Subject: AIDS Treatment News #105 Date: Jun 27 1990 (1055 lines) &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& J O H N J A M E S writes on A I D S &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& copyright 1990 by John S. James; permission granted for non-commercial use. AIDS TREATMENT NEWS Issue #105, June 15, 1990 Contents: [items are separated by "*****" for this display] Conflict of Interest: Cloud Over AIDS Research? Call for Action: Community Consensus on Treatments Needing Development Sixth International Conference News News Notes: SEARCH ALLIANCE; NIAID Answers ACT UP; Journalism Awards Announcements: AIDS Benefits Handbook; San Francisco Trials Directory; GM-CSF Corrections ***** Conflict of Interest: Cloud Over AIDS Research? by John S. James In December 1989 the U. S. Department of Health and Human Services (HHS) rejected proposed guidelines intended to control conflict of interest in research supported by the U. S. National Institutes of Health (NIH). These guidelines would have greatly restricted Federally-supported biomedical researchers from having consulting arrangements with, or owning stock in, companies affected by their research. Many scientists strongly objected to the proposed restrictions, on the grounds that they would not allow the best scientists to work for both industry and government, and also because, they believed, the paperwork would be unduly burdensome. Others are concerned that the present system means that anything is legal, as there are no rules or standards governing conflict of interest by academic biomedical researchers supported by public money. For example, nobody would allow Federal employees to have undisclosed consulting contracts with companies affected by their official decisions. But in biomedical research, the real funding decisions (and often regulatory decisions) are increasingly made by outside experts (not Federal employees), in peer-review or other advisory committees. These non-employees can legally have consulting arrangements with anyone; they might or might not disqualify themselves in cases of conflict. So just changing how the decision-makers are paid, from Federal salaries to Federal contracts or grants, summarily discards the entire structure of conflict-of-interest regulation which has developed over decades, potentially threatening the integrity of the public decision-making process. In recent months there has been public suspicion of conflict-of-interest abuses, but few cited examples. The lack of confidence may result because the public has no way to know how serious a problem exists. This article outlines some of the prevalent fears and issues, not only in the financial arrangements normally considered "conflict of interest," but also in other cases in which the public pays for research but is ill served by decisions which place private over public interests. This article will include these broader issues, suggest questions to raise, and show why conflict of interest may be a critical obstacle to AIDS treatment development. Does Conflict of Interest Impede New Drugs? In testimony against the NIH conflict-of-interest guidelines, it was revealed that almost all the principal investigators in the ACTG (AIDS Clinical Trials Group) system have industrial consulting arrangements -- usually not disclosed to the public. Could these private arrangements result in bias against competing drugs when decisions are made on how to spend public money? The current issue of Boston Magazine, June 1990, has a long article on the background of Peptide T, and on the widespread suspicions that this potential treatment may have been dismissed unfairly because of fears that it could be a competitor to CD4 ("Peptide T and the Research Establishment," by Seth Rolbein). Others are suspicious about exactly what pharmaceutical companies are buying through these consulting arrangements. Many view the ACTG system as unproductive, with little useful information to show for hundreds of millions of dollars and several years of time invested. Pharmaceutical companies have often been frustrated and unhappy in working with the ACTG. Why then are they paying money to almost all of its principal investigators? Are they buying scientific productivity -- or influence over the flow of hundreds of millions of dollars of public money for AIDS clinical research? Perhaps the worst suspicions concern the lack of promising new treatments in clinical trials. Dozens, probably hundreds of promising chemicals have emerged from laboratories, but then almost all of them are abandoned; they do not move on to human trials. The worst drug logjam occurs early in development, at the stage of finishing preclinical work (such as the manufacturing quality assurance and the animal toxicity testing required by the FDA), in order to obtain the "IND" (Investigational New Drug) approval which is required before human testing can begin. The public does not notice this early drugjam, because the potential drugs in question are not yet real treatment options for people; also, information about preclinical development is proprietary and usually secret -- even the existence of a Federally-granted IND is not public information. Only years later does the public realize that the pipeline is largely empty, and few or no new treatments are becoming available. Could conflict of interest be the major cause of this central problem? The possible scenario -- not proven, only a suspicion at this time -- is that products early in development do not have the commercial momentum to pay the consulting fees necessary to be taken seriously by the AIDS research establishment. Could new possibilities be abandoned in favor of still more research on products like AZT, which are already on the market and therefore have the cash flow necessary to buy their way into the professional community? Many researchers, not surprisingly, have a very different view. They see their decisions as reflecting only the higher worlds of Science and Medicine, independent of such mundane matters as who pays the bill. Many are angry that anyone would think otherwise. They feel that such ideas challenge their integrity. One middle-ground position acknowledges that the large majority of researchers do remain independent of undue financial influence. It sees the problem