Date: 27 May 1999 17:54:37 From: aidsnews@igc.org Subject: AIDS Treatment News #319 AIDS TREATMENT NEWS Issue #319, May 21, 1999 phone 800-TREAT-1-2, or 415-255-0588 CONTENTS: REMUNE Trial Will Stop; New Trials Planned Telephone Conference Call June 7 on HIV Treatment Updated HIV Treatment Guidelines Available Hundred Million Dollar Program for Public-Private AIDS Research and Outreach in Africa Medicaid Early Treatment Bill Now in Congress Medical Marijuana: AIDS-Related Information in the New Federal Report ***** REMUNE Trial Will Stop; New Trials Planned by John S. James The REMUNE(TM) HIV immunogen--the HIV treatment vaccine developed by the late Dr. Jonas Salk--is being tested in a large (2,500 volunteer) clinical-endpoint trial--meaning that this trial is looking for statistically significant differences in AIDS-related sickness or death between those who add REMUNE to their ongoing antiretroviral treatment, vs. those who add a placebo to their treatment. The REMUNE (or placebo) injections are given once every three months. The Immune Response Corporation is conducting this trial, with support from Agouron Pharmaceuticals. On May 17, the companies announced that the trial would end, after an analysis by the Data Safety Monitoring Board (DSMB), which found that differences in clinical endpoints were not observed and that the trial was unlikely to find statistically significant differences if it proceeded. There were far fewer clinical endpoints than expected when the trial was designed--apparently because of the use of modern antiretroviral therapies--illustrating the great difficulty of conducting clinical-endpoint trials of HIV therapies today. The companies did find a statistically significant difference in viral load at 48 and 96 weeks, in a randomly pre-selected cohort of 250 volunteers, only one tenth of the entire study--showing how much more efficiently a trial can be conducted with viral load, than with clinical endpoints. Viral load data may be analyzed for all the volunteers in the study; results may be presented as early as the ICAAC conference (Interscience Conference on Antimicrobial Agents and Chemotherapy, September 26-29, 1999, in San Francisco). The companies also announced that they are planning two new phase III trials using viral load, after an agreement with the FDA that such trials could be a basis for marketing approval. (The current surrogate-marker trial happened because when it was designed, the FDA had a policy of requiring clinical-endpoint proof for immune-based therapies- -a standard which today is usually prohibitive in the U.S. or other countries where modern HIV treatment is available.) Besides the low number of endpoints, this trial may also have been impacted by the fact that volunteers could use whatever treatments they wanted, monitor their viral loads, and change treatments whenever they wanted; the few endpoints which did exist might largely have represented random "noise." It is too early to make conclusions until the data have been collected and analyzed. As this article goes to press (a day after the May 17 announcement), the companies have not decided what arrangements will be made for persons in the trial who want to continue their REMUNE treatment (or switch to the active drug, if they have been receiving the placebo). Because the DSMB secretly unblinds the trial and says nothing about its findings unless it decides that the trial should be stopped, no one including the companies knew ahead of time what the result of its recent meeting would be. ***** Telephone Conference Call June 7 on HIV Treatment On a June 7 interactive telephone conference open to the public, three leading HIV physicians will review the 9th Annual Clinical Care Options for HIV Symposium, a June 3-6 meeting for frontline HIV physicians. Major topics at this meeting include new approaches to HIV therapy, resistance testing, lipodystrophy, metabolic abnormalities, vaccines, liver disorders, management of HIV disease, and treatment activism. You can participate in the teleconference and ask questions, or you can call in to hear a recording later. The teleconference is free, and the calls are toll-free in the U.S. The physicians reviewing the highlights of the Symposium are: * Donald Kotler, M.D., Professor of Medicine, Columbia University College of Physicians and Surgeons; * W. David Hardy, M.D., Associate Clinical Professor of Medicine, UCLA School of Medicine; * Stephen Becker, M.D., private practice in San Francisco, CA. The call will be moderated by Ronald Baker, Ph.D., Editor-in- Chief, HIVandHepatitis.com. It is supported by an unrestricted educational grant from Roche Laboratories. The teleconference will be Monday, June 7, 1999, 5 p.m. Pacific time (8 p.m. Eastern time). To participate in the live call, you must register in advance by calling 1-800-880- 5121 (first-names