Date: 18 Jun 94 08:54 PDT From: aidsnews@igc.apc.org AIDS TREATMENT NEWS #201, June 17, 1994 phone 800/TREAT-1-2, or 415/255-0588 CONTENTS: Roche Protease (Proteinase) Combination Trial: Triple Combination Results PML Treatment Update, Peptide T Possibility AIDS Research Strategy: Rapid, Small Trials for Promising Treatment Leads Merck Protease Inhibitor Combination Trial: Chapel Hill, Frankfurt (Germany), Hershey, Honolulu, Philadelphia, Portland, San Francisco, and Sherman Oaks International Issues -- Newsletter Available ***** Roche Protease (Proteinase) Combination Trial: Triple Combination Results by John S. James A study sponsored by the U.S. National Institute of Allergy and Infectious Diseases found that a three-drug combination (the Hoffmann-La Roche protease (also called proteinase) inhibitor saquinavir [formerly called Ro 31-8959], plus AZT, plus ddC) worked significantly better than two separate two- drug combinations against which it was compared (saquinavir plus AZT, and AZT plus ddC). This trial, in 302 patients, looked at changes in blood tests, such as T-helper count, and viral measures, over 24 weeks. This study was not designed to look for differences in clinical events, such as different rates of progression to AIDS, or death. And there were too few such events in this trial to allow any meaningful comparison. As a result, the researchers concluded that "standard clinical patient management should not be affected by this study." The improvement in blood work was modest, but still important. For example, the mean T-helper count at baseline was 156 in the triple-combination group; this increased to 195 after four weeks of treatment, 200 after eight weeks, 202 after 12 weeks, 189 after 15 weeks, and 180 after 24 weeks. In other words, the average T-helper count increase with the triple therapy was, at its maximum, 46; this average then began to fall, and at week 24 (the latest point at which data is now available), the average T-helper increase was only 24. All patients had been taking AZT for at least four months before beginning this trial -- and three quarters of them had been taking AZT for over a year. Therefore, AZT alone would not be expected to have accounted for a T-helper count increase. [Note: A new trial of saquinavir, a large, international study which could begin in a couple months, will test the combination in patients who have had little or no prior use of AZT. If AZT resistance limited the effectiveness of saquinavir in the current trial, which seems likely, the new study might show better results.] Viral load data, including HIV RNA, is still being analyzed. Some viral culture data is available, however; and it also suggests that the triple-drug treatment may be clearly better than the two-drug treatments. But even the three-drug combination never quite achieved a 10-fold reduction in viral load in the tests which have so far been run -- and early indications are that a hundred-fold or greater reduction may be necessary before dramatic benefits may occur (see "Antivirals and Immune Recovery," AIDS TREATMENT NEWS #200, June 3, 1994). This study also looked at safety, and found that, "The type, severity, and frequency of adverse experiences were the same in the three treatment regimens. The small number of AIDS- defining events and two deaths resulted from complications of advanced HIV infection and did not appear to be associated with the study therapies." (All patients had T-helper counts between 50 and 300 at entry to the study, in order to qualify for enrollment. About 52 percent were symptomatic but did not have AIDS; about 36 percent were asymptomatic; and about 11 percent had AIDS when starting the study.) The doses used were fairly standard: AZT 200 mg three times a day (a total of 600 mg per day), ddC 0.75 mg three times a day, and saquinavir 600 mg three times a day (probably the most common dose now used in trials). More data will become available from this trial, and results will be further analyzed for publication in a peer-reviewed journal. Comment This study represents a modest advance in learning how to use a new drug. The result does not have immediate practical use, however, because saquinavir is not widely available; according to Hoffmann-La Roche, it is very difficult and expensive to manufacture. No one knows how long it will take for saquinavir to be approved, even if future trials continue to look good. The big question is whether the FDA will allow accelerated approval -- approval based on blood tests, but on condition that the company complete the much longer lasting trials required for statistical proof that there is less death or progression to AIDS with the new treatment than with standard treatment. The FDA may be reluctant to grant accelerated approval, because saquinavir is a new kind of drug (a protease inhibitor), and the FDA may be cautious about trusting the blood tests in this case, since there are more unknowns. Also, there has been much unhappiness with how Roche handled the followup trials after its previous accelerated approval for ddC. Hopefully the new tests for viral load will provide a way out of this kind of dilemma. If they are found to be reliable as indicators of future patient outcome, in a wide variety of different