&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& J O H N J A M E S writes on A I D S &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& Copyright 1992 by John S. James; permission granted for non-commercial use. AIDS TREATMENT NEWS Issue #159, September 18, 1992 phone 800/TREAT-1-2, or 415/255-0588 CONTENTS: [items are separated by "*****" for this display] d4T (Stavudine) Background Alpha-APA: New Anti-HIV Compound Yohimbine: Accidental Discovery As Fatigue Treatment? ICAAC Conference October 11-14, Anaheim, California International AIDS Organizations Develop from VIII International Conference AIDS TREATMENT NEWS Developing International Treatment Newsletter Proposed Budget Cuts Threaten "San Francisco Model" From the Editor ***** This issue singles out three drugs for attention, for very different reasons: d4T (stavudine) is a close relative of AZT, but it may be somewhat more effective and less toxic. It is important because it will soon be more widely available, under a "parallel track" protocol, for persons who have failed treatment with AZT and with ddI. (Persons who are now using AZT may be able to volunteer for a separate program, a clinical trial comparing d4T and AZT, which is currently running at sites throughout the U. S., and at sites in Europe.) Alpha APA (a class of anti-HIV drugs, of which one member, R 89439, has been selected for clinical development) is at a much earlier stage of research; it has completed animal toxicity tests, and the earliest safety tests in humans. The next trials will be only in Europe, not in the U. S. This drug deserves attention because it has very good laboratory activity against HIV, and also is inexpensive to manufacture, so that it could potentially be used in all countries. The major possible drawback is that other drugs with a similar mechanism of action have had serious problems with HIV developing resistance; it is not known if that will happen with this drug too. Alpha APA has been presented at three scientific meetings, but has received little attention so far. The third drug, yohimbine, is not an antiviral; it is a prescription drug with one approved use, treatment of impotence in men. Recently there have been anecdotal but dramatic reports from a handful of patients that yohimbine relieved serious AIDS-related fatigue which could not be diagnosed as due to any opportunistic infection or other known cause. If this early and unexpected finding is confirmed, the drug might have important use in improving quality of life for some patients, and might even help in understanding the pathogenesis of AIDS. More research is needed, and community-based as well as academic research groups could contribute. ***** d4T (Stavudine) Background by John S. James d4T (also called stavudine; its chemical name has been spelled in various ways, including 2',3'-didehydro-2',3'- dideoxythymidine) is important now for two reasons: * A "parallel track" trial, run by d4T developer Bristol-Myers Squibb, will soon make this drug available to persons who have failed both AZT and ddI, and therefore have no approved HIV treatment options; and * Results of early trials, as well as the impressions of researchers and others who have worked with d4T, suggest that this drug might be somewhat better than either AZT or ddI as a single agent. If so, d4T could be a modest but important improvement in AIDS/HIV treatment. But the benefits are limited, as the drug does not totally stop disease progression. Like AZT, ddI, and ddC it can only prevent infection of new cells, but cannot reduce viral activity in chronically infected cells. [Comment: d4T would be less important today if any truly good AIDS treatment were on the near horizon. Where we are now in HIV treatment can be illustrated by comparison with the history of other diseases. For example, it has recently been noted that treatment of the opportunistic infection MAC is where treatment of tuberculosis was several decades ago -- in that one good drug had been discovered (clarithromycin for MAC, streptomycin for TB), although clearly other drugs would be needed too. Today we are not yet at that stage in treating HIV, as we only have poor to mediocre drugs: AZT, ddI, ddC, and now (an anticipated improvement, but still in the mediocre-at-best category) d4T. We suspect that the most likely source of a good drug today would be protease or tat inhibitors. But these are moving slowly -- mainly, it seems, because of technical difficulties in the former case, and corporate politics in the latter.] Until better drugs are developed, the available improvements in second-rate technology (in this case, blocking of reverse transcriptase, which will not work for chronically infected