only); in order to ask questions during the call, you need to be using a touch-tone phone. Another way to question the panel is to email them in advance to HIVTxLive@aol.com. You can hear a replay of the call later by calling 1-888-207- 2647, pass code 1393; it may take up to 24 hours after the call for the replay to be set up. Also, a transcript will be available about two weeks after the call, at www.HIVTreatmentLive.com. No registration is necessary to hear the tape or obtain the transcript. Comment A major advantage of this teleconference (and others in the series) is that later, anyone in the U.S. can call without charge, 24 hours a day from any phone, to hear an expert discussion of current HIV treatment, and prospects for the future. ***** Updated HIV Treatment Guidelines Available by Tadd Tobias On May 5, newly updated government guidelines for the treatment of HIV disease were published in print and on the Web. Intended to help in making HIV treatment decisions, GUIDELINES FOR THE USE OF ANTIRETROVIRAL AGENTS IN HIV- INFECTED ADULTS AND ADOLESCENTS was developed by a panel of over 30 leading AIDS treatment researchers, expert clinicians, and community advocates. Although written primarily for healthcare professionals, the document can also help patients who are interested in participating in their own care, and advocates or case managers coordinating HIV care for others. Included in the new version are recommendations for the use of the newly approved nucleoside analog reverse transcriptase inhibitor abacavir (Ziagen(TM))--listed in one of the "alternative" regimens, not listed as "preferred." Also, the panel considered recently published data that has suggested a more rapid disease progression for women living with HIV than for men who have the same viral load. Because of limited information at this time, the panel decided to monitor the situation but not to recommend different treatment for women. The new Guidelines also discuss the use of hydroxyurea; however, no formal recommendation was made at this time. The official Web site for HIV treatment guidelines is the AIDS Treatment Information Service, www.hivatis.org; links or copies will also be available at many other sites. The official document is provided as a PDF file, but you do not need to use that format; at www.hivatis.org, click on "Need help downloading the Adult Guidelines document?" and you will be given the option to use "HTML version with links to tables and figures," which may be more convenient. You can also obtain a print copy of the Guidelines, by calling 800-448-0440. Also, you can hear a recording of a May 10 telephone conference with expert panelists discussing the guidelines and answering callers' questions. To listen to the recording (about 75 minutes long), call 888-207-2647, pass code 5101. Also, an edited transcript will soon be available at www.HIVTreatmentLive.com. ***** Hundred Million Dollar Program for Public-Private AIDS Research and Outreach in Africa by John S. James On May 6, Bristol-Myers Squibb Company announced that it had committed $100,000,000 over five years for programs to improve HIV/AIDS research and community outreach in five countries in southern Africa: South Africa, Botswana, Namibia, Lesotho, and Swaziland. This region has some of the highest rates of HIV infection, illness, and death in the world. Most of the decisions on spending the money will be made by scientific and community boards in the countries involved. Most of the research and treatment will target women and children with AIDS, to address the vulnerable status of women, who are often dependent on others for their economic support and medical care; the decision to focus on women and children "was made through a consultation process between Bristol-Myers Squibb and governments, National Association of People with AIDS/South Africa, medical schools, and NGOs (non-governmental organizations)," according to the company. A major priority will be improving care of hundreds of thousands of children whose parents have died from AIDS. But the community program is flexible enough to also help women develop small businesses for their economic support--and to fund HIV prevention as well as treatment and care--if the community board decides to do so. The research component "will facilitate development of model programs for the management of HIV/AIDS appropriate for the resource-limited settings of the five participating countries," according to Bristol-Myers. "The company expects this research to generate clinically relevant data that can be used by the African medical community and policy makers to develop a range of practical, cost-effective initiatives." It is expected that approximately 20,000 patients will receive HIV treatment as part of this research; and the volunteers will continue to receive drugs for as long as it is medically