug will work provably better than some comparison treatment which will be used in the trial.
A central problem is the winner-loser mindset -- the insistence that clinical trials be designed (like horse races) to have winners and losers. To determine a winner requires having a loser -- some other treatment which leads to provably excess deaths or major illnesses -- yet which somehow can be ethically justified as acceptable to give to volunteers in a trial. Of course no one wants to be given the treatment which almost everyone involved expects to lead to statistically significant excess deaths or major disease progression. (While this expectation may be denied, its reality is shown by the fact that if enough extra deaths and illnesses do not occur to obtain statistical significance, the trial will be widely regarded as largely a failure, since it "did not prove anything," and only "trends" can be reported.) The result is endless conflict, and endless recruiting problems which cause major research delays.
It also makes it very difficult (usually impossible) to persuade different pharmaceutical companies to support a trial which would compare their products head to head with competitors'. No one wants their new drug to play the necessary loser role. When there is only one company involved, it will have enough control over the trial design to assure itself that something else will fill that slot.
And if the loser arm does perform as expected and the trial is a success, then just what has been proved? That the new drug can save lives or prevent major illness, if used in one particular way. That seems like important information, until one adds up how few patients will later use the drug in ways similar to the trial -- including having similar demographics, concurrent medications, prior therapy, and other medical history. In practice, the major clinical uses are likely to be quite different from the trial use, and to be largely or completely untested in any trial.
If the drug being tested fails to prove a survival or disease-progression benefit, then in theory it should be removed from the market. But everyone knows that this is unlikely to ever happen for a drug which has already come far enough to be in standard prescription use in thousands of patients, many of whom undoubtedly appear to be benefiting and would have no acceptable substitute if the drug were withdrawn. Would indinavir really be taken off the market if ACTG 320 fails to reach some arbitrary level of statistical significance? Would 3TC have been withdrawn if it had failed to get statistically significant clinical-endpoint proof -- which became known just in the last two weeks (see article below)? These questions raise the possibility that the whole project of today's confirmatory trials may really be a meaningless exercise, at least in regard to the central design goal of these studies. (There are, of course, incidental spin-off benefits from almost any trial. But these do not justify an erroneous design philosophy which addresses the wrong questions, resulting in enormous waste.)
If only we could move beyond the winner-loser mindset, then if we still need to have clinical-endpoint trials for antiretrovirals, they could be designed in better ways. For protease inhibitors, for example, each manufacturer with an approved drug would be invited to enter the strongest combination or combinations it could devise -- using its protease inhibitor, plus other treatments (usually approved treatments) from any company. The different combinations would then be tested in a diverse patient population. Each company would have a powerful incentive to enter its best possible treatment combination -- even if it meant including a competitor's drug -- to make its new product look as good as it could. Since there would be no expected loser arm in this trial, every volunteer would get one of the best therapies available, greatly reducing recruiting delays. Instead, the trial would usually conclude, perhaps in two or three years, with the different arms close enough to be statistically indistinguishable -- meaning that none of the treatments were proven to have a survival benefit over any other. The goal of the trial would be (1) to catch any unexpected problem with one or more of the treatments, which could show up as a worse outcome, and (2) to help answer practical questions (such as which patients benefit most from which therapy), by gaining experience and data from the different treatments under carefully managed research conditions.
What blocks such designs today is that many researchers think of clinical drug trials as they think of athletic competitions, events which would generate little interest unless they produce a winner (and therefore also a loser). Today, a trial without a loser is likely to be considered something of a failure, a negative result which may be hard to publish in medical journals. The resulting difficulties of finding persons or companies to fill the required loser slots is what generates many ongoing problems with today's clinical trials.
What Should Be Done?Much of what happens under "accelerated approval" today is exactly what should happen. The drug is approved based on viral load reduction and additional evidence of benefit, short of statistical proof of reduced death or major opportunistic infections. And as part of this approval, there are negotiations between the FDA and the company developing the drug, in which the company agrees to conduct further, confirmatory trials. All this is as it should be. What needs to be changed is the content of the negotiations. Instead of requiring one or two big "clinical endpoint" (death or major illness) trials which add little to the decisionmaking of doctors and patients, they should focus on smaller, more numerous, less burdensome trials which answer the major practical questions. For example:
* Since these antiretrovirals will already be approved (under accelerated approval), it will already have been proven that the drug or combination reduces viral load in some patients. Now doctors and patients will want to know how long this drug activity is likely to last. Careful followup of small trials should continue for years, perhaps indefinitely, even after volunteers leave the protocol and move on to other treatments.
