Date: Sat, 20 May 1995 17:11:26 -0700 (PDT) From: "John S. James" RETRANSMISSION: Many people did not receive #222 when it was sent two weeks ago; we are resending it to the entire list. AIDS TREATMENT NEWS #222, May 5, 1995 phone 800/TREAT-1-2, or 415/255-0588 CONTENTS: D4T: New Clinical Data Confirms Benefit Stanford Researchers Find Loss of "Naive" T-Cells ICC Trials: New Option on Laboratory Tests 3TC Expanded Access Program: New Requirement for CD4 Less Than 100 Agouron Protease Inhibitor AG1343: Activity in People Reported AIDS Research Meetings, May 1995 and Later ***** D4T: New Clinical Data Confirms Benefit by John S. James A major study of d4T (generic name stavudine, brand name Zerit) has shown that patients who have been using AZT did significantly better in disease progression if they switched to d4T than if they stayed on AZT. This new information is important for making treatment decisions; it confirms the decision to grant accelerated approval to d4T last year. Also, it shows that improvement in blood tests, including CD4 count and viral load in peripheral blood cells, can predict later clinical benefit to patients. The new information, from the '019' study sponsored by Bristol-Myers Squibb, was presented at the Eighth International Conference on Antiviral Research, April 23-28, in Santa Fe, New Mexico. This study included 822 patients, with CD4 (T-helper) counts between 50 and 500. All had taken AZT for at least six months, but many had been taking it much longer than that. Ten percent of the patients had a diagnosis of AIDS at entry. These 822 patients were randomly assigned to either continue using AZT, or to switch to d4T; neither the patients nor their physicians knew who was getting which drug. Patients were on the study for at least two years. Three outcomes were measured: (1) survival; (2) clinical progression (did the person either die, or contract any new or recurrent AIDS- defining opportunistic infection); and (3) treatment failure (death, opportunistic infection, or a 50% or greater drop in CD4 count). 90% of those assigned to the d4T group survived for the two years of the study, vs. 86% of those who stayed with AZT; this is a clear trend in favor of d4T, but did not reach statistical significance due to the small number of deaths. The other two outcomes -- disease progression and treatment failure -- were statistically significant in favor of d4T, however. Switching to d4T resulted in an average three months delay in clinical progression, compared to staying on AZT. (While three months may not seem like much, in actual practice the results are likely to be better than this group average, because those who do best on d4T can stay on it, while others can move on to other drugs or combination treatments. This study was analyzed on an "intent to treat" basis, meaning that those patients randomly assigned to d4T were counted with the d4T averages, even if they could not tolerate the drug -- therefore underestimating the treatment effect.) Throughout the study, CD4 counts were higher by an average of about 40 in those who switched to d4t. The treatment groups were also analyzed separately by CD4 subset -- 50-100, 100-300, and 300-500. All three groups showed a large "relative risk" in favor of d4T; these were statistically significant in the 50-100 and 300-500 groups. Viral load (HIV in peripheral blood cells) will be analyzed in this study; blood was collected and plasma HIV RNA will be measured. However, the tests have not been run yet; the only virological data now available is the measurement of virus in blood cells, which was presented to the FDA a year ago. There were several differences in side effects between the treatment groups, with d4T more likely to cause some side effects, AZT more likely to cause others. Side effects are a concern with d4T; we are hearing that a number of people are unable to tolerate the drug. This study does not answer a number of other questions about d4T, including how well it may work as initial therapy. Approval History D4T was approved by the FDA on June 27, 1994. This followed a cautious recommendation for approval by the Antiviral Drugs Advisory Committee, which met on May 20, 1994. At the time of the May 20 meeting, data from 359 of the 822 patients was available; the other patients were still in the blinded study, so their data could not be used. At that time, those who were assigned to switch to d4T had an average CD4 count about 50 higher than those who continued AZT. The amount of HIV in peripheral blood cells had dropped 53 percent for those on d4T, compared to an 11 percent increase for those on AZT. (This measure of viral load is not the same as the plasma HIV RNA which is more commonly used today, although it is related.) At the May 20 meeting, there were certain technical controversies concerning whether d4T should be approved. These controversies are outlined in "d4T (Stavudine): Approval Recommended," AIDS TREATMENT NEWS #200, June 3, 1994. The main concern is that while blood work showed clear improvement, there was not enough clinical data from the trial yet to prove that those who switched to d4T did better clinically. The FDA decided to approve d4T under its "Accelerated Approval" regulations, meaning that it granted full approval, but with the requirement that the '019' study be completed, in order to confirm that the benefit seen in blood work would be followed by actual benefit to patients. That confirmation has now been presented. It is likely that Bristol-Myers Squibb will now ask the FDA to broaden the "labeling" of d4T, so that it will be officially indicated for patients who have taken AZT for six months or longer. Comment Besides its immediate relevance to drug therapy for HIV, this trial strengthens the evidence that viral load reduction caused by a drug is predictive of clinical benefit. Since patients were assigned at random to one of two courses of therapy (either switch to d4T, or remain on AZT), the difference in viral load (virus in blood cells, in this case -- not virus in blood plasma, which is easier to test and therefore more commonly measured) was clearly caused by the difference in treatment. The big question has been whether a