&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& J O H N J A M E S writes on A I D S &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& Copyright 1993 by John S. James; permission granted for non-commercial use. AIDS TREATMENT NEWS Issue #179, July 23, 1993 phone 800/TREAT-1-2, or 415/255-0588 CONTENTS: [items are separated by "*****" for this display] Post-Berlin Strategies: Interview With Jay Lalezari, M. D. Thalidomide and HIV: Background Announcements: Early HIV Low-Dose Interferon Trial: San Francisco, Denver, Durham HIV, AIDS & Women Conference, September 3-5, La Jolla, California In Memoriam: Jon Greenberg; Lupin Loughborough ***** Post-Berlin Strategies: Interview, Jay Lalezari, M. D. by Denny Smith For people living with HIV, and for physicians treating them, the road to the right medical choices can seem like an information obstacle course. Victories against HIV disease, so far, have not come from a single absolute answer, but rather from an unfolding series of partial answers, of contributory bits of information that inspire more questions. The essence of progress in therapies has largely been distilled into three concepts: early intervention, combination therapy, and multiple prophylaxes. But these concepts are still only half-drawn, provoking confusion and sometimes public conflict. Which drugs should be combined? Exactly when is "early?" Which opportunistic infections can be prevented by which drugs? The answers to those questions depend for now on a context that changes from patient to patient, and on a dialog between physicians, researchers and the community. To foster that dialog, and to review the developments stemming from the IX International Conference on AIDS in Berlin, we interviewed San Francisco physician and researcher Jay Lalezari, M. D. Dr. Lalezari is Assistant Clinical Professor of Medicine and Co-Director of the HIV Clinical Research Center at Mount Zion Medical Center of the University of California San Francisco. He has treated many people with HIV infection, through clinical trials as well as primary-care practice, and is currently supervising several studies of critical potential, including a phase I CMV treatment trial of HPMPC, a CMV prophylaxis trial involving an oral formulation of ganciclovir, a study of HIV burden in lymph tissue, and a new trial of an HIV protease inhibitor. * * * * DS: Where are we now, after the Berlin Conference? Are you changing treatment recommendations for your patients? JL: Berlin was a bitter pill to swallow. The Conference itself was chaotic and the news was mostly disappointing. Basically it took away assumptions that we had made about AZT, or at least confounded them. For the last three years I had at least offered antiretrovirals to my patients, regardless of their CD4 count. HIV disease may present a long and highly variable course, but the virus is the culprit from day one of infection. We know there is viral activity throughout the period of "latency," and that this activity generates a gradually increasing curve of viral burden. Short of clearing the infection completely, the goal is to extend the time that the curve is flat. I couldn't believe, even as limited as nucleoside analogs are right now, that having some early impact on viral replication, on the viral burden, wouldn't favorably affect the course of the disease. Whatever you can do to shut down viral replication, at whatever point, would be a good strategy to try and survive. I still believe in the concept of early intervention, but after Berlin it may be a moot point until we have better drugs. DS: What do you say to your patients now about AZT? Years after it first appeared, the community is still polarized around it. Some people have been taking it for a very long time, and others still insist that it's poison. And then comes the Concorde bomb. [For more information on the Concorde study, which found only small and temporary benefit from early use of AZT, see AIDS TREATMENT NEWS #177, June 18, 1993.] JL: It's such an emotionally charged subject. The Concorde study had its problems, but it was such a large study that it's hard to not take it seriously. Basically the data out there can support any treatment approach to HIV disease. Anything you really want to do, you can defend. Therefore I don't think we're going to be coming up with any hard and fast prescriptions for people. Whether people want to be aggressive early or want to wait will be a personal choice. There are a lot of variables that will go into that decision, and we're on fertile ground for controversy, where patients are looking for reasons to not take AZT: expense, side-effects, politics, self-denial. But it comes down to this: the principle of early intervention was not challenged by Concorde or anything else. Early intervention remains the right strategy. The