Date: Thu, 02 Nov 1995 19:13:57 -0800 (PST) From: "John S. James" Subject: AIDS Treatment News #234 AIDS TREATMENT NEWS #234, November 3, 1995 phone 800/TREAT-1-2, or 415/255-0588 CONTENTS: Project Inform's THE HIV DRUG BOOK Now Available Thalidomide for Wasting Syndrome: Progress Toward Compromise NIH Research Evaluation: Last Meeting on Clinical Trials November 13, Public Comment Allowed NIH Role in Clinical Research CMV: Oral Ganciclovir for Prevention CMV: New Screening Program Cryptosporidiosis Information Phone/Fax Line Protease Inhibitor Trial Drops AZT-Only Arm Help Wanted: AIDS Treatment Activist, Atlanta Peptide T: Negative Trial Result ***** Project Inform's THE HIV DRUG BOOK Now Available THE HIV DRUG BOOK, a well-organized guide to what patients should know about the major drugs used to treat HIV and opportunistic infections, has just been published and is now reaching bookstores. We believe that everyone interested in AIDS treatment should have a copy of this important reference, published by Pocket Books at a cost of only $16 for the 688-page book. The contents have been reviewed by an advisory board of eleven well-know HIV physicians. Most of the book consists of drug profiles; the profiles are listed alphabetically, within the following categories: Antibiotics; Anticancer drugs; Antidiarrheal drugs; Antifungal drugs; Antihistamines; Antinausea/Antivomiting drugs; Antiprotozoal drugs; Antiseizure drugs; Antiulcer drugs; Antiviral drugs; Antiwasting treatments; Corticosteroids; Immune-based therapy; Neuropathy drugs; Pain relievers; Psychoactive drugs; Vaccines, and Miscellaneous drugs. All the drug profiles are organized in the same way, with the following sections always in the same order: Brand names/Manufacturers; Type of drug; Used for; General information; Treatment; Cautions and warnings; Side effects; Pregnancy/Breast feeding; Use in children; Use in the elderly; Drug interactions; Food interactions; and Other drugs used for similar conditions. In addition, each drug class has a short overview of the class as a whole. A number of experimental drugs are described, usually without full profiles but in a separate annotated list at the end of the section for their drug class. The book also includes an introduction by Martin Delaney, a preface by Donald Abrams, M.D., a forward by Joel Thomas, a glossary, and various practical articles -- from nutrition, to alternative treatments, to managing opportunistic infections, to communicating with your physician, to understanding clinical trials, to avoiding AIDS fraud and exploitation. There is also an extensive resource guide, including national hotlines, a state-by-state and city-by- city listing of major AIDS service organizations, Canadian resources, national AIDS publications, mail order pharmacies, buyers' clubs, state AIDS drug assistance programs (ADAP), and pharmaceutical company payment assistance programs. A 16- page drug identification guide provides color photographs of the various drug preparations available, and an extensive drug interaction chart warns of known problems of using certain drugs together. ***** Thalidomide for Wasting Syndrome: Progress Toward Compromise by John S. James The outline of a compromise to an intense dispute about access to thalidomide as a potential treatment for wasting syndrome -- a dispute that could have led to FDA raids on the largest AIDS buyers' clubs -- appears to have been reached at an October 24 meeting of the buyers' clubs, thalidomide developer Celgene Corporation, and the FDA. Under this compromise, physicians will be able to choose a dose of 50, 100, or 200 mg per day (the most common dose has been 100 mg), under an open-label safety study; patients will have to pay for the drug, with the price not yet worked out. (An earlier plan, which would have had patients pay for the drug without controlling which dose they got, raised concerns that it would set a dangerous precedent of allowing companies to charge volunteers for entering a randomized clinical trial.) The buyers' clubs -- the PWA Health Group in New York, and Healing Alternatives in San Francisco -- have worked for over two years so that people with AIDS-related wasting could get thalidomide under some form of official compassionate-access system. When the drug remained unavailable outside of a restrictive clinical trial, they organized a special Thalidomide Underground Compassionate Use Program, in order to force the creation of an official program. This goal now seems to have been reached. When the new open-label safety protocol is functioning, the underground program will end. Background: Wasting Syndrome Wasting syndrome -- extreme loss of lean body mass -- kills many people with AIDS. It has many different causes, and there is no single treatment for everyone. The first step in prevention or treatment is diagnosis and correction of a specific cause, such an intestinal infection, or an obstacle to sufficient food intake. Nutritional and life-style counseling can also be important, especially for early intervention and prevention. But there are many cases that do not respond to these approaches. The FDA has approved treatments for wasting syndrome: megestrol acetate (Megace(TM)), and