From notes@igc.apc.org Sat Nov 20 23:43:46 1993 AIDS TREATMENT NEWS Issue #187, November 19, 1993 phone 800/TREAT-1-2, or 415/255-0588 CONTENTS: Weight Loss: A Role for Growth Hormone and Anabolic Steroids? New Flu Medicine Approved, But Untested with HIV CMV Anti-Sense Drug Goes into Human Trials Tat Inhibitor Approach Still Alive Tenth International Conference on AIDS, Yokohama, August 7-12 1994 GAAN -- New Push for International Activism "Poppers" Medical Background: ACT UP Fact Sheet Available Announcements World AIDS Day, December 1: "A Time to Act" Clinical Care of the AIDS Patient, San Francisco, December 13-15 The First National Conference on Human Retroviruses and Related Infections, Washington, December 12-16 Until There Is a Cure, Fifth Annual Conference, Palmetto/Bradenton, Florida, December 3-4 ***** Weight Loss: A Role for Growth Hormone and Anabolic Steroids? by Dave Gilden Severe weight loss is a common and serious problem in people with advanced AIDS. Its relation to mortality has long been noted. Four years ago, an article by Donald Kotler, M.D., and colleagues(1) described a nutritional assessment of 32 deceased AIDS patients. The investigators found that these persons' final weight was about one-third their ideal weight. Total body cell mass was 54 percent of normal. These results were independent of the immediate cause of wasting, which could be any of a number of opportunistic infections. They suggested that maintaining body mass could prolong survival. Obviously, the first thing to do to minimize weight loss is to treat the underlying infections that trigger it. But people with AIDS may not regain the weight dissipated during acute illness. And wasting may occur without any apparent opportunistic infection. Karl Grunfeld, M.D., Ph.D., is an endocrinologist based at the San Francisco Veterans Administration Medical Center who has researched and written extensively on HIV-associated wasting. He says "Wasting is not inevitable, but a reflection of disease complications. People who rapidly lose weight almost always have opportunistic infections. And two-thirds of those with slow weight loss have gastrointestinal disorders. Everyone with HIV should have their weight charted, and when things change, the physician should look very carefully at the underlying condition." There are two therapies approved specifically for HIV-related weight loss, Marinol (or THC, the active ingredient in marijuana) and Megace (a progesterone analog), which are both appetite stimulants. There also are a number of dietary supplements, both oral and intravenous, for people with problems absorbing enough nutrients to maintain the heightened level of metabolic activity that occurs during HIV infection. (See AIDS TREATMENT NEWS #133 for a review of gastrointestinal conditions affecting nutrient intake.) Although appetite stimulation and nutritional supplementation are effective when the sole problem is insufficient nutrition, in people with HIV they usually contribute added pounds of fat, not the desperately needed protein stores in lean tissues such as muscle. Wasting in AIDS is not like starvation, where the body reduces its metabolic rate and utilizes fat stores to make up for reduced food intake. Marc Hellerstein, M.D., Ph.D., a University of California Berkeley endocrinologist who frequently works with Dr. Grunfeld observed, "In AIDS, and other diseases, too, the body switches to preferring to metabolize protein over fat. And it's hard to put lean tissue back on just by consuming more nutrients." As far as wasting is concerned, AIDS acts like any chronic disease. The body mobilizes its resources to meet the needs of emergency immune response and repair critical damaged tissue. This response, which includes breaking down existing cellular protein, is appropriate in the short-run but becomes literally self-destructive when extended in reaction to a chronic stressor like HIV.(2) Tumor necrosis factor and a number of other immune system activation chemicals (cytokines) as well as changes in hormonal balance, such as increased production of cortisol,(3) are thought to influence the shift to a wasting mode. Researchers more and more are turning to hormone-based therapies that overcome these basic wasting factors while, it is hoped, leaving valuable immune activity intact. Human Growth Hormone Recombinant human growth hormone (rHGH) has been approved for several years now to correct small stature in children. This synthetic biotechnology product, which mimics the natural hormone produced by the pituitary gland, has a two-fold mode of action. It reduces protein breakdown and nitrogen excretion while increasing fat metabolism. The availability of rHGH has led to considerable research into its use in adults to treat a wide variety of problems involving either lean tissue loss or obesity. Two preliminary studies published this year found that human growth hormone triggered significant weight gain in people with HIV wasting. The first was a University of New Mexico trial(4) comparing high