* What other combinations with the new drug will improve the amount and duration of viral load reduction -- including drugs from competing companies? Of course not all combinations which are mathematically possible will ever be tested in trials. But those with good theoretical, laboratory, or clinical justification can be tested selectively. Since these are viral load trials, many of them could be done for the same money and number of volunteers as the survival trials -- and no one would have to die.
* How well can the drug in combination reduce viral load in patients who are hard to treat (including those with very advanced HIV disease, or who have been heavily pretreated and failed the major treatment options currently available)?
* How does the drug interact with the other medications the are patients using? (Some interaction studies will have already been completed before FDA approval.)
* How safe is the new drug for those with liver problems or other common medical complications?
* How should the new drug be dosed in infants and children? In many cases the FDA now allows companies to get pediatric approval through simple dosage and formulation tests, without insisting on repeating survival tests in children. A few companies have been very good in carrying out this testing, but most are still abysmal. Why not require these easy pediatric trials as part of the process of accelerated approval, when there is an important public health reason to do so? This would not increase the economic burden of drug development, since these trials will cost a very small fraction of the expense of confirmatory death/major illness trials which would no longer be required.
* Is there any reason to expect sexual, racial, or other demographic differences in response to the drug? Instead of wishing for a separate survival trial for every demographic group, which would be impossible, do the simple pharmacokinetic and major drug-interaction trials -- as well as small, focused studies of particular health problems, to explore any specific medical or scientific concerns which may exist.
* And of course all these trials will contribute to the assurance of safety for the new drug, by providing controlled conditions and intensive data collection, allowing unforeseen problems to be noticed most easily.
Just as today, the FDA would decide what confirmatory trials would be required for each drug, in negotiation with the pharmaceutical company applying for accelerated approval. All that needs to be done is to broaden the definition of confirmatory trials in the accelerated approval process, so that they will reflect current needs instead of debates of the past.
Compared to the current system, these more responsive trials could be accomplished in no more time, for less cost, with less demand for scarce trained personnel, and with far less difficulty in recruiting volunteers. Unlike the current system (which doctors increasingly ignore, since they use the new drugs without waiting for the confirmatory-trial results -- consider indinavir, for example, or AZT+3TC), this approach would produce the information doctors most need and will use. And unlike proposals to simply abolish requirements for confirmatory studies, it would not allow drug companies to evade their responsibilities to the public, but would guide them in fulfilling these responsibilities in a rational way.
How To ChangeThe first and most critical step in changing the accelerated- approval system to make confirmatory trials more responsive to current needs is to build professional consensus for the changes needed. Once there is sufficient consensus (and we believe that it largely exists already), the FDA can probably change the requirements for confirmatory trials by modifying the accelerated approval regulations, without going to Congress or to other government bodies. This is because current law requires that drugs be proven safe and effective, while leaving it up to the FDA how this will be proven. Note that ALL the examples suggested above for new kinds of confirmatory trials relate to proof of safety and efficacy: In what doses is the drug safe and effective in children? Is it equally safe and effective in women? In different racial and demographic groups? In people with certain prior medical conditions? In untreated or in heavily pretreated patients? How long will the proven drug activity last? What combinations will make it last longer?
We doubt that pharmaceutical companies will strongly oppose such a change, for two reasons. First, since each clinical- endpoint trial can be as expensive as dozens of smaller trials, the revised accelerated-approval regulation would save them money. In addition, these trials will provide much more rapid data on their drugs (vs. clinical-endpoint trials which are often blinded for years, finally producing data when the drug may already be largely obsolete). And by addressing the practical questions of physicians (unlike the current system), through trial designs approved by the FDA which are likely to lead to improvement in the drug labeling, it will produce data which will support the marketing of their drug. Some companies are already running trials like the ones suggested for their own marketing purposes, even though they are not required to do so.
An ongoing series of meetings of clinical-trial experts, organized by The Keystone Center, is about to report to Vice President Gore on improving the use of currently available AIDS/HIV therapies. We hope this team has considered revision of the current accelerated-approval regulations -- away from huge clinical-endpoint trials of antivirals (to reconfirm at enormous cost what has already been shown by viral load), and toward more flexible confirmatory studies to answer the practical questions of physicians and patients.
