AIDS TREATMENT NEWS Issue #166, January 1, 1993 phone 800/TREAT-1-2, or 415/255-0588 CONTENTS AIDS Treatments 1992/1993: Where Are We Now? 1993 Nucleoside-Analog Trial Results Expected Shalala for HHS Secretary: Reaction Mostly Good Anabolic Steroids for Controlling Weight Loss: Australian Experience, U.S. Trial Report from the VIIth International Conference on AIDS in Africa Announcements: Alternative/Complementary Treatment Workshop U.S./Canada Tour; Assistance Sought. Media, Public Relations Professionals: ACT UP Needs Volunteer Help ***** AIDS Treatments 1992/1993: Where Are We Now? by John S. James Each new year we write an overview of treatment development, or a list of treatments to watch in the coming year. This year's overview is difficult to write. Why? More is happening in AIDS treatment now than ever before; it is harder than ever to keep up with the news. But almost all of it is little news, better than nothing, but not centrally important for saving lives. Examples include FDA approval of yet another marginal drug; more news on nucleoside trials that could never produce a decisive improvement; the latest basic-research advance that, with luck, might be a practical treatment in ten years; more "alternative" treatments with nothing decisive to offer; another seminar on how to turn on your immune system; or a new cure-all proposed (or old one recycled). What do all of these very different examples have in common? Even when legitimate and necessary, they also represent the kind of diversionary activity which occurs when there is no satisfactory way to address a major problem. When there are no alternatives, such substitute activities may be better than nothing. But what is disturbing today is that there are clear, meaningful, and widely accepted avenues for pursuing potentially major AIDS treatment advances. But due to mismanagement and disorganization (which stem, ultimately, from the lack of consistent national political will) they are not being pursued with even a shadow of the seriousness they deserve. The extended example below shows what has happened with what many scientists consider to be the most promising class of AIDS drug being developed. As you read it, keep in mind that every drug's story is different -- and that problems are normal in drug development. The real issue is not that problems occur, but that there is no effective effort to fix them. And this issue is not unique to the example below, but is common to almost every AIDS antiviral ever proposed or tested. Example: Tat Inhibitors For years leading AIDS scientists have believed that drugs to inhibit the "tat" gene of HIV would be perhaps the single most promising approach to developing better AIDS treatments. This article will not list the many reasons for the exceptional promise of this class of drugs (see "Tat Drug Development: Current Status," in AIDS TREATMENT NEWS #153, June 19, 1992). What most interests us is that almost all the antivirals now in use or being tested (including AZT, ddI, ddC, and d4T) can only help to prevent HIV infection of new cells, but have no effect on the virus in chronically infected cells, leaving a reservoir which can produce illness in various ways, as well as creating drug-resistant virus. In contrast, an effective tat inhibitor would shut down all HIV activity, even in already-infected cells. Tat inhibitors should be fairly easy to discover, because an efficient screening test for finding them is readily available. In fact, the fastest and least expensive approach to developing a tat drug might well be to screen the thousands of drugs and others substances already in human use; if a good tat inhibitor is found, then all the safety, pharmacology, manufacturing, etc. problems will have already been worked out, and the drug would be ready for use. No one is doing such screening, however, since there is no commercial incentive. Instead, the whole pharmaceutical industry (or rather, that small part of it which has any interest in AIDS) seems to be waiting to see what happens with the only tat inhibitor drug now in human testing -- code-named Ro-24-7429, being developed by Hoffmann-La Roche. Meanwhile, governments (and the rest of the AIDS world) wait for industry to develop tat drugs. In the middle of a major worldwide epidemic, the most promising approach to treatment development has been abandoned to a single project with a single drug in a single company. The problem is that the whole world waits for what might be the wrong tat drug, and almost certainly is the wrong company. Ro-24-7429 has been delayed because its complex and unusual pharmacology required additional studies to learn how to safely administer it. But the biggest problem has been the lack of commitment by Roche to the project. First, the company decided to abandon the drug, calling off an imminent human trial at Johns Hopkins University by a phone call to the researchers there on April 29, 1991. After AIDS scientists expressed great concern over the loss of the only tat inhibitor in development (see "Promising AIDS Drug Looking for a Sponsor," Science, July 19, 1991, pages 262- 263; also see the Wall Street Journal, May 30, 1991, page B4), Roche decided to sell Ro-24-7429 instead of abandoning it. It came within days of selling it (to Burroughs- Wellcome), but then changed its mind again and decided to develop the drug itself. A major problem now seems to be the lack of commitment of enough staff and resources to this drug within the company. Trials have repeatedly been delayed, and there is still no data on whether or not the drug reduces viral load in people, despite the fact that human testing began well over a year ago. Within Roche, two people are in charge of the tat inhibitor development; we do not know if there is any other professional staff on the project. During a conference call last month, we asked these two about an earlier attempt to develop a tat drug, which had apparently failed. At least as far back as 1988, German scientists had proposed that d- penicillamine, a prescription