dose versus low dose rHGH in a total of ten people with AIDS or ARC. The 12-week trial found that weight loss was reversed in the high-dose group, with trial participants gaining an average of 3.8 kg of lean body mass and losing an average of 1.3 kg in fat mass. (Including extra water retention, total average weight gain was 3.2 kg.) Muscle power and endurance also improved significantly. Six weeks after the trial's completion, most of these gains had disappeared, however. In a San Francisco trial published just last month,(5) six HIV-positive men and six HIV-negative controls were kept in a metabolic hospital ward for two weeks, where they were fed a uniform, controlled diet and received rHGH for a week. In the course of the treatment week, the HIV-positive men, who previously had lost nearly 20 percent of their original body weight, averaged a gain of 2.0 kg, compared to 1.6 kg in the HIV-negative men. Protein use as fuel decreased significantly in the HIV-positive group, while their use of fat increased -- hopefully sparing the body's protein. The San Francisco research group is now part of a new national trial that involves 160 men and women at ten sites. After an initial, placebo-controlled three-month period, all the trial participants will receive open-label rHGH for an indefinite period. "The FDA is calling this study 'pivotal,'" said Morris Schambelan, M.D., one of the study's investigators. "Besides being of longer duration and placebo-controlled, it will include endurance testing, better measurements of body composition, and quality of life data." There will also be immunological measurements -- several reports have indicated that human growth hormone has immune-stimulating effects. [Note: This study, sponsored by Serono Laboratories, Inc., of Narwell, Massachusetts, is now recruiting at two sites in San Francisco -- San Francisco General Hospital, and the VA Medical Center -- and at eight other sites in the U.S. Recruiting is expected to continue through 1993.] The University of New Mexico group is now conducting one of several studies that combine human growth hormone with insulin-like growth factor (IGF-1). IGF-1 is produced by the liver in response to human growth hormone. Many, but not all, of growth hormone's effects seem to be really the result of IGF. "We're just in the early data-gathering phase for IGF," said Dr. Grunfeld. "We started with growth hormone because it has a track record. Once we get preliminary data we can try combinations of the two in order to avoid particular side effect profiles." Side effects of rHGH can include swelling in the limbs, joint stiffness and increases in blood sugar and fat levels. Reversible carpal tunnel syndrome has been seen in people taking high doses of rHGH. Growth hormone is also reported to stimulate immune cell proliferation, but one group found that, in the test tube at least, rHGH also enhanced HIV replication.(6) For this reason, volunteers in the national ten-site rHGH study are required to be taking AZT or a similar antiviral medication. Among the reported side effects of IGF are jaw tenderness and low blood sugar. But long-term use of either of these drugs is an uncharted area. Anabolic Steroids It is noteworthy that the two completed growth hormone trials took two years to get into print after they were completed. This was true despite the fact that rHGH and IGF are both hi- tech, high-visibility products with very active corporate sponsors. As growth hormone research grinds on, alternatives exist at the grassroots level that cost one-tenth of what rHGH does. These are anabolic steroids, which body builders and other athletes use to increase their muscle mass and stamina. The anabolic steroid family includes testosterone and synthetic derivatives with fewer androgenic (masculinizing) effects. A number of knowledgeable AIDS specialists have been prescribing testosterone to patients complaining of weight reductions plus loss of libido [see the interview with Lisa Capaldini, M.D., in AIDS TREATMENT NEWS #184]. But just correcting the frequent mild testosterone deficiencies is often not enough, and boosting testosterone levels above normal can have adverse consequences, including liver toxicities. This is where the synthetic anabolic steroids come in. Despite anabolic steroids' "schedule III" legal status (they are controlled substances on the same level as aspirin- codeine combinations), a considerable anabolic steroid lore has accumulated in the sports world,(7) and HIV-positive body builders have brought that information to the AIDS community. One such bridge is Brian Chadsey, M.D., a Los Angeles physician who is a former football player and body builder. Chadsey has been looking at anabolic steroids' effect on HIV wasting for eight years. He currently has almost 100 patients using the substances. "I've had phenomenal results," said Dr. Chadsey, "with patients commonly gaining 20 or 30 pounds. Anabolic steroids are useful when people have unintentional weight losses of ten percent, low testosterone levels and