problem is that we don't have the right tools to block HIV early, irrevocably, and in all of the reservoirs where HIV may be hiding. I think it's worthwhile emphasizing the things that we know. There is a limited benefit of AZT, and I think we're surprised that it isn't more effective in early disease. Maybe this is because it is cell-cycle specific, and so doesn't affect all of the potential reservoirs of infection. At this point you can still use AZT early, and get two years benefit, and hope that there will be new antiretrovirals after that, or you can wait to spend that benefit at such time that you have low CD4 cells or clinical symptoms. Right now you can argue any strategy you want, but there is no doubt in my mind that AZT is of clinical benefit, particularly in the lower CD4 cell range. I get frustrated when people with less than 100 CD4 cells come in citing the Concorde data. I remain committed to the principle of early intervention. We know from our lymph-node study that HIV infection is a continuous process, that there is viral replication during the entire period of so-called clinical latency. There is just no reason for HIV to be the only infectious disease where we sit back and wait for advanced illness before we intervene. I personally favor an aggressive strategy. If it were my immune system, I would try to do whatever it took, as early as it took, to maintain the integrity of the system. Using AZT too early, as monotherapy, may select for syncytia-inducing strains, which could conceivably enhance disease progression. But going without drug intervention altogether leads to disease progression in most individuals. If someone tells me they want to treat themselves aggressively, I would probably recommend combination nucleosides up front, although I probably will be waiting to start at lower CD4 counts -- trends below 500 -- than I have in the last several years. I could return to earlier intervention as soon as I have access to newer antiretrovirals. DS: Aren't there some benefits derived from nucleoside analogs that are not related per se to CD4 cell protection, perhaps benefits affecting tissues of the digestive tract and nervous system? JL: Yes, some of the value of AZT, and ddC, is not measurable in CD4 counts. Unfortunately, CD4 fluctuations don't always correlate with clinical progression. DS: What about combination therapy? Are nucleoside analogs going to get tossed out if we get some newer drugs? JL: There is no question that we need combinations, and that those combinations should affect different stages of the HIV life cycle. I think that what we might say about the nucleosides is not how limited they are, which is true, but how much they do given that they act only on unintegrated virus. Unfortunately, the newer nucleosides, d4T and 3TC, are not looking any better than what we have. DS: The nucleosides seem to have acquired some more purchase with the proposal of "convergent" combinations. JL: That needs to be tested, of course. But along with convergent combinations, we need the continued testing of agents at other points of viral replication -- like the protease inhibitors. Unfortunately, the news was not great about the tat inhibitor. Flossie Wong-Staal presented evidence at Berlin that perhaps HIV doesn't need tat; that maybe the rev gene is a better target for therapies. DS: If you could fast-track any antiretroviral agent now in laboratory research, which one would you pick? JL: PMEA might be the one. PMEA is one of a new class of experimental antivirals called nucleotide analogs. Unlike AZT, ddI and ddC, it is not cell-cycle specific because it does not require that initial phosphorylation step, which is the limiting characteristic of the nucleosides. Consequently, it might be active against HIV wherever it is hiding. Cats exposed to FIV [feline immunodeficiency virus] will ordinarily develop an antibody response even if you treat them with AZT, ddI or ddC. But if you dose the cats with a regimen of PMEA while exposing them to FIV, they will not develop antibody, suggesting that their immune system is not seeing replicating virus. Then when you withdraw PMEA from the cats, they begin to produce antibodies, suggesting that a potent barrier to viral replication has been removed. [Note: PMEA is being developed by Gilead Sciences, in Foster City, California, which is also developing HPMPC.] Beyond PMEA, I think the protease inhibitors are important. And one surprise at Berlin was GEM 91, an anti-sense oligonucleotide. This is the first anti-sense agent to enter clinical studies, and much sooner than we thought any such compound would be available. DS: Is there a time-line for these drugs? JL: PMEA is in phase I trials now, and there are at least six protease inhibitors in some stage of development. DS: How do you use the currently