drug, might be a useful tat inhibitor; an article published in 1986 described a test of the drug as an HIV treatment in Germany. A later study, however, (presented in June 1990 at the Sixth International Conference on AIDS in San Francisco) reported harmful side effects and no evidence of benefit. We wondered what lessons had been learned from this apparent failure, and how they were being incorporated into future tat-drug development. But it turned out that the team developing Ro-24-7429 at Roche did not even know that d-penicillamine had been proposed or tested as a tat inhibitor, despite several published papers on the earlier work -- well over a year after Roche had its own tat inhibitor in people. This is the project that the whole world has entrusted, for two years, as the sole human developer of the most promising class of potential AIDS drugs, the most feasible development path for finding more effective treatments. Fortunately the AIDS Clinical Trials Group (ACTG) of the U.S. National Institute of Allergy and Infectious Diseases (NIAID) began a trial of Ro-24-7429 in December, 1992. This trial will, for the first time, measure indicators of viral activity before and after treatment, so that at last we will know whether or not the drug has biological activity in people. Our main misgiving now is that Roche has so little interest in its own drug. What might it know that we don't? And if this drug should fail, will there be a stampede to reject the whole class of drugs even if there is no rational reason to do so? Why would Roche decide not to sell its drug after all, if it had so little commitment to it? Since we cannot read minds, we can only guess at possible scenarios. If tat inhibitors are indeed promising but Ro-24-7429 had problems that would delay or rule out its final development and marketing, then Roche would stand to lose its valuable lead in tat drugs if another company entered the field with a better one. The best way to prevent that would be to avoid releasing the key data on the drug -- whether it has biological activity in humans -- since other companies would then be likely avoid risk by waiting to see what happened with Ro-24-7429 before committing themselves to tat drugs -- giving Roche time to either overcome the problems with Ro-24-7429, or to find a second-generation drug to replace it. Another speculation is that if there were anything embarrassing in the history of the tat drug project, Roche might not have wanted the evidence to go out its door and beyond its control. Tat inhibitors appear to be much easier to develop than other classes of drugs such as protease (proteinase) inhibitors. But the latter have received much more attention, with several companies competing to develop them -- probably because protease inhibitors present more professionally interesting challenges. With tat drugs, enough fundamental problems have already been solved that what is needed now is a straightforward, well-managed development effort. But scientists are attracted to scientific not management problems, and non-scientists have not understood the drug. And no one has had the national or international mandate to see that a first-class opportunity was being wasted, or the authority to do anything about it. The issue here is not Roche, but the rest of the world. How can the United States (which does the most biomedical AIDS research), or any other country, allow its vital interest in better AIDS treatment to remain so unguarded and unattended? Comment: Where Do We Go From Here? We believe that the most important AIDS treatment development in 1992 was the election of Bill Clinton instead of George Bush as U.S. president. But maybe not for the reasons people think. At AIDS TREATMENT NEWS we spend considerable time on the phone talking to people whose primary work is not AIDS -- mainstream reporters and corporate officials, for example. Already since the election there seems to be a difference in seriousness, in respect for the issues. The difference seems to go beyond AIDS, to reflect a national change toward dealing with public problems, instead of finding clever maneuvers to excuse an evasion of responsibility. But the hostile Reagan-Bush administration also provided an excuse for the AIDS community. With leaders like those, we were free to defend against the latest attacks as they occurred, without responsibility for setting our own agenda or for getting results. For example, Bush never received a consensus demand from the AIDS community for improvements in treatment research, except for faster access to treatments nearing approval (which he supported), and for more money (where he was not the leading obstacle). Maybe our lack of input made no difference anyway; the White House overruled the entire AIDS community, as well as the intent of Congress, on the HIV travel-immigration ban, apparently as a political payoff to bigots. But in the future, with a potentially responsive government, it will be disastrous if the AIDS community does not formulate workable research policies and make them known. The biggest problem in research is the lack of a consistent national commitment to save lives. Researchers have not had the support they need to do what they know is important. So trials have focused on commercial drugs -- known to be inadequate, but where the money is -- while clear prospects for decisive treatment advances have remained ignored or grossly under emphasized. And basic research has focused on high-tech, commercially viable toys with little regard for what could or could not be used in the foreseeable future. Covering the News When reading AIDS TREATMENT NEWSletters in 1993 and beyond, remember that we have to cover two kinds of news: what happens, and what doesn't happen. In AIDS treatment development, the latter has been by far the more important. (The mainstream press need only cover the former, however, since it is in the entertainment business and not responsible for conveying information that citizens could use.) We, too, must spend most of our