cells) will be important. For this reason we have prepared an overview of d4T itself, the ongoing phase II/III trial, and the parallel-track program which is expected to begin soon. d4T d4T is a close chemical relative of AZT, but it does not have the azido group (three nitrogen atoms) in the molecule. In test-tube studies with AZT, and in animal studies with other retroviruses, d4T often worked less well than AZT. But d4T may make up for this disadvantage by being processmore efficiently in human cells. Both drugs enter the cell unchanged, but are not active against HIV until they are chemically converted to a triphosphate form (with three phosphate groups added to the molecule) by enzymes within some (not all) cells. A major problem with AZT is that it tends to accumulate in the monophosphate form (with only one phosphate group attached, instead of three); in this form it is ineffective and may be harmful. d4T is converted much better to the triphosphate. d4T has very good oral bioavailability; and unlike ddI, it does not need a buffer to protect it from stomach acidity. Like AZT, it partially crosses the blood-brain barrier. And HIV strains which have become resistant to AZT are often still susceptible to d4T -- potentially an important advantage of the latter drug. d4T has been given to over 250 patients in early trials (not counting the almost 400 patients already enrolled in a large phase II/III trial now ongoing, who have been randomized to receive either d4T or AZT). The most important findings are: * T-helper cell increases last longer with d4T than with AZT, often lasting for more than a year before returning to baseline. (The size of the increase is probably larger, too, but we do not have exact comparisons.) * d4T also shows antiviral activity in humans by reducing p24 antigen. * The main side effect is peripheral neuropathy, similar to that caused by ddI or ddC. Some patients have had elevated liver-function tests. These toxicities happened most often at higher doses than are currently being used. We have not heard of any case of pancreatitis caused by d4T. * The maximum tolerated dose of d4T for long-term use is about 4.0 milligrams per kilogram of body weight per day; above this level, toxicities are unacceptable. The dose which will be used when the drug is approved is still not determined, but it will probably be not far from 1.0 mg/kg, four times lower than what can be tolerated -- probably no less than 0.5 and no more than more than 2.0. (A much lower dose, 0.1 mg/kg/day, has been tested and found to be too low.) * There is not enough data yet to know whether d4T will work better than AZT or ddI in preventing AIDS progression or death. (This is what the phase II/III trial should determine.) * d4T has not yet been tested in combination with other antiretrovirals in clinical trials. But experts suspect that a combination with AZT will probably not work, because AZT would prevent d4T from being effective; using the drugs in alternation might be OK. On the other hand, the combination of d4T and ddI looks good in laboratory tests; see V. Brankovan and others, "Strong synergistic anti-HIV activity of a purine and a pyrimidine nucleoside analog, ddI and d4T," V International Conference on AIDS, Montreal, June 4-9, 1989 [abstract # M. CP. 128]. This study found that the 50 percent effective concentrations were 5 and 32 uM respectively for d4T and ddI, but only 0.2 uM for the combination; in addition, the toxicity was not synergistic in this laboratory study. But in people, both drugs can cause peripheral neuropathy; therefore it would be risky to try them together, except in a carefully monitored scientific study. * "Underground" d4T was available recently, but then the supply dried up, apparently because of disputes among people involved, not because of government interference. We heard good reports about this d4T, which was used by people without other treatment options. However, underground d4T is unlikely to be important in the future, because the drug is expensive to manufacture in small quantities, and the parallel track will soon make it available without charge to those who need it most. And when d4T is approved it will be available to anyone, probably for no more than the underground drug would cost, eliminating the market for an underground version, which no one would use if they could get the pharmaceutical drug instead. * d4T is quite stable, and most of it is excreted unchanged in the urine. When cost or supply is critical, it might be possible to recycle the drug and provide treatment at a fraction of the price otherwise required. Phase II/III Ongoing Clinical Trial A large multicenter trial comparing d4T to AZT is now recruiting