trials and different kinds of patients, they might be trusted enough to be the main basis of drug approval, even without statistical proof of reduced death and progression to AIDS. (Fortunately, such validation of the tests can often be done quickly, without needing to wait for years to see if the predicted disease outcomes occur, by using frozen blood samples saved years ago in clinical trials.) And, alternatively, if a treatment were powerful enough to clearly restore many people to health when they were chronically ill, then this would be a "clinical" benefit which could be shown very quickly, leading to approval without the need to wait for rare "events." It is possible that saquinavir would work better if the dose were increased; a small trial at Stanford is now trying the drug at doses two and four times the one used in the recent trial. Unless manufacturing can be improved, however -- or unless the drug can be formulated to be more orally bioavailable, reducing the amount of it required -- there is concern that saquinavir may be too expensive to become widely used. ***** PML Treatment Update, Peptide T Possibility by John S. James PML (progressive multifocal leukoencephalopathy) is a brain infection caused by a virus, the JC virus. It is relatively rare, diagnosed in only about one percent of people with AIDS. But many cases are misdiagnosed, usually as toxoplasmosis or lymphoma. While PML most often occurs in late-stage AIDS, it can also be found in persons with a relatively high T-helper count; and it can be the first AIDS- related condition diagnosed. There is no cure for PML, and there are no FDA-approved treatments; therefore, persons who are diagnosed are often told by their doctors that there is no treatment, and that they will die in weeks or months. In fact, there are experimental or possible treatments; and a number of people with PML have stabilized or improved, and have lived relatively healthy lives for years. The treatments remain uncertain, however, because controlled trials have not been done. The best single source of information on PML treatments is a privately-published book, Progressive Multifocal Leukoencephalopathy (PML): Case Studies and Potential Treatments, by Peter and Lisa Brosnan; the latest edition was printed in July 1993 (see below for how to obtain a copy). The authors are not physicians or medical specialists. Lisa's brother was diagnosed with PML in 1988, and the Brosnans started searching the medical literature for possible treatments. Lisa's brother died in a month, however, before treatment could be started; the Brosnans continued their work, to make the information available to others. Because the disease can progress rapidly, it is important to start treatment as soon as possible. The book includes a brief description of PML, discussion of treatments which have been tried (ARA-C, or a combination of two or more of: acyclovir, heparin, interferon, NAC, and dexamethasone), and mention of possible treatments which apparently have not yet been tried in people but have some theoretical or laboratory rationale (foscarnet, ganciclovir, isoprinosine, and camptothecin derivatives such as topotecan). Recent anecdotal reports about peptide T arrived too late to be included in the current printing; they are discussed in the interview below. The book also includes: * Fifteen case studies, most from medical journals, but some collected by the authors; * A survey of 21 people with PML, compiled by the authors; * A resource section, including contact information for leading PML experts your physician can call; * Over two dozen articles and abstracts from the medical literature, AIDS newsletters, and elsewhere, and references to other articles. For the most recent information, AIDS TREATMENT NEWS interviewed co-author Peter Brosnan. Interview with Peter Brosnan: AIDS TREATMENT NEWS: What is the most important message for our readers? Brosnan: That there are treatments for PML. I continually hear from people who have been diagnosed with PML and told that there are no treatments. That makes me angry. There are treatments. There are no cures, but there is a wide range of drugs now that have shown themselves to be effective in at least some cases. They are readily available. All the evidence indicates that if treatment is going to be successful, it must be started early and aggressively. And there are a number of treatments to choose from. ATN: ARA-C (or its relative, ARA-A) is the treatment with the most mainstream medical support, but it also may be the most dangerous -- and there have been no controlled trials. What does the current information suggest? Brosnan: The jury is still out on ARA-C. I understand that a trial will be starting shortly, comparing intrathecal to intravenous ARA-C. It does seem to help in many cases. In other cases, however, especially intravenously, it can be very dangerous. In somebody who did not have AIDS, it would probably be immediately recommended. In somebody whose immune system or overall health is already compromised, it should be considered very cautiously, I think. ATN: Do people without immune deficiencies get PML? Brosnan: Very rarely. Before AIDS, it was usually seen in chemotherapy patients, and those who needed to take