DISTRIBUTED BY GENA/aegis * 714.248.2836 * 8N1/Full Duplex * v.34 ***************************************************************** AIDS TREATMENT NEWS #215, January 20, 1995 phone 800/TREAT-1-2, or 415/255-0588 CONTENTS: New Information on HIV Rapid Turnover - What Does It Mean? Kaposi's Sarcoma: Possible Foscarnet Treatment 1995 Outlook: Research Strategy Protease Inhibitor Task Force: Opportunity for Participation KS, DOX-SL: FDA Hearing February 14 FDA Advisory Committees: Hotline for Upcoming Meetings International Conference for People Living with HIV and AIDS, Cape Town, South Africa, March 6-10; Pre-Conference for Women, March 4-5 ***** New Information on HIV Rapid Turnover - What Does It Mean? by John S. James On January 12, many newspapers carried page-one stories about a major scientific advance in understanding AIDS. Some of the reporting has been unclear and confusing to readers, however. This article will outline what the discovery is and why it is important to people with HIV or AIDS. We will also explain our concern that this new understanding, while indeed important, shows signs of being misunderstood in ways that could seriously harm AIDS research. The occasion of the recent press coverage was the publication of two articles and a commentary in the January 12 issue of Nature,(1,2,3) which is one of the most prestigious scientific journals. The two articles are by two well-known research groups which independently arrived at essentially the same conclusions. AIDS researchers worked with mathematicians to help them reach a deeper understanding of the data -- which came from blood tests of patients with advanced HIV disease as they started taking certain experimental antivirals in small clinical trials. The discovery announced in the newspapers on January 12 was not news to the scientific community, which has heard the central idea at a number of public conferences during the last year. We published a preview last November, in an extensive quote from Douglas D. Richman, M.D., who spoke on November 12 to a physicians' conference in San Francisco (see "Viral Load, Small Trials, and Immune Recovery," AIDS TREATMENT NEWS #211, November 18, 1994). New Understanding of HIV The new understanding of how HIV behaves in the body was made possible by the development of better antiviral drugs, which can now shut off HIV reproduction almost completely (although so far only for a short time since resistant virus develops in a few weeks) -- and also by the new blood tests which measure plasma HIV RNA, a much more accurate indication than the old p24 antigen tests of how much virus is in the blood. The three antiviral drugs used were the Abbott protease inhibitor (ABT-538), the Merck protease inhibitor (L-524, also called L-735,524), and Boehringer Ingelheim's nevirapine (which is a non-nucleoside reverse transcriptase inhibitor); all three of these drugs are experimental and currently in clinical trials. AZT, ddI, and other approved anti-HIV drugs do not stop the virus well enough to make the new discovery obvious. [Note: the HIV RNA blood tests used are today available to physicians; for background, see "HIV RNA: New Blood Tests for Individualized Therapy and Faster Trials," AIDS TREATMENT NEWS #204, date August 5, 1994, and later issues.] Both the research teams measured the HIV RNA frequently (at least weekly) when patients started taking the new experimental antivirals. They found that once the reproduction of new virus was shut off, the viral level in the blood declined very rapidly; about 30 percent of the virus is cleared from the blood each day (and this percentage may be about the same regardless of stage of the disease). Since blood levels are fairly stable from day to day when the patient is not taking an antiviral, about as much new virus must be produced every day as is destroyed. The essence of the new discovery is that the "turnover" of new virus in the body is far more rapid than people had believed -- in just a few days, most of the virus in the blood has been removed and replaced with fresh virus. Also, these drugs work by stopping the infection of new cells -- not by shutting off viral production from chronically infected cells -- and still they often cause the amount of virus in the blood to drop by 99 percent or more. This means that almost all of the enormous amount of virus being produced continuously during HIV infection is coming from newly infected cells. The researchers also measured the recovery of CD4 cells (T- helper cells) while the reproduction of HIV was temporarily shut off. They found that CD4 cells increased very rapidly during this time. This seems to mean that they are also being destroyed equally rapidly when the virus is not shut down. (Although an alternative possibility, which we do not believe is ruled out by the new Nature articles, is that active HIV infection produces something that suppresses production of new CD4 cells; if this is the case, CD4 cell turnover in HIV disease