instead in the narrow outlook which develops when people interact constantly with small groups of others who have the same viewpoints they do. Activists as well as researchers face this problem. But research costs much more than activism, so research cliques will seldom come into being except where there is money to support them. Money builds influence which brings in more money, leading to increasing concentrations of power in small and narrow groups, whose members quite correctly do not see themselves as being bought off, but as doing what they sincerely believe is right. Yet new treatments may be abandoned just the same, shut out as the groups which have coalesced around cash- rich commercial products compete for increasingly scarce Federal funds. The issue is not personal integrity, but the fact that the system does not work. Publication Embargos: A Different Conflict of Interest An issue usually considered separately from conflict of interest, because it does not directly involve money, is the common requirement that scientists conceal their work for months or years, from the public and often from scientific colleagues as well, in order to enhance the news value of journals or conferences. (The common news embargos which last only a few days, and are intended to allow orderly release of information which does not depend on whose mail is delivered first, present much less serious problems.) A recent article in The New York Times (May 22, 1990) reported one particularly serious example. The Times interviewed the former head of the U. S. National Cancer Institute concerning a large 1981 study which found that breast cancer in women could often be treated as well by removing a small lump as by removing the entire breast. "But the data were kept secret for 14 months while the paper was considered at The New England Journal of Medicine. During that time...some 100,000 American women were found to have breast cancer and were unaware that complete removal of the breast was unnecessary." The article did not estimate how many thousands of women had their breasts removed needlessly so that the researchers could publish in the most prestigious journal, and so that the Journal could have a scoop to further its business interests. Recently The New England Journal of Medicine and some other major journals have allowed early release of information with urgent public-health importance; The New York Times article included several examples. But areas like AIDS, complex emergencies without a single solution, present a more fundamental problem. Scientists build on each other's work; long pre- publication secrecy, even when not immediately life- threatening, slows the entire research process and delays the ultimate development of better treatments, costing lives eventually although not immediately. A recent book (Covering the Plague: AIDS and the American Media, by James Kinsella, Rutgers University Press, 1989) traces the history of pre-publication secrecy to the large increase in the number of scientists, beginning in the early 1970s, which allowed The New England Journal of Medicine to be very selective. "The surplus of manuscripts at the Journal allowed then-editor Dr. Franz Inglefinger to demand an 'exclusive' on every article that appeared in the Journal. The publication would run no manuscript that had been reported in detail anywhere else, including the popular press." Since there was a backlog of articles, scientific results were regularly withheld from the public, and from many scientific colleagues, for months. Hundreds of other journals followed and imposed the notorious "Inglefinger rule," but others (such as the Lancet, according to Kinsella) have not. It might be hoped that the Sixth International Conference on AIDS would take the lead against this destructive system, but it has failed to do so. Authors had to certify that their abstract "has not been published elsewhere or submitted for presentation at another national or international meeting." Technically this wording does not require pre-publication secrecy -- authors could present the material elsewhere after they signed the certification, which, with the abstracts themselves, was due in January. But in fact researchers have been tight-lipped about what they plan to present, maintaining the five-month "shadow" which each annual Conference casts before it -- the time each year when researchers are most reluctant to talk about their latest results. (The Sixth International Conference also threatened journalists with loss of credentials, and therefore expulsion from the meeting, if they did not honor a press embargo on the Advance Program by withholding "all information related to program content...for release only after presentation at the Conference.") Early public discussion of results to be presented would improve the Conference, by letting participants orient themselves before the whirlwind of events begins. The value of this meeting is not in the release of scoops -- let us hope that nothing truly important was concealed for five months to be presented in San Francisco -- but rather in status reports from leading researchers. Good business meetings provide information in advance, so that participants can have in-depth discussions instead of spending their time figuring out what is going on. Unfortunately, next year's Seventh International Conference on AIDS, June 16-21, 1991, in Florence, Italy, already has similar restrictions on its form for submission of abstracts. What Can Be Done? The initial attempt to control conflict of interest in NIH- funded research (mentioned above) has been rejected, after vehement opposition by many scientists. Efforts are now continuing to develop milder standards -- perhaps not forbidding certain practices but only requiring disclosure. According to an assistant in the office of Congressman Ted Weiss, Democrat from New York, who has long pushed NIH to develop such standards, nothing will be in place for at least a year. (Congressman Weiss' subcommittee will soon publish recommendations on what it believes should be done. It has few specific examples of conflict of interest, however, and none concerning AIDS research. Anyone with a documented case -- clear evidence of something, not just suspicion -- should call or write to Weiss' office.) Dr. Janet