AIDS TREATMENT NEWS Issue #181, August 20, 1993 phone 800/TREAT-1-2, or 415/255-0588 CONTENTS: Triple-Drug Therapy Still Worth Testing, Despite Laboratory Error Six-Year Diet Study: Nutrients May Reduce AIDS Risk Regulation of Nutritional Supplements: Letter to FDA Berlin Conference: HIV Miscellaneous, Part I U.S. Surgeon General: Letters, Calls Needed Before Sept. 7 Announcements: International Conference of People with HIV/AIDS, Acapulco, September 23-28 Atlanta: Immune Restoration Forum August 29 Atlanta: NAPWA Seminar for Newly HIV Positive, September 11 and 12 In Memoriam: James Palazzolo ***** Triple-Drug Therapy Still Worth Testing, Despite Laboratory Error by Henry E. Chang The treatment approach called "convergent combination therapy" is the combined use of multiple drugs (usually three or more) which all act against the same target in a virus. This differs from the usual approach to combining drugs for treating infection, which is to target different stages in the life cycle of the bacterium, virus, or other infecting organism. The theory of convergent combination treatment is that viruses, which are much simpler than bacteria, may only have a limited range of possible changes in a key enzyme, before they become unable to reproduce. Therefore, it might be possible to stop the virus by a combination of drugs, each of which requires the virus to have one or more different mutations in the same enzyme. Either the virus has all the mutations and is not viable, or it does not have them all and is susceptible to at least one of the drugs. Convergent combination therapy first received widespread publicity in February 1993, after the publication of a major article in Nature (February 18) describing laboratory tests of the concept. (For background, see AIDS TREATMENT NEWS #170, March 5, 1993.) More recently a laboratory error has been found in the work reported in the February paper. The error also received widespread publicity, with a page-one article in The New York Times on July 22. We believe that both the original work and the error have often been overinterpreted by the public, which underestimates the degree to which laboratory results are only hints or guides to treatment development, and not strong evidence of what will happen in people. Convergent combination therapy never promised more than a limited advance; yet even after the discovery of the highly- publicized error, it is still well worth testing. The Nature paper reported two different experiments, which people have sometimes confused: * The Harvard team artificially constructed an HIV provirus (the virus in its DNA form) containing mutations giving resistance to AZT, and to ddI, and also to nevirapine. (Nevirapine, also called BI-RG-587, is an anti-HIV drug being developed by Boehringer Ingelheim Pharmaceuticals, Inc.; it inhibits reverse transcriptase, an enzyme which is required for HIV to reproduce, but which is not found in uninfected humans. AZT and ddI also inhibit reverse transcriptase. Resistance can develop to each of these drugs, through mutations in the reverse transcriptase, but different mutations are required for each drug.) In separate tests, the researchers also combined AZT, ddI, and pyridinone (also called L-661, a drug being developed by Merck & Co., Inc.). The Nature paper reported that one such engineered virus, labeled "mutant 4," was dead, and hypothesized that the accumulation of mutations in the reverse transcriptase had weakened the virus to the extent that it was no longer functional. The authors suggested that since one combination of mutations led to a dead virus, it meant that one mutational pathway to the development of multidrug resistance to AZT, ddI, and nevirapine might be blocked. * In a different experiment, the Harvard team showed that by using a combination of AZT, ddI, and nevirapine (or pyridinone), at concentrations achievable in patients' blood, viral spread in cell cultures was effectively prevented. Perhaps because of the way the two different experiments were reported in the same paper, many people have misinterpreted the goal of the treatment as using the drug combination to force HIV to mutate into a dead virus. In fact, the construction of mutated viruses in the laboratory only suggested that not every combination of resistance mutations to the different drugs automatically gave rise to multidrug resistance. From that, the researchers theorized that multidrug resistance might be delayed or made more difficult by use of multiple drugs against the same viral target (reverse transcriptase in this case). The Error At the Noordwijk Drug Resistance Workshop in the Netherlands, and at the IX International Conference on AIDS in Berlin, both in June of 1993, researchers from other laboratories showed that they could not reproduce the results of a