dronabinol (Marinol(TM), which uses the active ingredient of marijuana to stimulate appetite). For some people these are helpful; for others they are not. Both are expensive. Smoked marijuana appears to work better than the dronabinol pills for some people (for others, the pills are better), but marijuana is illegal. TPN (total parenteral nutrition, a very expensive intravenous feeding) can help in certain specific cases. Other possibilities are mentioned below. When other treatments have failed, some of the best results seem to have come from human growth hormone -- a very expensive prescription drug which has been FDA-approved in the U.S. for years for treating short stature in children, but has been tightly controlled to prevent abuse by athletes. Human growth hormone is now available to treat wasting syndrome in certain cases under a "treatment IND" -- a special FDA program which is intended to allow compassionate use of a drug when urgently needed by a group of patients, and which can allow companies to charge for "cost recovery" in supplying these drugs. The problem is that human growth hormone costs about $1,000 per week under the treatment IND, and will probably need to be used indefinitely. Some people can get coverage under insurance, Medi-Cal in California, or an indigent-patient program. The prescription versions of this drug are even more expensive. Incidentally, a similar hormone for cattle costs over a thousand times less. It cannot be used by people; we mention it to show that investigation is needed into how the price of human growth hormone has stayed so uniformly high for so long all over the world, despite the fact this drug is manufactured by a number of different and supposedly competing companies, and manufacturing cost is apparently not an issue. There are patents, but they have not effectively provided a monopoly; something other than the patents must be keeping the price very high. Because no single treatment for wasting syndrome works for everyone, and because several of the major treatments are economically out of reach for most people, there is urgent interest in low-cost options. The main ones now being examined are (1) anabolic steroids and/or testosterone, and (2) thalidomide. [In addition, thalidomide might also have other uses in AIDS; see "Thalidomide and Kaposi's Sarcoma -- Call for Information," below.] Background: The Thalidomide Controversy For some time thalidomide has been available through an FDA- approved program for compassionate use in treating certain AIDS-related aphthous ulcers which have not responded to other therapies. Until recently this program was not open to persons with wasting syndrome. Such persons had no way to get thalidomide in the U.S., despite a small placebo-controlled trial in which eight of nine patients with AIDS-related wasting gained weight when treated with thalidomide, vs. only two of nine in the placebo group, a statistically significant difference.(1) Another placebo-controlled study reported statistically significant weight gain with thalidomide treatment in tuberculosis patients, many of whom also had HIV.(2) There have also been anecdotal reports of weight gain in persons with AIDS-related wasting. AIDS buyers' clubs, after much thought and investigation, responded and obtained thalidomide for persons with wasting syndrome. (Thalidomide has long been used in Brazil and other countries -- including the U.S. -- in the treatment of leprosy.) The FDA was upset, and sent the clubs increasingly threatening demands that they stop supplying the drug. The buyers' clubs have made it clear that they are willing to do so -- but not until there is an FDA-approved program which is effectively supplying the drug to the people who desperately need it. The reason for the FDA's concern, of course, is that thalidomide can cause birth defects if taken by pregnant women. About 35 years ago, before this was known, thalidomide caused thousands of deformities in Europe, where it was prescribed for morning sickness. In the U.S., this disaster was prevented because the FDA had fortunately not approved thalidomide due to other safety concerns. This U.S. disaster which was averted by the FDA became a proud, defining historical moment for the organization. What is happening now is that the FDA is temporarily accepting persons with AIDS-related wasting into its small compassionate-use program for persons with aphthous ulcers. This will end when Celgene Corporation of Warren, New Jersey, the company which is developing thalidomide for treatment of wasting, is ready with a program for wider use of the drug. [Note: While thalidomide is being developed for wasting syndrome by Celgene, it is being developed for aphthous ulcers by another company, Andrulis Pharmaceutical Corporation.] All three parties gain from the apparent compromise, and all give something up. The FDA has been most anxious to shut down unofficial access to thalidomide through the buyers' clubs; the compromise will probably accomplish that. But the FDA has also been reluctant to allow a "treatment IND" compassionate access program with cost recovery, until more data is available than it now has about thalidomide and wasting. (A controlled trial