available drugs? JL: I try to stay open to what my patients want. It's their life and their choice. Some people, as we discussed, happen to have a prejudice against AZT: they had a friend who died while taking it, or they don't like the way Burroughs-Wellcome priced it, or they tried it once three years ago and it didn't help, etc. I ask those patients to try one AZT pill a day for two weeks and come back and see me. After they tolerate that one pill, I try to bring them up to five [100 mg five times a day]. If that takes three months, fine. Better they wade in slowly than jump in and experience a lot of toxicity and decide never to try it again. I happen to like ddC because I've worked a lot with it. I think it's gotten a bum rap. At first the dose was too high; it produced some bad cases of neuropathy. Then people complained that it wasn't as good as AZT. But a recent study has shown that ddC is at least as good and maybe better than ddI in AZT- intolerant patients with advanced disease. The main thing about ddC is that of the three approved nucleosides it is the best tolerated, and that is important. As for ddI, the potential for pancreatitis makes me very careful with the dosing. In general, if people can tolerate it, they should take 200 mg twice a day. Beyond that, the incidence of pancreatitis rises sharply. I do encourage patients to take the recommended doses of anti-HIV drugs. With the three nucleosides now approved, we are dealing with drugs that we know have limited value. So if you reduce the dose that's been approved, you quickly drop into ineffective ranges of the drugs. DS: Do you think "co-factors," such as other viral or bacterial infections, have to be reckoned with? JL: Again, there is no doubt that HIV causes AIDS. There may be a variety of co-factors that accelerate disease progression, and we should try to control them. We know, for example, that herpes viruses transactivate HIV in the laboratory; I have no problem with giving people acyclovir. But there is no co-factor of such pivotal importance that the suppression of that co-factor will prevent AIDS. AIDS is a manifestation of HIV infection. The way to deal with it is to use antiretrovirals early on, to start shutting down HIV replication in all of its target cells, and shutting it down in the lymph nodes as well as the peripheral blood. DS: Regarding opportunistic diseases, what new treatments or prophylactic measures do you see? What are we missing most? JL: What we need most critically is a way to prevent CMV disease. We may have that soon, with oral ganciclovir, or the acyclovir prodrug. I try to prophylax against MAC infection. I use clarithromycin or rifabutin. At Berlin there was some discussion of rifabutin as a treatment, not just prophylaxis. In people who take Septra [against PCP], I don't see toxoplasmosis anymore. And we have atovaquone as a salvage treatment for toxo if the standard drugs fail. We're really controlling fungal infections in people on fluconazole, although resistance may be looming as a problem. So really, the only OIs we're not preventing are CMV, and to some extent, MAC. And of course, there's the whole TB nightmare. DS: How is your research with CMV treatments going? JL: Well, HPMPC [an experimental CMV treatment] is certainly effective enough to begin phase II studies. We need to find the right dose for avoiding kidney toxicity, and then we will be developing a salvage protocol for people who are failing ganciclovir and foscarnet. Our oral ganciclovir trial [for CMV prophylaxis] is still accruing. We know that it is not absorbed as well as the intravenous drug, but there is definitely anti-CMV activity with the oral formulation. The goal is to determine if there's enough to prevent CMV disease without creating resistant strains. DS: I imagine that the kind of person who's drawn to clinical trials would represent an interesting patient to physicians like yourself. By virtue of their willingness to try an investigational drug, they're eager to challenge the status quo of HIV progression. JL: Yes, these people are curious, and spirited. They're smart and determined enough to wade through the morass of HIV information and get into treatment studies. The sheer scientific knowledge that some people bring with them is incredible. Which is good -- it keeps us honest. There is also an abundance of old-fashioned altruism -- a desire to help move the research effort forward. Over the course of a trial, we see patients for months or years, and develop a very close relationship. DS: Do you see patients in trials who are designing their own medical care? Who may meet the trial criteria quite legitimately, but are also perhaps using the trial to surpass what they can get by prescription? JL: Frequently. That started with the first AZT and ddC trials. Many aggressive people are