decreases in daily functioning. Most doctors tell their patients to just live with weight loss, that it's part of the disease process. But wasting syndrome is probably an escalating event that leads to early death." [See AIDS TREATMENT NEWS #150 and #166 for two other physicians' experience with anabolic steroids.] Dr. Chadsey also reports significant improvements in his patients' immune cell populations while on anabolic steroids. Three-quarters of his patients witnessed rises in their CD8 (cytotoxic lymphocyte) counts and 40 percent have had increases in CD4, or T-helper cell levels. In Sacramento, California, Michael Dullnig, M.D., a psychiatrist, also drew on his weightlifting past when trying to control his own HIV-associated weight loss. Dr. Dullnig started personally taking anabolic steroids last spring, when a bout of mycobacterium avium left him 50 pounds below normal weight, extremely weak, and disabled in one leg. After following an individual regimen since May that includes anabolic steroids, extensive use of nutritional supplements, and a rigorous weight-training schedule, Dullnig said, "I'm back to the way I looked before, and my energy has returned. I feel like my life was given back to me." Dullnig thinks that "exercise is the key. Steroids make cells receptive to building tissue, but you need exercise to stimulate the anabolic process. The right nutrients are also very important. This is like another period of adolescence." He does warn against overtraining, though. People need to pay attention to their physical limitations. Dr. Chadsey says that not all his patients are on exercise programs, although those who are get better results. The murky social and legal atmosphere surrounding anabolic steroids makes it difficult for people with HIV to obtain the substances or even reliable information about their proper use. Expert supervision when using anabolic steroids is especially important for women, who should take lower doses than men and need to follow a regimen with little potential for androgenic side effects. And following an extensive exercise and food supplementation program is an obstacle for many people who are sick and lack stamina or digestive capacity. These are just the people who need the most protection from wasting. Researchers justify focusing their attention on growth hormone because of such objections, but more clinical trials of anabolic steroids could also provide important information. Dr. Kotler, at St. Luke's/Roosevelt Hospital in New York, is in a unique position in that he is conducting separate clinical trials on both anabolic steroids and human growth hormone. Dr. Kotler says that, although the data has not been analyzed yet, the results of the two trials seem similar, with about half the people showing considerable improvement in body composition. Those who do not are people who come down with severe opportunistic infections. Meanwhile, no major side effects with either the anabolic steroid (in this case oral oxandrolone) or rHGH have been observed. So which therapy is more appropriate? Dr. Kotler said, "We can't tell yet whether anabolic steroids, human growth hormone, or just testosterone replacement, is best. I don't even know whether any of these are good long term or have hidden side effects." Dr. Chadsey is also looking into using growth hormone to combat wasting. He thinks a combination of anabolic steroids and growth hormone may be desirable. "You need some androgenic effect to increase the reaction to growth hormone," he said. Future therapies may well be tailored to the individual, based on an analysis of each person's hormonal and immune activity as well as overall disease state. Personal tolerance to the different therapies would be a factor, too. Dr. Hellerstein speculated, "We may use a mixture of approaches depending on what people need: anabolic steroids for those with low testosterone, human growth hormone to correct metabolic imbalances, immune modulators to balance the immune system's effects, nutritional supplementation for malabsorbers, plus exercise for those who are able to do it." References 1. Kotler DP, Tierney AR, Wang J, and Pierson RN Jr. Magnitude of body-cell-mass depletion and the timing of death from wasting in AIDS. American Journal of Clinical Nutrition. September 1989; volume 50, number 3, pages 444-447. 2. Grunfeld C, and Feingold KR. Metabolic disturbances and wasting in the acquired immunodeficiency syndrome. The New England Journal of Medicine. July 30 1992; volume 327, number 5, pages 329-337. 3. Christeff N, Gharakhanian S, Thobie N, Rozenbaum W, and Nunez EA. Evidence for changes in adrenal and testicular steroids during HIV infection. Journal of Acquired Immune Deficiency Syndromes. August 1992; volume 5, number 8, pages 841-846. 4. Krentz AJ, Koster FT, Crist DM, and others. Anthropometric, metabolic and immunological effects of recombinant human growth hormone in AIDS and AIDS-related complex. Journal of Acquired Immune Deficiency Syndromes. March 1993; volume 6, number 3, pages 245-251. 