useful, according to Bristol-Myers. The medical program will also train 100 African physicians and other medical professionals in HIV/AIDS treatment, and bring up to 50 U.S. physicians to teach in Africa. This program (called Secure the Future(TM)) happened because of a conversation a few months ago between Bristol-Myers board chairman Charles A. Heimbold, Jr. and United Nations Secretary General Kofi Annan, who asked if the company could help in the African AIDS epidemic. AIDS is now the leading cause of death in Africa, and in Botswana it has already decreased the average life expectancy of the entire population by 14 years, from 61 to 47. More than 8 out of 10 AIDS deaths in the world are in sub-Saharan Africa, a larger region that includes the five countries targeted by this program. The major partners in this effort are UNAIDS (the Joint United Nations Programme on HIV/AIDS), Baylor College of Medicine and Texas Children's Hospital (both in Houston, Texas), Morehouse School of Medicine (a historically black medical school in Atlanta, Georgia), MEDUNSA (the Medical University of Southern Africa, based in Pretoria), the National School of Public Health at MEDUNSA, Harvard AIDS Institute, and the Medical Research Council of South Africa. In addition, there are independent monitors of the program, including IAPAC (the International Association of Physicians in AIDS Care), which has been a leader in addressing the issues of access to care in developing countries. Questions Raised While reaction to the announcement has been largely enthusiastic or at least positive, activists have raised concerns: * While the program provides free drug for research, these studies will involve a tiny minority of those who need treatment. There are no provisions for price reductions which could make the company's drugs affordable in the five target countries or elsewhere in Africa. More than 20,000,000 people in sub Saharan Africa have HIV, according to UNAIDS and the World Health Organization; if the Bristol-Myers program provides treatment to 20,000 as hoped, then in five years it will have treated less than one person out of a thousand on the continent. * The research-based pharmaceutical industry, of which Bristol-Myers is part, is currently suing the government of South Africa over intellectual-property rights, to prevent local companies from making low-cost generic copies of important drugs--some of which were developed largely at U.S. government expense. * A questioner at the May 6 press conference noted that the $100 million for five countries for five years is less than what the company paid to Mr. Heimbold himself last year (estimated at $146 million, according to THE NEW YORK TIMES, "Business Leaders' Giving Runs the Gamut," December 22, 1998). For additional perspective, the budget of UNAIDS (the Joint United Nations Programme on HIV/AIDS) for the entire world is $60 million. Comment We are encouraged by the Secure the Future program, and commend Bristol-Myers Squibb for it. The company did not have to do anything. And when it did act, it did many things right--total commitment by top management, sending officials (including a vice president in charge of the program) to Africa for fact-finding and negotiation, providing significant funding, and creating local scientific and community boards to decide how the money will be used. Public-private partnerships like this one will certainly be a necessary component of the response to AIDS, in Africa as elsewhere. Our main concern is how well this program can address the most critical long-term needs. U.S. conventional wisdom holds that lack of infrastructure is the central problem in developing countries, but in fact, many places in Africa have good to excellent health infrastructure. We suspect that the central problem is not really lack of infrastructure, but rather lack of money to participate in the hugely expensive and inefficient Western medical system--and the consequent exclusion from patented medical technology (which in the case of HIV disease means exclusion from every drug which has been proved effective). About 90% of people with HIV live in developing countries, and almost all of them would be completely excluded from proven treatment by price alone, no matter what infrastructure they have. There is no chance that most of the world will be able to pay what the market will bear in rich countries for lifesaving drugs, any time in the foreseeable future. So we support this program, and hope it can be a precedent for other constructive partnerships. At the same time, we will continue to raise the issue of prevailing rules, policies, and procedures which reflect the narrow interests of the rich and powerful alone, and abandon the great majority of the world's people in the face of a deadly epidemic. ***** Medicaid Early Treatment Bill Now in Congress Federal guidelines