throughout the United States and in Europe. Volunteers must have T-helper counts between 50 and 500 and have received AZT for at least six months and currently be tolerating at least 500 mg of AZT daily; they must not have used d4T, ddI, or ddC at any time. There are also a number of other medical and laboratory criteria for entry into this study. This trial has now enrolled about 400 volunteers; it is seeking a total of 700. It has 45 U. S. sites in the following cities (list is alphabetical by state and by city within state): Tucson, Berkeley, Los Angeles, Sacramento, San Francisco, Torrance, Denver, Washington D. C., Ft. Lauderdale, Miami, South Miami, Tampa, Atlanta, Chicago, Indianapolis, Kansas City, Wichita, Boston, Baltimore, Charlotte, Durham, Omaha, Albuquerque, Bronx, New York, Stony Brook, Philadelphia, Pittsburgh, San Juan (Puerto Rico), Charleston, Dallas, Houston, San Antonio, Salt Lake City, and Milwaukee. For information about this trial, including locations and phone numbers of sites in your area, call the AIDS Clinical Trials Information Service, 800/TRIALS-A. ***** "Parallel Track" d4T Access About to Begin Bristol-Myers Squibb will soon begin a large parallel-track program which will provide d4T to persons with advanced HIV infection who have no other option for antiretroviral treatment because they cannot tolerate (or have failed to respond to) AZT and ddI. Details have not been released, pending final approval by the FDA, and some criteria for the program may not yet have been determined. Here is what we have learned so far: * The original proposal called for this program to be open only to persons with T-helper counts of 300 or less; however, there is a strong push to raise this limit to 500. * Patients will be randomly assigned to a high dose (somewhat more than 1.0 mg/kg/day, divided into two daily doses), or a low dose which is half that much. Dosage will be adjusted by body weight. * Efforts will be made to facilitate use of this program by persons receiving their care in public clinics, as well as those who have private physicians. Physicians who want to receive information about this program when it is ready should call the Bristol-Myers d4T Information Line, 800/842-8036, 7:30 a.m. to 4:00 p. m. Central time. ***** Alpha-APA: New Anti-HIV Compound by John S. James A drug code-named R89439, one of a class of chemicals called alpha-anilino phenyl acetamides (alpha-APA), has been discovered as a highly specific anti-HIV-1 agent at the Riga Institute for Medical Research in Leuven, Belgium, in collaboration with the Janssen Research Foundation in Beerse, Belgium. It has been presented at three scientific meetings so far, including the VIII International Conference on AIDS in Amsterdam. This potential treatment is interesting for several reasons: * In laboratory tests it is effective against HIV-1 at very small concentrations, a few nanograms per ml. It also has an unusually large ratio (about 1 to 50,000) between the concentration effective against HIV and that which is toxic to cells. * R89439 has been through standard animal toxicity tests and has been tested in people, in a few HIV-negative volunteers. It is orally available and will probably need to be taken only once or twice a day; eight hours after taking a single 100 mg dose, blood levels in humans are 30 times the amount needed to inhibit HIV. No particular toxicity is expected, although toxicity cannot be ruled out. Laboratory tests suggest that the drug is synergistic when combined with AZT or with ddI. * Some alpha-APA derivatives are relatively easy to manufacture, and could be available in any country in the world. The alpha-APA derivatives act by inhibiting reverse transcriptase and are very specific to HIV-1, which suggests that resistance may develop to this class of compounds, as it has with other drugs that are specifically targeted at the HIV-1 reverse transcriptase. At this time, however, no one knows how serious any resistance problem might be. Alpha-APA (R89439) will next be tested in phase I/II trials in several European countries. (AIDS TREATMENT NEWS article includes structural formula of R89439 here.) References Pauwels R, Andries K, Debyser Z, Van Daele P, Schols D, Janssen MAC, Desmyter J, De Clercq E, and Janssen PAJ. HIV-1 specific phenylacetamide derivatives: A novel class of reverse transcriptase inhibitors with potent and selective antiviral activity in vitro. Fifth International Conference on Antiviral Research, Vancouver, March 8-13, 1992; abstract published in Antiviral Research, Supplement 1, March 1992 [abstract #5, page 45]. Pauwels R, Andries K, Schols D, Van Daele P, Debyset Z, Janssen MAC, Vandamme A, De Vreese K, Desmyter J, De Clercq