for wasting is now ongoing, but it has had serious problems recruiting volunteers, because of exclusion conditions, and because it is placebo controlled when there is a standard of care (Megace or Marinol); persons with wasting syndrome severe enough to qualify for the trial are unwilling to risk getting no treatment.) Something had to be done to justify shutting down the buyers' club supply -- hence the pressure to speed up plans for a second Celgene randomized trial, to provide alternative access. But at the October 24 meeting, it became clear that the resulting trial would not produce the kind of efficacy information the FDA wanted in any case, so there was no need for it to be randomized. The company had to give up its hope for randomized data. But it can charge for the program, and will get safety information from it. The buyers' clubs are convinced that they have given better service to patients than the official program will -- and at a much lower cost. They had to give this up, but they did achieve their central goal -- the creation of an official program to distribute the drug for persons with wasting syndrome. Thalidomide for Aphthous Ulcers: New NIAID Results On October 31, as this issue went to press, the U.S. National Institute of Allergy and Infectious Diseases announced that thalidomide had worked well enough in treating severe mouth ulcers (oral aphthous ulcers) that a major ongoing government study (ACTG 251) was being changed to no longer require persons with that condition to take a chance of receiving a placebo. Instead, the trial will continue, in order to collect data on maintenance use of thalidomide for this purpose; but all current and new volunteers with mouth ulcers will get the active drug. In the trial so far, the ulcers healed in 14 of 23 patients receiving thalidomide, but only one of 22 who received the placebo. Volunteers with aphthous ulcers of the esophagus will still be randomly assigned to thalidomide or placebo, however, because there has not yet been enough enrollment in the study to prove that the drug works for these ulcers as well. This study is still open for enrollment in about 20 U.S. cities; it is seeking a total of 164 volunteers. For more information, call the AIDS Clinical Trials Information Service, 800/TRIALS-A. Comment: This result is no surprise. The medical literature has been full of successful reports of thalidomide use in aphthous ulcer treatment for the last five years. Other AIDS-Related Uses: Kaposi's Sarcoma? Microsporidiosis? If anyone using thalidomide also has Kaposi's sarcoma (KS), we would like to hear if the drug seemed to have any effect on that disease. An animal study published last year found that oral thalidomide inhibited angiogenesis (the growth of new blood vessels), and concluded that the drug had promise as a possible treatment "of many diverse diseases dependent on angiogenesis."(3) (The abstract did not mention Kaposi's sarcoma specifically, and is not included on the AIDSLINE computer database.) A small study (17 volunteers) in England, reported at the recent AIDS conference in Copenhagen, found improvement in diarrhea due to microsporidiosis after treatment with thalidomide, in patients who had failed to respond to previous treatment with albendazole.(4) This trial was organized after earlier research found that persons with AIDS-related microsporidiosis had abnormally high levels of TNF (tumor necrosis factor, which has many effects on the body) in their feces. Thalidomide reduces TNF levels. In addition, there is interest in thalidomide as a possible treatment for other illnesses which are not AIDS related, including lupus, and some cancers. We are concerned that removal of thalidomide from the buyers' clubs will make it more difficult to explore new possible uses for the drug. Official clinical research is usually years behind the leading front-line scientists, physicians, and patients. FDA Compassionate Access Program The FDA program for compassionate access to thalidomide -- originally set up for persons with aphthous ulcers, then temporarily used for persons with AIDS-related wasting syndrome -- is still open for wasting syndrome. This program is free; but its use for wasting will be ended when the Celgene open-label safety protocol is ready. For information about the FDA compassionate-access program, contact Matthew Tarofsky or Brenda Atkins, 301/443-9553. Comment - Charging for Trials The entire issue of charging patients for the costs of research -- research undertaken not for their benefit, but for the benefit of the pharmaceutical company which owns the rights to the drug -- needs much more attention. This problem must be seen in the larger context of pharmaceutical companies big and small shedding costs of developing their own proprietary drugs. Insurance companies and government programs alike are usually adamant that they will not pay for the pharmaceutical companies' research -- and strong enough to avoid having to do so. The bills, then, go to desperate patients who have to pay out of their own pockets if they can pay at all, and give up the treatment they need if they cannot. The PWA Health Group was concerned that the earlier, randomized thalidomide trial-for-sale