immune- suppressive drugs because they had organ transplants. Contagion is not an issue, since almost everybody has the virus already; the immune system keeps it in check. ATN: You mentioned a number of possible PML treatments that have been tried, alone or in combination: acyclovir, heparin, interferon, dexamethasone, and NAC. What can you say about them? Brosnan: Acyclovir was a surprise to us when we first began doing this, six years ago. We began hearing more and more from people who claimed that their PML was either stabilized or in remission without any treatment at all. But when we questioned these people carefully, we found out over and over again that they had herpes and were being treated with acyclovir. I understand there are some basic similarities between the JC virus and the herpes virus. And we have seen many people now who seem to be responding to the acyclovir, especially at high oral doses, 2000 to 4000 mg per day. Heparin [a drug usually used to prevent blood clotting] was first suggested by Dr. Sidney Houff, with the National Institutes of Health and the Veterans Administration near Washington, D.C. His theory was that the JC virus apparently has a receptor on the B lymphocytes, and it is these cells that transport the virus across the blood-brain barrier into the brain. Heparin seems to interfere with that transport, keeping the PML out of the brain. We have heard from a number of people who haven't gotten better, but their PML seemed to stabilize. The drug has few side effects. Most of the people I have heard of who are using alpha interferon are combining it with something else, such as ddI or acyclovir. There do seem to have been some positive responses, and there are some instances in the medical literature in which either alpha or beta interferon has had a positive effect on PML. Beta interferon is in very short supply right now, after it has been approved for multiple sclerosis. Multiple sclerosis, like PML, is a disease that destroys myelin. There is one encouraging case in the medical literature, from Japan, in which intrathecal beta interferon seemed to be very effective. As far as I know, that is the only time it has been used for PML. NAC [n-acetylcysteine, not approved in the U.S. in oral form, but available in buyers' clubs and health-food stores] is listed because, for three or four years now, we have seen improvement of symptoms in people with PML who have taken NAC. Dexamethasone is a steroid which decreases inflammation -- although it also suppresses the immune response. It is not a primary treatment, but may help with the symptoms in some cases. The best results we've seen are from people using a combination of these drugs. Whether there is synergy [meaning that the drugs work unexpectedly well together], or whether these people just happened to hit the drug that is right for them, we don't know. Peptide T ATN: You mentioned peptide T -- which has long been a popular semi-underground treatment for some other AIDS-related neurological complications. The information is too recent to be included in your current book (third edition, July 1993), however. What are you hearing about it? Brosnan: Peptide T is something we've had an eye on, ever since starting this in 1988, because it seemed very promising. But because of all the problems peptide T has encountered [political and commercial problems in its development, not problems with the drug itself], there has been little information until recently. Just in the last couple of months we have heard four or five reports of its use against PML, with what seemed in some cases to be promising results. I don't want to get too excited -- we have all seen these kinds of things come and go before. But it does seem very promising. And certainly it is a non-toxic substance. ATN: Do you think peptide T may be giving only symptomatic relief? Brosnan: We don't know if we are seeing treatment of symptoms, or treatment of the underlying problem. I am aware of a couple of people who seem to have been stabilized by it, for up to a year. If it were just treating the symptoms, I don't think that would have happened. I've spoken to one neurologist who is familiar with both PML and peptide T. He sees a couple possibilities. Peptide T may itself be a neurotransmitter. It might also be a very strong anti-TNF factor. And TNF might be involved in demyelination [loss of the myelin sheath from nerve tissue, which happens in PML, and also in other diseases such as multiple sclerosis]. If that is the case, it would be an argument for peptide T directly affecting the PML, not only relieving symptoms. ATN: You mentioned people stabilizing on peptide T for up to a year. Did they then get worse, or is there only one year's experience at this time? Brosnan: A doctor in New York called me in March. She had a patient who had completely stabilized for one year after taking peptide T; but now he was beginning to show signs of progression, she was looking for a newer treatment. I believe all he was taking was AZT and peptide T. I have not been able to check up on what has happened since then. In another case from New York, a man developed PML in the fall of 1993. By December he was unable to walk, and losing a lot of weight. He started taking peptide T, and by