space on mediocre news -- about the marginal nucleoside analog, antibiotic, drug combination, or "alternative" treatment -- because usually that is all there is. And as the standard of care changes, there may be disruptive ripples through ongoing clinical trials, which were not designed with the real world in mind. We will cover the ethical debates, the endless meetings, the marching in place of hundreds of well-paid professionals going nowhere. But we should also remember that, with a potentially friendly government for the first time in the AIDS epidemic, it is more important than ever before to occasionally step back from the ritual of the moment to consider what is truly important for saving lives, and what is not. There is no longer any excuse for a no-win war in AIDS treatment development. No one can guarantee a date when a better treatment might be found. But we can insist that the obvious good leads in front of us be promptly followed up. ***** 1993 Nucleoside-Analog Trial Results Expected By Larry Tate The past year has seen significant developments in the area of basic nucleoside analog antiretrovirals -- AZT, ddC, ddI, and d4T. DDC was finally approved, for combination use; ddI's approved indication was expanded, and promising data on combination use with AZT was revealed; d4T began a parallel- track program; and a European-Australian study supported the use of AZT by people with T-helper counts up to 750. The coming year will bring further developments for these drugs and combinations of them, as well as for 3TC, another nucleoside analog, and a three-drug combination of AZT, ddC, and alpha interferon. It is rarely possible to say exactly when data from specific trials will be made public; the timelines mentioned below can only be approximate. The first key development in 1993 will be the long-awaited release of data from ACTG 116A, a study comparing AZT to ddI in people with fewer than four months' prior AZT use. This amounts to comparing the two drugs as first-line therapy -- and suggesting which drug patients starting anti-HIV therapy should use. By mid-January, it should be known whether ddI in this circumstance is more effective, less effective, or about the same as AZT. The study group had T-helper counts under 300, but the results might well apply to people starting treatment at all T-helper levels. AZT has so far been the standard first-line therapy; should this study prove it to be less effective than ddI, there would be a major reassessment of how these drugs are used, affecting not only clinical practice but probably some ongoing trials as well. If the two drugs show equivalent efficacy, or if AZT is more effective than ddI, the current standard of care may not be much altered. Also long-awaited are the results of ACTG 019, a large and very long-running trial that compared AZT to placebo in people who started with a wide range of T-helper counts -- about half of them over 500. Data on the group who started with counts over 500 should provide the clearest answer from any U.S. study on the value of AZT (and, by implication, other nucleosides) in people in early stages of infection. If AZT delays disease progression in this group, there could for the first time be an FDA-approved therapy for people with T- helper counts over 500. Data from ACTG 019 may be available as early as February, or if not, by mid-year. The comparable and equally long-running Concorde study in Europe also looks at AZT versus placebo in people starting with a wide range of T-helper counts. Data from the Concorde study also may be available early in the year, or by mid- year. By late spring, final data is expected from ACTG 155, a study which compared AZT to a combination of AZT and ddC in people with fewer than 200 T-helper cells. The FDA, on the basis of two smaller studies, approved ddC for combination use with AZT, but the data from ACTG 155 will be critical in confirming the value of combination therapy. If the results show an advantage for the combination, the current label indications for AZT/ddC use (which are widely considered to be somewhat tentative and confusing) may be clarified and strengthened by the FDA. At the 1992 International AIDS Conference, three small studies reported interim data on combinations of AZT and ddI. All three have been completed or are near completion, and are likely to publish final data in the first half of the year. These studies used different doses and entry criteria and monotherapy control groups, making it difficult to compare results; however, should final data indicate an across-the- board advantage for combining AZT and ddI, there would then be at least as much data on the AZT/ddI combination as there was on the AZT/ddC combination when the FDA approved ddC. A change in clinical practice and in FDA indications might result. (It should be noted that ACTG 175, the large trial comparing combinations of AZT/ddI and AZT/ddC to AZT and ddI as single agents, is not expected to make public any results in 1993.) The ongoing d4T trials are not expected to announce any results this year. At least one pilot study combining d4T with ddI is planned; others may follow. Only one nucleoside in early trials appears to be moving smoothly toward wider use. 3TC is now in late dose-ranging studies, and is expected to start large Phase II comparative studies in the spring (similar in some ways to the d4T trials now in progress). Sources have told us that this drug has so far shown clear anti-HIV activity and no serious side effects. It could be speculated that, when these Phase II trials start, there might also be a role for a 3TC expanded- access program, but it is too soon to know. Finally, two studies comparing the combination of AZT and ddC to a three-drug combination of AZT, ddC, and alpha interferon will be continuing through the year. Late in the year, some interim data might be available from the larger of these studies, looking at people with T-helper counts between 300 and 500. Obviously, there are a number of possibilities for studies of various