Date: Thu, 06 Apr 1995 10:21:06 -0700 (PDT) From: "John S. James" Subject: AIDS TREATMENT NEWS #220 AIDS TREATMENT NEWS #220, April 7, 1995 phone 800/TREAT-1-2, or 415/255-0588 CONTENTS: Merck Protease Inhibitor MK-639 -- Trial Cities Announced ICC Trials -- Enrollment Problem 3TC: Expanded Access Will Be Limited Infected Infant Appears to Clear HIV National AIDS Treatment Information Project Topotecan Now Available for HIV, PML Research FDA Reform in Congress: AIDS Community Absent 3TC and Protease Inhibitors: Citizen's Petition Asks Faster Approval Proposal: Monitoring Program for Early Rapid Testing of New AIDS Treatments ***** Merck Protease Inhibitor MK-639 -- Trial Cities Announced Two large trials of the Merck protease inhibitor MK-639 are now recruiting in the U.S. One is for people who have never taken AZT or other antiretrovirals (less than two weeks is permissible), and the other is for those who have used AZT. Protocol 033: AZT Naive This trial is seeking 780 volunteers who have not taken AZT, and who have CD4 (T-helper) counts between 50 and 500. They must be willing to take AZT, because they will be randomly assigned to either MK-639 alone, AZT alone, or the combination, during the 12 months of the trial. After 12 months, if the drug is found to be safe and effective, those who have completed the study, no matter what treatment they were assigned, will be offered MK-639. Patients will also be excluded for certain abnormal blood- chemistry tests, or for active infections or certain cancers. This trial will be conducted at sites in the following U.S. cities: Birmingham, Boston, Chicago, Dallas, Ft. Lauderdale FL, Hampton VA, Hershey PA, Honolulu, Houston, Irvine CA, Lexington KY, Los Angeles, Memphis, Miami, Nashville, New Orleans, New York, Newark, Philadelphia (2 sites), Portland OR, Prairie Village KS, Providence RI, Redwood City CA, Salt Lake City, San Diego, San Francisco, San Juan, Sherman Oaks CA, Stonybrook NY, Tampa, Washington DC. Besides the U.S. sites, there are sites in Canada, France, Germany, Spain, and Switzerland. In Canada, call 515/428- 2369; in France, 33-147-54-89-90; in Germany, 49-89-45611104; in Spain, 34-1-321-9726; and in Switzerland, 41-18287308. For information about enrolling in this trial, call the Merck Protease Inhibitor Information Line, 800/379-1332, between 8 a.m. and 7 p.m. Eastern time Monday through Friday. Protocol 035: AZT Experienced This trial is seeking 90 volunteers with CD4 counts between 50 and 400. They must have used AZT for at least six months but have never used 3TC or any protease inhibitor; however, prior use of ddI, ddC, or d4T is OK. They will be tested and must have plasma HIV RNA of at least 20,000 copies, and they must not have certain abnormal blood chemistry values. Volunteers will be randomly assigned to receive either MK-639 alone, AZT plus 3TC, or the combination of all three drugs. Trial sites are in Chapel Hill, New York City, Pittsburgh, and San Diego. For information, call the Merck Protease Inhibitor Information Line, 800/379-1332, between 8 a.m. and 7 p.m. Eastern time Monday through Friday. ***** ICC Trials -- Enrollment Problem The last issue of AIDS TREATMENT NEWS included information on enrolling in ICC 001, the first study of the Inter-Company Collaboration for AIDS Drug Development, a consortium of 15 major pharmaceutical companies. However, there is a potential problem in the enrollment process that we did not know about when that issue went to press. Before patients will be screened for this trial, they must bring in blood work showing that they will probably pass the screening. According to the ICC protocol, this blood work must be within 30 days, and must include specified lymphocyte subsets, hematology testing, and serum chemistry. Since most people get their blood work done every three to six months, this can create scheduling problems. Check with the site about exactly what the requirements are. $150 per patient has been budgeted for miscellaneous expenses in the trial; sometimes it can be used if the patient's insurance will not cover the required tests. Comment We have never heard of this pre-screening requirement before. It raises two concerns: (1) The 30-day limit will delay enrollment by up to several months, further slowing a study which has already had major delays. (2) This is a new example of medical cost shifting. The usual result is to shift the burden of treatment and of research onto the party least able to pay -- the individual already facing the stress of major illness -- because the institutions which could easily pay can avoid the cost. In this case, the additional cost of the usual flexibility -- taking whatever blood work is available, and accepting the risk of more unsuccessful screenings -- would probably average well under $100 per patient, or well under $22,500 for all the patients in the trial -- a small amount of money compared to the costs of doing clinical research. ***** 3TC: Expanded Access Will Be Limited Starting April 3, Glaxo is limiting enrollment in its 3TC expanded access program to 350 new patients per week in North America. In late March, 800 per week or more had been enrolling. Those who qualify for the program will be placed on a waiting list, first come first serve. This means that number 351 in one week will be number 1 the next. Presumably the wait will be relatively short for the