Newburgh, of the Institutional Liaison Office at NIH, told AIDS TREATMENT NEWS that development of proposed conflict of interest rules is proceeding in two parts. The faster track concerns commercial products, or items close to being commercial products. The slower track concerns invention development, ideas farther from commercialization. Unfortunately it seems clear that if we have a major problem, these NIH efforts will not solve it in the time frame needed. Nothing is likely to be done for over a year. And then if anything happens to restrain conflict of interest, and if it is successful, it will only gradually lead to improvement in government research priorities, which in turn will gradually lead to improvement in research and then to better treatments. This effort must be pursued, but we cannot hold our breath. Another approach that we can take now is to investigate the problems around conflict of interest, understand the situation better ourselves, and increase awareness within the professional community and the public. Better awareness, and the resulting informal pressures and influences, may bring effective change faster than formal regulation can. Activists and investigative reporters can make a critical contribution, by informing the public about the dimensions of the problem. Still another approach, suggested in the article below, is to continue to strengthen the ability of PWA, activist, and front- line physician organizations to work together to develop the community's own priorities for treatment research. Developing consensus on a few treatments which most deserve public help to shepherd them through the research system will also build the constituency to overcome the obstacles blocking their progress. ***** Call for Action: Community Consensus on Treatments Needing Development by John S. James Recently a number of AIDS treatment stories have appeared in the press. Most of this news is good, although sometimes there is less to it than meets the eye. Yet critical problems remain. This article shows how community organizations can help to overcome the perennial problem of the lack of development of major new drugs. The bad news is what isn't happening. Most policy problems in AIDS stem from lack of national coordination, lack of anyone responsible for developing, implementing, and monitoring coherent national strategy. In treatment development, there is no public office able to investigate any potential treatment (regardless of who owns it, or its stage of development), select those few which are most critical for the public interest and most urgently need attention, identify obstacles to their speedy development, and place those obstacles on the national agenda. As a result, the most important drugs today are failing to move into the clinical-trials pipeline. Unless we act now to invest in the future, little will come out over the next two to three years except ddI and ddC -- important new options, yes, but not enough by themselves to prevent many deaths. Ideally, some official body with well-respected medical and scientific leadership and staff would have done this job for the last ten years. It would take time, however, to bring any such group into being, and it would be difficult to assure its independence from the problems of the past. But there is an alternative which could be started immediately, and would in some ways be better than an official body. By working with the organizations and the networking which already exist, we can develop community consensus -- among PWA groups, advocacy groups, front-line physicians, research organizations, and others -- on which potential treatments are most important, and what must be done to move them forward. While such an effort would not have the automatic authority of a government body, it could in practice have even more influence. Official reports often collect dust on library shelves, because they have no constituency. But the process of building a consensus also builds a constituency for carrying it out. Is Anyone Doing This Already? Several existing or proposed bodies are concerned with setting AIDS treatment research priorities: * The ACDDC (AIDS Clinical Drug Development Committee). This committee within the ACTG (AIDS Clinical Trials Group) meets four times a year to divide drugs into four priorities: high, medium low, and not recommended for clinical trials at this time. The meetings are closed, and we do not know the committee's operation in detail, but there have long been serious concerns about drug priorities within the ACTG. About two years ago, a physician trying to get a drug into the ACTG system said that the drugs were taken up by the committee in no particular order. Usually at least one of the drugs proposed would provoke argument among the competitive scientists, and once the time for the meeting had elapsed, all the other proposals behind it in the queue were put off for the next meeting, months away. While we have never seen an ACDDC meeting, this scenario rings true, in that a committee charged with setting priorities could hardly pre-prioritize without raising questions about the need for the committee's existence. We question whether a committee meeting four times a year, with busy members presumably supplied with stacks of paper to inform them about the decisions they are to make, is the best way to set priorities for treatment research. In almost every other aspect of human affairs, a new idea needs a "champion" to push it, or it will not progress. Without an ongoing relationship with the advocate, committees almost always reject important new ideas, because of political dynamics. It is easy to score points by criticizing a novel proposal, but dangerous to become identified with something unfamiliar. For this article, we picked the three drugs that we would most recommend for urgent attention: hypericin, TIBO derivatives, and HPMPC (see below). The most recent list of ACDDC priorities which we have obtained -- through the December 1989 meeting -- included none of these three in any category, suggesting that none had been considered by that time; we have heard that one or more have been given high priority since. (For TIBO derivatives, the first paper was not published until February 1, 1990; however, study results usually circulate