key experiment performed by the Harvard group. The discrepancy between the original report, and the independent findings of two teams, one led by Dr. Brendan Larder at Wellcome Research Laboratories in the UK, and the other led by Dr. Emilio Emini at Merck Research Laboratories in the U.S., centers on the artificially constructed HIV mutants. In an effort to confirm the original report by the Harvard team, Drs. Larder and Emini constructed HIV mutants with the intended four mutations (at positions 74, 103, 215, and 219 in the genetic code for the reverse-transcriptase enzyme). The result was a virus that could reproduce. Immediately following these reports, the Harvard team went back to their laboratory and discovered that one of their artificially constructed viruses, "mutant 4," had at least one unintended mutation in addition to the intended ones. Additional experiments should have been performed to confirm that all HIV mutants were built as specified and did not have any unwanted mutations. All other data in the original Nature paper have been reviewed and were found to be correct. According to the Nature paper, HIV did not develop resistance to the triple-drug combination after passing the virus 10 generations in the presence of the drugs in cell cultures. But, using recent data obtained from longer-term cell culture experiments, the Harvard team reported at the Berlin conference that they found multidrug resistance after 20 to 40 generations under different conditions. These new findings are in agreement with those from Dr. Larder's group. They suggest that HIV which is resistant to AZT, ddI, and nevirapine may emerge in treated patients, especially those who started this triple-drug regimen with viruses already resistant to AZT and ddI. Clinical Trial Continues A large clinical trial sponsored by the National Institute of Allergy and Infectious Diseases' AIDS Clinical Trials Group (ACTG), designed to evaluate the effectiveness of convergent combination therapy with 400 patients, is currently underway. Despite the announcement of the experimental error, the clinical trial will proceed as originally planned. All study participants will be contacted and will have an opportunity to discuss the information with their investigators. In addition, a "Letter to Patients" has been sent out to all participants in the study. These recent findings have demonstrated to the research community that the HIV reverse-transcriptase enzyme has more adaptability and ability to evade antiviral treatments than previously believed. And caution must always be used in trying to apply laboratory findings to clinical treatment. Nevertheless, the current trial should determine whether triple-drug combination is a more effective anti-HIV strategy than the more standard combination of only AZT and ddI. In addition, the study should provide a better understanding of the overall biological activity of nevirapine in combination with AZT and ddI, and show whether the three-drug combination will delay the development of resistance in patients. About the author: Henry E. Chang is an AIDS treatment activist and the director of research and development at Shared Medical Research Foundation in Los Angeles, California. He can be reached at 818/345-2172. ***** Six-Year Diet Study: Nutrients May Reduce AIDS Risk by John S. James A major epidemiological study published this month suggests that a number of nutrients, whether obtained from food or nutritional supplements, might reduce progression to AIDS in persons with HIV. The study is difficult to interpret, and it does not prove that any nutrient is helpful in preventing progression; to do that would require assigning people randomly to take different amounts of nutrients for a long time -- a very difficult and expensive study to do. Since we will probably never have definitive proof, people need to make decisions on information already available. The new information suggests that nutrition should be taken more seriously than in the past. But it would be a mistake to base recommendations too quickly on a preliminary study. The recent paper(1), published in the August 1993 Journal of Acquired Immune Deficiency Syndromes, is based on data from the San Francisco Men's Health Study. In 1984 this study enrolled single men, ages 25 to 50, both HIV positive and HIV negative, from the 19 census tracks in San Francisco with a high incidence of AIDS; then the men were seen every six months. They filled out a standard nutritional questionnaire, and returned it to the study before they received their first HIV test result. Therefore, the study has the advantage of representing the entire population in the AIDS-impacted areas, not just those who were ill and sought treatment. And the questionnaires were returned before participants knew their HIV