Note: There are other approaches which this Keystone process should consider as well -- such as moving away from rigid protocols designed to test one drug alone or in combination (whether or not it is working for individual volunteers), in favor of more flexible studies designed around giving each volunteer the best treatment possible, under research conditions, as decided by a team of leading research physicians with full access to all available drugs or other treatment methods. But that is a different discussion.
3TC: Combination Trial Stopped Early by John S. James
A major trial of 3TC (also called lamivudine, or Epivir(R))
in combination with other antiretrovirals has been stopped
early, after a data analysis of the ongoing study showed a
54% reduction in the rate of HIV disease progression or death
when 3TC was added to other antiviral regimens, vs. when
placebo was added. This trial, conducted in Australia,
Canada, Europe, and South Africa, had been scheduled to end
in March 1997. The combination regimens all included AZT;
some also included ddI or ddC, and some also included an
experimental non-nucleoside reverse transcriptase inhibitor.
On July 15 the DSMB (data safety monitoring board, a group which secretly monitors the data from an ongoing trial, in order to end the trial early if necessary for ethical reasons) reviewed the data from 1,892 volunteers, and unanimously recommended that the trial be discontinued, in order to allow all participants to use the combination treatment.
3TC was approved in the U.S. on November 17 of last year, based on smaller trials which showed improvement in markers of disease progression, especially viral load reduction. None of those trials was big enough to show reduction in the number of people dying or progressing to AIDS. This is the first trial to show such clinical benefit; however, a meta- analysis of four smaller trials considered together, with a total of 972 volunteers, found a statistically significant reduction in HIV disease progression of at least 49%. (Stazewski S and others, Reductions in HIV-1 Disease Progression for AZT/3TC Relative to Control Treatments: A Meta Analysis, XI International Conference on AIDS, Vancouver, July 7-12, 1996, abstract number Th.B.948.)
A separate clinical-endpoint trial on the effects of 3TC in delaying disease progression or death in pediatric patients is continuing in the U.S.; sponsors are Glaxo Wellcome and the AIDS Clinical Trials Group of the U.S. National Institute of Allergy and Infectious Diseases. According to Glaxo Wellcome, final results are expected in 1999. A DSMB will review the data, probably starting in early 1997.
ADAP Treatment-Access Emergency by John S. James
The AIDS community now faces a major emergency, as thousands
of people in the U.S. are likely to be denied medically
indicated treatment for HIV disease because they have no way
to pay for it. People must mobilize on this issue now. When
AIDS Treatment News asked experts how to begin, what
organizations our readers could contact, the answer was that
one could ask almost any AIDS organization, since all the
service organizations will be under increasing pressure to be
involved. If your organization does not have an existing
program around this issue, work with them to start such an
ADAP (the AIDS Drug Assistance Program), supported by Federal Ryan White money, by appropriations from states, and by pharmaceutical companies in the form of rebates on purchases of their products, pays for certain drugs for people who do not have private insurance coverage and are not poor enough to go on Medicaid. This program has worked well for years. But now with the medical community moving toward more aggressive combination anti-HIV therapy, including the expensive protease inhibitors, ADAP programs do not have the money to keep up with the need.
The ADAP Working Group, an unusual coalition of AIDS organizations and pharmaceutical companies, has had considerable success in improving ADAP funding, and has also helped persuade companies to help finance the program by providing rebates from purchases of their drugs. But there is still a gap likely to deny treatment to thousands of people. We asked William Arnold, Co-Chair of the ADAP Working Group, what people need to know now. (In this interview he is speaking as an individual.)
ATN: How fast is the ADAP funding crisis developing?
Arnold: No one can predict what physicians and patients will decide to do in the future, as a result of the good news from Vancouver and elsewhere about antiviral combination treatments. But consider one example. Recently the state of Washington updated its computer system; the old system provided ADAP data as of 90 days before the current date, while the new system reduces that lag to 10 days. Washington found that its demand and enrollment were up 75% just by closing that 80 days of gap. The state immediately closed its ADAP program to new enrollment, and may call an emergency session of the legislature so that it can cover the people it already made commitments to.
We are hearing of problems in state after state, where medically indicated treatments are being restricted in various ways. Very few states have added protease inhibitors to their ADAP formularies. And some have added them knowing they will be unable to pay.