may be less than now thought.) [Note on terminology: Until now AIDS TREATMENT NEWS has preferred the term "T-helper cell" to "CD4 cell," as being better for communicating with the public. But now the more accurate term "CD4 cell" (or "CD4+ cell," which is the same thing) is coming into wider use, and will be our preferred usage in the future.] Through simple calculations based on this data, the researchers estimated that about 100 million virions (individual virus particles) are normally being produced and destroyed each day. (Note that this applies only to patients with fairly advanced HIV disease, who were studied in this research; they had a median CD4 count of 102 in one of the papers, a mean of 180 in the other. In earlier stages of asymptomatic HIV infection, the number of virions would usually be much less.) Also, the researchers estimated that about two billion CD4 cells are also being created and destroyed each day in these patients. Each infected cell can produce many copies of the virus; the researchers suspect, therefore, that most infected CD4 cells are destroyed by the immune system before they ever have a chance to produce complete virus. Importance These findings are important to people with AIDS/HIV because: * They strongly suggest that if HIV reproduction could be largely stopped for a longer time, and kept at a very low level indefinitely, then the immune system would have much more ability to recover, even without immune-based treatment, than most physicians and scientists had believed. Note that this does NOT mean that the virus will be eradicated. Huge reservoirs of latent virus will still likely remain, in the DNA of cells in lymph nodes and elsewhere. While it is latent, it is not doing damage. But some of the latent virus may become activated later and re-establish the active infection. It will probably still be necessary to take drugs to keep the virus suppressed -- although if the immune system recovers, it may be an important help in this process. * It is now clear that researchers can test potential antiviral drugs and combination treatments in people in small, rapid trials -- which get results in weeks. This means that it is feasible to test many new treatments quickly, greatly speeding the development of better AIDS/HIV treatments. Of course it will be necessary to continue testing the treatments which do show antiviral activity, to see how long they work before viral resistance develops. This should not be hard to do, since patients will naturally want to continue taking a treatment which is working. Other steps are also necessary before FDA approval. [We analyze the critical bottleneck in the whole process -- the need to prove actual clinical benefit to patients -- in "1995 Outlook -- Research Strategy," below.] * They emphasize again the major problem of HIV developing resistance to drugs. The very rapid turnover of HIV in the blood means that in just two to four weeks, the drug- susceptible viral population in a patient can be replaced by a drug-resistant population, meaning that the drug will no longer work, or at least not work as well. The researchers emphasized the need to use combination treatments to prevent drug resistance. Drug combinations help to prevent resistant viruses from developing, because only a small fraction of the virus will initially be resistant to any candidate drug. If a second drug is added, only a small fraction of that small fraction will be resistant to both. The more drugs that are added to the combination, the less likely it will be that any virion will be resistant to all of them. But with billions of virions in the body, it may take a number of drugs in combination to stop all of them. Some researchers have suggested that combination treatments should be used early in infection, when the viral load in the body, and also the variation of the virus, is less. (It is generally believed that HIV infection starts with only one variant of HIV, but as the disease progresses, this one strain evolves into a great many different "quasispecies" within the individual patient. In each patient, this evolution is different.) Comment: What This Discovery Does Not Explain The most important unanswered question about HIV disease may be how it progresses from early, asymptomatic infection to late-stage illness. For years the immune system controls the virus to a degree, and blood levels stay relatively low. But somehow the body gradually loses this ability (in most people, but not in all), allowing the virus in the blood to increase by as much as hundreds of times, leading to the development of AIDS. Many theories have been proposed to explain how HIV suppresses the immune system -- including, for example, direct killing of CD4 cells, and also indirect mechanisms such as molecular mimicry, cytokine or possibly endocrine dysregulation, autoimmunity, abnormal apoptosis, loss of CD8 cells, etc. If researchers knew why the immune system gradually loses its ability to control