E, and Janssen PAJ. Potent and highly selective HIV-1 specific inhibition by a new series of alpha-anilino phenylacetamide (alpha-APA) derivatives targeted at HIV-1 RT. VIII International Conference on AIDS, Amsterdam, June 19-24, 1992 [abstract # PoA 2320]. Janssen PAJ, Stoffels P, Andries K, Van Daele P, Woestenborghs R, Pauwels R, Heykants J, Mesens J, Cauwenbergh G, Desmyter J, De Clercq E, and Janssen MAC. Inhibition of HIV-1 by a new series of alpha-anilino phenyl acetamide (alpha-APA) derivatives. VIII International Conference on AIDS, Amsterdam, June 19-24, 1992 [abstract # PoB 3020]. ***** Yohimbine: Accidental Discovery As Fatigue Treatment? by John S. James Yohimbine is a chemical found in the bark of the Corynanthe johimbe tree and in certain other plants; in the U. S., yohimbine is available as a prescription drug approved for treating impotence in men. Recently we interviewed two persons with AIDS or HIV, and a physician who is treating one of them and two others, about their successful use of yohimbine to treat severe, long-lasting fatigue for which no specific cause could be found. The effect of the drug was rapid and dramatic, leading to a major improvement in quality of life. Both persons we interviewed discontinued yohimbine after two to three months, for varying reasons; one of them has since restarted the treatment. Physicians would not have expected yohimbine to be helpful in treating fatigue. A recent computer search, for example, found 3,255 articles, letters, etc. published in medical journals between 1985 and 1992 which mention yohimbine; but only one of these references mentions fatigue, and that did not relate to the yohimbine but to another drug used in that particular study. In addition, there are no references to yohimbine on the AIDSLINE file, suggesting that little or nothing has been published concerning its use in AIDS. (AIDSLINE, published by the U. S. National Library of Medicine, is an online database which includes many conference abstracts as well as selected abstracts and other information from over three thousand medical journals.) Most of the articles on yohimbe describe its use in basic research, not as a drug. Interviews We first heard about yohimbine in a January 9, 1992, letter from a person with AIDS. He had been taking Yocon (one of several yohimbine brands available) for one week. He had taken the drug for impotence and was not sure if it had had any effect on that, but "it has changed my life in a big way regarding the fatigue I had been experiencing [since a recent case of MAC, which had been treated successfully]. My productivity has more than doubled...I haven't felt this well since the fall of 1987 before I began to feel ill, and was almost devastated by simultaneous PCP and TB in January 1988." We were unsure what to do with this information, since we could not publish it without confirmation. We decided to wait to make sure the drug was still working weeks or months later. We temporarily lost contact with the patient, but reached him again in early September. He had continued to feel good until March, when he became depressed, and was diagnosed with toxoplasmosis. He stopped using yohimbine during the toxoplasmosis treatment, and started again about six weeks ago, reporting that the drug still works; he is "feeling incredibly well" and plans to spend most of the winter in Europe. "I don't see death in front of me like I used to." We asked about his general health. Five years ago his T- helper count had been 6; except for a temporary rise to about 60 after starting AZT, it has been near zero for five years. Still, he "looks perfectly healthy...I don't know what has been keeping me going." He has been taking acyclovir and pentoxifylline "since the beginning"; he is seeing a leading AIDS specialist and "takes all the pills every day." He is on prophylaxis for pneumocystis, TB, and MAC, and also is taking testosterone and Marinol among other medications. He asked his endocrinologist (a different physician) for the yohimbine, and was prescribed it when that doctor did not see any harm in trying the drug. Our second report on yohimbine and fatigue came from a patient of Marcus Conant, M. D., in San Francisco; he is also a friend of one of the staff of AIDS TREATMENT NEWS. He had had serious fatigue for four to five months, and was able to work only six-hour days (instead of his usually 10 to 12), and then do little else but sleep. All attempts to diagnose the fatigue were unsuccessful. Dr. Conant had heard about yohimbine and fatigue "through the grapevine," and suggested trying it after investigating the drug and finding no reason not to. After starting yohimbine, the patient was back to his baseline