January he was fine. Then in February he ran out of money and had to stop taking the peptide T; he got worse. In March he started taking it again; he got better, and he seems to have stabilized. A week ago I talked to a woman in Louisiana, whose husband has had PML for a year. He had not walked in a year; he had not been able to speak for six months. Two days after starting peptide T he took his first steps, and spoke his first complete sentence. You don't want to get too excited. But I'd certainly like to see peptide T used more frequently, because it's something we need to look into. ATN: We should point this out to community-based research groups. This is a study that could be done quickly, to get some more-than-anecdotal data, less affected by self- selection of the group of people who called you. There would be ethical concerns that would have to be addressed carefully in planning any trial. Would a control group be ethical? You could not ask people to avoid other PML treatments. Maybe the way to start would be to give peptide T to all study volunteers, in addition to their other treatments, and carefully collect uncontrolled data. Brosnan: We have only seen a handful of cases. But it may be the most exciting development in several years, and I'd certainly like to see more studies done. LTR Inhibitors ATN: You briefly mentioned the experimental cancer treatments camptothecin and topotecan [the latter is a camptothecin derivative, engineered to have better pharmacologic properties than camptothecin]. AIDS TREATMENT NEWS has covered this class of drugs as potential HIV treatments -- they are in human trials for cancer, but as far as we know no one with HIV has ever taken any of them. In the laboratory these drugs inhibit the LTR (long terminal repeat) of HIV, forcing the virus to remain inactive. How did they come up in relation to PML? Brosnan: Apparently there have been two separate, unpublished studies that show that these drugs cut off replication of the JC virus, when it is combined with ARA-C. We don't have details at this time. Diagnosis Problems Brosnan: I suspect that PML is being greatly underdiagnosed. There have been some consecutive autopsy studies from Europe, in which PML has been seen in from 7 to 18 percent of the people they autopsied. I suspect that some patients who are being unsuccessfully treated for toxoplasmosis are suffering from PML. About two thirds of the people I speak to who have PML were originally misdiagnosed as having toxo -- or strokes, or inner ear infections, but usually toxo. I wish more AIDS doctors would keep PML in the back of their mind as a possibility. For More Information You can obtain a copy of Progressive Multifocal Leukoencephalopathy (PML): Case Studies and Potential Treatments, from Peter Brosnan, 1709 N. Fuller Avenue, #25, Los Angeles, CA 90046. To cover his costs, he asks physicians and institutions to send $30, people with AIDS $20, and in cases of hardship he will send it free. In an emergency, call Peter Brosnan at 213/874-7885, so he can send the book immediately. ***** AIDS Research Strategy: Rapid, Small Trials for Promising Treatment Leads by John S. James [Note: The following article began as a memo to treatment activists who were to meet with William Paul, M.D., Director of the Office of AIDS Research. We were invited to the meeting, but were unable to attend.] In the history of medicine, advances have often come from unexpected places -- chance observations or discoveries that could easily be overlooked because they do not fit into the prevailing, theories. We cannot manufacture chance discoveries, we cannot make them happen. But we can be more receptive to them. We can design a research system to move quickly to follow up attractive leads, moving them as far as a small pilot study with a few to a few dozen people. Then, if the results are promising, and the study is entirely credible, the treatment lead will have enough momentum to proceed on its own, through institutions and arrangements which already exist. Most of these tests will fail, in that they will not identify practical treatments. But it only takes one success to make a big difference -- and with persistent and intelligent followup of promising leads, such a success is likely. And even the failures can be important, by providing practical information about the disease, which may help other researchers focus their thinking. Key to Selection of Treatments to Test: Feasibility to Research, and Feasibility of Use How should we choose which treatment leads are most important to test? When considering ideas which may not fit well within existing theories, it may be difficult or impossible (almost by definition) to rationally decide which are most likely to work. But another approach to prioritization is entirely possible. We can prioritize based on which treatment leads are most feasible to test -- meaning that a pilot trial can be safe, rapid, inexpensive, and not difficult to conduct -- and also on which are most feasible to move quickly into widespread use, if they are found to work. Since a treatment which passes one of these tests is likely to also pass the other, it should be quite possible to choose treatment leads which are feasible in both respects. Therefore, this