HIV, then it might be possible to treat HIV infection by correcting this specific problem, and keep people healthy indefinitely, perhaps without the need for antivirals. We are concerned by indications that some researchers, as well as medical reporters, may uncritically assume that the new understanding of HIV also explains how the infection progresses from the early, asymptomatic stage, to the later stages of greatly increased HIV levels and clinical illness. Such a premature conclusion could suppress interest and research in other potential mechanisms of progression. The new information recently published in Nature was based only on studies of persons with advanced HIV infection. And each patient was studied only for a brief snapshot of time; there was no long-term data on how infection progresses over time. The Nature papers do not claim to have shown how HIV infection progresses. But they are often being implicitly interpreted that way. Some of these interpretations do not stand close scrutiny: * One assumption is that, due to the great number of CD4 cells infected and destroyed, the immune system eventually becomes exhausted and unable to keep up, and then the disease progresses because the body cannot produce enough CD4 cells to replace those that are lost. But this theory ignores the fact that HIV disease progression occurs also at earlier stages, when the level of HIV infection and destruction of T-cells is a small fraction of what the body will be able to keep up with later. For example, there is data showing that in persons with a CD4 count around 200, the level of virus in the blood may be ten to a hundred times more than the level when the CD4 count is 500.(4) How could this exhaustion theory explain the progression from a CD4 count of 500 to 450 or 400, if at 500 the body still has at least ten to a hundred times the capacity needed to replace the cells which are lost at that stage? * Another assumption -- seen repeatedly in the January 12 New York Times article -- is that HIV infection progresses because the virus has a "slight statistical edge" over the immune system, leading to its eventual victory. But this theory is unlikely to hold up to an analysis of the dynamics of stability vs. instability. The levels of both the opposing sides in the battle -- the virus, and the CD4 cells -- can change greatly in a time frame of days or weeks. It seems unlikely that these two opposing forces, which each can change in days, will just happen to stay approximately balanced for the much longer time period of years that it takes for HIV disease to progress. To visualize the problem, imagine an acrobat on a high wire who momentarily loses balance, and fights in an attempt to regain it. Usually only seconds will pass until either balance is regained, or the acrobat falls off. We do not expect to see the struggle go on for ten years. In other words, some mechanism other than a slight statistical edge must be controlling the timing of HIV disease progression. No one knows what sets this clock; it should be a central goal of AIDS research to find out. The statistical-edge theory, by giving false confidence that the answer is already known, could distract research from this key goal. Note that in most viral and other infections, the dynamics of the interaction between the replicating organism and the immune system does not lead even temporarily to a homeostasis, to a balance or steady state. Instead, the immune system either eradicates or almost eradicates the disease-causing organism, or the infection progresses until the person dies. (Nor does the limited supply of cells to infect explain the limited growth of HIV, except perhaps at end-stage illness; at earlier stages, the supply of CD4 cells would clearly allow more viral growth, as shown by the fact that viral levels will substantially increase later, when there are fewer such cells available.) No one knows why HIV reaches a certain blood level and then stops (until the level changes over months or years). When we discover the mechanism by which this control becomes established and maintained, but then gradually lost, we will very likely have a new way of controlling HIV disease. * One of the recent Nature articles(1) noted, "The difference in lifespan between virus-producing cells and latently infected cells (PBMCs) suggests that virus expression per se is directly involved in CD4+ cell destruction. The data do not suggest an 'innocent bystander' mechanism of cell killing whereby uninfected or latently infected cells are indirectly targeted for destruction by adsorption of viral proteins or by autoimmune reactivities." We are concerned that readers may take away from this statement something different from what it actually says. While the data cited may not support indirect mechanism for the decline of CD4 cells, they do not rule out such mechanisms, either. Again, our concern is that important research could be prematurely downgraded or closed off, due to the rush of