energy level almost immediately, and for two to three months had no side effects. But then he started getting "a different kind of nausea and headaches, occasional agitation," so he stopped the yohimbine. (A week later Dr. Conant's office called to recommend that he go off the drug for a time and then re-evaluate the treatment, because there been off the drug now for a month and a half, and some fatigue has returned, although it is not as bad as before. His T-helper count and blood work are the same as before he started yohimbine. This patient has had no AIDS-defining illness. His T-helper count has been very stable at around 230-250 -- except for one spike, a rise of about 75 one month after starting yohimbine. The rise did not last, however; his count had gone down again to its usual value by the next test. He summarized his use of yohimbine by saying it had a significant impact on his life and health. "A long period of severe fatigue can cause despair, pessimism, and resignation. (Yohimbine) catapulted me out of that...I felt better for a significant time, and still feel better now." He said he might use the drug again. Next we spoke with Dr. Conant, who has a large AIDS practice in San Francisco, and has prescribed yohimbine for fatigue to three AIDS/HIV patients so far. Dr. Conant noted that fatigue can have a variety of causes, such as infection, very low T-cells, or depression. He emphasized the importance of physicians making sure they have ruled out known causes of fatigue. "The biggest mistake (physicians) make is to jump to a diagnosis; then a treatable condition may be covered up, when it should have been treated." He said that his patients have reported that yohimbine was effective in decreasing fatigue; he cannot determine yet if it affected libido. The usefulness against fatigue seems to dwindle after three months. At this time, Dr. Conant said, he can neither endorse nor reject this use of the drug. "If we continue to hear reports of benefits, it will be important to sort out what types of fatigue this drug is useful for." Cautions, Dose, Availability The Physicians' Desk Reference notes various precautions and side effects, and should be consulted before yohimbine is used. Particular warnings include not using the drug in persons with kidney disease, nor combining it with antidepressants. "Generally, this drug is not proposed for use in females acertainly must not be used during pregnancy" (Physicians' Desk Reference, Yocon entry). We do not know if there is any particular danger to women, or if this warning only reflects the fact that U. S. testing and approval was for men. Yohimbine has been successfully tested in women, for purposes including weight loss. The patients who have used the drug for fatigue so far have used the standard dose, one tablet (5.4 mg) three times a day. The drug is inexpensive. Yohimbine is also contained in a yohimbe tea, which is sold in health-food stores and used as an aphrodisiac. We have not heard of anyone trying this tea for fatigue. Research Questions If yohimbine is confirmed to be useful in treating fatigue (many drugs have a period of early enthusiasm, perhaps due to coincidental improvement by patients, but then are abandoned), a number of important questions will need answers: * What kinds of patients are likely to benefit? This research could readily be done by community-based groups. * Could this treatment help in some cases of chronic fatigue which is not AIDS related? * A question for endocrinologists or academic researchers is whether this unexpected effect of yohimbine could help in understanding part of the pathogenesis of AIDS. This drug has been used extensively in basic research because of its effects in blocking certain receptors; but much of its mechanism of action (especially with the low doses used medically) is not understood. Sometimes an accidental discovery, especially one which is unexpected, opens new avenues for productive research. ***** ICAAC Conference October 11-14, Anaheim, California The annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) will take place at the Anaheim Convention Center in Anaheim, California, October 11-14, 1992. This technical conference focuses on the development of new antibiotics; recent meetings have increasingly covered AIDS. Another meeting, of the Infectious Diseases Society of America, is held in conjunction with ICAAC. This year it will take place shortly before ICAAC, in Anaheim. This year's ICAAC includes symposia on tuberculosis, cytokines, antiviral therapies, antiviral resistance, protease inhibitors, prophylaxis in persons with HIV, new antibiotics and antifungals, and a joint symposium on AIDS with the Infectious Diseases Society