next month or two, and then will grow longer. According to Glaxo, this change is needed because of limited drug supplies. Glaxo hopes that new supplies will be available by the fall, when production facilities have been upgraded. It is generally believed that 3TC will be approved by early 1996. ***** Infected Infant Appears to Clear HIV A baby who was HIV infected at birth appears to have cleared the virus and become HIV-negative, according to an article in the March 30 NEW ENGLAND JOURNAL OF MEDICINE. Viral culture tests were positive at 19 and 51 days of age, but all later tests have been negative. Because samples were saved, the virus could be tested again later; it was found to be identical, and related to the mother's virus, largely ruling out the possibility that the HIV-positive sample had been mislabeled and was really from someone else. Other cases of seroreversion in infants, in which an HIV infection appears to have cleared, have been found by the same research group (at the University of California Los Angeles School of Medicine), and have been reported in the medical literature by others. But these reports have usually been attributed to laboratory mistakes. While testing can be repeated to make sure that the person is indeed HIV negative, usually it is impossible to rule out a mistake in the original test which found them to be positive. The current case is important because it was documented well enough to convince the researchers, and the NEW ENGLAND JOURNAL OF MEDICINE. Many other cases may have been missed; researchers will be more open to this possibility in the future. These cases may be important in helping researchers discover what kind of immune response is effective against the virus -- information which could contribute to both vaccine and treatment development. ***** National AIDS Treatment Information Project The National AIDS Treatment Information Project, funded by the Kaiser Family Foundation, is producing a series of fact sheets of AIDS treatment information, to be available in June of this year. The information, designed for self-education and for counseling by community advisors, case managers, social workers, and clinicians, will be available by mail, by a fax-back system, and by computer. It will be available in English, Spanish, and Haitian Creole. Several dozen fact sheets are being produced, in five topic areas: Overview of HIV Disease, Clinical Manifestations, Opportunistic Diseases, Therapeutics, and Special Topics. This project is a collaborative effort of three institutions: Boston's Beth Israel Hospital/Harvard Medical School; San Francisco General Hospital; and the Gay Men's Health Crisis in New York. For more information, contact Helen E. Woods Wogan, Project Manager, Libby 317, Beth Israel Hospital, 330 Brookline Avenue, Boston, MA 02215, phone 617/667-5520, fax 617/667-2885, Internet hwoods@bih.harvard.edu, or HandsNet HN4722. Comment This information should meet much of the need for fact sheets which physicians and assistants can give to patients on such topics as the importance of taking pneumocystis prophylaxis, etc. We are happy to see that it will be made readily available by mail, fax, and computer. ***** Topotecan Now Available for HIV, PML Research The drug topotecan, being developed as a cancer treatment by SmithKline Beecham, will be made available to certain outside researchers interested in studying its possible use in treating HIV or PML (progressive multifocal leukoencephalopathy). Prospective researchers must have their pre-clinical or clinical plans approved by SmithKline Beecham, and must sign an agreement that they will NOT file for a use patent on the drug. Topotecan was discussed several times in AIDS TREATMENT NEWS in 1994. Researchers at Dana-Farber Cancer Institute showed that it has a strong anti-HIV effect; however, SmithKline Beecham is not interested in developing it for AIDS, and believes it would be too toxic as an AIDS or PML treatment. SmithKline Beecham is testing chemical derivatives, however, to learn whether the toxicity and anti-HIV effect can be separated. Researchers interested in more information should call Sharyn Arnold at 215/751-7074, or send a fax directed to her at 215/751-7655. ACT UP/New York has taken the lead in efforts to revive AIDS- related research on this drug. ***** FDA Reform in Congress: AIDS Community Absent by John S. James Far-reaching FDA reforms are now being proposed by Congressional Republicans, who may have the votes to force major changes in how FDA operates. The goal of many of these changes is faster and less expensive approval of important new drugs; but some proposals could also increase the risk of ineffective drugs being approved (the advocates insist that standards for safety will not be affected). As FDA reform moves with unexpected speed into prominence in the Republican Congressional agenda, it is important that those concerned about AIDS be involved in the process and make our views known. But so far the AIDS community is largely ignorant and unengaged in what is happening with this issue. A number of proposed reforms will be discussed next week in hearings by Senator Nancy Kassebaum (Republican, Kansas) of the Senate Labor and Human Resources Committee -- who, incidentally, is regarded as an important friend of people with AIDS, due to her work on reauthorization of the Ryan White Care Act. At