status, avoiding possible bias in how they were filled out. A total of 296 men, all healthy and HIV positive, met all necessary criteria and were included in the nutrition study. Thirty six percent of them progressed to AIDS during the six years. Special computer software analyzed the nutrition questionnaires, with peoples' reports of their dietary habits, to estimate how much of various nutrients they received from food. Those who also took nutritional supplements were asked to provide the relevant information, often directly from the labels on the bottles. After six years, the data were analyzed to see if total intake of particular nutrients was associated with a difference in the rate of progression to AIDS. Results The results can be confusing and hard to interpret, because often they depend on which statistical corrections were used; the researchers tried different ways. But the data seems to show that: * With certain statistical adjustments, "The hazard of AIDS decreased as consumption increased for all 11 micronutrients [vitamin A, carotene, retinol, vitamin C, vitamin E, folic acid, riboflavin, thiamine, niacin, iron, and zinc]; this relationship was statistically significant for iron, vitamin E, and riboflavin, and approached significance for vitamin C, thiamine, and niacin." But with other ways of looking at the data, there was no statistically significant association of any of the micronutrients with AIDS. * "Higher intake of all 11 micronutrients was associated with higher CD4 counts at baseline, and was significantly so for six of them." * With certain statistical adjustments, those who took daily multivitamin supplements were only 70 percent as likely to progress to AIDS as those who did not. * On the other hand, those who smoked cigarettes were significantly more likely to develop AIDS than those who did not. However, because this study was not a randomized trial, and because of difficulties in interpreting the data, the researchers could only conclude that "the possibility that higher nutrient intakes may delay the development of AIDS cannot be ruled out." A different limitation of the study is that it could not measure certain other potentially important nutrients, including vitamin B12, vitamin B6, and copper, because the computer software used to analyze dietary habits did not assign values for them. Comment During the AIDS epidemic, some physicians and nutritionists have developed nutritional-supplement recommendations for persons with AIDS or HIV. (For example, see Immune Power: A Comprehensive Healing Program for HIV, by Jon Kaiser, M.D., who has an AIDS practice in San Francisco; this book was published last month by St. Martin's Press in New York.) Since some vitamins and minerals can be dangerous in overdose, especially for persons in poor health, it is important to find out what has already been done in HIV care, before starting any high-dose regimens. It is also important to check with one's physician, because there may be particular reasons that one should not take certain nutritional supplements. Incidentally, the median intake of the nutrients measured in the study was not especially high. A graph in the published paper showed intake levels for nine of the 11 micronutrients. Vitamin C was highest, with a median intake between eight and nine times the RDA (Recommended Daily Allowance of the U.S. Food and Drug Administration, for healthy men between ages 25 and 50 -- many suspect that the RDAs are too low for persons with HIV, because of malabsorption or for other reasons). None of the other eight nutrients even reached four times the RDA. References 1. Abrams B., Duncan D., and Hertz-Picciotto I. A prospective study of dietary intake and acquired immune deficiency syndrome in HIV-seropositive homosexual men. JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES. August 1993; volume 6, number 8, pages 949-958. ***** Regulation of Nutritional Supplements: Letter to FDA by John S. James AIDS TREATMENT NEWS sent the following letter to the U.S. Food and Drug Administration in response to its request for public comments on its plans to increase regulation of nutritional supplements and related compounds. This particular public comment period has now passed (see AIDS TREATMENT NEWS #178, July 9, 1993, and #180, August 6, 1993), but the issue will be with us for some time. * * * People with HIV are concerned that amino acids, certain herbs, and other substances may become difficult to get, without very good safety reasons. They care much less about regulation of labels and claims. Patients want treatment options, not treatment promotions. Especially in the last few months, leading AIDS researchers have agreed that so much is still unknown about AIDS that nobody can be confident that any particular scientific approach will be productive. We