of America. For more information, call the American Society for Microbiology, 202/737-3600. ***** International AIDS Organizations Develop from VIII International Conference by Dave Gilden The Eighth International Conference on AIDS left many of the people who actually have AIDS, or some degree of immune deficiency, dissatisfied. This was true although this year's conference organizers went to greater lengths than ever before to include community concerns in its agenda and community activists in its planning. "The Conference still didn't 'get it.' Organizers don't understand why people with HIV are central to the fight, and we remain in a ghetto, never fully integrated," observed Arawn Eibhlyn of ACT UP/San Francisco. Moreover, Eibhlyn, noted, "Every year, we get together and whine and complain. There's never a mechanism for an ongoing effort. It will really be a drag to have the same meeting in Berlin as we had in Amsterdam, Florence and San Francisco." Perhaps because of the liberal atmosphere, though, international grassroots networks sprung up at the conference as never before. They especially aim at making future international sessions more useful to people looking for treatment information that they can take home and use immediately. Here are four examples of the way activists around the world are connecting up: * A pre-existing "Global Network of People Living with HIV/AIDS" was reorganized and reinvigorated, reports Cindy Robins of Toronto, who is president of the network's new management committee. After a tumultuous session with the steering committee for next year's conference, in which 100 demonstrators barged into the steering committee's meeting during the Amsterdam conference, the global network is trying to arrange a more central position for people directly affected by the epidemic. In addition, the network is planning another in its yearly series of international conferences by and for people living with HIV/AIDS. Next year's event will take place in Acapulco, Mexico in September. Past such conferences have been criticized for their haphazard organization; also, they have had few participants from the U. S. Acapulco promises to be different on both counts. The Global Network of People Living with HIV/AIDS is in the process of obtaining a central coordinating address. In the meantime, its U. S. representative, Peter Uitdenbosch, can be reached at: 813/922-9286. The address of the local organizing committee for the Acapulco conference is: Sixth International Conference for People Living with HIV/AIDS, Queretaro no. 219-H, Col. Roma, Mexico, DF 06700. * Women have felt a lack of visibility even at past international meetings of people with AIDS. Before the official Amsterdam conference, an international pre- conference of 59 women meeting over four days discussed women's particular needs as the epidemic continues. A new network, the "International Community of Women Living with HIV/AIDS," grew out of that meeting. "There never has been an international organization of women, but our issues won't be addressed if we don't link up. The compassion and commitment [at the preconference] was incredible. This will be a great resource for women," said Sharon Lund, the network's West Coast representative. Besides trying to send material aid directly to HIV-positive women in poorer countries, the network will function as an information exchange on treatment as well as reproductive, family and psychosocial issues. It will also set up women's gatherings before future international AIDS conferences. The International Community of Women Living with HIV/AIDS can be contacted by leaving a message for Sharon Lund in Los Angeles (213/624-3448) or Wendi Modeste in Syracuse, NY (315/472-6955). * The above women's group is particularly interested in traditional and alternative therapies because they are treatment strategies women around the world can apply "right now." Many of the traditional herbal pharmacopeias are largely the work of women, and women also function as the planet's chief dieticians and nutritionists. To ensure that basic therapeutic information is disseminated, the Center for Natural and Traditional Medicine in Washington, D. C. (as well as other groups) pressured international AIDS conferences to include a "fifth track" on alternative medicine. Although that effort has not been successful, the Center has obtained permission to organize an alternative medicine caucus within the International AIDS Society, the annual conferences' official sponsor. The caucus will give proponents of alternative, low-tech medical strategies more input into conference decisions, helping to ensure that the IAS faithfully keeps its promise to incorporate more