recommend early treatment for HIV for many patients. But Medicaid, which is the largest provider of HIV care today, will not provide treatment no matter how low one's income unless one is also disabled. Therefore many people have to wait until they become ill before they can obtain treatment--resulting in very poor medical care. Recently a bill was introduced in the House by Rep. Richard Gephardt and Rep. Nancy Pelosi, and in the Senate by Senator Robert Torricelli, to change the law so that low-income persons do not need to wait for advanced illness before receiving treatment. You can help by calling your Senators and your Representative, and asking them to support the bill (in the Senate it is S.902; in the House it is H.R.1591). Most importantly, get family members and friends throughout the country to do the same. The full text of this bill (less than two pages) is at http://thomas.loc.gov; search one of the bill numbers above (or search for the word 'HIV', to also check what else Congress is doing). The following press release was sent by Pelosi's office: * * * "Gephardt, Pelosi and Torricelli Introduce Legislation to Provide Early Treatment for HIV "April 28: House Democratic Leader Rep. Richard Gephardt (D- MO), Rep. Nancy Pelosi (D-CA), and Senator Robert Torricelli (D-NJ) today introduced the Early Treatment for HIV Act. The legislation, introduced in both Houses of Congress, would give states the option to expand their Medicaid programs to provide treatment for low-income, HIV-positive individuals who have not yet developed symptoms of AIDS. "Early treatment for HIV can extend and improve the lives of people with HIV disease," Pelosi said. "But, tragically, many people are going without this powerful and cost effective therapy. This legislation will extend access to the drug therapies and primary care that people with HIV should receive." "We must take this important step to address the Catch-22 faced by thousands of low-income HIV-positive Americans who don't have health insurance," Gephardt said. "Medicaid should be providing them with the therapies that help keep them healthy and live longer, more productive lives." "This bill is simple logic," Torricelli said. "It is a real step toward improving the quality of life for thousands of low-income people with HIV. This legislation eliminates a glaring flaw in the Medicaid program by allowing access to vital medical services." Fifty-nine other members of the House joined Gephardt and Pelosi as original cosponsors of the bill. Earlier this month, the Presidential Advisory Council on HIV/AIDS wrote the President urging his active support of the Early Treatment for HIV Act. HIV treatment guidelines issued by the federal Department of Health and Human Services recommend the use of antiviral therapy early in the course of HIV infection, before development of symptoms. Yet because Medicaid does not define individuals with early infection as disabled, many low-income individuals are unable to receive HIV-related drugs and health care through the program. "Powerful new drugs have given people with HIV renewed hope in fighting this disease," Pelosi said. "It is imperative that our government health care programs catch up with the recommendations of government health care experts." ***** Medical Marijuana: AIDS-Related Information in the New Federal Report by John S. James MARIJUANA AND MEDICINE: ASSESSING THE SCIENCE BASE, the major report of the prestigious Institute of Medicine (IOM) of the U.S. National Academy of Sciences, was released on March 17. The conclusions and recommendations were a major news story, but the details received less attention--partly, we suspect, because the version released on the Web is hard to use, while the printed book is expensive and may have been difficult to obtain immediately when the national media spotlight was on. The Institute found substantial consensus that certain cannabinoids (a class of chemicals found in marijuana) may have important symptom-management uses for some patients--but that marijuana smoke, like tobacco smoke, is harmful. The report found no reason to believe that medical use of marijuana would increase non-medical use, or that marijuana makes people more likely to use other drugs. The IOM made six recommendations: more research into the physiological effects of cannabinoids (a class of chemicals which includes THC, the main active ingredient of marijuana); development of rapid- onset, reliable, and safe delivery systems; studies of psychological effects such as anxiety reduction and sedation; studies of the health risk of smoking marijuana; clinical trials of marijuana use for medical purposes under certain conditions (including that efficacy data should be collected); and that use of smoked marijuana for patients with debilitating symptoms should meet certain conditions. Inhalers, Vaporizers