the hearings, scheduled for April 5 and 6, legislation to amend the Food, Drug, and Cosmetic Act is expected to be introduced. As we go to press we do not know what the legislation will contain, but the following proposals have been discussed: * Accelerated Approval. Under current law, a drug cannot be approved without "adequate and well-controlled trials" (generally interpreted as more than one trial). A proposed change would require the FDA to approve a drug if the risk of the drug is no greater than the risk of the condition, and the drug is reasonably likely to be effective in a significant number of patients. This judgment could be based on expert opinion; under the proposal, phase III efficacy trials would not necessarily have to be done before approval. FDA's refusal could be taken to court, and conceivably the courts could order the FDA to approve the drug. * Phase I/II Testing. Another proposal would allow IRBs (institutional review boards) to approve a phase I or phase II test of a new drug; the FDA would have to be notified, but its approval would not be required before the trial could proceed. The FDA would still have to approve phase III trials; and sponsors could submit phase I and phase II protocols to the FDA, instead of to an IRB, if they wished. [Comment: This change could be important in reducing the great difficulty of getting the earliest human data on new treatment ideas. Current law gives the FDA 30 days to reply to an application for an IND; if it does not reply, the trial can go forward. But sometimes, just before the deadline, the researchers receive a long list of objections which would be almost impossible to satisfy. Some experts believe this happens because the FDA does not have the staff to meet the 30-day requirement, and is controlling its workload by effectively eliminating some research proposals. In any case the impact may be greatest on creative ideas that do not already have widespread support -- and may in part be responsible for the lack of creative ideas in AIDS treatment research. Allowing IRBs to approve early trials could bypass this bottleneck.] * Off-Label Information. Currently the FDA greatly restricts the ability of companies to distribute information about unapproved uses of approved drugs -- even though some unapproved uses become the standard of care in widespread use by physicians. A proposed change would allow companies limited distribution of information about unapproved uses, through a special section in advertisements or by giving peer-reviewed scientific publications to physicians or others. This could help physicians be more educated about de facto new uses of drugs when those uses have not been approved by the FDA. These are only a few examples of some of the proposed legislative changes which would affect the FDA. Other proposals are intended to speed the advisory-committee process, allow easier export of experimental drugs when legal in the receiving countries, allow minor manufacturing changes without prior FDA approval, and preventing the RAC (Recombinant Advisory Committee) at the U.S. National Institutes of Health from having separate jurisdiction over clinical trials, in order to focus this jurisdiction in a single agency, the FDA. ***** 3TC and Protease Inhibitors: Citizen's Petition Asks Faster Approval Log Cabin Republicans, a gay and lesbian Republican organization, has formally petitioned the FDA to speed approval of three drugs -- 3TC, saquinavir, and MK-639. The petition states that it should be possible to approve 3TC by September 1995, saquinavir by November 1995, and MK 639 by May 1996; this is well ahead of the expected timetable, in which approval for 3TC, for example, is not expected until winter 1996 -- a time frame everyone agrees is too long. The petition also explores the possibility of approving critical drugs even earlier, as soon as they are ready for expanded access. The FDA is required to respond to a formal petition, and David Feigal of the FDA met with petitioners on March 28 to discuss practical obstacles to approval, and means of speeding the process. Note: A similar petition, seeking more rapid approval of ddI and ddC, was filed with the FDA in December 1990; it may have contributed to the FDA's relatively rapid approval of ddI. ***** Proposal: Monitoring Program for Early Rapid Testing of New AIDS Treatments by John S. James The Problem With the development of protease inhibitors and other new approaches for treating HIV disease, there are more potential treatments, and many more combinations, which are worth trying. At the same time, the resources available for research, both public and private, may be shrinking. Efforts toward small, rapid trials must be encouraged; still, it has always been difficult to get even small trials of leading- edge ideas off the ground. Usually they do not happen at all, or take place only after months or years of delay. The main task is to address the apathy and lack of commitment that makes it so difficult to get studies done -- not to learn to live with the problem. But also, there is always a place for learning how to accomplish the most with limited resources. We propose a program for careful, consistent monitoring of experimental treatments which are already being used by patients and physicians. The goal is to greatly reduce the time and cost of getting the first widely credible information