alternative medicine presentations in all the present conference tracks. "The participation this year of people from developing countries, women and AIDS activists made for a turning point. Scientists now realize that every medical idea at least has to be considered," said Kaiya Montaocean, co-director of the Center. The caucus is just establishing itself on a regional and democratic basis. It seeks participation from medical doctors, alternative health practitioners, people with AIDS, activists, social scientists, legal experts, and others. Those wishing more information can contact Montaocean at the CNTM, PO Box 21735, Washington, D. C. 20009 (telephone: 202/234-9632). With partners in four Third World countries, the Center has also applied to the World Health Organization for funding to found the "Healing Roots Network" which would connect traditional medicine groups in an anti-AIDS information and training exchange. * Finally, here is an idea for a meta-network from ACT UP/New York. It is meant to link existing networks together and was presented at the official "global town meeting" that took place at the Amsterdam conference. According to Eric Sawyer of ACT UP/New York, the concept is to contact existing AIDS networks and hook them together through a fax and electronic mail system. HIVNET, a computer bulletin board based in Amsterdam, is coordinating the European component of this effort. Such a system would be comparable to the PEACENET computer network that has joined together a range of peace and environmental activists for some years. The hi-tech nature of the proposed global HIV network will allow for quick and close coordination between distant groups when campaigning around specific points. In particular, Sawyer mentioned all the concerns raised about the Berlin conference. To join the mailing list or contribute ideas, contact Eric Sawyer (attn.: Global Network Committee) at 135 W. 29th St., tenth floor, New York, NY 10003 (telephone: 212/564-2437). ***** AIDS TREATMENT NEWS Developing International Treatment Newsletter AIDS TREATMENT NEWS has begun a collaborative project with the International Gay & Lesbian Human Rights Commission to distribute an international edition of the newsletter to communities that are not now receiving treatment information. The international edition will be translated into multiple languages and distributed free to grassroots organizations, which would then distribute the newsletters to people with AIDS, doctors, health care providers and researchers. In its first year, a pilot project would target countries with the highest AIDS caseload: Mexico, Brazil, Thailand, Uganda, Zaire, Tanzania, Kenya, India, Poland and Rumania. During this first phase, the newsletter staff will seek out people working in grassroots AIDS organizations to survey the treatment information needs in their communities. Meanwhile, a quarterly version of AIDS TREATMENT NEWS will be distributed to meet the immediate need for information. As we learn more about each community, we will change the international edition to better reflect those needs. During the first decade of the AIDS epidemic in the United States, people with AIDS took pioneering action to inform themselves and get involved in their own treatment decisions. AIDS TREATMENT NEWS grew out of and helped create that movement. Yet information is not reaching people throughout the world, despite the global nature of the AIDS pandemic. "In the first decade of response to AIDS, remarkable successes in some communities contrast dramatically with a growing sense of collective, massive global failure," writes Jonathan Mann and others, in AIDS in the World 1992. AIDS TREATMENT NEWS periodically receives requests from people in other countries who write about the desperate need for treatment information. "We are studying new drugs for AIDS treatment and (are) badly in need of the information on this field," a researcher from China wrote. "By chance I read an issue of AIDS TREATMENT NEWS edited by you, and like it very much. Would you please send us all sample issues on Compound Q." Preliminary investigation has shown that although representatives from countries all over the world attend the International Conference on AIDS, vital information does not trickle down to grassroots organizations and people with AIDS. Also, organizations in Europe currently take AIDS TREATMENT NEWS and translate it into German and Dutch for European distribution, but organizations in the developing world can seldom afford translation and distribution costs. The international edition staff met recently with eight doctors from seven countries who are visiting scholars at the Center for AIDS Prevention Studies at the