enthusiasm which has greeted the new findings. (And if it turns out that active HIV infection somehow suppresses development of new CD4 cells, or suppresses their release into the blood -- and CD4 counts increase rapidly when the infection is stopped, not because they are usually being created and destroyed that fast, but because the suppressive effect is removed -- then the whole issue of the turnover and lifespan of infected CD4 cells will have to be rethought.) Research Strategy Summary The most important impact of the new understanding of HIV disease, published in two articles and a commentary in the January 12 Nature, will be on the strategy of research and development of new AIDS treatments. We see the following consequences: * The new work validates the use of small, rapid screening trials, in a few patients, to learn which potential drugs have antiviral activity in people. * It also shows that if the virus can be suppressed completely enough, the immune system has much more ability to recover than many had suspected. * It also confirms the belief that overcoming drug resistance is likely to be the biggest challenge to making anti-HIV treatments work. * On the minus side, possible misinterpretation of the new findings (in the current atmosphere of great attention and enthusiasm for them) may impede important work of learning how HIV infection progresses -- work which could lead to a completely different class of treatments which do not attack the virus directly, but preserve the immune system's ability to control it. References 1. Wel X, Ghosh SK, Taylor ME and others. Viral dynamics in human immunodeficiency virus type 1 infection. Nature. January 12, 1995; volume 273, pages 117-122. 2. Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, and Markowitz M. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature. January 12, 1995; volume 273, pages 123-126. 3. Wain-Hobson S. Virological mayhem. Nature. January 12, 1995; volume 273, page 102. 4. Phillips AN, Sabin CA, Elford J, and others. Viral burden in HIV infection. Nature. January 13, 1994; volume 367, page 124. ***** Kaposi's Sarcoma: Possible Foscarnet Treatment? by John S. James Foscarnet (Foscavir) is an antiviral used to treat CMV (cytomegalovirus) infection; it is also used in serious cases of acyclovir-resistant herpes simplex. It is active not only against CMV (which is a member of the herpesvirus family) and herpes simplex, but also against all other known herpesviruses; in addition it has some anti-HIV activity, although it is not generally used as an anti-HIV treatment. Foscarnet is often the initial choice of anti-CMV treatment in Europe, while ganciclovir is usually the initial choice in the United States; this difference appears to be due to historical reasons, as foscarnet was developed by Astra, a Swedish company, while ganciclovir was developed in the U.S. Foscarnet must be given intravenously with an infusion pump, and can cause many serious side effects -- especially kidney toxicity, which occurs to some degree in many patients treated; the drug must be used by a physician who has experience with it. Another disadvantage is that the drug is very expensive. Until recently there was no reason to think that foscarnet would have any use in treating Kaposi's sarcoma (KS). But last year a laboratory study, published in December 1994, found evidence that KS might be caused by a previously- unknown herpesvirus(1) (see AIDS TREATMENT NEWS #213, December 23, 1994). And another article, also published in December 1994,(2) reported on a pilot study of five patients, which was conducted after physicians noticed that KS regressed in two patients who were treated with foscarnet for other purposes. Three of the five patients in the pilot study had a long-term remission of KS, after a single 10-day treatment (or in one case, two 10-day treatments) with foscarnet; the lesions disappeared slowly over several months. In the other two patients, the disease progressed despite the treatment. KS regressions without treatment are fairly rare. (These five cases were the ones reported at the recent conference in Glasgow, Scotland, as mentioned in AIDS TREATMENT NEWS #213.) The five patients in the pilot study had low CD4 (T-helper) counts (24, 26, 270, 6, and 24) when treatment began. The two who progressed had ongoing, active opportunistic infections at the time; the three who had long-term regression did not. All five were also being treated with AZT following the course of foscarnet. We talked to Linda Morfeldt, M.D., Dr. Med. Sc., of the Karolinska Institute in Sweden, who organized the pilot study. She said that the results so far suggest: (1) The effect of foscarnet on KS is not proven; however, other small studies are now being designed to confirm or to rule out the early findings; (2) The researchers suspect that the drug may be effective in relatively early KS which is confined to the skin and mucous membranes (even if the CD4 count is low) -- but not effective, or