need to maintain openness so that many avenues can be explored. In addition to high-tech treatments like gene therapy and protease inhibitors, low- tech approaches based on nutritional substances like amino acids, or on herbs or other generally available substances which are already in wide human use, also need to be considered. The problem is getting these substances researched. Making amino acids prescription drugs would make them more expensive and scarce, but how long would it take for this higher cost and easier monopoly to bring about trials and drug approvals? AIDS -- and perhaps cancer and other life-threatening diseases -- might well be last in line, as entrepreneurs seek their fortunes on approvals for minor ailments, where success is easier. Top-down drug development, which starts when some corporation decrees a project, is only part of the picture. Until the last few decades, most drugs throughout human history have been developed bottom up. Individual physicians, "outsider" experts, or even patients, took the initiative and did informal testing. Momentum built gradually, only later bringing the treatments to serious mainstream attention. The example of antioxidants as potential cancer preventives shows that this development path is still active. But few physicians are willing to prescribe a drug in the early stages of bottom-up development, because of professional risks to them. Most, however, are willing to monitor and advise their patient on the use of the same substance, if the patient can obtain it elsewhere. Therefore, making amino acids prescription drugs, or otherwise making substances now available illegal or difficult to obtain, could choke off bottom-up research (the only kind we are likely to get, in many cases) in its beginning. The history of epidemics suggests that it is impossible to predict where important treatment advances will come from. The experts are often surprised. Let's not create a system so highly controlled that the unexpected becomes impossible. ***** Berlin Conference: HIV Miscellaneous, Part I by John S. James The IX International Conference on AIDS, Berlin, June 6-11, 1993, included thousands of presentations. This mass of information is difficult to organize, report, or otherwise know what to do with. But there are some overall organizing principles: * Much, if not most, of the information is unlikely to be useful to anyone, often because it consists of reports of whatever data some doctors or scientists happened to have on hand, unrelated to any particular rationale or purpose. * Most of the information which is potentially useful fits into larger topics (for example, particular treatments or classes of treatments which are being actively developed, such as protease inhibitors, or therapeutic vaccines, or other treatments already in major human trials). These larger topics are not covered below, since each one needs a separate, longer article to describe the Berlin results within the larger context of other information which is available. Just saying what happened in Berlin would either be misleading, or would require the reader to already understand the previous history of the treatment, and we do not assume that when writing AIDS TREATMENT NEWS. Still, there were some miscellaneous presentations in Berlin which we found interesting enough to report, but which may not fit into larger articles which we are likely to publish. Some of these reports are treatment ideas, and others are theories about the pathogenesis of HIV disease (how the disease develops). The selection below was guided by photographs we took of some of the posters in Berlin. In most cases, we ended up relying on the published abstract; the pictures of the actual poster did not change what we wrote. But in some cases the photographs were important -- especially on allergy and HIV, and also on the immunosuppressive peptide, both in the HIV pathogenesis section, below. To keep this article focused, we restricted it to HIV disease (as opposed to opportunistic infections, etc., which might become a separate article), and to posters instead of oral presentations (which usually require a longer article). The selection below is largely arbitrary and not at all complete. When we finish analyzing our photographs, and the published abstracts, we may publish reviews of other presentations. HIV Pathogenesis Allergy and HIV: A report from Greece found that patients with HIV who had allergies had a faster drop in T-helper count than those without allergies -- and that the two may have benefited differently from different treatments. Allergy was detected by a questionnaire, and by skin and blood tests. Both asymptomatic patients and those with AIDS had a more rapid decline in their counts if they had allergies than if they did not, and the difference