about the effects of new treatments, combinations, and treatment strategies in people. Background The new therapies of interest are already being tried by individual patients and physicians. Reports of results often circulate anecdotally. But for many reasons it is difficult to rely on these reports. For example: (1) Our interview with Dr. Feigal (AIDS TREATMENT NEWS #219, March 24, 1995) noted that even in the most research- intensive settings, sponsored by the largest pharmaceutical companies, there is concern that results of individual cases may be reported selectively. (2) Most experiences with new treatments are in a clinical, not research, setting. Often there is no advance planning to assure that the data will be credible to third parties. (3) There is little standardization among clinical physicians regarding which tests and laboratories to use, exactly when to give the tests, how to keep compatible records, etc. (4) Even if the data is completely in order for research purposes, there is still the credibility problem of convincing others of this. It is much more difficult for each physicians' practice to establish research credibility independently, than for one research organization to build its credibility over time. New therapies of interest are also tried in pharmaceutical company development programs. Here there are different problems: (1) Leading-edge approaches are seldom considered, since the needs of corporate drug development are different from those of patient care. Usually the best to hope for is monotherapy with one experimental agent, combined with approved drugs; for example, see the current ICC protocol [Inter-Company Collaboration for AIDS Drug Development], which at most combines one experimental drug with two approved ones. (2) Even unimaginative trials take excruciatingly long to actually begin; again consider the ICC trials, starting only now despite the high-level attention and support long put into them. (3) Early trials of new agents or new approaches often do not measure viral load or any other indication of activity; or they start by testing doses known to be ineffective. These trials, by design, can only be pieces in a long, expensive development process; no possible outcome could establish a rationale for human use of any treatment. When considering options in trial design, we should be aware that certain limitations of randomized clinical trials have long been known and analyzed in the medical literature, but ignored in AIDS research. Arvin R. Feinstein, from the Yale University School of Medicine, examined these limitations in a paper published in 1983 ("An Additional Basic Science for Clinical Medicine: II. The Limitations of Randomized Trials," ANNALS OF INTERNAL MEDICINE, volume 99, pages 544-550); Robert J. Levine, in ETHICS AND REGULATION OF CLINICAL RESEARCH, Yale University Press, 1986, recommends that this article "should be required reading for all persons who conduct or review plans to conduct randomized clinical trials." Feinstein noted that randomized trials have been successful when studying treatments to remedy an existing condition, but have "sometimes created rather than clarified controversy" when used in studies of either primary or secondary prevention of conditions which the patients do not have yet. And there has long been a seemingly irreconcilable conflict between "pragmatic" investigators (usually clinicians), who want the trial to provide useful clinical information, and "fastidious" investigators, usually biostatisticians, who want a clean study. Feinstein also considered many ethical and logistical limitations of randomized trials. He concluded, "The scientific resolution of most future problems in clinical management will have to come from analyses of events and observations that occur in non-experimental circumstances, during the interaction of nature, people, technologic artifacts, and clinical practitioners. By recognizing the informal "experiments" that are done whenever a clinician treats a patient, and by developing better observational methods for acquiring and analyzing the data, clinical investigators can be liberated from their previous intellectual restrictions and can take the fundamental steps needed to develop an additional basic science for clinical practice." Proposal: Monitoring Project A research organization could implement a monitoring program for systematic data collection, analysis, and reporting about treatments of interest which are already being tried. One way to both greatly decrease the cost of research, and simultaneously increase its relevance, is to study the treatments which physicians and patients have decided to use anyway. Since the actual treatment is already planned or underway, aside from the research project, the costs and obstacles involved in making a human trial happen are not a problem. Financially, the costs will be largely for lab work and administration. But the real costs of any clinical research includes not only the money, but also human costs (including increased risk and lost-opportunity cost) of asking patients and physicians do to something different from what they would have chosen to do otherwise. By studying treatments which would have been used in any case, this larger cost is also greatly reduced or eliminated. A protocol for this project would not specify the treatment to be used, as the