If the fundamentals of a sound program are not addressed, states will be in the position of rationing life and death, with thousands being denied treatment they need. And there are financial consequences as well, since the total cost of care may well increase. Already there are reports of medical practices which are using the new treatments having far fewer hospitalizations and infusions, as well as fewer deaths; at least one AIDS hospital ward has already closed because of the smaller number of patients needing hospitalization. The financial costs of extra hospital care, additional major illnesses, and people on disability and Medicaid when they could be working and paying taxes, could more than wipe out the money saved by not paying for antiretroviral treatment. But the data are not yet available to project these costs exactly and answer this question definitively.
ATN: What about the additional $65 million for ADAP for fiscal year 1997 (on top of his earlier $52 million request) which President Clinton just announced he will ask Congress for?
Arnold: We are certainly grateful for that. Congress has also been helpful; for example, when the House approved the $52 million Clinton had earlier requested, it added $23 million more. But look at the arithmetic. If we estimate the cost of combination antiretroviral treatment as about $10,000 per year average, $65 million will provide that treatment for 6,500 additional people, in the entire country. ADAP now has about 70,000 people already enrolled; it is unlikely that 6,500 slots will be enough to provide the new therapies even to those already in the program. And others are likely to enroll -- or come in for their first HIV test -- as they hear that there is more that they can now do about the infection.
The ADAP Working Group has called for an additional $196 million in Federal funding for fiscal year 1997, based on a conservative, minimal estimate of the need. This estimate assumes that there are substantial state and pharmaceutical- industry contributions as well.
ATN: What organizations can people approach to show them how to work on this issue?
Arnold: All AIDS organizations will soon be under pressure to take a stand. Access to treatment is becoming the central issue for people with HIV and AIDS.
Some have been slow to understand. For example, the President's HIV/AIDS Advisory Council recently made recommendations to Clinton, without including a word on ADAP.
Your readers can help by working through their local or national AIDS organizations. Remember that ADAP is not only a Federal issue, but also a separate issue in every state -- and an issue for pharmaceutical companies as well, which are providing major support to the program through price rebates.
By mid August, our ADAP Working Group will begin releasing much detailed data, including computer forecasting models. People can do the arithmetic for their own states, to project the costs of various coverage policies, and see if their state will have enough money.
The ADAP funding problem will become much more severe in the near future, over the coming year. But if we wait to mobilize until the situation is more critical, there will be no money in the pipeline and it will be too late to provide many people the care they need.
Free Viral Load Testing From Roche by John S. James
As reported earlier, Hoffmann-La Roche has offered two free
baseline viral load tests to everyone with HIV in the U.S.
But the free program only lasts until August 16; after that,
there will be a charge which varies with different
laboratories. (The physician's office must request enrollment
forms, and the form with the sample for the first test must
be in the participating laboratory by August 16. The second
test sample and form must be in the lab by August 30.)
This test is the Amplicor HIV Monitor(TM) viral load test, using PCR technology -- the only viral load test officially approved by the FDA at this time.
For more information about this test, and about this free testing program, call toll-free 1-888-TEST-PCR.
San Francisco Area:
On August 20, Thomas Sharpton, M.D., FACP, will review the
medical and scientific advances presented at the XI
International Conference on AIDS in Vancouver, in a forum for
Kaiser plan members and the public. The meeting will be
divided into basic and advanced segments, with a break
following each segment.
The time and location are 6:30 to 8:30 p.m., room 1200C, 12th floor, Hospital Tower, Kaiser Permanente Medical Center, 280 W. MacArthur Blvd., Oakland. For more information, call 510/596-6848.
DHEA: Modest Viral Load Reduction by John S. James
Researchers at Twelve Oaks Hospital in Houston found a modest
average viral load reduction after treatment of 20 patients
with relatively high doses of DHEA (dehydroepiandrosterone,
also called prasterone).(1) Another poster by the same group
reported that when blood levels of DHEA in these patients
reached 400 mg/dl, viral load levels began to decline.(2)
This is important because DHEA is available (it has long been
used as an "alternative" treatment for various conditions,
and is now in mainstream research as a potential treatment
for lupus), appears to have few known side effects, is not
very expensive, and may be unlikely to lead to viral
In the Houston study, the 20 volunteers (18 men and 2 women) had CD4 counts from 28 to 242. All but three said they had never taken antiretrovirals; these three had a 30-day washout of their previous treatments, so that effects of the study drug could be distinguished. The volunteers were randomly assigned to receive either 300 mg or 600 mg of DHEA twice a day for 28 days. Then the treatment was stopped. After the data were analyzed, treatment was restarted at 600 mg twice daily for all the volunteers.