strategy would prefer to test drugs that have already been used or tested in people in some way. The toxicology, pharmacokinetics, etc. required for a totally new compound can be a substantial project. New compounds could still be included in some cases, however, if the resources are available. This is not to say that difficult research ideas should not be developed -- only that the strategy we are proposing here will not develop them. When substantial resources are required to test a treatment lead, other kinds of priority- setting become necessary. Unfortunately, it is usually politically impossible to test resource-intensive leads which are outside the mainstream, prevailing theories -- an inherent obstacle to rapid progress in medical research. But when the trials needed are easy to do, then this path to rapid progress becomes feasible, since unexpected discoveries and insights can be followed up quickly. Credibility These pilot studies will be exploratory; usually they will not be controlled trials aiming to establish statistical proof that one treatment is better than another -- that comes later. The first test of a treatment or strategy might be with a single patient -- then three or four -- then ten, 20, or 50. For the early pilot studies, credibility is established not with large numbers and small p values, but with excellent quality control of the research process, under the leadership and oversight of known, well-regarded researchers or institutions. For example, top quality labs must be used, and there must be no question of results looking good because of selective reporting. If the research is conducted with good quality control, the results will have the credibility needed to support the development of larger, controlled trials to confirm the early results. Examples There are dozens, probably hundreds, of credible treatment ideas published in peer-reviewed journals, usually by academic scientists, and suggested by the scientists closest to the work as potential HIV treatments. Almost always the work stops there. It gets published because the authors are academics who are very familiar with publishing their work, and motivated to do so. But they do not have the resources or background to move the idea further toward human trials. The examples below focus on research strategies, rather than particular compounds. This list could be greatly extended. * Dr. Michael Saag, working with the Merck protease inhibitor L-524, has reported a few cases of very dramatic benefit (even at late-stage AIDS) when HIV RNA could be reduced by 100 times or more (compared with a ten-fold reduction which can often be obtained with AZT). [See interview in AIDS TREATMENT NEWS #200.] It may be the case that if you reduce HIV activity enough, perhaps 100 times or more -- no matter how you do it, as long as the treatment is not seriously toxic, or immune suppressive -- then major benefits may be likely. But we do not know this for sure. One way to explore this area would be a trial to provide top- quality labs, data management, and support for reporting of results, and then to allow leading physician-researchers to follow their intuition and use almost any drug or combination they wanted to, in patients at any stage of disease. The investigators could change the treatment when they chose, with the goal of bringing the HIV RNA down. The likely result would be (1) finding drug combinations or other treatment strategies which worked well to reduce HIV activity, and keep it low, and (2) confirming that doing so confers clinical benefit -- or learning about the circumstances in which it is likely to do so. * It is possible that we have not seen the full benefit of viral suppression with AZT, as its bone-marrow effects can be immune suppressive, which may be reducing immune recovery. The trial setup outlined above could address this question by exploring strategies with and without AZT. It could also look at the early switch from AZT to ddI (following up on ACTG 116A), or initial use of the combination, providing practical guidance in use of these approved drugs. This differs from large, conventional trials in that physicians will be able to treat patients individually, under research conditions, and then report what they learned -- instead of treating groups according to standard protocols, and then reporting averages. * Dr. Arthur Pardee's group at the Dana-Farber Cancer Institute is finding a number of potential AIDS treatments, by using an established laboratory test to screen for inhibitors of the long terminal repeat (LTR) of HIV. Many but not all of the drugs are camptothecin relatives. Most of them are in human use already. Using the same test, the researchers have also found a strong synergy between the abandoned Roche tat drug and pentoxifylline, allowing the concentrations of each drug to be reduced ten fold and achieve the same LTR inhibition. But because Dr. Pardee's background is cancer, not AIDS, leading AIDS researchers have often not even heard of this work, and little or nothing is being done to follow it up with human tests. It would be technically easy to screen some of these drugs and combinations to see how much they reduce HIV RNA in patients -- and in which patients, and for how long, and how