change in viral load caused by a drug will predict a change in clinical outcome for the patient. In this case it did; those in the treatment group which had the lower viral load were also found, a year later, to have done better clinically. More information will be available when the viral tests are completed. It also appears that a LARGE increase in CD4 (T-helper) count as a result of drug treatment may be a much better predictor of future clinical improvement than a small CD4 increase. Acknowledgment AIDS TREATMENT NEWS did not attend the conference in Santa Fe, where these d4T results were presented. We obtained the information from Ben Cheng of Project Inform, who is preparing a more detailed article which will appear in the next issue of PI PERSPECTIVES. You can receive that issue when it comes out by joining the Project Inform mailing list; to do so, call the Project Inform hotline at 800/822-7422 (415/558-9051 in San Francisco), Monday through Saturday10 a.m. to 4 p.m. Pacific time. Project Inform has set a rare example of putting public interest above organizational considerations in giving us this information and allowing us to publish it before their article comes out. What a contrast to the professional journals which routinely delay important information for months so that they can time its release for maximum advantage to themselves. ***** Stanford Researchers Find Loss of "Naive" T-Cells by John S. James Two studies by researchers at Stanford University have questioned "conventional wisdom" on AIDS by finding a relatively early, selective loss of "naive" CD4 and CD8 cells in both HIV infected adults and children, respectively. In view of these results, important beliefs about the pathogenesis of HIV disease will need to be re-examined. AIDS may be primarily a disease not of loss of CD4 cells, as in generally believed, but of loss of naive cells of all types. "This study forces us to re-evaluate all of the experiments that have been done in the past 10 to 12 years on T-cell function with cells from HIV patients," according to Mario Roederer, the lead author of the adult study. Both CD4 and CD8 cells can be subdivided into "naive" and "memory" subsets. The ratio of naive to memory cells has now been found to change greatly with HIV infection. For example, about 50% of CD8 cells in uninfected adults are naive cells -- while less then 15% are naive in most HIV-infected adults. Naive cells are cells which have never encountered the antigen (foreign substance such as a protein produced by a bacterium or virus) to which they are genetically able to respond. These cells, therefore, are important because they allow the body to develop immune responses to new challenges. Loss of naive cells is expected to result in greater susceptibility to certain opportunistic infections. In addition, this loss may also erode the body's ability to control HIV, since many different variants of HIV evolve in each patient, and without enough naive cells the body cannot respond effectively to the new ones. The new findings are important for clinical trials, because trials might be more accurate if volunteers were grouped according to how many naive cells they have, as well as by how many CD4 (T-helper) cells. And these findings may be especially important for vaccine trials, since the lack of naive cells will probably prevent the vaccines from working, due to lack of immune response to the new antigen which a vaccine provides. Naive and memory cells also produce different cytokines. For example, naive cells tend to produce IL-2, while memory cells produce other cytokines such as IL-4, IL-10, and gamma interferon. Therefore, measurements of the proportions of different cytokines (the basis of theories about the switch from a "Th1" to a "Th2" immune response) may be reflecting differences in the number of naive and memory cells. The study in adults tested blood samples from 266 HIV-infected study volunteers, and from 44 uninfected healthy adults who served as controls. The HIV-positive subjects were being screened for a study of NAC (n-acetylcysteine), which was seeking patients with a CD4 count under 500, and who were not taking large amounts of antioxidants, vitamins, or minerals. The parallel naive cell/memory cell study in children tested 19 HIV-infected children (who were recruited for a separate study of glutathione levels) and 17 HIV-negative controls. How the Measurements Were Made Many different kinds of blood cells are best distinguished by "markers" on their surface. These markers are large protein molecules which are at the surface of the cell, and can therefore interact with substances outside the cell. For example, the CD4 (T-helper) and CD8 cells are distinguished by the presence of CD4 or CD8 markers on their surfaces, respectively. There are a number of other kinds of markers in addition. Some kinds of cells have several different kinds of markers on them. Usually each cell will have 10,000 to 100,000 copies of a marker; for example, CD4 or CD8 cells usually have 50,000 to 100,000 copies each. These markers are detected by specially prepared antibodies which are chemically attached to a substance which fluoresces (glows) when exposed to a certain wavelength of light. Each antibody is selected to attach only to a specific kind of marker. Therefore, when one of the antibodies is mixed with cells, many antibody molecules will attach to each cell which expresses the target marker. These cells will then glow under the special light, and they can be counted under a microscope. This is how T-cell counts used to be done. But several years ago a much better way of measuring T-cells (and others cells distinguished by their markers) became available. In this technology, called flow cytometry, a stream of cells, one by one, rapidly moves in front of an ultraviolet laser. When the laser hits the cell, the attached antibodies glow, and this glow is measured and recorded in a computer; the intensity of the glow indicates how many markers are on that individual cell. Different antibodies can be engineered to glow in different colors, allowing two or three different markers to be measured simultaneously. Thousands of cells are typically measured