would set a new, dangerous precedent in this direction. There is widespread fear that many pharmaceutical companies will happily make patients pay for research if they can get away with it -- a "Republican wet dream," one activist called it. [It has long been noted that people are cheaper than monkeys for some clinical trials; they will be cheaper still if they have to pay their own way as guinea pigs.] Already it has become a widespread practice to force volunteers to pay for laboratory tests required by research protocols. Note that charging for COMPASSIONATE ACCESS (including "treatment IND" and other programs set up primarily for treatment, not for research) is also an issue, but a different one than charging clinical-trial volunteers for DRUG RESEARCH AND DEVELOPMENT. Compassionate access is for the patient's benefit, not the pharmaceutical company's; it should be reimbursed as part of medical care. The problem is that insurance companies and other third-party payers, public and private, have control of the rules, and have abused their power by extending their understandable refusal to pay for other companies' drug development to also refusing to pay for treatment on the grounds that it is "experimental" -- even when the clear purpose of the medication is treating the patient, not drug development. These compassionate access programs provide some of the most important medical treatment, simply because they are seldom set up except in cases of desperate need. To single out this most urgent medical expense for refusal of coverage is unconscionable. This issue has been obscured because pharmaceutical companies have been expected to pay for compassionate access out of their research and development budgets; patients and payers alike did not see the bill. It has been argued that it is inherently immoral to charge for a drug which has not been proven safe and effective. We believe this whole area needs more attention. Sometimes the drugs are not available at all unless companies can charge for them. And requiring that research funding cover these programs might slow development of new drugs. These problems would be greatly reduced if, when an unapproved drug is the best option for a patient's therapy, it could be reimbursed like any other medical care. (In addition, pharmaceutical companies need to continue to help patients obtain reimbursement for which they are qualified, and to set aside some proportion of the drug for an indigent program for patients who cannot be reimbursed.) Research and medical costs which should legitimately be paid by others must not be dumped onto the individual patient, just because powerful institutions are fighting among themselves over who should pay. Patients, physicians, and the general public are in an excellent position to organize politically against this. References 1. Reyes-Teran G, Sierra-Madero JG, Martinez del Cerro V. and others. Effects of thalidomide on wasting syndrome in patients with AIDS. A randomized, double-blind, placebo controlled clinical trial. International Conference on AIDS, Yokohama, August 7-12 1994 [abstract # 536B]. 2. Tremontana JM, Utaipat U, Molloy A and others. Thalidomide treatment reduces tumor necrosis factor alpha production and enhances weight gain in patients with pulmonary tuberculosis. MOLECULAR MEDICINE May 1995; volume 1, number 4, pages 384- 397. 3. D'Amato RJ, Loughnan MS, Flynn E, and Folkman J. Thalidomide is an inhibitor of angiogenesis. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, USA, April 26, 1994; volume 91, number 9, pages 4082-4085. 4. Sharpstone D, Rowbottom A, Francis N and others. A novel therapy for microsporidiosis. Fifth European Conference on Clinical Aspects and Treatment of HIV Infection, Copenhagen September 27-29, 1995 [abstract #92]. ***** NIH Research Evaluation: Last Meeting on Clinical Trials November 13, Public Comment Allowed The Office of AIDS Research (OAR) -- which recently was given budgetary authority over the U.S. National Institutes of Health (NIH) AIDS research program, which is by far the world's largest -- is finishing up a one-year process of evaluating AIDS research at NIH. Due to a closed, secretive atmosphere around this evaluation process, most of the AIDS community has not been informed of what is going on, or able to give input. Protests by ACT UP/New York and ACT UP/Philadelphia against the closed process -- including three arrests -- led to some increase in openness, including the appointment of two community representatives. (Two other community representatives, both active in Treatment Action Group (TAG), were on the panel from the beginning.) The final report is due in January. The last meeting of the Area Review Panel on Clinical Trials (one of six Area Review Panels of the NIH AIDS Research Program Evaluation Working Group) will be held November 13 and 14 at the Chevy Chase Holiday Inn, 5520 Wisconsin Avenue, Chevy Chase, Maryland. Only the morning of November 13, from 8:00 a.m. to noon, will be open to the public. Individuals and organizational representatives (no more than one from each organization) may be able to speak for five minutes; however, the deadline for making prior arrangements to speak has passed. Written