in the scientific community for months before publication.) The ACTG is built on investigator-initiated research. Almost all of its principal investigators have consulting arrangements with pharmaceutical companies (usually not disclosed), in addition to their Federal grants or contracts. It seems unlikely that a drug would come to the ACTG (and therefore to the ACDDC within it), unless it has a sponsoring pharmaceutical company, and that company was ready to move the drug and had decided to seek Federal help in doing so. The ACDDC, as an advisory body of the ACTG, presumably considers only drugs which the ACTG could test. It does not seek out new drugs (even if they are not yet ready for clinical trials, or are not commercially viable, and/or if their owner is busy elsewhere or does not want to bother with an AIDS drug) and then mobilize whatever resources are needed, including public pressure, to get them tested quickly. Yet this is what needs to be done. * The ARAC (AIDS Research Advisory Committee). This group, to include people with AIDS, is part of the proposed "parallel track" system published last month in the Federal Register (see article on parallel track in AIDS TREATMENT NEWS #104, June 1). If parallel track is accepted, after the 60-day period for public comments, then the ARAC will be a major advance; for the first time there will be an official body able to take an integrated approach in deciding which drugs are important. (Pharmaceutical companies cannot do so, because each will only promote its own products; and the FDA usually does not compare different drugs, but says "yes" or "no" to each drug separately, based on paperwork placed in front of it.) But the ARAC has not yet met. And even if parallel track is accepted and the system works perfectly, it will focus primarily on drugs well along in clinical trials and ready for parallel- track access. Yet today the biggest bottleneck seems to be the business negotiations which occur as a promising compound finishes its pre-clinical development and moves into human trials for the first time. At that stage, an organization focused only on parallel track can do nothing. * HIV/AIDS Biomedical Research Priorities document. Over 45 major AIDS and health organizations have endorsed 15 recommendations to the U. S. National Institutes of Health on AIDS/HIV biomedical research priorities (see article in AIDS TREATMENT NEWS #104, June 1). This important effort embodies the kind of consensus building which is needed. We are suggesting a companion effort, to develop consensus on specific treatments which need public and professional attention to facilitate their progress through the research system. The May 17 document does not mention any treatments. Both kinds of efforts are needed. * New ACT UP list of potential treatments. ACT UP/New York is preparing a list of drugs and treatment approaches which the ACTG has not researched. The pre-publication draft we have seen lists dozens of drugs and classes of drugs, mostly high-tech approaches to treatment, some of which we had not heard of. The research to create this list is exactly the kind of effort needed to develop community consensus on a research agenda. The information comes from scientist, physicians, and others with specialized knowledge. The activists make sure that priorities reflect the interests of persons with AIDS or HIV, above those of companies with products to sell, or of professionals with careers to advance. Even harder than preparing the initial list will be setting priorities. We believe that this effort should focus on finding a short list, perhaps five to ten treatments most needing public and research attention -- not on trying to rate or categorize every treatment suggested. Treatment Examples Show Unmet Needs Since U. S. media coverage of AIDS research usually consists of rewriting official press releases, most of the public believes that the slow pace of treatment development primarily reflects the scientific difficulty of the problem, and appropriate medical caution. In fact, business and administrative problems cause most of the delays in treatment development. Glaring past examples include aerosol pentamidine, used to prevent pneumocystis, and fluconazole, an important new antifungal. These cases are not unusual; most drugs suffer similar delays, only there is less publicity about what happened. (A few drugs have been developed rapidly -- for example, the initial approval of AZT, and the progress of ddI since last summer.) In the cases of aerosol pentamidine and fluconazole, the delays occurred after considerable human experience with the drugs in question was already available. But the biggest problem today seems to be the obstacles to taking a promising compound from pre-clinical laboratory and animal studies into the first human trials and then into early efficacy studies. The three drugs below were not picked as examples of delays -- indeed they are progressing faster than most. They do show how much could be gained if there were a public voice to insist that the most critical potential treatments be expedited, not left to usual procedures. * Hypericin. This chemical, in human use in Europe as an antidepressant and long used in herbal medicine, has been extensively covered in AIDS TREATMENT NEWS starting August 26, 1988 (issue #63). It works very well against HIV in the test tube, and against other retroviruses in animals. A community- based study in San Francisco, using available herbal extracts, showed sustained T-helper improvements in those who started with high T-helper counts (the average baseline value was over 500); these patients were not using any other antiviral. But with the very small hypericin doses in the herbal extracts now available, most of those with low T-helper counts (mean under 200) continued to show T-helper declines. P-24 levels did decrease or become negative in four of six patients, but they were also using AZT, which might have caused the improvement. (For more information about this study, see AIDS TREATMENT NEWS #96, February 2, 1990.) Another study of the herbal extract found no significant improvement in T-helper counts or p24 levels, whether or not the extract was combined with AZT (see AIDS/HIV Experimental Treatment Directory -- published by AmFAR -- December 1989, page 