less effective, in advanced KS; and (3) Patients who also have ongoing active infections, such as CMV organ disease, pneumocystis, MAC, or fevers of unknown origin, may not respond to foscarnet as a KS treatment; but the KS may possibly respond if the opportunistic infections are successfully treated first. AIDS TREATMENT NEWS (December 23 issue) asked our readers to let us know of any experience of persons with KS who used foscarnet, regardless of the outcome; so far three people have contacted us as a result. One had fairly mild KS since June 1992, but he was still getting new lesions, and those treated with liquid nitrogen would re-appear. He started foscarnet for CMV retinitis in mid January; by early March the KS had mostly disappeared. After six weeks on foscarnet, there were no new lesions, and those treated with liquid nitrogen did not return. Another person, before he started using foscarnet, had about 20 KS lesions; these had been removed successfully with Velban or liquid nitrogen. Since he started using foscarnet, no new lesions have appeared. The third person had only one small KS lesion, which was removed and biopsied in 1992. For three years since he has been on foscarnet, and no new lesions have appeared. Early KS Foscarnet Study Now Recruiting in New York A 20-patient study of foscarnet treatment for early KS is planned at New York University Medical Center by Drs. Alvin Friedman-Kien, Miriam Keltz, Abraham Chachoua, Geoffrey Chazen, Linda Morfeldt, and others. The goal is to confirm whether or not foscarnet can have any therapeutic benefit in treating KS. To answer this question most effectively, this study is seeking patients with early KS -- approximately five lesions, and for no longer than six months, and with no prior treatment for KS. Also, they must have a CD4 count of at least 50. References 1. Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, and Moore PS. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science. December 16, 1994; volume 266, pages 1865-1869. 2. Morfeldt L. and Torssander J. Long-term remission of Kaposi's sarcoma following foscarnet treatment in HIV- infected patients. Scandinavian Journal of Infectious Diseases. December 1994; volume 26, number 6, pages 749-752. ***** 1995 Outlook: Research Strategy by John S. James As 1995 begins, we have more opportunities for progress toward major improvement in AIDS/HIV treatments than ever before. And we have clear, feasible paths to follow -- of safe, rapid, low-cost, high-quality treatment trials in people, to get solid preliminary information on how certain potential treatments work in practice. Researchers now have better tools to run these trials than in the past -- and some of the new tools, especially tests for plasma HIV RNA, are also available to individual physicians and patients. Also, we are hearing more cases of unexpected improvement in people with HIV or AIDS -- sometimes beyond what would be thought possible. The most dramatic examples are usually from clinical trials of experimental treatments such as protease inhibitors. But there are others who are lucky enough to do quite well with approved treatments or treatment combinations which happen to work for them. And some do well with "alternative" treatments, or their own combinations of approved, experimental, and/or alternative approaches. We have long believed that the best strategy available is to try many different treatments, keeping the ones that seem to work for oneself, and discarding the ones that seem not to work. Strategy, Part I: Small, Rapid Screening Trials These success stories are not the answer, however. They do not work for everyone, and usually there is no way to predict who will benefit. Also, no one knows how long the successes will last -- although often they seem to work for years, with no evidence of failure in sight. These success stories, instead, should be seen as treatment leads, entry points for further research. For each lead, physicians and scientists should use their best judgment to try to define a class of patients who might reproducibly benefit. The next step is to run a small, rapid "proof of principle" trial -- usually in only a few patients, perhaps ten to 20 -- looking for consistent changes in measurable indicators of improvement. There might or might not be a control group in this trial. What would happen then? Most of the proposed treatments tested this way, perhaps 80 or 90 percent, would probably be found not to work. But there are dozens of good-quality leads waiting for such a test, and a number of them would come out with strong support. These would then have the social/political momentum needed to move rapidly into further research. This proposal for many short, rapid screening trials is not controversial, but is generally accepted as something that can and should be done. The cost and other resource requirements would be modest. The problem today is finding the political and institutional will to make the