statements will be accepted; but the deadline for having them distributed in advance to the panelists has passed. Since both deadlines were October 30 and the meeting was announced in the FEDERAL REGISTER (page 53793) on October 17, there was little time to get the word out. Not surprisingly, few people signed up. To submit written comments, send three typewritten copies, including a brief description of your organization, to the attention of Dr. Judith Feinberg, Office of AIDS Research, NIH, 31 Center Drive, MSC 2340, Building 31, Room 5C08, Bethesda, MD 20892-2340, phone 301/496-0358, fax 301/402- 8638. "Comments should be confined to statements related to the current status of NIH AIDS research in the areas of therapeutic clinical trials and recommendations for consideration by the panel in assessing and reviewing the relevant research in these areas." If you want to speak at the meeting, those who have not made any advance arrangements may be permitted to do so at the end of the meeting, if there is time and the chairperson agrees. We suggest contacting OAR in advance, even though the deadline has passed, as preferable to just showing up. To do so, send a letter of intent and three typewritten copies of the presentation, along with a brief description of the organization represented, to Dr. Feinberg at the above address. ***** NIH Role in Clinical Research by John S. James [This is our statement to the Office of AIDS Research NIH AIDS Research Program Evaluation Working Group Area Review Panel on Clinical Trials, November 13-14 (see notice above). [Do not rely on us to get this message across. We cannot attend the meeting, and we missed the deadline for advance distribution of this statement. Nor do we know what issues are being addressed in the evaluation process, as that is not public information; sometimes it has not been available even to Working Group members themselves.] ***** We are hearing widespread concern that OAR may go overboard in the shift to basic research, and seriously limit the NIH role in AIDS trials. Granted, previous AIDS clinical-trial research often lacked focus, and as a result was unproductive. But some AIDS trials clearly belong at NIH. Here are four kinds of AIDS trials (not a complete list) that NIH must do: (1) Pathogenesis-intensive trials. For example, one ACTG trial now being designed will suppress viral replication as completely as possible with multiple drugs, in a small number of patients, to allow intensive study of the changes in CD4 and other blood cells as the CD4 counts increase. Clearly this clinical trial is basic science as well -- basic science which is especially relevant, as it is done in people. Industry is unlikely to do such work, and community organizations are seldom equipped for it. Note that pathogenesis-intensive trials -- the most scientific of all trials -- do not always need to be controlled. (2) Small, rapid, proof-of-principle trials of treatment leads, including "alternative" treatments. The history of medicine is full of surprises; treatment progress seldom moves in predictable straight lines. Testing the dozens of treatment leads which have known safety information and some credible rationale will almost certainly find no measurable benefit from most of them. But a few probably will prove unexpectedly interesting -- producing incalculable SCIENTIFIC benefit by opening new research avenues, in addition to any immediate value the potential treatments may have to patients and physicians. (Other benefits at no extra cost include the public-health importance of showing that many popular treatments fail to work as intended -- as well as the economic value of any positive discovery in reducing the cost of medical care, since most of the treatment leads in this class are non-proprietary and readily available at negligible cost.) The primary outcome could be viral load, immunological markers, or other credible measurements. The aim of this research would be to find some measurable, reproducible effect indicating drug activity. Once activity is known, further research could be planned from there. The National Cancer Institute has traditionally done such early testing in cancer; but in AIDS, no one has done much of it so far. Community organizations could conduct these trials, but usually they have not. Part of the problem may be regulatory cost, as many treatment leads in common human use do not exist in forms that meet FDA requirements for research -- prepared under GMP (Good Manufacturing Practices) rules, and with the active ingredient properly standardized from batch to batch (which is probably impossible if the active ingredient(s) are unknown). Running a trial legally in the U.S. could require the major expense of setting up a new production facility -- in addition to laboratory research to identify, test for, and perhaps synthesize active ingredient(s). Because of these barriers, nothing happens -- when a safe, simple trial could quickly identify the few valuable leads, which then could easily find the support required for further research. NIH could deal with this problem more effectively than community organizations can. Another problem for community research is that only organizations