35). However, the herbal preparations contain very low concentrations of hypericin; animal studies suggest that larger amounts of the chemical are needed. Animals can tolerate large doses of pure hypericin, suggesting that people might be able to do so (long-term human tolerance of low doses is already established through the history of use of the herbal extracts). And hypericin works very differently than AZT; it is not a nucleoside analog (like AZT, ddI, and ddC). Therefore if it does work in people as an anti-HIV treatment, it could open a new world of therapeutic options, used either alone or in combination with AZT or other drugs. All this, except for the community studies of the herbal extract, was known two years ago, and was published in a leading journal (Proceedings of the National Academy of Sciences, USA, July 1988). But because of the lack of effective national mobilization for AIDS treatment development, this very promising compound had to go through the usual procedures: finding investors, chemistry research to improve methods for synthesis, creation of a large enough batch so that the same supply could be tested in animals before begin given to humans, and toxicity tests in animals. According to the February 19 issue of FDC Reports (The Pink Sheet), hypericin was being tested in monkeys at that time (February 1990), and if all went well, could begin human efficacy testing in late 1990, with filing for an NDA (permission from the FDA to market the drug) in early 1993, "if the drug shows 'dramatic' efficacy and lack of toxicity in humans." (And if no ordinary problems develop in business, administration, personnel turnover, etc.) By the standards of business as usual, four and a half years from the first published laboratory report of antiviral activity to application for the NDA is fast. But if the nation would mobilize to save lives, it could have been done many times faster, without undue risk. Once the drug looked promising, enough could be extracted from plants, or synthesized by the already-known procedures, for animal tests for acute toxicity, then small, efficient human tests of safe doses for short-term evidence of efficacy (p24 decrease, T-helper improvement, weight gain, decline of AIDS-related symptoms, etc.) If the drug showed clear signs of working, then an all-out effort would be justified to solve any supply problems, get the treatment to those who had no other alternative, continue collecting data on long-term toxicity, begin combination trials with AZT, and begin trials to establish conclusive proof of efficacy. Note that despite its speed, this approach to developing key drugs would cost little until a drug was all but known to work, at which time money would be easy to raise. What we are suggesting here is not very different from what in fact was done with AZT, ddC, and ddI. The early phase I trials, in theory designed to test for toxicity and determine maximum tolerated dose, in fact also provided the efficacy information which motivated larger trials. But the early human testing of all three of these drugs depended on a single individual -- Samuel Broder, M. D., who has since been promoted to director of the National Cancer Institute (NCI). Since Broder now has other duties, new drugs are not following expeditiously from preclinical work into clinical trials. We suspect that the fundamental problem is that new drugs have not yet built (bought? ) a constituency within the AIDS research establishment. The lucky chance of the right individual in a strategic position (the NCI has more power than pharmaceutical companies to overcome Federal obstacles in early stages of clinical trials) temporarily masked the major weakness and bottleneck in the whole U. S. drug- development process -- the lack of movement of promising compounds through completion of preclinical development and into trials. With Broder no longer in position, this stage in the AIDS drug- development process has largely shut down. But the public has not noticed, because the problem is at the beginning of the clinical-trials pipeline, so its practical effects are delayed. Only a year or two later does the public become aware that the new drugs are not there. When government experts say that there are no new antivirals ready to test, most people accept their statements on faith, because few have been prepared to challenge them. But the AIDS community can do its own investigation, by networking among organizations and individuals with many different talents and skills. With our own consensus about which treatments most urgently need public attention, we can discuss options like hypericin when experts say that no new drugs are ready. Sometimes the experts may be right. And sometimes they may be protecting themselves, as bureaucrats often do, by providing standard answers suggesting that whatever is already happening is all that could or should be done. * TIBO derivatives. This class of drugs was developed in Belgium, by researchers using a process of intelligent trial and error to create new anti-HIV drugs. The first report, published in Nature on February 1 of this year, especially concerned one compound called R82150. Laboratory tests showed that the drug was effective against HIV in extremely small concentrations -- 31,000 times less than the dose which harmed cells (compared to 6,200 for AZT). Then in another test, dogs were given in a single dose a thousand times the amount expected to be effective, with no harm. Finally, six healthy people volunteered to take the drug, and no toxicity was found. On May 16 the U. S. National Institute of Allergy and Infections Diseases (NIAID) distributed a reply to ACT UP/New York, which had strongly criticized NIAID's ACTG research system. ACT UP had urged that TIBO derivatives be tested, but NIAID replied that they were not yet ready for clinical trials. We find it hard to understand how a drug which appears to have a huge margin of safety, and which has already been given to humans, is not ready for clinical trials -- especially when there is so urgent a need for new anti-HIV drugs. We suspect that this drug "is not yet ready for clinical trials" because the business and administrative arrangements are not ready. A small clinical trial has in fact started in Europe. If the United States, with