the effect is changed by concurrent treatment with AZT, the Merck protease drug, and other antivirals. Small, rapid trials of promising treatment leads will not substitute for better understanding of HIV disease. But they are something we should do. The Next Step This list of examples, of trials which could rapidly produce information which might lead to major treatment advances, or at least to practical groundwork for further research, could easily be extended to several dozen. But usually there are no plans for any human trials. A critical opportunity is being lost. Note that these trials would cost relatively little. The money could come from either government or private sources. All the technology needed is already available, all the facilities exist, the money is there, no special training is required. All we need is the communication and consensus to make it happen. Why, then, has it not happened already? Because this approach to research has not had a constituency. Pharmaceutical companies are interested in proprietary drugs, scientists in high-tech projects -- both of which will take a long time to be ready. Front-line physicians are usually too busy for research, and most other physicians avoid AIDS. Patients and activists are a natural constituency; but they have not yet organized powerfully enough to overcome the barriers that make it hard for any trial to happen. What we can do is to develop this research strategy as a consensus document, especially in the activist and professional communities, then use the consensus to bring about change. By listening to many peoples' input, and combining the best ideas from all sources, we could build the consensus to bring such research into the national agenda. ***** Merck Protease Inhibitor Combination Trial: Chapel Hill, Frankfurt (Germany), Hershey, Honolulu, Philadelphia, Portland, San Francisco, and Sherman Oaks An important new trial will compare combination treatment with L-524 (the Merck protease) plus AZT, vs. L-524 alone and AZT alone. Volunteers must have a T-helper count under 500, and no prior treatment with AZT for more than two weeks. Prior use of ddI, ddC, and investigational drugs is OK, but a short wash-out period will be required before starting the study treatment. There are some other entry criteria, including a viral load of at least HIV RNA copies of at least 50,000 per milliliter (so that improvement in viral load can be measured). HIV RNA will be tested at the study sites; there is no other way to know what your level is, as the test is not widely available. This trial is scheduled to last 24 weeks. A total of 60 volunteers will be enrolled. For more information and possible enrollment, contact a study site convenient for you: * Chapel Hill, North Carolina: University of North Carolina, Luigi Troiani, 919/966-6712. * Frankfurt: Klinikum der Johann Wolfgang Goethe -- Universitat, Renata Tiebel, 49-69-6301-7860. * Hershey, Pennsylvania: Milton S. Hershey Medical Center, Fran Damianos, 717/531-7488. * Honolulu: Leahi Hospital, Nancy Hanks, 808/737-0036. * Philadelphia: 2 sites. (1) Thomas Jefferson University, Barbara Osborne or Janet Pientka, 215/955-8575. (2) University of Pennsylvania Hospital, Heidi Lehman, 215/662- 2473. * Portland, Oregon: The Research and Education Group, Brian Fodell, 503/229-8428. * San Francisco: San Francisco General Hospital, Nelson Murcar, 415/476-9296x84092. * Sherman Oaks, California: Pacific Oaks Medical Group, Paul M. Prosser, 818/906-6279 [Note: This is a different trial from the one mentioned in AIDS TREATMENT NEWS #199 (May 20, 1994), which will test a triple combination of L-524 plus AZT plus ddI, vs. two other treatment regimens. The trial described here does not include ddI.] ***** International Issues -- Newsletter Available AIDS TREATMENT NEWS editor John S. James has volunteered to edit a newsletter for the Global AIDS Action Network (GAAN), on international AIDS advocacy. The new GAAN Bulletin will appear four times a year. GAAN -- founded by Paul Boneberg, who also founded the San Francisco-based Mobilization Against AIDS -- is now one year old. GAAN has already made an important difference. Last year, huge funding cuts (over 30 percent) were proposed for the AIDS programs of the U.S. Agency for International Development. GAAN played a major role in the successful effort to oppose those cuts, which ultimately were held to about five percent. If current trends continue, an estimated 40 to 100 million people will be infected with HIV by the year 2,000. What is done now can greatly reduce the ultimate toll. Because of the current neglect of international AIDS issues, GAAN can be critically important. Its primary mission is not do do advocacy itself, but to assist other AIDS organizations in doing international advocacy through agencies of their own governments, through international agencies such as the United Nations, and through private organizations. For a copy of the GAAN Bulletin, or for other information, contact GAAN, P.O. Box 376, Lagunitas, CA 94938, phone (message) 415/448-1453, email globalaids@aol.com. ***** 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: 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 1994 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.