with a highly "respectable" face can raise the money required, and those groups tend to follow the same scientific fashions as NIH and others, reducing their potential contribution to that of a small drop in the big bucket of research already being done. Technically these trials would be easy to run; but it is hard to find the required money, expertise, good judgment, and also openness to new ideas, all in the same organization. (3) Development and standardization of "markers" and other tests. NIH is already the leader here. Industry can develop specific tests, but there are major gaps that industry will not fill. NIH should do more to develop new immunological markers -- especially those which can be measured by flow cytometry or related methods, since this technology is well suited to standardization and quality control. (4) Confirmatory trials -- or rather, a single master protocol for clinical confirmation of antiretrovirals which have received accelerated approval. When new treatments are likely to become part of the standard of care and be administered to hundreds of thousands of people, many researchers, physicians, and patients want long-term clinical data, to confirm that treatments approved based on short-term trials really are ultimately beneficial, and do not have detrimental surprises later. There is no way that every new treatment and promising combination can continue to have its own confirmatory trial, with its own control group, etc. We need a master protocol to compare the most important possibilities; and government must be involved in the administration and data management, instead of leaving this to the competing companies. Government should pay for and control the aspects of this research which are not drug-specific. Confirmatory trials will become much more feasible if we can accept a certain philosophical shift. We need to realize that these trials -- although they are randomized and controlled -- do not need to produce a winner and a loser. Therefore, this master protocol does not need to have a loser arm (traditionally provided by an obsolescent standard of care, such as AZT monotherapy before the ACTG 175 and Delta results were reported), and can avoid all the ethical, recruitment, and compliance problems that requiring a loser entails. And these trials do not need to prove equivalence either; they do not need to reject any null hypothesis. Instead, their purpose should be to monitor the major therapeutic options likely to become part of the standard of care, looking for any unexpected problems (or unexpected benefits as well). If the master protocol we propose never proves that anything is better than anything else, and also never proves that anything is equivalent to anything else, it will still have been a complete success. It will have safeguarded the public from unexpected toxicities or treatment failures in all of the treatments tested. (All these treatments will already have proven superiority or at least equivalence to standard of care -- in the surrogate-marker trials required to gain accelerated approval -- before being eligible to enter the confirmatory master protocol.) Such a master-protocol trial will also produce a treasure chest of associated information, such as which patients are likely to do well on which treatments -- information not as readily available from separate confirmatory trials which are not designed to be comparable. And additional substudies can be nested to address specific questions. To illustrate with specific drugs, such a protocol could randomize volunteers to the Roche, Merck, Abbott, or other protease inhibitor -- or any other drug combination with equally good safety and surrogate-marker results -- after those drugs have received accelerated approval. Each developer would recommend other drugs (for example, AZT plus 3TC) designed to make the combination with their product work as well as possible; and volunteers would not have to pay for these recommended drugs. (Volunteers would be allowed to use other, non-recommended drugs on their own; therefore, they would have no reason to conceal anything from the researchers, but could fully report what they did.) NIH, as administrator of the master protocol, would decide which combination treatments were good enough to become an arm in the trial -- meaning that participation would be a major marketing advantage for a company (not an unavoidable burden like confirmatory trials today) because it would imply official recognition that, based on all current knowledge, the company's treatment was as good as any treatment known. And participation would of course fulfill the accelerated approval confirmatory trial requirements -- almost regardless of the result of the trial, as there would be no loser arm, and therefore no winner/loser relationship expected. Only the discovery of a serious toxicity or other drug failure would be held against a drug, greatly reducing the developer's risk from the head-to-head comparison with competitors. With these incentives, industry will compete to get into these trials, greatly facilitating inter-company cooperation (since a winning combination will usually require products of more than one company), and helping to