Viral load was measured at baseline, at 14 and 28 days after start of therapy, at restart of therapy, and 14 and 28 days after restart -- both by HIV PCR and by viral culture. Early in the study, there were some increases in the average viral load as measured by PCR, especially at the lower dose, but there were consistent decreases (below baseline) at later times. The initial increase might have been due to measurement error -- or possibly to increased secretion of IL-2 (which has been reported in a different study of DHEA, in cells from persons with lupus), since IL-2 might stimulate HIV when other antiretroviral therapy is not being used. It is difficult to summarize the size of the viral load changes from this small study, because that depends on how the data are interpreted.
There are different formulations of DHEA, which might have different bioavailability. The material used in the Houston study was micronized DHEA from Diosynth, Inc. in Chicago (which sells the product only to pharmacies; some compounding pharmacies sell DHEA by prescription).
Comment: Need for Attention to DHEA
A number of published papers, many of them describing studies relatively early in the epidemic, suggested that DHEA might have value in AIDS treatment. In laboratory tests it was found to modestly inhibit HIV and FIV (feline immunodeficiency virus, which infects cats). In persons with HIV, levels of DHEA are often abnormally low (although they may be higher in persons with KS); in addition, low levels of DHEA were found to be associated with faster progression of HIV disease. In lupus patients, low levels of DHEA seemed to cause deficient IL-2 production by lymphocytes. An earlier trial by the Houston group administered lower doses of DHEA to 12 patients with low CD4 counts, mostly under 100; 10 of these 12 patients were also receiving standard antiretroviral therapy. After 12 months two had died, but 9 of the other 10 had CD4 count increases, with 5 having over a 25% increase.
But the most thorough study of DHEA in HIV disease, a phase I trial in 31 patients enrolled between April 1989 and March 1990, failed to find sustained CD4 count increases, and concluded that a randomized controlled trial would be necessary to evaluate the efficacy of DHEA as a treatment for HIV disease. Viral load testing was not available when that trial was run.
So while there has been fragmentary information from a number of studies suggesting the possibility of benefit in HIV disease -- and anecdotal reports of people feeling better when they supplement blood levels which are low (tests for DHEA blood level are available to physicians) -- there has until now been little or no direct evidence that taking DHEA is helpful for persons with HIV. This may only reflect that the research has been poorly funded (due to limited corporate interest, since DHEA is a natural compound already in the body and would be difficult to protect by patents), and also because most of the studies of DHEA in HIV disease were done years ago, before viral load testing was accepted or available. The new report of viral load decrease -- even though it is a small one -- would be important if it helps to renew research interest.
We believe it is unlikely that there will ever be a definitive clinical-endpoint study of DHEA in HIV disease -- due to the patent/business situation, and the lack of non- pharmaceutical money for AIDS research in the U.S. and elsewhere. But what CAN be done now, and is urgently needed, is for one or more other research teams to measure the effect of DHEA on viral load. (For example, could adding DHEA to approved therapies produce larger or more sustained viral load reductions compared to those treatments alone?) If viral load reductions are confirmed by several small studies, this low-cost, readily available substance would probably find a use in HIV treatment. Viral load testing, which is becoming standard anyway, could then help to tell which patients seem to be benefiting. The main "down side" to DHEA is that much is unknown about its role in the body.
Since DHEA is relatively inexpensive, if it is found to be useful, this treatment might reduce the total cost of HIV care in the U.S. -- as well as being the first potential antiretroviral affordable in much of the world. Community- based research organizations could make an important contribution by raising the funds and running additional studies. They would not need to cost very much. FDA approval of the research should not be too difficult, since the FDA has already approved other trials of DHEA.
Note: Eight years ago AIDS Treatment News published a warning that DHEA should only be used if it is pharmaceutical grade -- manufactured for human use (issue #49, January 28, 1988). Pharmaceutical grade DHEA is available because it is widely used as an ingredient for the manufacture of other pharmaceuticals, including certain birth-control treatments. But since the health-food market is largely unregulated, there is a risk that impure DHEA could be packaged and sold. Any potential contaminants could be particularly dangerous for persons with HIV, who are likely to take many times the doses used by most health-food customers (who most often use DHEA as a possible "smart drug," or in the belief that it might slow the aging process or reduce certain effects of aging).