University of California in San Francisco. The doctors were supportive of the international edition and offered specific advice about what kind of information their communities need. In Brazil, one doctor said, clinicians do not have access to laboratory work to determine the T-cell counts of their patients. Yet drugs produced by U. S. and European pharmaceutical companies are prescribed on the basis of those counts. "When do we begin AZT and why? When do we start PCP prophylaxis?" The doctors said that their communities would be interested in breakthroughs in medicine not yet available in their communities as well as information that would be immediately useful, such as therapies based on nutrition, which can be an affordable treatment. By collaborating with the International Gay & Lesbian Human Rights Commission (IGLHRC), the project combines the expertise of producing an AIDS treatment newsletter with the experience of IGLHRC, which has worked for two years at international organizing and distribution of HIV prevention materials internationally. What AIDS TREATMENT NEWS needs most is help in finding foundations or other organizations who could fund international distribution of treatment information. If you could help us with this project, contact Nancy Solomon at AIDS TREATMENT NEWS (415/255-4659 (fax); or P. O. Box 411256, San Francisco, CA 94141). ***** Proposed Budget Cuts Threaten "San Francisco Model" Proposed cuts to the San Francisco city health budget could destroy what is left of the once highly regarded "San Francisco model" of AIDS care, activists and care providers say. San Francisco Mayor Frank Jordan is proposing that up to $25 million of the $64 million recently lost to San Francisco (due to the California budget crisis) be cut from the Department of Health. Health officials, service providers and activists say the cuts will cause "the Manhattanization" of health services in San Francisco, meaning that the shortage of services in New York will soon be felt here. "Pretty much whatever model we had left is going to be decimated by these cuts," said Jerry Windley of the Harvey Milk Democratic Club. "The mayor says he is going to protect the AIDS budget. But there is no way not to cut the AIDS budget [while cutting overall health care]. People with AIDS go to the health centers. People with AIDS go to (San Francisco) General Hospital. People with AIDS go to the pharmacy at General." Raymond Baxter, director of the Public Health Department, said he is opposed to the cuts but has had to suggest how his department would handle the reduction. He is proposing the closure of one of the city's five community health clinics, the reduction of 75,000 appointments at San Francisco General Hospital, removal of one-quarter of the psychiatric beds at the hospital, and massive cutbacks to the department of mental health. The cuts would also mean the closure of the Center for Positive Care, a one-year-old program that created a "one- stop shopping" center for AIDS services in the city. Activists working against the cuts have organized a broadly- based City Health Budget Coalition, which has scheduled a demonstration for Wednesday, Sept. 23, at 5:30 p. m. at City Hall, and will give public testimony to the Finance Committee of the Board of Supervisors later that evening, and to the full board on Saturday. For more information, call Alex Vitale at the Coalition on Homelessness, 346-3740. ***** 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 415/255-4659 fax Editor and Publisher: John S. James Medical Reporters: Jason Heyman John S. James Nancy Solomon Reader Services and Business: David Keith Thom Fontaine Tadd Tobias Rae Trewartha 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. AIDS Treatment News does not recommend particular therapies, but seeks to increase the options available. Subscription Information: Call 800/TREAT-1-2 Businesses, Institutions, Professionals: $230/year. Nonprofit organizations: $115/year. Individuals: $100/year, or $60 for six months. Special discount for persons with financial difficulties: $45/year, or $24 for six months. If you cannot afford a subscription, please write or call. Outside North, Central, or South America, add air mail postage: $20/year, $10 for six months. Back issues available. Fax subscriptions, bulk rates, and multiple subscriptions are available; contact our office for details. Please send U. S. funds: personal check or bank draft, international postal money order, or travelers checks. VISA, Mastercard, and purchase orders also accepted. ISSN # 1052-4207 Copyright 1992 by John S. James. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used. &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&