One theme of the report which has become influential on both sides of the debate that the main danger of marijuana is from non-drug substances in the smoke--which studies have suggested may cause respiratory disease. While marijuana or its components can be taken orally, the oral route does not provide the rapid effect which is important both for relief, and to allow the patient to adjust the dose. There is now considerable interest in vaporizers for smokeless inhalation- -especially for medical use, as patients may be especially vulnerable to harm from the smoke. The report sees the future of marijuana as isolated chemicals (whether from the plant or synthetic), not crude plant materials. It recognizes that the development of these drugs and associated delivery systems (probably inhalers) will take years and may never happen due to the politics and economics of this issue, and that some patients need relief now. "If there is any future for marijuana as a medicine, it lies in its isolated components, the cannabinoids and their synthetic derivatives. Isolated cannabinoids will provide more reliable effects than crude plant mixtures. Therefore, the purpose of clinical trials of smoked marijuana would not be to develop marijuana as a licensed drug, but such trials could be a first step towards the development of rapid-onset, nonsmoked cannabinoid delivery systems." (from the executive summary). "It will likely be many years before a safe and effective cannabinoid delivery system, such as an inhaler, will be available for patients. In the meantime, there are patients with debilitating symptoms for whom smoked marijuana might provide relief. The use of smoked marijuana for those patients should weigh both the expected efficacy of marijuana and ethical issues in patient care, including providing information about the known and suspected risks of smoked marijuana use." (from the executive summary). Meanwhile--*not* noted in the IOM report--vaporizers are now readily available for smokeless inhalation of cannabinoids from the plant material. These devices heat marijuana to a controlled temperature, enough to release active ingredients, but not enough to cause combustion. Early results seem positive, but laboratory testing is needed to see how well these vaporizers are actually working. (Incidentally, "hash oil," a traditional purified extract of the marijuana plant, has generally been heated and inhaled, not burned--showing that heating can indeed deliver active ingredients of marijuana.) We are researching vaporizers now available and the current state of knowledge about them, and plan to publish a report in a future issue of AIDS TREATMENT NEWS. Note: The quoted text in this article is from the "Prepublication Copy, Uncorrected Proofs," the only version available when this article went to press. The changes to the final edition are expected to be minor, though the page numbers may be different. AIDS-Related Clinical Information Most of the AIDS-relevant information is in Chapter IV, "The Medical Value of Marijuana and Related Substances," pages 4.9 to 4.22, and the summary, pages 4.42 and 4.43 (see below for instructions on how to obtain this information either in print, or on the Web). Major sections are: * Nausea and vomiting, pages 4.9 to 4.17. While not about HIV in particular, this discussion is relevant because these are side effects of antiretroviral medications for many patients. The report notes that in recent years there has been much improvement in standard treatments for nausea and vomiting due to cancer chemotherapy--for example, serotonin receptor antagonists such as ondansetron or granisetron, sometimes used with dexamethasone, and given prior to chemotherapy. But control of delayed nausea and vomiting (occurring more than 24 hours after chemotherapy) is still a problem. (This writer does not know how feasible it is to use the new antiemetics-- treatments for nausea and vomiting--with antiretrovirals, which must be taken continuously.) It is clear that marijuana does relieve nausea and vomiting in some patients, although not as well, on the average, as the modern antiemetics. But these approved drugs cannot be used by all patients, or in all situations. "Until the development of rapid onset antiemetic drug delivery systems, there will likely remain a subpopulation of patients for whom standard antiemetic therapy is ineffective and who suffer from debilitating emesis. It is possible that the harmful effects of smoking marijuana for a limited period of time might be outweighed by the antiemetic benefits of marijuana, at least for patients for whom standard antiemetic therapy is ineffective and who suffer from debilitating emesis. Such patients should be evaluated on a case by case basis and treated under close medical supervision. (page 4.17) * Wasting syndrome and appetite stimulation, page 