Note: For previous coverage of DHEA in AIDS Treatment News, see issue # 239, January 19, 1996 (DHEA and AIDS; also, DHEA Clinical Experience: Interview with Jon Kaiser, M.D.); issue #242, March 1, 1996 (DHEA: Threat to Access?); issue #140, December 6, 1991 (Endocrine Complications in HIV Progression); issue #48, January 15, 1988 (DHEA: Mystery AIDS Treatment).
1. Salvato P, Thompson C, and Keister R. Viral load response to augmentation of natural dehydroepiandrosterone (DHEA). XI International Conference on AIDS, Vancouver, July 7-12 [abstract # We.B.3385].
2. Thompson C, Salvato P, and Keister R.Effects of plasma dehydroepiandrosterone (DHEA) levels on HIV RNA plasma levels as measured by PCR. XI International Conference on AIDS, Vancouver, July 7-12 [abstract # Th.B.4352].
For a list of references to many of the previous technical papers on DHEA, see AIDS Treatment News #239, January 19, 1996.
San Francisco Cannabis by John S. James
As this issue went to press, the Cannabis Buyers' Club (CBC)
in San Francisco, which supplies marijuana to thousands of
people with AIDS, cancer, glaucoma, and other conditions who
need the drug for medical treatment, was raided; thousands of
patients' medical records were seized. The San Francisco
office of Californians for Compassionate Use -- backers of
Proposition 215 to legalize medical use of marijuana in
California, which received over 700,000 voters' signatures
and will appear on the ballot in November -- was also raided,
as were five homes of persons associated with the
organizations, according to the CBC. A number of persons were
detained and interrogated, but no formal arrests were made.
The raid was conducted by the office of California Attorney
General Dan Lungren, possibly with Federal help, with
officers carrying machine guns and wearing body armor,
according to CBC. San Francisco police and the district
attorney were not involved, and apparently not informed.
Within hours of the raid about 200 people joined a protest rally and marched to the CBC office at Market and Van Ness. CBC founder Dennis Peron, in Canada at the time, addressed the gathering by telephone. At least three additional rallies have been set for Monday August 5. People were asked to talk to their families and friends and call Mayor Willie Brown and of the Board of Supervisors (see below).
Lungren's office said that it executed a search warrant "to gather evidence... of sales above and beyond medicinal use" -- and that it could be weeks before any decision is made on possible arrests. The CBC said that anyone entering the club and making a purchase must show their membership card and photo ID twice, that membership requires an original letter from a doctor indicating a diagnosis of AIDS, cancer, glaucoma, or multiple sclerosis, and that in case of doubt the club will call the physician directly.
The CBC sees politics, noting that Lungren is on Republican presidential candidate Bob Dole's "short list" of potential nominees for Vice President, and that this raid generated national publicity for him in the week the Republicans must select Dole's running mate.
The CBC asked people to focus for the next 90 days on passing Proposition 215, the Compassionate Use Act of 1996. The group has a four-part strategy including registering new voters (it is aiming for half a million, and has registered well over 45,000 so far), educating the public that sick and dying people are being incarcerated, raising money to spend in October, and signing up doctors, nurses, patients, clergy, public figures, and other endorsers of the Compassionate Use Act of '96. This act would allow certified patients to purchase or grow marijuana for medicinal use, and would allow doctors to prescribe marijuana. Polls have shown strong support for medical marijuana even in notoriously conservative Orange County, but Californians for Compassionate Use is avoiding overconfidence.
The president of the Harvey Milk Lesbian/Gay/Bisexual Democratic Club, Jeff Sheehy, told the protesters at the CBC, "The most alarming thing about what happened today is that thousands of names of people with HIV have been confiscated by the State government, in violation of law that requires that those names be kept confidential. Our next fight is to get our names back. Those people are at risk, they're sick, and they need their medicine. We cannot let the State hold them hostage. We must demand our names back."
"This is only the beginning of something that's going to change the world, it's going to be big," said John Etwhistle of the CBC. "We thought it was going to be the Initiative, but it could end up being this case."
How to HelpSan Franciscans should call Mayor Willie Brown, (415) 554- 6141, and the Board of Supervisors, (415) 554-5184. Ask for their continued support on the medical marijuana issue.
To learn what else you can do, contact Californians for Compassionate Use, (415) 621-3986, fax (415) 521-0604, or visit their World Wide Web site, http://www.marijuana.org .