physicians and patients would choose that in each case. The protocol might include formal selection criteria for the treatments and the patients to be considered. But since different patients' results will not usually be averaged together, inclusion/exclusion criteria need not be severe; the real question is whether there is a clinically interesting question that might be addressed, and this decision can best be made case by case by a medical review board. For example, such a project might study patients who are trying to lower their viral load (plasma HIV RNA) by using an experimental treatment or combination. Those entered into the study would be given specified baseline and after-treatment viral load tests -- as well as a physical exam, medical history interview, and immunological and other tests widely used in HIV trials. These results could be reported quickly; but there might also be scheduled followup which continues much longer (for example, through interviews at six months and then annually, continuing indefinitely whether or not the treatment is continued). To avoid any question of selective reporting, everyone accepted for study by the review board would immediately be given a sequence number and be accounted for in the published reports -- even if they never received the tests, or never used the intended treatment. This is only a matter of thoroughness of reporting; it does not affect statistical results, since the different patients are usually not averaged together. Protocol Outline The particular tests, schedules, and other details will ultimately be chosen by the researchers. This outline is intended as a basis for discussion. Inclusion/Exclusion: Volunteers who are using antiretroviral therapy must not change that therapy for at least a month before beginning the treatment to be monitored by this program. And they must be starting a treatment which might affect the overall course of HIV disease; it could be an antiviral, or work by some other mechanism, or have an unknown mechanism. But treatments for opportunistic conditions will not be studied in this protocol. Tests: The primary test to be monitored will be plasma HIV RNA, by the Hoffmann-La Roche quantitative PCR. Other standard panels -- immunological, hematological, blood chemistry -- will also be specified. A physical exam and medical history will be given when the volunteer enters the program, and a physical exam and exit interview (including questions on compliance) at the end of the primary monitoring period. Visits: Ideally three baseline viral load tests will be given; on the day treatment begins, half a week (3 or 4 days) before, and one week before. Other baseline blood tests will be included as necessary. Length of Study: The primary monitoring period will be eight weeks. After treatment begins, blood draws will be at half a week, one week, two weeks, four weeks, and eight weeks. Test results will not be batched or blinded, so that the volunteer can use them in making treatment decisions, including whether or not to stay in the monitoring program. Volunteers can change their antiviral regimen and still remain in the program. Ideally the entire panel of tests would be given at each blood draw; however, the protocol may specify reduced testing, for economic or practical reasons. Followup: After the primary monitoring period, the treatment being studied may or may not be continued. In either case, follow-ups will be scheduled at six months after treatment began, one year after, and annually after that. Ideally each followup would include the blood tests; but at a minimum, followup could be by phone interview. At the end of the primary monitoring period, results would be published, or otherwise made available to other investigators and physicians. An Ethical Concern When an individual case is reported, the person is easier to identify than if they are one of many who are summarized statistically. This problem may be reduced, if the only test results reported are those done specifically for this research; the numbers would not be identical with those in the person's medical record. And some results might be reported in summary form -- for example, percentage changes might be given instead of absolute values in some cases. But ultimately the volunteers will need to understand that this research does not offer the anonymity of a large trial, and accept or reject participation with that in mind. Specific Questions We believe that patients and physicians will find more interesting treatments to test than we could list by ourselves. But there is no harm in discussing some questions that might be addressed by this kind of screening study. AIDS TREATMENT NEWS occasionally publishes a list of about 30 treatments which have a valid rationale for testing in HIV disease, are not in a major development project currently, and are already widely used in people for other purposes (making research much easier than with a new chemical); this list last appeared in issue #218, March 3, 1995. In many cases, the possible mechanism of action is not known, and therefore it is not known how relevant a viral load test would be for measuring drug effects. But it may still make sense to include such treatments in an exploratory study based on viral load; there is little cost of doing so, and the results might give some insight into a mechanism of action. (1) For