4.17-4.22 "The profile of cannabinoid drug effects suggests that they are promising for treating wasting syndrome in AIDS patients. Nausea, appetite loss, pain, and anxiety are all afflictions of wasting and all can be mitigated by marijuana. Although there are medications that are more effective than marijuana for these problems, they are not equally effective for all patients. Thus we recommend the development and clinical testing of a rapid onset (that is, within minutes) form of THC for such patients. We do not recommend smoking. The long- term harms from smoking make it a poor drug delivery system, particularly for patients with chronic illnesses. "Terminal patients raise different issues. For those patients, the medical harms of smoking are of little consequence. For terminal patients suffering debilitating pain or nausea and for whom all indicated medications have failed to provide relief, the medical benefits of smoked marijuana might outweigh the harms." (page 4.22) * From the chapter summary (pages 4.42 and 4.43): "Advances in cannabinoid science of the last 16 years have given rise to a wealth of new opportunities for the development of medically useful cannabinoid-based drugs. The accumulated data suggests a variety of indications, particularly for pain relief, antiemesis, and appetite stimulation. For patients, such as those with AIDS or undergoing chemotherapy, who suffer simultaneously from severe pain, nausea, and appetite loss, cannabinoid drugs might thus offer broad spectrum relief not found in any other single medication... "Although marijuana smoke delivers THC and other cannabinoids to the body, it also delivers harmful substances, including most of those found in tobacco smoke. In addition, plants contain a variable mixture of biologically active compounds and cannot be expected to provide a precisely defined drug effect. For those reasons, there is little future in smoked marijuana as a medically-approved medication. If there is any future in cannabinoid drugs, it lies with agents of more certain, not less certain composition. While clinical trials are the route to developing approved medications, they are also valuable for other reasons. For example, the personal medical use of smoked marijuana--regardless of whether or not it is approved--to treat certain symptoms is reason enough to advocate clinical trials to assess the degree to which the symptoms or course of the disease are affected..." "There are two caveats to following the traditional path of drug development for cannabinoids. The first is timing. Patients who are currently suffering from debilitating conditions unrelieved by legally available drugs, and who might find relief with smoked marijuana, will find little comfort in a promise of a better drug ten years from now. In terms of good medicine, marijuana should rarely be recommended unless all reasonable options had been eliminated. But what then? It is conceivable that medical and scientific opinion might find itself in conflict with drug regulations. This presents a policy issue that must weight-- at least temporarily--the needs of individual patients against broader social issues. Our assessment of the scientific data on the medical value of marijuana and its constituent cannabinoids is but one component of attaining that balance. "The second caveat is a practical one. Although most scientists who study cannabinoids would agree that the scientific pathways to cannabinoid drug development are clearly marked, there is no guarantee that the fruits of scientific research will be made available to the public. Cannabinoid-based drugs will only become available if either there is enough incentive for private enterprise to develop and market such drugs, or if there is sustained public investment in cannabinoid drug research and development. The perils along this pathway are discussed in chapter 5 [Development of Cannabinoid Drugs]. Although marijuana is an abused drug, the logical focus of research on the therapeutic value of cannabinoid-based drugs is the treatment of specific symptoms or diseases, not substance abuse. Thus, the most logical research sponsors would be the several institutes within the National Institutes of Health or organizations whose primary expertise lies in the relevant symptoms or diseases..." Anti-Inflammatory Potential The possible use of marijuana as an anti-inflammatory is a hot scientific topic, but much less is known than about the other potential medical uses. The following section appears in Chapter II, "Cannabinoids and Animal Physiology," page 4.42: "Anti-inflammatory Effects "As discussed above, cannabinoid drugs can modulate the production of cytokines, which are central to inflammatory processes in the body. In addition, several studies have shown directly that cannabinoids can be anti-inflammatory. For example, in rats with autoimmune