three-drug combinations, and results from this trial could stimulate that research. Comment Nucleoside analogs are often discounted by people who argue, incontestably, that there are stringent limits to what these drugs can do and that their various side effects often cause great problems to patients. Nucleosides have always been regarded as a stopgap until better treatments arrive. That may be true, but there is a fairly clear understanding of how they work and how their side effects can sometimes be managed; three are FDA-approved and two more may be on the way to approval; and they are backed by big drug companies with the resources to develop them quickly. Although nucleosides are of limited efficacy, those limits may not turn out to be so stringent as was once thought, if up to five drugs come to be used serially and in combinations. Therefore, any new availability of nucleosides or new information on how to use them is important. ***** Shalala For HHS Secretary: Reaction Mostly Good by Keith Griffith The announcement that Dr. Donna Shalala will serve as Cabinet Secretary of Health and Human Services (HHS) for President- elect Bill Clinton is viewed favorably by most persons with whom AIDS TREATMENT NEWS has spoken. Most believe Dr. Shalala would bring excellent managerial skills to the job, but almost everyone who has observed her performance at University of Wisconsin-Madison said there were controversies in her record that might indicate a need for caution. Dr. Shalala will oversee agencies that account for 40 percent of all federal spending including the National Institutes of Health, the Food and Drug Administration, and the Centers for Disease Control and Prevention. Additionally, she must deal with entitlement programs such as Social Security, Medicare, and Medicaid which appear to be headed for major changes in an effort by Clinton to address the federal deficit. Dr. Shalala, in remarks delivered at the news conference to announce her appointment, included AIDS as one of the top five priorities in her first year. She has so far not elaborated on what that might mean, and requests from AIDS TREATMENT NEWS for an interview were denied. This article is based on interviews with AIDS policy specialists in Washington, community leaders and university officials in Madison, and a close study of numerous interviews given in recent years by Dr. Shalala. Background In her role as chancellor at University of Wisconsin-Madison, a job she took in 1988, Dr. Shalala (pronounced shuh-LAY-luh) has been in charge of the nation's sixth largest university and the largest public research university in the country. Previous to the chancellorship, she was president of Hunter College in New York and an assistant secretary in the Department of Housing and Urban Development under President Carter. Her first major exposure to public service was on the Municipal Assistance Corporation, the agency that was created to return New York to financial solvency in the mid- seventies. People use terms like "crackerjack administrator" and "perfectionist" in describing her management style. Dr. Shalala has little experience in public health, and with AIDS in particular. AIDS TREATMENT NEWS has found few hints of her likely positions regarding treatment research, access to care, and other critical AIDS issues. Dr. Shalala is credited with filling some key positions at the university with persons who have experience in the field of AIDS. Additionally, Mary Alice Mowry, executive director of Madison AIDS Support Network, the primary AIDS agency in Madison, applauded Dr. Shalala for using her influence to bring key people into the struggle against AIDS who had previously been hesitant. Past Controversy The primary concern we heard was that Dr. Shalala would not "stick her neck out for us," as one activist stated it. Dr. Shalala has faced the condemnation of protesters because of a belief among some in Madison that she was not acting entirely responsibly on behalf of vulnerable groups including people living with AIDS. Members of one senior class wore latex gloves to accept their diplomas from Dr. Shalala in protest over her silence regarding one particular incident. At a protest over the presence of ROTC on campus (ROTC, like all U.S. military programs, does not allow recruitment of gay men and lesbians, and numerous college campuses have removed the program in recent years), several persons engaged in civil disobedience were removed by campus police who were wearing latex gloves, a signal many interpreted as supporting irrational fears of persons who might have AIDS. Activists claim Dr. Shalala failed to provide leadership, instead choosing silence. Perhaps more importantly, many we spoke with fear this incident, and several others which were not AIDS-related, may indicate an unwillingness to aggressively speak out if it is too politically sensitive. "I never heard a word from her on the issue. She did not condemn the protesters, but she also didn't condemn police behavior," remembers Maria Hanson, Outreach Coordinator for a Madison group, United, and one of those arrested. This issue (ROTC is still on campus) is considered by many to be one of the low points of Dr. Shalala's stay in Madison. "I think she played politics regarding ROTC," stated Mowry. "It was one of the things she could have done better." Management Skills In spite of concerns from some that Dr. Shalala might not be willing to use her political capital on a controversial issue such as AIDS, most people we spoke with expect her to bring positive administrative change to HHS. "Clearly she has not had a lot of experience on AIDS issues," stated Jeff Levi, Director of Government Affairs at AIDS Action Council. "It is the frame of mind she brings to the job that is important." Her management skills and theories appear to be why Clinton appointed her. In remarks at the recent Economic Conference in Little Rock, Dr. Shalala referred to "the myth that complex bureaucracies can't improve." In one analysis she is described as someone who will "call on a management style that has served her well in federal government, city politics and academia: She targets a problem precisely, aims carefully and then attacks it from several angles at once -- verbally, publicly, forcefully."1 This may be good news for persons who have pleaded for forceful leadership on AIDS. Additionally, Dr. Shalala told one interviewer, "I would say that I have essentially the skills of skilled managers and that means I am strategic. If you look at corporate executives in this country who are successful, they are strategic thinkers...My ability [is] to put all of the pieces together in an overall strategy."2 Jane Silver, Director of Public Policy for AmFAR, agrees that this is exactly what is needed. "Dr. Shalala needs to develop a national plan, implement it and continue identifying AIDS to the public as the important health issue it is." Silver believes it is a very good sign that AIDS has already been identified by the Secretary-designate as a top priority. Dr. Shalala has spoken about other issues of concern to the AIDS community, although not in the context of AIDS: The need to address greed, waste and duplication in spending federal money, especially in universities; the ongoing problem of scientific research fraud; and a strong desire for federal government to recognize that research and development in basic sciences must continue to grow even in a time of deficits. Comment Perhaps the biggest uncertainty right now is how strong a mandate President-elect Clinton will provide his cabinet appointee to HHS. Many we spoke with who have observed Dr. Shalala say she is far too much of an "insider" to stand firm on controversies that Clinton would rather ignore. Maria Hanson, who has been monitoring Dr. Shalala on numerous issues in Madison, urges that people "not let down their guard just because there may be a less hostile secretary overseeing HHS. Unless Dr. Shalala has a lot of people in the roles of watchdog, she may not order priorities where they need to be." No matter how progressive Clinton may look compared to his predecessors, there will be much that the AIDS community feels is essential that will not fit into his agenda. Whether Dr. Shalala will be an advocate for people living with HIV or someone who only carries out White House policy is a critical determination yet to be made. References 1. Cleveland C. (campus CEO at the University of Wisconsin). Working Woman, December 1991; pages 60-63. 2. Bernstein A, Mow S. On Changing Academic Culture From the Inside. Change, January/February 1989; pages 20-29. ***** Anabolic Steroids for Controlling Weight Loss: Australian Experience, U.S. Trial by John S. James Anabolic steroids are best known to the public through the bad press resulting from non-medical use by athletes for muscle building in competitive sports. Unfortunately the resulting controversy has held back legitimate medical research and use of these important drugs. (Anabolic steroids should not be confused with corticosteroids, which have entirely different effects.) Recently we called Julian Gold, M.D., at the Albion Street (AIDS) Centre, the major AIDS medical facility in Sydney, Australia, about an unrelated subject (a dose and toxicity study of hypericin, an antiviral). Dr. Gold also told us about the Centre's experience with a trial of low-dose nandrolone decanoate (Deca-Durabolin), an anabolic steroid, for preventing further loss of body weight which has no obvious cause. We interviewed Dr. Gold, and also called Donald Kotler, M.D., a leading specialist in gastroenterological complications of AIDS, who is now conducting a trial of a different but related anabolic steroid in New York. Interview with Julian Gold, M.D. ATN: What patients are you treating with nandrolone decanoate (Deca- Durabolin)? JG: We started to use this drug two years ago, at first with patients at very late stages of HIV infection, who had lost considerable body weight, 15 to 20 percent or more. We treated over 30 patients with the injectable Deca Durabolin, using 50 to 100 mg per week. This was not very useful, as after nine months the weight loss continued. In the last year, we have started instead to treat people who have lost between five and ten percent of body weight. We are now using a dose of 100 mg every two weeks. ATN: So it's just one shot every two weeks? JG: That's right. We have had about 50 people who have used this regimen. The objective is to stabilize weight loss, rather than to have these people put on large amounts of weight -- not to try to replace, because these patients have not lost too much weight. And for this study we chose people who can still eat, and preferably can still get at least minimal exercise, including walking or perhaps they can still go to the gym. We tried to pick people who were just on the precipice, where if nothing were done they would lose a lot of weight. We looked for patients on an adequate and nutritious diet but who still continue to lose weight. They need to have dietary counseling first, before entering the study, to be sure it is not a bad diet that is causing the problem. And they must not have any obvious cause of the weight loss, such as gastrointestinal infections, malabsorption, or untreatable diarrhea. ATN: Who should not use the drug for safety reasons? JG: Underlying diabetes or other endocrine problems, or liver disease, would be among the contraindications. But we have now monitored almost a hundred people taking this drug, and we found no adverse effects on liver functions or any of the blood biochemistry; in fact it has improved hemoglobin in some people. We found no adverse effect on HIV antigen or T- helper counts. ATN: How long have patients been on the new regimen so far. JG: For 12 months. ATN: Are any women using it? JG: Deca-Durabolin is a testosterone derivative, which could cause problems for women. We have not used it in women, but possibly we may try in the future. We are doing this step by step. ATN: Do you have industry support? JG: Our research is sponsored by Organon, a