5. Mulligan K, Grunfeld C, Hellerstein M and others. Anabolic effects of recombinant human growth hormone in patients with wasting associated with human immunodeficiency virus infection. Journal of Clinical Endocrinology and Metabolism. October 1993; volume 77, number 4, pages 956-962. 6. Laurence J, Grimison B, and Gonenne A. Effect of recombinant human growth hormone on acute and chronic human immunodeficiency virus infection in vitro. Blood. Jan 15 1992; volume 79, number 2, pages 467-72. 7. Phillips WN. Anabolic reference guide. Mile High Publishing, Golden Colorado, 1991. ***** New Flu Medicine Approved, But Untested with HIV by Dave Gilden and John S. James With a particularly severe flu season predicted, Forest Pharmaceuticals of St. Louis has received FDA approval to market a new drug aimed specifically at the influenza A virus. The new drug, rimantadine (brand name: Flumadine), supplements an older anti-influenza medication, amantadine. Both drugs are believed to be about equally effective in combating influenza A -- shortening the number of sick days by half. But use of amantadine has been restricted by its considerable central nervous system side effects (for example, insomnia, nervousness, depression). Rimantadine, according to the FDA-approved package insert, cuts the rate of adverse reactions by 50 percent. However, its price is triple that of amantadine. The use of flu vaccine is officially recommended at this time for people with HIV. But an anti-influenza drug (if it is well tolerated) could still be important because: * It is not known how well the vaccine works for people with serious immune deficiencies; * The vaccine must be used well in advance of exposure to the virus to provide protection. But the drugs are still partly effective even if used shortly after symptoms have begun; * Rimantadine can be used to prevent the flu when somebody's personal contacts come down with the disease; * If the influenza strain mutates, it may escape control by the vaccine but still be susceptible to the drug. The anti-flu medications cannot replace the flu vaccine. One reason is that rimantadine and amantadine do not protect against influenza B, as a vaccine can. Also, partially resistant strains of influenza have developed in up to one- third of the people treated with either of the drugs. The implications of this observation for widespread use of rimantadine or amantadine are not known. Comment Rimantadine has not been tested in persons with HIV. Persons with AIDS or symptomatic HIV disease often have more serious side effects from some drugs than other patients do. Because of the lack of information, it is difficult to compare risks and benefits of rimantadine for those patients. If any clinical research organization could move very rapidly, it could make an important contribution by running a small safety test of this drug on volunteers with symptomatic HIV infection, even before the flu season arrives. Then, if a severe flu epidemic does develop, the medical community will have more guidance on this use of this potential tool. ***** CMV Anti-Sense Drug Goes into Human Trials by Dave Gilden Isis Pharmaceuticals of Carlsbad, California is set to begin initial human trials of a radically new drug to treat CMV retinitis. CMV (cytomegalovirus) retinitis causes blindness if left untreated; it eventually infects the retinas of 20 percent or more of people with advanced AIDS. There are currently two CMV drugs available, ganciclovir and foscarnet, but both only retard the course of the disease for a few months in most cases. They also frequently cause severe side effects. Ganciclovir reduces white blood cell counts, while foscarnet can cause kidney toxicity. Isis 2922, for which the company filed an Investigational New Drug application with the FDA on October 27, is one of the furthest developed of a new class of medications -- antisense RNA. These compounds are synthetic creations that are exactly complementary to the RNA sequences produced by viral (or cancer) genes within a cell. The function of RNA is to convey instructions to the rest of the cell from any of the multitude of DNA-based genes in the cell nucleus. RNA encodes the structure of individual enzymes and other proteins necessary for cell function. Antisense RNA locks onto the RNA produced by the disease- provoking genes, thus preventing the "bad" RNA from directing undesired protein production within the cell. It is hoped that antisense RNA will be so specific that it will nullify the disease process while leaving cells' natural chemical machinery alone. The Isis drug blocks the functioning of CMV's IE2 gene. This gene encodes instructions for a protein that regulates the production of new CMV virus particles. Since Isis 2922 does not kill cells already infected with CMV, it is a long-term maintenance therapy and not a cure. Isis plans to try the drug by injecting it directly into volunteers' eyes on a weekly or biweekly basis. The initial 12-week safety trial will involve 25 people with CMV retinitis who are