encephalomyelitis (an experimental model used to study multiple sclerosis), cannabinoids were shown to attenuate the signs and the symptoms of central nervous system damage. (Some believe that nerve damage associated with multiple sclerosis is caused by an inflammatory reaction.) Likewise, the cannabinoid, HU-211, was shown to suppress brain inflammation that resulted from closed head injury or infectious meningitis in studies on rats. HU-211 is a synthetic cannabinoid that does not bind to cannabinoid receptors, and is not psychoactive; thus, without direct evidence, the effects of marijuana cannot be assumed to include those of HU-211. CT-3, another atypical cannabinoid, suppresses acute and chronic joint inflammation in animals. It is a nonpsychoactive, synthetic derivative of 11-THC-oic acid (a breakdown product of THC), and does not appear to bind to cannabinoid receptors. Cannabichromene, a cannabinoid found in marijuana, has also been reported to have anti-inflammatory properties. No mechanism of action for possible anti-inflammatory effects of cannabinoids has been identified and the effects of these atypical cannabinoids and effects of marijuana are not yet established. "It is interesting to note that two reports of cannabinoid- induced analgesia are based on the ability of the endogenous cannabinoids, anandamide and PEA, to reduce pain associated with local inflammation that was experimentally induced by subcutaneous injections of dilute formalin. Both THC and anandamide can increase serum levels of ACTH and corticosterone in animals. Those hormones are involved in regulating many responses in the body, including those of inflammation. The possible link between experimental cannabinoid-induced analgesia and reported anti-inflammatory effects of cannabinoids is important for potential therapeutic uses of cannabinoid drugs, but has not yet been established." For More Information The report can be purchased as a printed copy, or read online without charge, at www.nap.edu, the Web site of the National Academy Press. (Note: the final version should be available in early June for $39.95, with a 20% discount for ordering it through the Web; until then only a "prepublication copy, uncorrected proofs" is available). Unfortunately the official site's online copy is hard to use, because the pages are on the Web as images, as if each page were photographed with a digital camera--and the pages are numbered differently than in the printed copies. We do not know if the format will be improved when the final version becomes available. Thanks to private organizations and individuals, web copies which are much easier to use are currently available at two sites (at least): http://mall.turnpike.net/~jnr/marmed.htm, and www.fgi.net/~lstevens/iom/iompreface.htm. Each chapter has many references, sometimes hundreds, to scientific and medical articles. To find other Web sites on the topic, search for "medical marijuana" using a search engine (for example, www.metacrawler.com). ***** AIDS TREATMENT NEWS Published twice monthly Subscription and Editorial Office: P.O. Box 411256 San Francisco, CA 94141 800/TREAT-1-2 toll-free U.S. and Canada 415/255-0588 regular office number fax: 415/255-4659 email: aidsnews@aidsnews.org useful links: http://www.aidsnews.org Editor and Publisher: John S. James Associate Editor: Tadd T. Tobias Reader Services: Tom Fontaine Operations Manager: Danalan Richard Copeland Statement of Purpose: AIDS TREATMENT NEWS reports on experimental and standard treatments, especially those available now. We interview physicians, scientists, other health professionals, and persons with AIDS or HIV; we also collect information from meetings and conferences, medical journals, and computer databases. Long-term survivors have usually tried many different treatments, and found combinations which work for them. 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ISSN # 1052-4207 ***** How to Subscribe Call 800-TREAT-1-2 (800-873-2812), or 415-255-0588. AIDS TREATMENT NEWS is published 24 times per year, on the first and third Friday of every month, and print copies are sent by first class mail. Email is available (see below). Annual Rates: business/professional $270; nonprofit community organization $135; individual $120 ($70 for 6 months). Email: Priority Email Delivery. Business, nonprofit and full- rate individual subscribers can receive a copy by email, in addition to their regular print copy, at no extra charge. These email copies are sent before the printed copies are mailed. Email: Free Delivery for Individuals (delayed one week). For instructions, send email to majordomo@aidsnews.org; the first line must be "info aids-treatment-news" (without the quotes). Back issues are available at http://www.immunet.org/atn. Copyright 1999 by John S. James. 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