research happen. Strategy, Part II: A New Way to Prove Clinical Benefit The next step after the screening trials is more controversial. Those short trials will look for a measurable, reproducible improvement, usually in blood work. But what then? Change in a blood test may not prove that the treatment actually benefits patients. Usually we need other kinds of trials to show this. Here we face a serious problem. The prevailing thinking so far has focused on a kind of clinical-benefit trial design which will take hundreds of patients for each drug studied, and take years to produce conclusive answers. This kind of trial randomly assigns the treatment being tested to some patients, while others are assigned to standard treatment instead. Then both groups are observed to see which one gets sick faster. It takes a long time because AIDS progresses slowly; even if the new treatment being tested were a complete, instant cure, the trial might still take years, because it would have to wait for a statistically significant number of those on the standard treatment to get sick or die. And even aside from the time required to run the study itself, it usually takes years to politic for, finance, design, organize, and recruit for such a large trial (in addition to the time to analyze the data, distribute the results, and get them into standard medical practice). Even aside from the problem of making people wait for years to get better treatments, it is clear that there will not be enough patients available, let alone enough money or trained researchers, to test more than a few of the treatments which are likely to pass the small screening trials. There is a better approach. The treatments which pass the small screening trials in all probability do benefit patients -- the difficulty is in finding a feasible way to prove that conclusively. What we suggest is combining a number of treatments which work well in the screening trials, until the cumulative benefit of all of them is great enough to be clearly visible -- not only in delaying illness, which takes a long time to see, but also in getting sick people well, which usually happens much more quickly. When patients regularly get out of bed and go back about their lives, when those who were disabled can work again, when chronic infections disappear with no further need for antibiotics or other specific treatments, then the value of the AIDS/HIV treatment will be unambiguous. Statistical proof could be rapidly obtained, through small, rapid trials (much like the screening trials) which compare immediate vs. delayed therapy -- for example, randomly assigning volunteers to either start the treatment now, or to start it in six weeks. Long-term followup would of course be included, to make sure that the benefits last, and to watch for long-term side effects. This research strategy offers definitive proof of clinical benefit in small, rapid, inexpensive trials -- instead of the huge years-long trials that are usually believed necessary to prove clinical benefit. It may not prove the benefit of each individual treatment -- only of a certain, partly-arbitrary combination. But the information available today suggests that this strategy could quickly provide relief and save lives; those who want more refined information could pursue it later. This approach to proving clinical benefit, unfortunately, is not yet part of the ongoing conversation on how to improve AIDS research. We have never heard it discussed or proposed anywhere. Hopefully our readers will help to get this idea onto the table, to be considered professionally and accepted or rejected on its merits. None of the alternatives offers an acceptable outcome. This proposal for proving clinical benefit turns the small, rapid screening trial into part of a complete strategy for going from where we are now to where we need to be to save lives. Let's further develop and improve this strategy, and use it as an organizing tool to get the research done. Strategy, Part III: New Mechanisms of Action A third potential research strategy would seek to develop treatments which control HIV through new, previously-unknown mechanisms of action. This could be done through intensive research into what might be called mystery treatments -- accidental or lucky discoveries of drugs or other treatments which seem to be helping in some way, but which have no known mechanism of action. Mystery treatments may include prescription drugs (one possible example is sulfasalazine), certain nutrients (see "Some Vitamins Associated with Decrease Risk of AIDS and Death," AIDS TREATMENT NEWS #214, January 6, 1995), or other approaches such as exercise. The goal is not so much to develop these treatments themselves, as to discover how they might work. If a new mechanism of action is found, then a whole new approach to AIDS treatment would become possible. The key is to direct more research attention and resources into investigations of mystery treatments, which could lead to