example, it would be interesting to see if viral load can fall after a patient starts acyclovir (due to an indirect effect of the drug, which is not believed to have anti-HIV activity). Apparently no one has tried this yet. Any effect on viral load might be seen in only some patients -- those who have another virus which may act as a cofactor for HIV and which is susceptible to acyclovir. Therefore, a single negative result obviously does not mean that this line of research should be abandoned; instead, a number of patients will need to be tested. (2) Another area where we do not know the mechanism concerns micronutrients. Consumption of certain micronutrients (either in food or in supplements) during asymptomatic disease has been found to be associated with substantial delay in disease progression, and increased survival; for other micronutrients, no such effect was found (see "Some Vitamins Associated with Decreased Risk of AIDS and Death." AIDS TREATMENT NEWS # 214, January 6, 1995.) Could a well-designed supplementation regimen (perhaps given by injection to avoid absorption problems) have an effect which could be seen in viral load reduction? (3) Some physicians have suggested doxycycline as possibly beneficial in AIDS treatment, for unknown reasons. Possible mechanisms include controlling possible mycoplasma infections, or treating other infections which may not be diagnosed. These rationales are probably too weak to get this drug into a formal trial, even a small one; but still it would be interesting to see if there are any consistent changes in viral load or other tests when patients start the drug. We should remember that some of the most important leads in the history of medicine have been completely unexpected in advance. The proposed monitoring project brings down the cost of research to the point where such a study could happen. (4) Hydroxyurea has had a strong rationale as an antiviral at least since the Berlin conference over a year and a half ago, but it has been notoriously difficult to get a formal trial going, in part because no one has exclusive rights to the drug. And the drug is dangerous enough that physicians who are not experienced with it are reluctant to use it without a good reason. Only recently have a number of patients started to try it. With the proposed monitoring study in place, drugs like this could be tested in a research setting as soon as someone wanted to try them; if strong antiviral activity is found, it would bring more attention to a potential treatment. This is a drug that physicians can learn to use safely, if they first have a reason for doing so. (5) Ribavirin, a broad-spectrum antiviral, was rejected prematurely as an AIDS treatment years ago, after an intense conflict between the Commissioner of the FDA at that time, and the president of ICN, the company developing the drug. Ribavirin might have a role for some patients, especially in combination with ddI or certain other drugs; and today, its antiviral activity could be followed with viral load tests. Despite continuing popular interest, ribavirin has not been revived as a potential treatment because of the lack of commercial motivation for organizing new formal trials. The proposed monitoring project -- based on viral load testing, which was not available when ribavirin was studied previously -- could greatly reduce the cost of getting new credible data about this drug. (6) The monitoring project could also be used for early information to guide clinical trials of combinations of protease inhibitors or other drugs in mainstream development -- combinations that would not otherwise be tested. One important question here is the effect of these drugs and combinations in people who already had much experience with antiretrovirals, and were unable to lower their viral load further with conventional treatments. The mainstream trials are now focusing on antiviral-naive subjects; but the main use of the new drugs, at least initially, will be for people who have already failed other available treatments. We need to know what combinations are likely to work in these difficult cases, and we may not get that knowledge from the trials currently planned. The Next Step This monitoring project should probably begin at one site (AIDS Research Alliance [formerly SEARCH Alliance, in Los Angeles] would be ideal); the tests and treatments could be administered either there, or in the offices of physicians associated with the organization. Later, other research institutions or clinical practices might also use the same protocol. The first critical step is to refine this proposal and develop a detailed protocol, incorporating the views of medical and research experts. A working monitoring project will mean that as soon as the first patient is ready to try a treatment, that treatment can be tested, with results becoming available almost immediately. While the results from the first few patients will clearly be limited, they will be completely consistent, without selection bias, and collected exactly as specified. If early results are favorable, more people will try the treatment, strengthening the confidence in the results of the monitoring, and also generating early interest in other studies, including larger, controlled trials. ***** 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. 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