more AIDS cases and also more research resources than any other country, is behind in the development of some of the most important treatments, no one would be surprised. By building a community consensus on the most important priorities for development, we can focus on the critical drugs and make sure that all necessary resources are available for their development. Without community input, it will take many years for drugs like R82150 to become available. * HPMPC. This chemical, now being developed by Bristol- Myers, acts against CMV and herpes (not against HIV). HPMPC was discovered in Belgium by a team which included one of the researchers who discovered the TIBO derivatives. Technical articles about HPMPC have appeared in journals for several years. Much of the research on HPMPC has tested it for herpes, but in AIDS the most important use may be for treating CMV (cytomegalovirus), which can cause blindness, or other serious infections. Two drugs, ganciclovir and foscarnet, are already used for CMV, but both have drawbacks. In the laboratory HPMPC is active against human CMV in very small concentrations, .04 micrograms per milliliter. Yet a toxicity study found that mice could tolerate up to 200 milligrams per kilogram per day. One animal study (abstract #751) was presented last September at ICAAC (Interscience Conference on Antimicrobial Agents and Chemotherapy), an annual conference on new antibiotics. Animals cannot be infected with human CMV, so a related virus, murine cytomegalovirus, was used in mice instead; experience with foscarnet had indicated that this animal model might help predict which drugs would be useful for human CMV infection. The study compared ganciclovir, the only CMV drug approved in the United States, with HPMPC. Ganciclovir reduced viral titers in blood and organs by 10 to 100 times, during the 21 days of the test. HPMPC reduced the titers by 100,000 to 1,000,000 times (to undetectable levels) in four to six days. Another study presented at the same conference (abstract #739) reported that laboratory tests with cell cultures suggested that infrequent dosing might be effective. In all the animal studies we have seen, the drug has been administered by injection (or applied topically to herpes lesions); one paper found some efficacy with oral administration of a related drug (HPMPA), but large doses were necessary, suggesting that oral availability might be poor. Supply problems are unlikely for HPMPC, as at least three papers have published methods for making it. We do not know the current status of HPMPC at Bristol-Myers; pharmaceutical companies seldom release details about their preclinical drug development. Apparently the next step is for Bristol-Myers to complete preclinical tests, obtain an IND (permission for human testing) from the FDA, and begin clinical trials. We do not know whether or not development is moving rapidly. There does seem to be considerable enthusiasm for this drug among the few medical and research professionals who are familiar with it. On the other hand, there may be a limited market -- for CMV because the infection does not need treatment except for persons with immune deficiencies, and for herpes because there is already a well-established treatment, acyclovir. Under the U. S. system of drug development, companies which have exclusive rights to even vitally important drugs have no obligation to do anything with them; the public interest has no place in the decision. The FDA can bring pressure informally if it wants to, because companies must stay on its good side. But the law requires the FDA to keep much of its information secret, so usually the public does not know what is happening until there are clinical trials, which are hard to conceal. Often it is difficult to know whether a drug is being actively and effectively developed, or whether there are unnecessary obstacles. Fortunately, some companies have done much more than they had to in support of the public interest. Perhaps the remaining problems will be ameliorated by the growing belief that the lives of persons with AIDS are worth saving. * Other treatments. While preparing this article we made a list of treatments which might deserve high-priority, expedited development. We made no attempt to be complete; for example, we omitted some important drugs like ddI and ddC, which are already in high-profile development. Also, we did not include non-drug treatments such as nutrition or exercise in this particular list. The treatments are in alphabetical order. This list should show that there are many treatments which need to be investigated, and it may suggest leads that others will want to pursue: AS101 (for HIV) AzdU (HIV) Azithromycin (MAI; toxoplasmosis) ddC or ddI in combination with AZT (HIV) Compound Q (HIV) d4T (HIV) Diclazuril (cryptosporidiosis) G-CSF (a colony stimulating factor) Glycyrrhizin (HIV) HIVIG, or other passive immunotherapy (HIV) HPMPC (CMV; herpes) Hypericin (HIV) Imuthiol (immune modulator) Itraconazole (many fungal infections) KS secret treatment Levamisole (immune modulator) Milk antibodies (cryptosporidiosis) NAC (HIV, indirectly) Oxophenarsine (HIV -- see 1989 Montreal conference abstract #M. C. P. 133) Peptide T (treatment for neurological effects of HIV) Sulfolipids (HIV) TIBO Derivatives (HIV) Vaccines: Salk, HGP-30, some others (HIV) The Next Step The way to develop community consensus on which treatments need a public voice to assist and expedite their development is through expanding discussions among PWA, advocacy, physician, and other organizations. No one needs to play gatekeeper to designate who is or is not part of this process; treatment investigation is labor intensive, and it is clear who is doing the work. People usually start by investigating treatments which interest them, and bringing what they find to others. Leadership emerges spontaneously, without formal machinery. Such discussions are already going on; for example, ACT UP groups in several cities (including New York, San Francisco, Boston, Providence, and Washington, DC) now have treatment committees. PWA coalitions have long been interested in treatments. Front-line physicians and community-based research organizations are primary sources of information -- as well as friendly researchers in academia, government, or