failing on standard therapies. This trial is not available to the general public. The volunteers will come from the practices of four physicians, whose identities have not been disclosed. If the first trial is promising, Isis will conduct larger trials in the future. It is also considering some kind of expanded access program for people outside the official trials. Future development plans include trying Isis 2922 as first line therapy for CMV retinitis and as a treatment for CMV infections elsewhere in the body. Antisense is a new and speculative field. In the past the use of antisense drugs has run into problems with unthinkably high cost, finding a critical target gene, delivering the drug to the proper tissues and cells, stability within the body, and low effectiveness. Whether antisense drugs really leave normal body processes alone also remains open to question. The local injection method Isis is using for CMV retinitis minimizes most of these concerns. Similarly. the company's other antisense drug in human trials is an anti- genital wart medicine that is administered directly to the warts. Isis is considered among the leading companies in antisense technology. However, another company, Hybridon, of Worcester, Massachusetts, is embarking on human trials of an antisense compound aimed at HIV. (See AIDS TREATMENT NEWS #185.) Isis has set up a voice mail line for inquiries about its CMV therapy. Questions can be left by calling (619) 929-3898. ***** Tat Inhibitor Approach Still Alive by Dave Gilden A small Canadian company, Allelix Biopharmaceuticals, is embarking on initial human safety trials of a new kind of compound that inhibits the action of HIV's "tat" gene. A single-dose test of human tolerance of the substance will take place in Canada this fall. HIV's tat, or transactivator, gene regulates the replication of the virus within the cells where it has taken up residence. The tat protein produced according to the gene's instructions binds onto a sequence known as the TAR, or transactivator response element, located at the end of the HIV genetic chain. There, the tat protein helps assemble new copies of HIV. This transcription process is the reverse of the original infection step, in which the RNA form of HIV genes is converted into DNA, which integrates into the cell's genetic machinery in the nucleus. Nucleoside analog drugs like AZT, ddI and ddC interfere with that preliminary step. The tat protein-TAR complex speeds up the rate of viral reproduction by about a thousand times. If it is not present, the transcription process frequently stops short, and few functional HIV particles are produced. The pharmaceutical company Hoffmann-La Roche was the leader in tat inhibitor development until it abandoned the program as a failure. Roche had used a laboratory screening process to select a potential tat inhibitor from its private stock of chemicals. The company's choice was an off-the-shelf benzodiazepine derivative related to Roche's well-known tranquilizer Valium. The compound ultimately failed to show any benefits in humans, as Roche revealed during the International Conference on AIDS last June. Company researchers then tried increasing the dosage, but that just produced more side effects. Roche announced August 2 that it would not continue work on tat inhibitors. In contrast, Allelix is following a "rational" drug design strategy. "Our company focuses on regulatory genes," Martin Sumner-Smith, Ph.D., Allelix's research director told AIDS TREATMENT NEWS. "We studied the interaction between tat and TAR and found the specific part of TAR that tat binds to. Then we developed a peptide [short protein fragment] that blocks that binding site." A fundamental reason Roche cited for giving up on the whole tat concept was new speculation, brought to a head at the last International AIDS Conference by Flossie Wong-Staal, of the University of California San Diego, that tat was not essential to HIV replication. Other substances produced by the host cells themselves also help establish the proper conditions for replication. Dr. Sumner-Smith rejects this analysis of the failure of the Roche project. "The Roche drug didn't really target the tat protein, but a cellular factor that bound to the TAR site along with tat. Tat remains an important target for inhibiting HIV." Gary Nolan, Ph.D., who has studied the HIV transcription process extensively at Stanford University, agreed that tat was essential for complete virus replication. He did worry, though, that HIV could develop resistance to an effective tat inhibitor if this compound was administered alone. "You have to be ready for even supposedly invariant regions of the virus to mutate," he said. "Theoretically you might need to attack HIV in three ways to stop it -- well, we've already lost our ability to employ nucleoside analogs as one of those ways by using them as single agents and creating a pool of resistant virus." Dr. Sumner-Smith said he doesn't expect his company's product to be a cure for AIDS by itself. "It's pretty clear