in multiple studies, and in doing so, some people are violating the terms of some studies. If you have a good relationship with your study participants, they want to tell you what they're doing. And I want them to be able to trust me with that information. But it puts us in an awkward position with the drug developer. So now I tell everyone involved that I have to be honest with the data. My patients get to tell me what they're doing outside of my trial without any threat of getting kicked out, and I tell the drug company what's going on. That's a lot better than the data getting diluted by confounding variables you don't hear about. DS: When you have been caring for someone for a while, there must come moments when they have been through numerous infections or other crises, and they are really debilitated and tired of the whole process. How do you advise them? Do you encourage them to try and persevere until we have better HIV treatments? JL: I often tell them to try and persevere through the particular crisis they're in. For example, when people are diagnosed with a CMV infection, it's usually the worst day of their life. I will say "hang in there -- after we start treating the CMV, you'll feel better; if you hold on, I'll get you to a better place." I think it makes a difference whether you continue your anti-HIV drugs. There are some studies of retinitis that show that people who stay on HIV treatment along with their CMV treatment do much better. I think this is indirect evidence that even in advanced AIDS, there is a role for antiretrovirals. Sometimes, though, it is time to let go, and that process is at least as important as any other aspect of HIV care. DS: If a truly effective HIV therapy was available right now, would it allow people who are very sick to recover completely? JL: We are not going to be able to restore a seriously damaged immune system with an anti-HIV therapy alone. It is conceivable that if you completely shut down HIV replication, a relatively healthy immune system could clear itself of the infection. But that by itself would not reverse fundamental damage, like the degraded architecture of the lymph nodes seen in advanced disease. Health Care Ethics, Cost, and Politics DS: In issues of drug development, do you, as a researcher, feel you have any leverage with drug developers? Will they modify a protocol, or step up the pace of development if you express yourself? JL: That's been possible at Gilead, where I think I've enjoyed a lot of influence with the direction of HPMPC. Larry Drew [Chief of Infectious Diseases at Mt. Zion] and I have sat down with the people at Gilead and discussed what makes sense with the handling of HPMPC. What motivates the developer, of course, is not always what motivates the physician providing clinical care. But it's exciting to discuss science with them and ask questions like "what is it we're after? How are we going to get there?" I think that members of the pharmaceutical industry, for all of the criticism they catch, generally do try to cooperate for the sake of progress. They meet with each other, they share information about what doesn't work. Do you see that in the fashion industry? The cosmetics industry? DS: Maybe not, but wouldn't you hold pharmaceuticals to a higher level of ethics to start with? JL: Sure, but I'm saying there is already a level of cooperation within the pharmaceutical industry that you just don't see elsewhere. It's easy to vent anger and blame when you see commercialism, but I wouldn't want to take the commercial incentive away from them. On a personal level, remember that the researchers working for commercial concerns are not working in the marketing department; they want to bring an end to this epidemic as much as anybody. DS: I imagine that's true. But what about wasted resources? President Clinton was on the mark, I thought, when he spoke of the excessive amounts of money the drug companies spend on advertising. Month after month after month you see the medical journals absolutely bloated with glossy, repetitive drug ads. How many Biaxin and Diflucan ads does the world need? JL: I would argue that, as a capital enterprise, those companies are entitled to spend, or misspend, their profit margin how they want. Perhaps there should be some discussion of limits on that kind of stuff. Nevertheless, most of the money spent in the industry as a whole is still spent on research and development. Without a provision for making profits, there is little incentive for development. Would you have wanted to have AIDS in the Soviet Union? DS: No, and yet I wish that we had the same access to health care that the Russians are accustomed to. The irony attached to putting incentive ahead of access in this country is that if we had a cure for AIDS, a lot of people with AIDS would not get it. How