industry. This work is not new. More people need to become involved, however, and let each other know what they are doing. Also, we should discuss specific goals for this effort -- for example, do we agree that we should reach consensus on a few high-priority treatments, and then focus on expediting their development? Many people are ready to contribute money or other resources to research, but are stopped by the confusing jumble of so many voices advocating so many different approaches and directions. Potential investors or contributors cannot find information they can trust, because those close enough to the research to evaluate it usually have personal interests in the decisions or personal loyalties to those who do. A public process of dialog and consensus, centered in organizations interested in treatment of patients instead of commercial or professional promotion, could provide a clear context in treatment research and open the door for those ready to apply their talents and energies. ***** Sixth International Conference News Boycott Update * At this time over 130 AIDS and health organizations are boycotting or withdrawing from the Sixth International Conference on AIDS in protest of U. S. visa and immigration policies, according to a list released June 14 by the NAMES Project in San Francisco. * The Bay Area Physicians for Human Rights, a San Francisco gay physicians' organization which will attend the Conference, has suggested wearing red armbands at the Conference in solidarity with those boycotting. * The second International NGO (Non-Governmental Organization) AIDS conference, originally scheduled for San Francisco during the three days before the Sixth International Conference but called off because of the travel restrictions on persons who are HIV positive, has now been rescheduled for Paris, November 1-4. Its co-sponsors are the National Minority AIDS Council in Washington, DC, and the Comite France SIDA in Paris. For more information, call Chris Castle, National Minority AIDS Council, 202/544-1076. * Harvard University has announced that it will not co- sponsor the 1992 International AIDS Conference in Boston if U. S. policy continues to make it difficult for HIV-positive persons to attend. It is possible that the 1992 Conference could be cancelled, as two years may not be enough time to reserve space and make necessary arrangements elsewhere. Rejected Abstracts: Progress in Sight On April 25 the Sixth International Conference announced that 50 percent of the 4,900 abstracts submitted to the conference had been rejected -- compared to almost no abstracts rejected last year at Montreal. The high rate of rejection raised concern because: (1) no one can be sure what will turn out to be important in AIDS; (2) it is hard to judge short abstracts because so little information is available, leading to summary judgments based on who is known to the reviewer, or on superficial "gotcha" criteria; and (3) there was no way for the public to ever see the rejected abstracts. Today progress is being made in addressing these concerns. About 800 more abstracts have been accepted, leaving 1,600 still rejected. While arrangements are not final, it is likely that the Conference will be willing to inform the authors of the rejected abstracts that another organization -- probably Project Inform in San Francisco -- is willing to publish them. Publication will probably consist of delivering one 8.5 by 11 inch sheet (21.5 by 28 cm) for each abstract to a photocopy shop which will fulfill orders as received; a similar system was used two years ago to make copies of the Stockholm Conference abstracts available. ***** News Notes SEARCH ALLIANCE: New Los Angeles Research Organization SEARCH ALLIANCE, a new organization with major medical and community support to conduct community-based trials, announced its existence on June 14. It already has dozens of people involved in its medical review board, institutional review board (IRB), community advisory board, board of directors, and project directors, and had two studies underway before the first public announcement. The studies are trials of oral interferon, and of nimodipine (Nimotop), a prescription drug which laboratory tests suggest might reduce AIDS-related dementia (see AIDS TREATMENT NEWS #101, April 20, 1990). In both cases, SEARCH ALLIANCE is the first research group in the U. S. to study these AIDS treatments. "We cut through red tape and did these studies now -- while everyone else was just thinking about them; we've demonstrated what distinguishes SEARCH ALLIANCE from the other AIDS researchers," according to Board president Paul Rothman, D. O. "Because SEARCH studies bypass the traditional bureaucracy, they cost only thousands -- not millions, and take only months -- not years." SEARCH ALLIANCE, a nonprofit organization, is raising money primarily from individual and community donations, rather than governments and corporations. For more information, including literature about the organization and its studies in English or Spanish, contact SEARCH ALLIANCE, 7461 Beverly Blvd., Suite 304, Los Angeles, CA 90036, 213/930-8820. Comment This writer co-founded the Community Research Alliance (now Project Inform Community Research Alliance -- PICRA) in San Francisco. Both PICRA and SEARCH ALLIANCE successfully avoided the danger of focusing on infrastructure and procedure instead of on research -- a trap which stems from indecision about what research to conduct. SEARCH ALLIANCE has also been exceptionally successful in quickly obtaining medical and financial support. It is well positioned to produce useful treatment information quickly. NIAID Answers ACT UP Charges In April ACT UP/New York published A Critique of the AIDS Clinical Trials Group (see note in AIDS TREATMENT NEWS #101, April 20, page 5). On May 16 Anthony Fauci, M. D., Director of the U. S. National Institute of Allergy and Infections Diseases, released a reply, including background on the AIDS Clinical Trials Group and replies to specific allegations. For a copy of the NIAID reply to ACT UP, call the AIDS Clinical Trials Information Service, 800/TRIALS-A. ***** AIDS TREATMENT NEWS Receives Journalism Awards by Tim Wilson John S. James, editor and publisher of AIDS TREATMENT NEWS, received two journalism awards last month in recognition