local branch of Akzo, which is headquartered in the Netherlands. Akzo makes the drug available to us. ATN: What are your future plans? JG: First, we are analyzing our existing data for publication. So far we have only conducted a pilot study, looking at any toxicity or problems. Now we are planning a more structured clinical trial, to give selected people the drug for 26 weeks and monitor more test results than before, including different measures of body composition. Then we will move into a comparative study, possibly comparing this drug with one of the other weight-loss treatments. The politics of AIDS, together with the politics of anabolic steroids, has meant that we have to go slowly. But we are optimistic; people on the treatment feel better, their appetite improves, and we have not noticed the potential problems like virilizing [masculinizing] effects and excessive muscle gain, because we do not use a high dose. ATN: Can people contact you for more information? JG: They can contact the Albion Street (AIDS) Centre, in Sydney; phone 61-2-332-1090, fax 332-4219. They can ask for Chris Oliver our clinical nutritionist, or ask for me. Oxandrolone Trial in New York: Interview with Donald Kotler, M.D. To get another perspective on the use of anabolic steroids in AIDS, we spoke briefly with Donald P. Kotler, M.D., at St. Luke's/Roosevelt Hospital Center in New York, who is currently running a trial of another anabolic steroid, oxandrolone, and is familiar with the work in Australia. ATN: How does oxandrolone differ from the nandrolone decanoate which is being used in Australia? DK: Both are testosterone derivatives; they differ in strength. Testosterone has both anabolic and androgenic (masculinizing) effects. Because of the androgenic properties, both are largely ruled out in women. Other drugs which have the anabolic effect without the strong androgenic effect might be more suitable for women. ATN: Why are anabolic steroids being tried for treating HIV? DK: This treatment is supported by a good theory. But does the theory work? That is what the trials are designed to find out. We know that there are metabolic changes in some AIDS patients that keep the body from holding onto proteins. Anabolics help the body hold onto proteins. But will they actually benefit patients? That needs to be shown. Our trial compares two doses of oxandrolone to a placebo. We are recruiting 24 patients for the four-month trial; the 7th started today. Only one has finished so far. We have seen no side effects at all from the treatment, and some weight gain. We are still waiting for body-composition measurements. ATN: Do physicians have trouble prescribing these drugs because of the controversy around them? DK: These are controlled drugs in the U.S.; a triplicate prescription is required. There is abuse potential, with danger to the liver from the high doses sometimes used by bodybuilders. ATN: So physicians may be reluctant to prescribe these drugs, without a clear consensus for their use. DK: We are pushing to get the data as soon as possible. The question is, will the experience fit the theory. Note to potential volunteers: Dr. Kotler's trial in New York is testing two doses of oxandrolone for the treatment of malnutrition associated with HIV infection. One third of the volunteers will receive a placebo. The trial lasts for four months, and followup treatment will be made available. This trial is sponsored by Gynex Pharmaceuticals, Inc., of Vernon Hills, Illinois. The study includes nutritional assessments, and measurements of food intake, muscle strength, quality of life, and immune function. There is no cost to the volunteers. If you believe that you are suffering from malnutrition as a result of HIV infection and are interested in volunteering for this trial, please call Jodi in Dr. Kotler's office, 212/523-3670. Oxandrolone Trial for Muscle Weakness: Miami, Chapel Hill, New York A separate but related trial of the same drug for a different use is also being conducted by Gynex Pharmaceuticals. "A Phase II Double Blind Placebo Controlled Study of Oxandrolone for HIV-Associated Myopathy/Muscle Weakness" is seeking HIV- positive men 18 or older with generalized or proximal muscle weakness. Antiretroviral treatment is not required, but patients on any FDA-approved antiretroviral must have been on the drug for at least eight weeks before enrollment. There are several other entry criteria, mostly for assuring patient safety. This trial is being conducted at three sites: the University of Miami School of Medicine, Miami; the University of North Carolina, Chapel Hill; and Mt. Sinai School of Medicine, New York. Twenty three volunteers are already enrolled, of the total target enrollment of 48. Oxandrolone is already an approved drug. If these trials are successful, the company will obtain FDA approval to market it for the AIDS-related uses which are now being tested. ***** VIIth International Conference on AIDS in Africa By Jason Heyman For only the third time in its history, the VIIth International Conference on AIDS in Africa took place in an African city, Yaounde, Cameroon, from December 8-11, 1992. Previously, the conference has been held in Europe with sponsorship from European and Canadian health organizations including the World Health Organization. Two reporters from AIDS TREATMENT NEWS (this writer and Nancy Solomon) attended in order to learn about international treatment issues. However, little treatment information was presented. The conference took place in what felt like an atmosphere of failure. Prevention, which was the main topic, has been failing to stop the rapid spread of HIV in Africa. According to Michael Merson, the director of the World Health Organization's Global Program on AIDS, "There have already been over 7.5 million infections in adults [in Africa] since the start of the pandemic, close to 4 million of them in women." A different AIDS virus, HIV-2, was discussed in detail at the conference. HIV-2 has come to be known as the virus of developing countries and has not