HIV will need a cocktail of drugs that act synergistically," he concluded. One idea that is attracting increasing interest is a multidrug regimen that includes both a tat inhibitor and a chemical to block or limit normal cell substances that HIV also needs to induce replication. One such substance is a molecule known as NF-kappa B, which usually serves to switch on T-helper cell genes as part of the natural immune response. NF-kappa B is overactive in HIV-infected T-helper cells. Glutathione, a major cellular antioxidant, may help prevent overactivation of NF-kappa B. Glutathione levels are low in HIV-infected cells for reasons that are not entirely clear, and supplementing the diet with n-acetylcysteine (NAC), an amino acid precursor to glutathione, has been suggested as a means of replenishing those levels. Other dietary antioxidants, including vitamin E and beta-carotene, also may have a role in treatment of HIV disease. Although antioxidants have become popular in the AIDS community, questions remain as to their effectiveness and appropriate dosage. This is also true of drugs such as pentoxifylline that have been found to have an NF-kappa B inhibiting effect. ***** Tenth International Conference on AIDS, Yokohama, August 7-12 1994 The Tenth International Conference on AIDS will take place in Yokohama, Japan, August 7-12, 1994. It will be the first time this meeting, the major AIDS conference of the year, is held in Asia. Researchers who are preparing submissions should note that the deadline for abstracts is February 28, 1994 -- and abstracts must be submitted on the forms provided and cannot be faxed, because they are photocopied for the abstract book given to participants. Gil-Kenes Travel in Philadelphia, 800/223-3855 215/568-6655, fax 215/568-0696, offers a travel/hotel package for the meeting. The lowest price listed for airfare and hotel is $1850 (for travel from San Francisco or Los Angeles); reservation requires a $200 deposit, with full payment due by May 15. Those buying the travel package can also pay the conference registration fee ($590 to March 31, 1994, $785 after that date) through Gil-Kenes Travel; or it can be paid directly to the conference secretariat in Japan. For U.S. citizens, a valid passport is required, but not a visa. See the Gil-Kenes Travel brochure for more information. Professor Yuichi Shiokawa, Chair of the Organizing Committee, has addressed some of the concerns about travel to Japan: "No one will be denied a Japanese visa or entering into Japan simply because he or she is HIV-positive or has AIDS. No questions about a person's HIV status nor sexual orientation are asked when applying for a visa or entering into Japan. HIV testing is not required for a visa to Japan nor for entering into Japan." (From the current International AIDS Society newsletter, #8.) For more information, contact the Tenth International Conference on AIDS/International Conference on STD, c/o Congress Corporation, Namiki Bldg. 5-3 Kamiyama-cho Shibuya- ku, Tokyo 150, Japan, phone 81-3-3466-5812, fax 81-3-3466- 5929. Comment After the Yokohama conference, the International Conferences will take place every two years, instead of every year. This decision was made after the San Francisco conference in 1990, but since it takes years to plan for each conference, it took four years for one to go away. These conferences have been important for facilitating international contacts and organization that would otherwise not occur. The Yokohama conference is especially important, because it is the last for two years. Unfortunately it is also expensive. What is needed now is much more use of electronic mail and other computer communication for AIDS work -- especially international communication for research, organizing, dissemination of prevention and care information, and other purposes. The International Conference would be much more useful if abstracts could be submitted by computer and be available to the public before the meeting. [One reason this hasn't happened is that a different group (in a different country) runs the meeting each year, so it is nearly impossible to organize such a change before it is too late to do so. Another problem is the academic-journal habit of wanting to hide information until a specified publication date -- apparently in the belief that doing so increases authors' or journals' prestige, even if, as in this case, it destroys much of the usefulness of the information, as attenders who first see the abstract books on site cannot make good use of the five conference days, due to information overload.] Computer communication is much less expensive than meetings or phone calls, and often less expensive than mail. It allows immediate written communication, with forwarding of information to groups when appropriate. It is always available and avoids time-zone problems. Other areas of biology and other sciences are far advanced over AIDS research in using computers (especially the Internet) for international communication among researchers. Now that the