do you think the HIV community stands in relation to the coming changes in health care? It doesn't look like we're going to get what we need, which, I think, is single-payer universal access. One analysis in The New York Times implied that Hillary Clinton was pushing for the most generous plan, while her husband leans toward favoring competition. JL: It may be hard to visualize big, new government programs at a time when the deficit is growing and the government is already perceived as managing so many things poorly. I can think of a lot of places where government should stay out, but I would argue that national health is an appropriate place for government to intervene. Medicine [as opposed to research] should not be a commercial, for-profit operation. When you make medical decisions based on financial considerations, you get something other than good health care. In fact, what you get is more expensive and more wasteful. Health care happens to be an appropriate realm for government sponsorship. DS: Do you think we can create a system that fosters development and initiative, as well as the compassion to make that development mean something to those who need it? JL: Sure, and there's no question that a single-payer health system would cut out a lot of obstacles and costs -- maybe even a third of all the resources now squandered could be conserved. It ought to be possible to get everyone motivated to provide universal health care in the most fair and cost- effective way. ***** Thalidomide and HIV: Background by John S. James Starting in early July, extensive news reports appeared about possible use of thalidomide in treating certain AIDS patients, including accounts of rapid regaining of normal weight in some cases of wasting syndrome. There is also a new interest in using this drug in treating tuberculosis. Because the reports were positive and from credible sources, and because of the prevailing pessimism about other treatment options, this news received mtion, and many people called AIDS TREATMENT NEWS and other treatment organizations for more information. At this time our information is incomplete, since we were not able to reach some key people by press time. We need details on the human experience which is behind much of the current interest -- such as what kinds of patients might be likely to benefit from this treatment. (The news reports were set off by the publication of a major article in the July Proceedings of the National Academy of Sciences, USA.(1) This article is readily available, but it only reports laboratory results -- not tests in which thalidomide was given to people.) Thalidomide is related to a large and potentially important area of immune suppression as a potential HIV therapy -- a therapy which might be used in both early and late disease, although probably in different forms, and probably only in carefully selected patients, so that the treatment does not do more harm than good. In early infection, one possibility is to prevent immune activation in order to slow down viral activity. In late-stage AIDS, some patients have symptoms very much like those of certain kinds of graft-versus-host disease, a serious complication of organ transplantation -- and it is possible that some might benefit by being treated for that condition. We hope to cover such possibilities in future articles. Thalidomide is not new in AIDS treatment. Before the current news, 32 published reports were cited in the AIDSLINE database produced by the U. S. National Library of Medicine; most of them concern human use in one or a few cases. These reports appeared between February 1989 and February 1993. Taken as a whole, they suggest (1) that the drug is highly effective in relieving or curing one condition, aphthous ulcers which are not due to infectious causes, but (2) that because of side effects, especially neuropathy, many physicians try other treatments first and use thalidomide only when necessary. We are still investigating whether the new results have changed this picture by using thalidomide in different ways, or with different patients. Thalidomide History Thalidomide was the horror drug of the early 1960s, because it caused thousands of birth defects when taken by pregnant women; this had not shown up in the animal species on which the drug had been tested before it was released. Most of these cases occurred in Europe, because the FDA had not approved the drug for U. S. use. Before the problem was known, doctors had seen thalidomide as a safe substitute for barbiturates, since animal tests had found the drug nontoxic enough that a lethal dose could not be determined. But later it was also discovered that long-term use could cause nerve damage. It was also learned that thalidomide is highly effective for treating certain complications of leprosy; as a result, the drug started to come back into limited medical use. It has also been tried for a number of conditions, many of them autoimmune, including lupus, rheumatoid arthritis, and graft-versus-host disease. The best single source for background information on thalidomide and HIV is "Thalidomide in Human Immunodeficiency Virus (HIV) Patients: A Review of Safety Considerations," a 19- page review article published in 1992.