was statistically significant. The researchers also found in the allergic patients, AZT alone did not increase T-helper counts of patients with AIDS -- as it did in non-allergic patients. But alpha interferon (Intron) "helps the (T-helper count) in allergic patients to come even to a higher level than that of the non-allergic." These conclusions were based on experience with a total of 80 HIV-positive patients. T. Dikeakou and others, Contribution of Allergy to the Establishment and Evolution of HIV Infection, abstract #0422. Comment: One way to follow up on this potentially important report would be for physicians to check their records (perhaps with the help of research specialists provided by community-based research organizations, or by pharmaceutical companies interested in improving the usefulness of their products) to see if their experience has been consistent with it. Sjogren Syndrome, Parotiditis. These conditions which are believed to be autoimmune seemed to be associated with slower progression of HIV disease, in a prospective cohort of 35 patients at an autoimmunity clinic in Brazil. The authors remarked that Sjogren syndrome is unusual in young men. M. Neto and others, Parotiditis and Sjogren Syndrome are Associated with Better Outcome and Longer Survival, abstract #0421. Apoptosis. A number of posters concerned apoptosis, or programmed cell death, indicating an increasing interest in this possible mechanism of depletion of immune-system cells in AIDS. Apoptosis, which can be recognized in the laboratory and distinguished from other ways cells can be killed, results from a genetic program built into the cell. It is believed that apoptosis is necessary early in human development, as part of the process by which the immune system learns to distinguish "self" from "non-self" -- so that it will attack foreign bacteria, viruses, etc. but not the body's own tissues. According to this widely held theory, during the development of the fetus, the body creates a great many different kinds of T-cells by random combinations. Many of these cells would be activated by the body's own proteins; others would not. At one point in development, something turns on the genetic program for apoptosis; then those cells which are activated die, while those which are not survive. In adult life, after a person's immune system has developed, apoptosis should not occur; the genetic machinery for it is still there, but it should be turned off. Abnormal apoptosis is believed to occur in persons which HIV. Some of the posters exploring apoptosis in HIV disease are: * F. Pandolfi and others, Increased Rate of Death by Apoptosis In Vitro in Cells Isolated from Patients with HIV-1 Disease, abstract #0215. This poster noted that both IL-2, and fibroblast-conditioned medium, reduced cell death in laboratory tests. * N. Kobayashi and Y. Nakanishi, Induction of Apoptotic Gene by HIV Infection, abstract #0267. * A.G. Laurent-Crawford and others, Induction of Apoptosis in CD4 Lymphocytes by HIV Envelope Glycoproteins, abstract #0278. * M.A. Rey and others, HIV-2 EHO Is a Highly Cytopathic and Divergent Virus That Induces Single Cell Killing by Apoptosis, abstract #0279. * G. Lombardi and others, HIV-1 Gp120-Dependent Induction of Apoptosis in Antigen-Specific Human T-Cell Clones, abstract #0282. * N. Oyaizu and others, Apoptosis Inducing Mechanisms Resulting in CD4+ T Cells Depletion, abstract #0314. Immunosuppressive peptide. One theory of how HIV causes damage is that a small part of one of the HIV proteins mimics a crucial part of a protein used in the immune system. This could cause dysfunction either by generating too much of the substance, or by causing the production of antibodies against it. One research team suggested that a particular sequence of eight amino acids (positions 583 to 590 in gp41) might be critical. This sequence is highly conserved not only in HIV, but also in other retroviruses -- including cancer-causing viruses which are also known to cause immune suppression. ("Highly conserved" means that this sequence does not change as the virus mutates, suggesting that it is essential in some way for retroviruses.) The researchers suggest that whether or not a retrovirus causes disease in a particular species may depend on whether or not in can reproduce well enough in that species to create enough of the immunosuppressive sequence to cause serious problems. J. Denner and others, The Immunosuppressive Peptide of HIV-1: Functional Domains and Binding to Lymphocyte Surface Proteins, abstract #270. Potential Treatments The following posters report early laboratory work on potential treatments. This section omits treatments which are approved or being intensively developed. Instead, it focuses on possibilities which are getting little attention and could slip through the