finance the project as well. But this whole structure requires government management of the master protocol, requires an outside party which answers to the public interest. Competing companies probably cannot organize such a program on their own. NIH has already shown that it can fulfill this kind of management role, for example in ACTG 175. No one else could do so. ***** CMV: Oral Ganciclovir for Prevention On October 31 Hoffmann-La Roche announced that it had received FDA approval to market oral ganciclovir (Cytovene(TM)) for prevention of CMV disease in persons with advanced HIV infection. Oral ganciclovir had previously been FDA approved, but only for maintenance treatment of CMV retinitis (after the disease had already developed, and been stabilized with intravenous treatment). A Roche Biosciences (formerly Syntex) clinical trial in 725 volunteers with CD4 count less than 100 found a 49% reduction of risk of CMV disease in those randomly assigned to preventive treatment with oral ganciclovir, compared to those who received the placebo. Side effects of the treatment included anemia, neutropenia, and elevated serum creatinine. ***** CMV: New Screening Program Hoffmann-La Roche also recently started a CMV Retinitis Screening Program, to teach patients at risk for CMV retinitis to recognize symptoms of the disease between doctor visits, so that they can get rapid treatment. Patients can obtain a kit -- including a videotape "Recognizing CMV Retinitis," a brochure, and an Amsler grid, which is used to help diagnose CMV retinitis -- by calling the voicemail number 800/624-CHECK. AIDS service organizations can request a physician-led seminar about CMV retinitis and the screening program; call 800/293-7428 or 212/698-1662. ***** Cryptosporidiosis Information Phone/Fax Line The U.S. Centers for Disease Control has started a phone and fax service for information about cryptosporidiosis. Callers can listen to recorded messages, or receive printed information by fax. The phone number is 404/330-1242. ***** Protease Inhibitor Trial Drops AZT-Only Arm Hoffmann-La Roche has changed its trial of the protease inhibitor saquinavir, due to new information from the ACTG 175 trial and the Delta trial showing that AZT alone was inferior to combination therapy (for background on ACTG 175, see AIDS TREATMENT NEWS #231, September 23, 1995; for background on Delta, see AIDS TREATMENT NEWS # 232, October 6, 1995). Those in the saquinavir trial (named SV 1406) who were randomized to AZT will be offered a chance to switch to the triple combination of saquinavir plus AZT plus ddC. New volunteers entering the trial will be randomized to one of the three combination-therapy arms (saquinavir plus AZT, AZT plus ddC, or the triple combination). ***** Help Wanted: AIDS Treatment Activist, Atlanta The AIDS Survival Project, an Atlanta, Georgia coalition of people affected by HIV, is seeking a full-time treatment resource specialist. This program-management position involves treatment activism as well as supervising and maintaining a large treatment resource library. Applicants need the ability to work with a wide variety of people, strong writing skills, strong knowledge of HIV treatments and treatment issues, and the desire and ability to advocate for treatment reform both locally and nationally. Salary range $24,000-26,000 plus benefits. If interested, send resume, cover letter, and references to: Jeff Graham, Executive Director, AIDS Survival Project, 828 W. Peachtree St., Suite 208, Atlanta, GA 30308. People of color and HIV positive individuals encouraged to apply. [Note: AIDS TREATMENT NEWS does not usually publish help- wanted announcements, but we do consider them for TREATMENT SPECIALIST positions.] ***** Peptide T: Negative Trial Result by John S. James A government study of 215 volunteers with AIDS-related cognitive impairment found no proof that peptide T was helpful for treating this condition. The volunteers were randomly assigned to receive either peptide T (intranasally, up to six mg/day) or placebo for six months; for the next six months, everyone was given peptide T, and they could continue the medication beyond one year if they wanted. Cognitive impairment (which includes difficulties with memory, attention, language, problem solving, spatial ability, and visual-motor coordination) was measured by standard neuropsychological tests. The treatment group showed no statistically significant improvement compared to the control group. The study also found no toxicity from peptide T. Recruiting for this study began in March 1991. It took a long time to find volunteers -- probably because AIDS-related cognitive impairment is less common than had been expected, and because it can often be treated effectively with AZT. This clinical trial was conducted by the U.S. National Institute of Mental Health, with additional funding from the U.S. National Institute of Allergy and Infectious Diseases (NIAID). ***** 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@aidsnews.org Editor and Publisher: John S. James Reader Services and Business: Richard Copeland Thom Fontaine Denny Smith 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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