been given the attention that HIV-1 has received. One interesting difference is that HIV-2 is much less likely to be transmitted from mother to child. Prevention vs. Treatment At a symposium held during the conference by The Wellcome Foundation, prominent African community activists expressed frustration at the failure of current efforts to stop the spread of AIDS. One of the most inspiring speeches was delivered by Sy El Hadj Amadou, the African Secretary of the International Council of AIDS Service Organizations (ICASO), who drew a connection between the failure of prevention efforts and the lack of AIDS treatments available to Africans. He explained that as a result of the African AIDS community's defeatist attitude towards access to treatment, and the West's view of Africa as a lost cause, all anti-AIDS efforts are seen as half-hearted and are not taken seriously by the public. Prevention tactics, he explained, must be based on a re-affirmation of life and the promise of hope. Such efforts are doomed to fail in this climate of neglect. "How can we be credible in this field if we adopt this defeatist attitude, by accepting in advance that even if there is an efficient drug against this disease, the population that we want to educate to change their behavior won't have access to this medication." "The fight for better access of the African population to treatment.....is the only way that we will overcome the problems created by poverty and lack of resources. Through this we will create a credible education program, and we will make our message obtainable and support the population to change their attitude." (Translated from the French, by the official conference translator). John Ziegler, M.D., from the University of California San Francisco Medical Center, spoke on, "The Management of HIV Infection," which included an "Introduction to Antiretrovirals." To an American observer it seemed as if he were going back in time to the introduction of AZT, but AIDS treatment in Africa with pharmaceutical products is almost non-existent. Dr. Ziegler was in fact looking forward to a time when basic antiretroviral therapies will be available. "In anticipation of more effective and cheaper drugs in the near future, studies should commence in selected centers to define a clinical role for antiretroviral therapy in Africa." At the end of the Wellcome symposium one questioner asked if he could direct a question to Wellcome itself. He asked what they are doing to make Burroughs Wellcome drugs, specifically AZT and acyclovir, available in Africa. With some hesitation a Wellcome employee explained that he was not at liberty to give that information, but that we should rest assured they are working on it. The only treatment discussed at any length at the conference was PCM-4, a little-known alternative treatment made from extracts of pig spleen and Siberian genseng, Eleutherococcus senticosus; it is being studied in the United States and in Uganda, and is sold in buyers' clubs and health-food stores. The U.S. Agency for International Development (USAID), which controls all government money spent on AIDS in developing countries, even has legal guidelines that restrict money to prevention uses only. A USAID representative, Gordon Murchie, explained that they do support research efforts abroad, but to take on the issue of treatment "would be a vast undertaking, comparable to taking over the health care systems of all the countries concerned." The World Health Organization is the only international organization that is currently distributing drugs for the treatment of AIDS, but according to recent rumors their Essential Drug Program has recently cut its AIDS drugs for lack of funds. Some of the drugs available through this program are as basic as acetaminophen and petroleum jelly. African Traditional Medicine Traditional African medical practitioners were largely absent at this conference. Speakers such as Susan Anderson from the World Health Organization, who discussed community care, spoke about the important role that traditional healers play in the African health care system, but these practitioners themselves had no presence on the podium. Most Africans go first to a traditional healer when they are ill. This important link has been generally ignored by the Western-oriented development agencies that are re-creating African health care systems in the image of European and American ones. With their direct access to the population, traditional practitioners can have an important role in education, prevention, and treatment. One traditional healer, Fokoundang Adam Usumanu, was present at the conference, and was excited by the prospect of working together with the formal health care system. Currently he is trying to organize a group of approximately forty traditional medical practitioners in Cameroon to pool their knowledge and resources to help treat people with AIDS. One of the treatments he uses is yohimbine, which in the United States is a prescription drug found in the bark of the Corynanthe johimbe tree and used for treating impotence in men. AIDS TREATMENT NEWS #159 (September 18, 1992) reported on the experiences of two people with HIV who had positive results using yohimbine for the treatment of fatigue. This coincidence suggests again that traditional healers have knowledge of useful treatments, many of which are unknown to western pharmacists. Fokoundang Adam Usumanu has 30 treatments that he currently employs. Comment One hopeful sign is that African governments are beginning to openly confront AIDS. The Organization of African Unity, for the first time in its history, addressed AIDS in its "Declaration on the AIDS Epidemic -- July 1992." Its treatment goal: "By mid 1993, we will have adopted a rational AIDS care plan, including essential drugs for HIV-related illnesses, and a rational plan for family-based or community care and support of AIDS survivors, including orphans." At the closing ceremony, Jonathan Mann, M.D., announced the creation of a new center at Harvard University