cracks. Nanoparticles. Nanoparticles are small particles designed to be taken up by monocytes and macrophages, which normally ingest bacteria and other potentially harmful substances. The idea is to deliver drugs efficiently to these particular cells. Nanoparticles are ingested efficiently by macrophages from persons with HIV, regardless of the stage of the disease. In laboratory tests, nanoparticles with a payload of AZT or ddC showed no advantage over the free drug. They might be more useful for drugs which are not water soluble or otherwise are difficult to deliver. V. Sch fer and others, Inhibition of HIV Infection In Vitro by Antiviral Drug Targeting Using Nanoparticles, abstract #565. Ethyloxime 25. This is a reverse-transcriptase inhibitor being developed by Hoechst AG and Bayer AG in Germany. A. Paessens and others, Dibenzoazepindione Oximes: A New Class of Allosteric Inhibitors of HIV-1 Reverse Transcriptase; Part 2: Biological Characterization, abstract #0617. Active ether lipids. Kucera L. and others, Novel Membrane Active Ether Lipids that Inhibit HIV-1 Induced gp 160/120 Functional Expression and Pathogenesis, abstract #0578. This substance is believed to block interactions between infected and uninfected cells. Melittin. M. Wachinger and others, Amphipathic Peptide Melittin: Inhibitory Effects on HIV-LRT Activity, HIV-RNA Levels, and HIV Protein Expression, abstract # 0072. Melittin has been found to reduce activity of the HIV LTR (long terminal repeat of HIV, which makes the virus more active). [Note: Do not confuse "melittin" with "melanin."] Glycyrrhizin. Glycyrrhizin is a chemical found in licorice; AIDS TREATMENT NEWS noted its potential anti-HIV use in November 1986, and in May and in November 1990. Most of the interest in glycyrrhizin for HIV and other viral infections has been in Japan. A poster in Berlin presented results of a Japanese study with 16 patients, ten of whom started the treatment between 1986 and 1987. "In the treated group, neither progression of immunologic abnormalities nor development to AIDS has been seen." K. Akatani and others, Prophylactic Effect of Long-Term Oral Administration of Glycyrrhizin on AIDS Development of Asymptomatic Patients, abstract #0596. Note: In the U.S., a few people with HIV have been using the same tablets (Glycyron brand) as tested in this study, but as far as we know this potential treatment has never caught on widely. There may never be enough momentum to do a definitive test of glycyrrhizin as an anti-HIV treatment, at least not in the way that major trials have been done in the past. We hope that newer antiviral tests will make it possible to get clear results quickly in relatively few patients; then a community-based research organization could organize and finance small trials, and we might have better information about whether, or when, the treatment is helpful. What is holding this back is that (1) the most desirable tests, such as QC PCR or the branched DNA assay, are not widely available at present, and (2) these tests have not yet been validated with clinical results (to show that a drug which improves the test result also improves the long-term prognosis of patients). Hopefully the validation can be done on blood samples frozen years ago in clinical trials, so that it is not necessary to wait for years before a test is considered adequately validated. And hopefully, too, the medical community and the public will not allow the understandable desire for validation to get out of hand. If a drug reduces viral activity in patients and is reasonably safe, it should be allowed to be used in medical practice until something better is available. ***** U.S. Surgeon General: Letters, Calls Needed Before Sept. 7 by John S. James Letters and calls to both your U.S. Senators are needed before September 8 to support President Clinton's nominee for U.S. Surgeon General, M. Joycelyn Elders, M.D. Dr. Elders has achieved outstanding results as Arkansas State Health Commissioner, but is now the target of a right-wing campaign against her. The American Public Health Association, a strong supporter of Dr. Elders, has outlined example after example of her achievements. She made prenatal care, and also children's health assessment and care, immunization, and food programs easier to obtain. For example, she changed the rules, so that when pregnant women came for prenatal care under Medicaid, care was given immediately, and Medicaid eligibility was determined later. Under her administration, women who received prenatal care in the first trimester rose from 66.5% to 71.4%, and the pre-natal death rate decreased from 13.0 to 12.6. Health assessments for Medicaid-eligible children increased from 4,186 to 45,252 per year, and immunization of 2-year-olds rose from 34% to 60%. Infant mortality declined, teenage