(2) This article points out how much is unknown about the drug. No one knows how it works, either to produce its therapeutic effects or its harmful ones. There may be up to 50 metabolites (different chemicals produced from thalidomide in the body); no one knows which ones are responsible for the different effects. The paper also reviews a number of studies on immune effects of the drug, and of adverse reactions in HIV patients, such as neuropathy and skin rash. It includes over 300 references on thalidomide. Although focusing mainly on safety, the review briefly summarizes a number of reports on the use of thalidomide for treating aphthous ulcers which were not caused by infectious organisms such as candida, herpes, and CMV. Infectious causes need to be ruled out first, since thalidomide does not suppress these organisms. A published letter, too recent for inclusion in the review, reported a case of an esophageal ulcer in AIDS, which could easily have been misdiagnosed as lymphoma even after initial histologic examination, but which healed completely with thalidomide treatment.(3) The authors suggested that there could be other cases wrongly diagnosed as lymphoma which could be easily treated if diagnosed correctly. More recently, a group in Madrid reported that two patients with Mycobacterium avium complex (MAC) responded to thalidomide, after they had failed standard treatments. Laboratory tests, however, found no activity of thalidomide against MAC directly, suggesting that the drug worked by affecting the immune response.(4) References 1. Makonkawkeyoon S, Limson-Pobre RNR, Moreira AL, Schauf V, and Kaplan G. Thalidomide inhibits the replication of human immunodeficiency virus type 1. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, USA. July 1993; volume 90, pages 5974-5978. 2. Gunzler V. Thalidomide in human immunodeficiency virus (HIV) patients: A review of safety considerations. DRUG SAFETY. 1992; volume 7, number 2, pages 116-134. 3. Ryan J, Colman J, Pedersen J, and Benson E. Thalidomide to treat esophageal ulcer in AIDS. THE NEW ENGLAND JOURNAL OF MEDICINE. July 16, 1992; volume 327, number 3, pages 208-209. 4. Vicente T, Ortega A, Muoz P, Diaz MD, and Bouza E. In vitro activity of thalidomide against Mycobacterium avium complex. ARCHIVES OF INTERNAL MEDICINE. February 22, 1993; volume 153, page 534. ***** Announcements ** Early HIV Low-Dose Interferon Trial: San Francisco, Denver, Durham Persons with HIV and a T-helper count over 500 are needed for a short trial to measure immunological effects of low-dose alpha interferon injections. This is an important study of the management of early HIV disease. Participants may benefit by getting the results of extensive immunological tests, at no cost to them. The drug is already approved and widely used in higher doses, so there should be no substantial risk from participating. This study is sponsored by Schering-Plough, which markets alpha interferon. It is known that T-helper cells in many patients have subtle defects in their functioning, such as impaired response to recall antigens, even when HIV disease is completely asymptomatic and the count is over 500. The purpose of this trial is to see if these early defects can be corrected, perhaps by promoting the "TH1" immune response, which may be important in controlling AIDS. Besides having a T-helper count over 500, volunteers must not have taken antiretrovirals, IL-2, or systemic interferon. They must not have had systemic immunosuppressive treatments, such as corticosteroids, within 90 days of entering the trial, and must not have been in any other trial of an investigational drug within 30 days. Most "alternative" treatments, such as NAC, are allowed, however. Women must not be pregnant, and birth control is required for both men and women. Volunteers cannot currently be using illegal drugs, including marijuana. Normal values are required on a number of blood tests, which will be given at the screening visit for the trial; hepatitis serum anti-HCV and serum HBsAg cannot be positive. Volunteers will be tested and must be deficient in one or more of three specialized tests of T-helper cell function (responses to recall antigens, alloantigens, and PHA), so that there will be a potential improvement for the experiment to measure. Patients will be randomly assigned to either receive 0.2 MU of interferon alpha three times a week (by subcutaneous injection), or 