of his coverage of AIDS treatments and related issues. * First Place Award (tie) from the 1990 Newsletter Association Journalism Awards in the category of Instructional Reporting (during 1989) for the series on hypericin. * First Place Award for Health Coverage (during 1989) from the Gay and Lesbian Press Association and the Media Fund for Human Rights. His work with AIDS TREATMENT NEWS had previously received a 1989 Civic Achievement Award from the Bay Area's Gay and Lesbian Alliance, a 1988 Outstanding Journalist from San Francisco's Cable Car Awards, and a 1988 Community Service Award from the Bay Area Physicians for Human Rights. ***** Announcements National AIDS Benefits Handbook The AIDS Benefits Handbook, subtitled "Everything You Need to Know to Get Social Security, Welfare, Medicaid, Medicare, Food Stamps, Housing, Drugs, and Other Benefits," by Thomas P. McCormack (Yale University Press, 1990), tells how to qualify for medical and disability benefits throughout the United States. The first half of the 257-page paperback provides an easy-to- read introduction to the different programs, including how procedures differ in different states. The second half consists of appendices with addresses, phone numbers, tables of benefit amounts, government regulations, and forms. We asked a benefits expert at AIDS Benefits Counsellors in San Francisco to help us evaluate the book. She said that because they specialize in California, they could not judge the information for other states, but that everything they could evaluate was correct. We believe that this book will be especially useful in providing introduction and background on different benefits programs and how to meet their requirements. Persons with AIDS or HIV may want to read it before seeking local advice about the programs in their areas. San Francisco: New Clinical Trials Directory The Summer 1990 edition of the Directory of HIV Clinical Research in the Bay Area, compiled by the Community Consortium (formerly County Community Consortium) is now available. It lists several dozen AIDS-related clinical trials in or near San Francisco. For a copy of the directory, send your name and address to the Community Consortium, attn: Zach Weingart, 995 Potrero Ave., Bldg. 90, Ward 95, Room 514, San Francisco, CA 94110. San Francisco: GM-CSF Trial Recruiting A new trial of GM-CSF, a drug to treat low neutrophil levels sometimes caused by AZT or ganciclovir, is now recruiting at R. K. Davies, and at Children's Hospital, in San Francisco. Volunteers need an ANC (absolute neutrophil count) between 500 and 1500. They should be on AZT, or be willing to be rechallenged. Volunteers will usually be persons with AIDS or related conditions who believe that AZT is helping them and want to continue using it, but have difficulty tolerating the drug because of the low neutrophil levels, which can cause dangerous infections. The formal trial will last 90 days; then volunteers will begin a maintenance phase for a total time in the study of one year. The drug is injected once per day subcutaneously, starting with one microgram per kilogram of body weight, and going higher. When patients respond well to the drug, neutrophil counts can increase greatly in days. One disadvantage for the patient is that volunteers will be randomized to either begin the drug immediately, or wait 90 days in order to provide control-group information. Patients who develop an opportunistic infection can go on the drug immediately, however. This trial should not be confused with an earlier GM-CSF trial at Children's Hospital in San Francisco. The current trial has had difficulty in recruiting, because AZT is used in lower doses today, so few people have neutrophil problems. Also, ddI provides another option to people who have depressed neutrophil counts on AZT, as ddI does not cause this toxicity. The sponsor, Schering Plough, has applied for marketing approval for GM-CSF. However, the drug will be approved for patients with low neutrophil counts due to cancer chemotherapy, so insurance companies may be able to avoid paying for it for low counts caused by AZT. Many physicians familiar with colony-stimulating factors (the class of drugs to which GM-CSF belongs) would prefer to use G- CSF, instead of GM-CSF, for treating persons with HIV. But G- CSF is not available. For more information about the GM-CSF trial at Davies Hospital, call Stephanie LaCarrubba, 415/565-6524. At Children's Hospital, call Jaime Geaga, 415/750-6529. ***** Corrections * AIDS TREATMENT NEWS #102 listed the hypericin herbal extract study by San Francisco's Community Research Alliance (now Project Inform Community Research Alliance) as one rejected by the Sixth International Conference on AIDS. In fact, this abstract was accepted by the Conference, for publication only. We had heard unofficially that it was rejected, and were unable to reach the principal investigator to confirm. * Issue #103 incorrectly reported the date on which Skip Harris died. The correct date is May 14. * The parallel track article in issue #104 gave incorrect page numbers of the proposal in the May 21 Federal Register. The correct pages are 20856-20860. * Some copies of #104 misspelled the name of the physician who used hyperthermia to treat an AIDS patient. The correct spelling is Kenneth Alonso, M. D. Back issues of AIDS Treatment News are available. For more information, send a self-addressed stamped envelope to: AIDS Treatment News, P. O. Box 411256, San Francisco, CA 94141, or call 415/255-0588. ***** STATEMENT OF PURPOSE AIDS TREATMENT NEWS reports on experimental and complementary treatments, especially those available now. It collects information from medical journals, and from interviews with scientists, physicians, and other health practitioners, and persons with AIDS or ARC. Long-term survivors have usually tried many different treatments, and found combinations which work for them. AIDS Treatment News does not recommend particular therapies, but seeks to increase the options available. We also examine the ethical and public-policy issues around AIDS treatment research and treatment access. [Obsolete subscription information has been removed. See the latest issues for up-to-date information. -- sysop] &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& End of display