abortions decreased 14%, and teenage syphilis decreased, despite rising in the South as a whole. Under Dr. Elders, the number of student health centers in Arkansas increased from 1 in 1988 to 24 in 1992. In all cases, the local school boards decided to install the centers and decided what services would be provided. Two of the 24 school boards decided to provide condoms, and only to students with parental permission. This was turned into an accusation that Dr. Elders of distributed condoms in the schools. Senators in both parties have said they will vote for Dr. Elders, but currently their mail and calls are running 5 to 1 against her -- because right-wing extremists have been better than anybody else at turning out calls and letters to politicians. The Senate must confirm her nomination, and is expected to vote on September 7 or 8. What you can do is: * Write or call both your Senators to support the confirmation of Dr. Elders. Address your letters to: The Honorable ______________ United States Senate Washington, D.C. 20510 Or call your Senators, who can be reached through their local offices, or in Washington through the Capitol switchboard, 202/224-3121. * You can help even more by finding friends and associates who will write or call on this issue, and can respond to future action alerts as the need arises. If you can help in this way, and want to receive action alerts in the future so that you can activate your own personal network, contact this writer at AIDS TREATMENT NEWS, and we will try to connect you to national or regional networks compatible with your interests. Believe it or not, we do not yet have a national, grassroots, coalition response network for AIDS issues -- mainly because our political organizations have often behaved as rivals instead of cooperating for the common good. For now, people everywhere need to take the initiative, start their own networks, and press the organizations to do a better job. Dr. Elders is important because she has shown that progress can be made against social problems often considered intractable; we do not need to fatalistically accept them. And the Elders nomination symbolizes the need to take our country back from extremists who play with life-and-death issues for personal power and aggrandizement. Note: Some readers may ask how this issue concerns AIDS treatment, since the Surgeon General usually focuses mainly on disease prevention. The answer is that AIDS research, prevention, and care will all be more successful if we work together in coalition. Similarly, AIDS needs coalitions with cancer and other disease groups, to make medical research more prominent in the national agenda, so that there will be better treatments and cures for everyone. ***** Announcements ** International Conference of People with HIV/AIDS, Acapulco, September 23-28 The Global Network of People with HIV/AIDS (GNP+) will hold the Sixth International Conference for People with HIV/AIDS at the International Center Acapulco, Acapulco, Mexico, from September 23-28. The official language is Spanish, with simultaneous translations into English. The registration fee is U.S. $230. "This year's theme is 'Communication and Solidarity for a Better Quality of Life,' with workshops that promote skills building, information exchange, and empowerment. Each day, a plenary session and several small workshops will address a key issue in the fight against AIDS: human rights, health, technical assistance and skills building, communication/outreach, and the identities of people with HIV/AIDS -- gay, drug using, hemophiliac, or sex worker, to name a few. Some workshops will be very specific, such as 'How to Hold a Meeting Effectively," or 'Income-Generating Projects,' while others will address the broader issues of health, self-empowerment and human rights. Each day will also provide time and meeting space for caucuses, networks, and informal gatherings to form." For more information and registration forms, contact Mr. Rodney Jones, PPS Europe Ltd., Wicker House, High Street, Worthing, BN11 1DJ, West Sussex, UK, phone 44-(0)-903-205213, fax 44-(0)-903 210296 by September 1. Delegates may also register on the first day of the conference. Note: More than 500 people have applied to attend, but cannot afford to make the trip. GNP+ is asking AIDS service organizations to help sponsor local people who want to go. For more information about sponsoring someone, contact Pascal van den Noort, Executive Director of GNP+, in London, phone/fax 44-71-935-0208. ** Atlanta: Immune Restoration Forum August 29 The Atlanta chapter of the National Association of People with AIDS (NAPWA) will present a free forum on immune restoration for those affected by HIV. Paula Sparti, M.D., of Miami, will outline the latest news on immune-system restoration. The seminar will be