2 MU three times a week, or will be assigned to an untreated control group (there is no placebo injection). The trial will last 28 weeks, which includes 12 weeks of treatment and 12 weeks of followup. After early visits for screening, entry, and at one week, later visits will be monthly. A total of 75 volunteers are being sought, 25 at each of the three sites. The trial has not yet started, but the San Francisco site is ready to begin, and all three should be running within about a month. For information about volunteering, call: * San Francisco General Hospital: Linda Johnson, 415/476- 9296x84099; * University of Colorado, Denver: Virginia Waite, 303/270- 8340; or * Duke University, Durham: Robert Dodge, 919/684-5260. ** HIV, AIDS & Women Conference, September 3-5, La Jolla, California A three-day conference "to assist physicians, nurses and other health care providers and HIV infected women in meeting the challenges of the HIV epidemic" will be held at the La Jolla Marriott, La Jolla, California, September 3-5. It is sponsored by the University of California. Enrollment is $175 before August 16 or $200 after that date; the convention hotel rate is $76 for single or double occupancy, with a reservation deadline of August 25. The program includes sessions on natural history and manifestations of HIV disease in women, opportunistic infections, neuropsychological manifestations, legal issues, insurance, benefits, immigration and migrant populations, antiretrovirals, vaccine development, HPV, nutrition, stress management, housing options, early intervention, model service programs, and other topics. Support groups and other social support activities will be available. Childcare will be provided. For more information and a copy of the conference brochure, phone the University of California, San Diego, Office of Continuing Medical Education, 619/534-3940, or fax to 619/534- 7672. ***** In Memoriam: Jon Greenberg Jon Greenberg, AIDS activist, writer, and lecturer, died on July 12, 1993. He was the co-founder of ACT UP/New York's Alternative and Holistic Treatment Committee in 1988, and founder of the Treatment Alternatives Project (TAP) of the PWA Health Group in 1991. For years, Jon sought to make effective and affordable treatments available to all people with HIV and AIDS. His work focused on getting alternative treatments studied in controlled clinical trials, so that their risks and benefits could be better understood and people with AIDS could make informed treatment choices. Jon helped organize many of ACT UP/New York's most famous demonstrations, including the 1990 "Storm the NIH," and the 1991 "Day of Desperation," when Jon protested at The McNeil/Lehrer News Hour. In 1991, Jon wrote a column on alternative health care for Outweek. He was an advisor to the National League for Nursing, GMHC's Medical Information Department, and NIAID's Community Program for Clinical Research on AIDS (CPCRA). He spoke at two International AIDS Conferences, and countless other forums, emphasizing the importance of people with AIDS speaking for themselves. In his many lectures and writings he was always encouraging people to be creative and look beyond their normal boundaries for solutions to the AIDS crisis. "AIDS breaks down intellectual and spiritual barriers leaving one open not only to ideas but also spiritual insights, many of which some of us have spent years trying to keep out with cleverly constructed intellectual and spiritual walls." Over the years Jon worked with AIDS TREATMENT NEWS and was an inspiration to us. A funeral procession through Manhattan and a memorial service in Tompkins Square Park were held on July 16th. Lupin Loughborough Respected San Francisco Bay Area activist Lupin Loughborough died on July 4. Lupin was well known in the gay and HIV communities as an experienced and dependable leader, and served pivotal roles in severaations, including the Kaiser Patient Advocacy Union (KPAU), the East Bay AIDS Resource Organization (EBARO), the East Bay Gay and Lesbian Democratic Club, and the Berkeley Gay Men's Health Collective. Lupin had worked for a number of years as a neonatal nurse at Alta Bates Hospital in Berkeley, and shared his knowledge of medicine very effectively as an activist. He produced a well-written news bulletin for KPAU, which had chapters in Oakland, San Francisco and Santa Rosa, and was a key member of a KPAU team that negotiated better care for HIV-infected Kaiser health plan members. Lupin improved the options and lives of many people. A memorial was held on July 17th. ***** 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 1993 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. &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& End of display -- ben@maggadu.QueerNet.ORG AIDS Info BBS 415)_626-1246 free since July 25, 1985