for the study of health and human rights. He underscored the connection between these two fields, making the observation that around the world it has become clear that those people with power who have their rights generally have their health. The slow pace with which Africans with AIDS are being given access to treatment is an example of this. Although many people in the United States are frustrated by the lack of effective treatments for many AIDS-related conditions, we should follow the advice of Sy El Hadj Amadou and make the treatments that we currently have available to all those who need them. One panelist remarked that the difficulty of getting AIDS treatments to all Africans who need it can be put into perspective when we realize that many cannot even get clean water. Still, we should make the effort instead of taking the defeatist attitude of powerful groups like USAID. The success stories that exist offer hope that progress can be made to stop the spread of HIV and treat those that are already infected. The Know AIDS Society, in Nairobi, Kenya was started by Joe Muriithi, who is one of the first Africans to be open publicly about his HIV-status, and his wife Jane Muriithi. Their work educating their community, with a special focus on women, is an example of the success some small groups have had, an example for the large development agencies about what can work in Africa. And the skills and knowledge of traditional African healers should not be ignored. The effective work of small African grassroots organizations like the Know AIDS Society, and of activists like Sy El Hadj Amadou, shows that improvements can be made. ***** Announcements ** Alternative/Complementary Treatment Workshop U.S./Canada Tour; Help Sought "Staying Healthy with HIV," a well-regarded nonprofit workshop in alternative/complementary/traditional treatments for AIDS or HIV, is planning a tour of 25 cities in the U.S. and Canada during March, April, and May 1993. At this time the organizers are seeking help from local contacts in making arrangements for the workshops, which they hope to provide free. Staying Healthy with HIV has been developed during the last two years by David Baker, R.N., who specializes in teaching health promotion to people with HIV, and Richard Copeland, managing director of the Healing Alternatives Foundation (the AIDS buyers' club in San Francisco) for almost four years. The workshop has been presented twice through the San Francisco Kaiser Medical Center, twice through the Sonoma County Public Health Department, at the AIDS, Medicine, and Miracles conference in Boulder, June 1992, and in San Francisco at the Immune Enhancement Program and the Quan Yin Healing Arts Center. Baker and Copeland presented a related poster at the VIII International Conference on AIDS in Amsterdam, July 19-24, 1992 ("Collected Research Findings and Anecdotal Reports on the Optimal Dosage, Side Effects and Benefits of Selected Alternative Medications in Gay Men with HIV," abstract #PoB3391). Their workshop is a project of the Center for Natural and Traditional Medicines in Washington, D.C. The workshop consists of a two to three hour session focusing on alternative medications, together with discussions of nutrition, stress management, understanding laboratory test results, prophylaxis for opportunistic infections, and holistic healing. Over 25 alternative treatments are discussed in the 32-page handout given to participants. The organizers do not recommend any particular treatments, but provide information and guidelines to help evaluate different options. (There is also a one-day version of the workshop, limited to 10 people, which includes experiential exercises.) If you could help to bring Staying Healthy with HIV to your city, contact the organizers at the address or phone below. They need assistance in finding a free or low-cost facility, publicity (including outreach to underserved communities), arranging computer/modem access during their stay, finding a host who can provide lodging and some meals, learning about specific needs of your community, and locating additional funding. If you could help, or want further information, contact David Baker & Richard Copeland, Staying Healthy with HIV, 13-B Belcher Street, San Francisco, CA 94114, 415/255-0690. ** Media, Public Relations Professionals: ACT UP Needs Volunteer Help The acyclovir price-cap issue (reported in AIDS TREATMENT NEWS #165) shows the need for professional assistance to help treatment activists advocate for the interests of the AIDS community. ACT UP/Golden Gate, Project Inform, and AIDS Action Baltimore, although kept in the dark about details of the Burroughs-Wellcome program, were able to reply with a faxed press release on the same day the program was announced. But only one mainstream newspaper (the San Francisco Examiner) used the activists' information; the Wall Street Journal covered only the Burroughs-Wellcome view. Most of the press ignored the story entirely -- despite the fact the issue of pharmaceutical prices is central to President- elect Clinton's effort to control health-care costs, and will probably be a major battle in Congress during the coming year; a bill to discourage pharmaceutical price increases is being sponsored by Senator David Pryor (Democrat, Arkansas). Activists can do the footwork -- writing, word processing, faxing or mailing. But they need professional advice on getting information into the media -- for example, on building their lists of key people to send it to. They also need strategic advice, for example in evaluating what stories will or will not work even before negotiations begin with pharmaceutical companies, government officials, or others. In San Francisco, ACT UP/Golden Gate is seeking media assistance now; if you can help, call Virg at 415/648-2758 or Mark at 415/863-8797. In other areas, local treatment or other AIDS organizations may also be able to use assistance. ***** 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. 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