Sunday, August 29, from 2 p.m. to 4 p.m., at the Colony Square Hotel at 14th and Peachtree Streets. Earlier (11:30 to 1:00), Dr. Sparti will speak about immune therapies to a brunch for physicians, also organized by NAPWA. ** Atlanta: NAPWA Seminar for Newly HIV Positive, September 11 and 12 "Operation: Survive!", a free two-day program for persons who have tested HIV positive, will be presented by the Atlanta chapter of the National Association of People with AIDS (NAPWA). This program "offers a wide variety of information and support, including presentations on HIV treatment, public benefits, insurance, legal issues, community resources, and stress management. It is designed to educate and empower those with HIV so that they effectively live with HIV infection and have the knowledge to "beat the system" and work in partnership with their health care provider." The seminar is expected to reach full capacity, and registration is required. To register, call Atlanta NAPWA at 404/874-7926. ***** In Memoriam: James Palazzolo James ("Giacomo") Palazzolo, a long-term survivor who became a leading expert in both conventional and experimental AIDS treatments, died August 7 in Cambridge, Massachusetts. He was 37 years old. Jim helped AIDS TREATMENT NEWS with a number of stories, often anonymously. Our early article on fluconazole (published on September 25, 1987, when the drug was available experimentally but largely unknown to physicians) was made possible by documents which he obtained and provided to us. We first met Jim while researching our article on BHT (published August 15, 1986); he appears in that article under the name Jim Gulli. In our article on bee propolis as a treatment for thrush (published July 31, 1987), he was identified only as "Jim." Recently he appeared under his own name, Giacomo Palazzolo, to write a two-part series on CMV experimental treatments, published in AIDS TREATMENT NEWS in January and February 1993. Jim was a professional translator of Japanese technical articles; he had attended Tokyo University, and was very interested in Japanese life and culture, and in other Oriental languages. He often used his skills and contacts in Japan to help AIDS TREATMENT NEWS and other AIDS organizations. He was also one of the first to travel to Mexico to get ribavirin for use as an HIV treatment. More than anyone we knew, Jim could "work the system" to get the treatments he needed -- even to the point of enrolling in multiple trials without telling experimenters, when telling them would result in his being expelled. In one trial he had a potentially life-threatening side effect which was likely due to the study drug, and asked to reduce the dose, but was refused. Convinced, probably correctly, that the experimenters wanted him to get sick enough for the problem to be definitively documented, he reduced his own dose without telling them. Another time he went to a screening exam with an eye patch, claiming an injury, so that the eye would not be examined and the researchers would not know that he had CMV retinitis, which would have excluded him from his only access to a drug he wanted. Although we are strongly committed to the importance of accuracy in clinical trials, we never preached to Jim, but instead listened as he raised the question of how it is possible to learn to give good medical care through trials which, too often, give bad care by design. A few months before his death, Jim discussed these matters on videotape; but it was impossible to conceal his identity -- meaning that release would have threatened his access to care -- so the tape was never edited. Jim considered Massachusetts Medicaid the most generous in the nation, but there are limits to what even he could get. During the last few weeks of his life he started campaigning for human growth hormone, a prescription drug which is plentiful, but very expensive (and also carefully regulated to prevent unscrupulous families from using it on their children to produce athletes). Besides building the Medicaid case, he also considered raising money by going to Harvard Square with a begging bowl and a sign telling why he needed the money. He never did, however. And he never got the drug. A recent picture of Jim, taken at the April 25, 1993, March on Washington for Lesbian, Gay, & Bi-Sexual Rights, has been published in A Simple Matter of Justice, (a book of photographs of the march) by Doug Emerson, page 15. The book is available through Cricket Publications, 549-A Castro St., San Francisco, CA 94114, 415/626-4942. A memorial service, and possibly a permanent memorial, are now being planned. For more information, call Maurice Mollan, 617/547-7392, or Stan Butler, 617/524-6210. ***** 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. 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