potentially major advances in understanding and treating HIV disease. This is the opposite of what happens now, which is that potential treatments without a known mechanism of action are largely ignored. How does one begin to study a possible treatment with no known mechanism of action? One way is to look for consistent changes in any of the virological, immunological, and other tests which are available. Any repeatable, predictable treatment effect could serve as a lead or clue. And of course this research would be done in collaboration with specialists, usually outside the AIDS field, with expertise in the treatment being studied; they can help to identify and evaluate research leads. Political Strategy: Organizing National Will AIDS research and AIDS prevention have always suffered from a lack of full national commitment to AIDS. Today this problem is becoming more critical than ever before. As it affects research, it takes many forms: * AIDS research has long overemphasized large, high-tech, complex, and product-oriented projects, because those are the ones people get paid to do, the ones that build a politically powerful constituency (lobby). Corporate research is almost always oriented toward proprietary products; in theory, government and foundation research should fill in the gaps by doing necessary work which companies will not do -- including basic research, and also including the small trials that we suggested above, for those treatment leads which are not products that corporations will study. But due to conflict of interest, revolving-door employment, and increasing reliance by academic institutions on entrepreneurial funding, non- corporate institutions have not adequately set their own agendas. As a result, academic, government, and foundation researchers have tended to study the same drugs and approaches that corporations already are studying, or should be. Part of the problem is the ever-increasing difficulty of making anything happen in clinical research (due to ever- growing costs and regulatory requirements, as well as increasing scarcity of funds). This creates a conservative bias, by making it hard to get any trial off the ground unless it has a large, pre-existing constituency. Since new ideas almost never come into being with a large constituency, they almost always suffer great delays while the necessary professional/commercial/regulatory momentum develops. In other circumstances, it would be possible to correct these structural defects. But due to the widespread attitudes around AIDS, the nation has not found the will to do so. * The recent elections have created new and serious problems. Many members of Congress seem to be interested in representing only one group of people -- white, heterosexual men with good incomes -- and have little interest in anyone else's concerns. (A more accurate statement would be that they represent the frustrations of certain voters, and the interests of multinational big business.) Since relatively few such people have AIDS, money may be taken from AIDS for tax reduction, military spending, and other rewards for those who financed the recent political campaigns. * Recently we spoke with two business reporters not connected with AIDS, and found a well-developed ideology of fatalism tailor-made to justify not bothering with AIDS research. One compared AIDS research to a swamp, in that the farther you go in, the deeper you get, without end. The other compared AIDS to the common cold -- more serious, he acknowledged, but similar in that despite ongoing progress, we do not expect to ever see a time when people do not get colds (or, by obvious analogy, a time when people do not die of AIDS). These images did not come from their personal experience, but from somewhere else. This ideology does not reflect anyone's experience, but appears to have been constructed for a purpose -- to justify abandoning people with AIDS or HIV. * Other national-will problems are closer to home. AIDS service organizations have never shown much interest in research -- and neither has organized medicine. And public- policy experts, in Washington and elsewhere, seldom understand science and technology issues, or have any serious interest in them. * Also close to home is the lack of popular mobilization on AIDS. Most people affected by HIV do nothing, ever, to help the cause of AIDS research. One major reason is that organizers have not created effective channels for them to use in doing so. In most locations, the only options, the only ways to interact with the issue, are to send a check to a distant national organization -- or possibly to sit through many hours of high-tension, ego-battle meetings, before the new person is allowed to actually do anything which contributes. Many people want to meet with friends and neighbors to write and call Congress to support AIDS funding -- perhaps the most important thing they could be doing now -- but nobody has organized to give them the information they