conferences will be happening only once every two years, it is more important than ever for the AIDS world to catch up. [For background on electronic mail, see AIDS TREATMENT NEWS #172.] ***** GAAN -- New Push for International Activism by John S. James In the U.S. and some other countries, AIDS activists have influenced official policies, to the great benefit of people with AIDS. But there have been little international grassroots advocacy -- coordinated efforts by activists in different countries to work with the foreign-policy arms of their own governments, and/or directly with international organizations such as the Global Program on AIDS or the International Monetary Fund. This absence is likely to cost millions of lives. For example, at the closing session of the last International Conference on AIDS, M. H. Merson, M.D., Director of the Global Programme on AIDS, presented research results showing that a comprehensive prevention program for the developing world would cut in half the number of new HIV infections between now and the year 2000, saving $90 billion in costs by the turn of the century, and having even greater impact in lives saved and financial cost in the next century. The cost of the program would be $1.5 to $2.9 billion dollars a year (1990 dollars) -- about the same cost as buying one can of soft drink per year for every person in the world. Yet this program is unlikely to happen if there is no public advocacy for it. In addition, international advocacy will be important for protecting human rights of persons with HIV in all countries, and for helping to coordinate treatment and vaccine research and information access. To develop resources for international advocacy, Paul Boneberg, founder and for nine years executive director of Mobilization Against AIDS, has left that organization to found the Global AIDS Advocacy Network (GAAN). This writer is a member of its founding board. Now is an especially critical time, because AIDS efforts at the United Nations, and in the U.S. Agency for International Development, are undergoing major restructuring and reform. Just one indication of the need for advocacy is the fact that neither the U.S. nor the U.N. have included their human- rights offices in these restructuring efforts. GAAN's mission is to facilitate advocacy on global AIDS programs. It will provide policy analysis to concerned organizations, develop an advocacy and policy network, and facilitate coordination between advocacy groups. Current projects include researching the ongoing but unpublicized reforms of AIDS programs at the United Nations, coordinating advocacy efforts at major events (including the Stonewall march at the United Nations in June 1994), and developing a quarterly newsletter on global AIDS policy issues. GAAN can help organizations and individuals who are already involved in national AIDS policy or activism, who also want to have some input into shaping U.S. (or other countries') AIDS policy internationally. GAAN will also coordinate the annual International Candlelight Memorial events outside the United States. Mobilization Against AIDS, which has organized the event for ten years, will continue to coordinate the sites within the U.S. The next memorial is scheduled for May 24, 1993. Last year 240 cities in 45 countries participated. For more information, contact GAAN at: phone, 415-488-1453; fax, 415-488-1942; Internet, globalaids@aol.com; or mail, P.O. Box 376, Lagunitas, California 94938. ***** "Poppers" Medical Background: ACT UP Fact Sheet Available by John S. James "Poppers" are nitrite inhalants, originally made for treating certain heart conditions, which came to be used as sexual stimulants in the gay community. Due to concern about the dangers of long-term use, especially by people with HIV, they were banned by Federal law in 1988 (amended in 1990, to specify a broader class of nitrites, not just the chemical named in the 1988 law). But manufacturers found a way around the ban, by substituting different kinds of nitrites; these chemicals are now widely sold in adult bookstores, sex clubs, and bars. The result is that unknown chemicals, never tested for human consumption, have come into widespread use with no regulatory or public-health oversight. For those who want an accessible summary of what is known about the medical risks of the original poppers (no studies have yet been done on the chemicals sold today), ACT UP/Golden Gate has published a two-page annotated list of studies which have been published over the last ten years. (An earlier annotated list appeared in AIDS TREATMENT NEWS #160, October 2, 1992). While there is no definitive proof that poppers are harmful, they come up again and again as associated with immune suppression, Kaposi's sarcoma, and increased risk of HIV transmission. It has been difficult to inform the public about the medical risk, for two reasons. First, poppers fall between the cracks of Federal and State drug-control agencies; nobody has wanted to take responsibility for them. And it is difficult