need. The public motivation certainly does exist; as we pointed out in the last issue of AIDS TREATMENT NEWS, at least 50 million people in the U.S. alone have a relative, friend, or acquaintance whom they know has AIDS or HIV. What must be done is to establish a social movement so that these millions of people can make their voices heard, instead of remaining silent as is almost always the case today. In summary, we now have excellent opportunities for progress in treating AIDS. But they are not being exploited effectively. Solutions have been identified; it is up to us to organize and insist that they be implemented. ***** Protease Inhibitor Task Force: Opportunity for Participation The February 23-24 meeting of the National Task Force on AIDS Drug Development (NTFADD), especially February 23, may be a pivotal moment in the development of protease inhibitors. Activists want the NTFADD to appoint an official protease inhibitor task force which can work effectively to find ways to make the drugs accessible to patients; to facilitate research in combination therapies, cross resistance, etc.; to facilitate collaboration and sharing in research; and to overcome corporate and regulatory barriers. Note that those who want to speak at the meeting should make advance arrangements by February 9 (see AIDS TREATMENT NEWS #214, January 6, 1995, page 8). For background on the proposed protease inhibitor task force, see AIDS TREATMENT NEWS #210, November 4, 1994. If you can help, call Jules Levin at 718/624-8541. ***** KS, DOX-SL: FDA Hearing February 14 The Oncologic Drugs Advisory Committee will consider approval of DOX-SL, for persons with AIDS-related Kaposi's sarcoma who have failed systemic chemotherapy, either because of toxicity or because of disease progression. This meeting, which is open to the public, will be at the FDA's Parklawn Building, in Rockville, Maryland. Persons interested in speaking should call Adele Sefried at the FDA, 301/443-4695, by February 10. It is particularly important for physicians or patients with personal experience with DOX-SL to address the committee. Later in that meeting, the committee will also consider approval of Zoladex (goserelin acetate) for palliative treatment of advanced breast cancer in pre- and peri- menopausal women. ***** FDA Advisory Committees: Hotline for Upcoming Meetings You can find out about upcoming meetings of any FDA advisory committees through a voicemail system run by the FDA. Information is updated as soon as it becomes available, and is often more current than meeting notices in the Federal Register. To use the voicemail system, call 800/741-8138, or 301/443- 0572. There are several dozen different advisory committees; you can select the one you want through the voicemail system. However, you can save time if you have the five-digit code for the committee you want, as you can enter the code immediately and bypass the voice menus. The codes for the advisory committees most involved with AIDS are: Antiviral Drugs Advisory Committee (code 12531); Oncologic Drugs Advisory Committee (code 12542); Vaccines and Related Biological Products Advisory Committee (code 12388). Also, the National Task Force on AIDS Drug Development (code 12602) announces its meetings on this system. ***** International Conference for People Living with HIV and AIDS, Cape Town, South Africa, March 6-10; Pre- Conference for Women, March 4 and 5 The Seventh International Conference for People Living with HIV and AIDS, sponsored by the Global Network of People Living with HIV and AIDS (GNP+), will be held in Cape Town, South Africa, March 6-10, 1995. March 6 includes registration and opening plenary, March 7 has a theme of health, March 8 of human rights and identities, March 9 skills building and technical assistance, and March 10 is a business day for GNP+. For more information, contact the Conference Secretariat, P.O. Box 27262, 8050, Rhine Road, Cape Town, South Africa, phone 27-21-4181011, fax 27-21-4181015, email sn0298@connectinc.com. Note: On March 4 and 5, the ICW (International Community of Women Living with HIV and AIDS) will hold a pre-conference for HIV-positive women, in Cape Town. For information, contact the conference secretariat in Cape Town, or contact the London office of the ICW, phone 44-171-222-1333, fax 44- 171-222-1242. ***** Notice: Next Issue Delayed One Week Our next issue, scheduled for publication on February 3, will be delayed a week so that we can include coverage of the Jan. 29 - Feb. 2 Second National Conference on Human Retroviruses and Related Infections, as well as the HIV Immune-Based Therapies Workshop, and the CPCRA 16th Group Meeting. We will return to our regular schedule with the February 17th issue. ***** 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 Reader Services and Business: Richard Copeland Thom Fontaine Tadd Tobias 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 1995 by John S. James. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used.