to get the information into the gay press. Many of the papers accepted advertising for poppers; most stopped when contacted by ACT UP, but they did not tell their readers about the risk. The huge profit margin in the business -- pennies worth of chemical put into a small bottle can sell for about $10 -- leaves plenty of money for promotion. Incidentally, ACT UP/Golden Gate is not calling for new laws against poppers; its effort, instead, is to get medical information to the public. For a copy of the fact sheet, send a self-addressed stamped envelope to: Committee to Monitor Poppers, ACT UP/Golden Gate, 519 Castro Street, San Francisco, CA 94114. ***** Announcements ** World AIDS Day, December 1: "A Time to Act" World AIDS Day, "the only international day of coordinated action against the spread of AIDS," has been held December 1 since 1988; it was first proposed by the World Health Organization of the United Nations. In 1993 it will be commemorated in about 180 countries. World AIDS Day provides an occasion for officials and organizations to announce policies or release information that would have come out anyway; we note it here because some of our readers may want to watch the news for developments. The U.S. Postal Service will introduce its AIDS Awareness red-ribbon stamp on that day. Various events, fundraisers, and demonstrations are planned. The organization for World AIDS Day is decentralized. For the U.S., the coordinating organization is the American Association for World Health in Washington, D.C. It puts out a World AIDS Day kit -- this year, a 40-page book, with background about AIDS, suggestions for events, tips on how to organize, ten talking points on AIDS, a sample news release, etc. -- for groups that want to participate. The local organizations decide what they want to do, and 200 have so far replied to AAWH about their plans for U.S. events. Organizations that want to be on the mailing list to receive the kit for next year can write or call the American Association for World Health, 1129 20th St. NW, Suite 400, Washington, DC 20036-3403, 202/466-5883. ** Clinical Care of the AIDS Patient, San Francisco, December 13-15 This advanced conference on clinical care is designed for practicing physicians. Topics include: guidelines and initial workup; current strategies of antiretroviral therapy; drug toxicities and interactions; gender-specific issues; practical management of advanced HIV disease; and specific infections including pneumocystis, MAC, tuberculosis, toxoplasmosis, etc. The conference will be at the Sheraton Palace Hotel. The fee is $335 for physicians, $250 for allied health professionals. Continuing education credit is available. To obtain the brochure for this conference, call 415/476- 5208. Note: Each year this conference provides material for an updated edition of the book, The Medical Management of AIDS, edited by Merle A. Sande, M.D. and Paul A. Volberding, M.D., published by W. B. Saunders Company, Philadelphia. This authoritative textbook for physicians is published remarkably rapidly; information from the December conference will appear in the fourth edition, expected to be available in the spring of 1994. ** The First National Conference on Human Retroviruses and Related Infections, Washington, December 12-16 This technical conference on both research and clinical care is cosponsored by the National Foundation for Infectious Diseases and the American Society for Microbiology, in collaboration with the U.S. National Institutes of Health and the U.S. Centers for Disease Control and Prevention. Topics listed in the preliminary program include pathogenesis, vaccines, drug resistance, combination therapy, viral-load testing, lymphokines, immune-based therapy, rational drug development, regulator genes and proteins, STDs as cofactors, and some clinical topics including tuberculosis lymphoma. It is too late to register by mail, but you can register on site. For more information, call the American Society for Microbiology, 202/737-3600. ** Until There Is a Cure, Fifth Annual Conference, Palmetto/Bradenton, Florida, December 3-4 This Friday and Saturday meeting includes talks by Western physicians and also by holistic healers. There is also a section on minority issues. Featured speakers include Bob Hattoy, who works with the White House on AIDS, and Martin Delaney of Project Inform. The conference will be at the Manatee Civic Center, U.S. Highway 301 at the Manatee River. The fee is $50 for a person with AIDS or HIV patient, $100 other, not including hotel. Some scholarships and community housing are available. For more information, call the AIDS-Manasota Conference, 813/954-6011, fax 813/951-1721. ***** AIDS TREATMENT NEWS Published twice monthly Subscription and Editorial Office: P.O. Box 411256 San Francisco, CA 94141 800/TREAT-1-2 toll-free U.S. and Canada 415/255-0588 regular office number fax: 415/255-4659 Internet: aidsnews.igc.apc.org 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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