in one run; and the results can be plotted on graph paper as clusters of dots, where each dot represents one cell. By looking at these charts, it is possible to see if certain populations of immune cells are missing or deficient, resulting in specific immune defects. Two patients can be very different in reality, even if their usual blood-count numbers are the same. Some previous studies have failed to find a selective loss of naive T-cells. The Stanford researchers -- many of whom work at the laboratory at Stanford where flow cytometry was developed -- believe that earlier researchers failed to measure naive cells correctly. Naive cells have the CD45RA marker. But measuring that one alone may not be enough, since two research groups previously determined that it is necessary to measure three markers simultaneously (CD45RA, CD62L, and either CD4 or CD8) to get an accurate count of naive cells. This requires a "three color" flow cytometry machine, which many though not all labs have. Questions Remaining Many important questions remain. For example, nobody knows why the naive cells are selectively depleted. One theory is that they are killed by HIV before they get out of the thymus gland, where they develop. Damage to or deficiency of the thymus might also contribute. But a completely different possibility is that the immune system is overstimulated, and abnormally causing naive cells to mature into memory cells. Also, nobody knows what maintains the level of T-cells in anyone's blood, whether or not they have HIV. More basic research will be needed to answer these questions. The new Stanford studies show the value of conducting basic research in conjunction with clinical trials. Here, a basic research study was piggybacked onto an ongoing trial of the effect of NAC in persons with HIV; additional expense was minimized, since their blood was being drawn and tested anyway. But usually it is hard to include basic research in a drug trial, since the pharmaceutical company sponsoring the trial only want to know how well its drug works, and is unlikely to pay for gathering knowledge which will help design better treatments in the future. References Rabin RL, Roederer M, Maldonado Y, Petru A, Herzenberg LA, and Herzenberg LA. Altered representation of naive and memory CD8 T cell subsets in HIV-infected children. JOURNAL OF CLINICAL INVESTIGATION. May 1995; volume 95, pages 2054-2060 Roederer M, Dubs JG, Anderson MT, Raju PA, Herzenberg LA, and Herzenberg LA. CD8 naive T cell counts decrease progressively in HIV-infected adults. JOURNAL OF CLINICAL INVESTIGATION. May 1995; volume 95, pages 2061-2066. ***** ICC Trials: New Option on Laboratory Tests On April 7 AIDS TREATMENT NEWS reported that some volunteers had had trouble enrolling in ICC 001, the first trial by the Inter-Company Collaboration for AIDS Drug Development, a consortium of 15 major pharmaceutical companies. At some sites, the volunteers may have had to pay for pre-screening blood tests, which required the blood to have been drawn within the last 30 days. ICC has recently written to the investigators at all of its sites, explaining that it was never the intention to make volunteers pay for blood tests, and providing an additional option for financing these tests. In this new procedure, laboratory specimens are submitted to Roche Biomedical Laboratory (RBL), using requisition forms provided by RBL, and the cost will be billed to the ICC. There are also funds available to assist in enrolling women, minorities, and indigent patients in these trials, and this money can sometimes be used as an additional option for financing the pre-screening blood tests. ***** 3TC Expanded Access Program: New Requirement for CD4 Less Than 100 The expanded access program for 3TC has in the past required a CD4 count of under 300. But due to the greatly increased demand for the drug after reports of good results with the combination of 3TC and AZT, Glaxo was unable to manufacture enough, and announced on April 3 that it was limiting enrollment to 350 new patients per week, and starting a waiting list. At that time, 800 or more per week had been enrolling. Enough supplies for everyone should be available in the fall of this year. On April 24 Glaxo announced two other changes in the program. It changed the entry criterion to require a CD4 count of less than 100 (instead of 300). And it is requiring physicians to provide a copy of the lab slip to verify the CD4 count. Glaxo made this change after hearing from community representatives that, if there is not enough of the drug for everyone, those with more advanced disease should have priority. However, a cutoff at a CD4 of 100 was not what was agreed in those meetings. Now there is discussion of a waiting lists for those with counts from 100 to 300, so that they can receive the drug immediately when it becomes available. ***** Agouron Protease Inhibitor AG1343: Activity Reported by John S. James Early results from a handful of patients, reported at the Santa Fe meeting of the International Society of Antiviral Research, show that the protease inhibitor AG1343, being developed by Agouron Pharmaceuticals of La Jolla, California, does have biological activity against HIV in people. This finding is important because another protease inhibitor, produced by Searle, was recently abandoned after it was found to have no antiviral activity in people despite good activity in the laboratory. It is believed that the problem with the Searle drug is that it bound to a protein in the blood. Agouron presented the new data earlier than usual in Santa Fe, in order to show that AG1343 does not have the same problem. Agouron reported that 300 mg of AG1343 have been given three times a day to eight patients, for periods ranging from three to 28 days. No clinically significant adverse events, nor adverse laboratory changes, have been seen; but clear evidence of anti-HIV activity has been found in some patients. One had a reduction of HIV in the blood by more than 99 percent, and an increase in CD4 count of 116. Viral load results for the others are not yet available. Agouron specializes in the rational design of small-molecule drugs based upon molecular structures of proteins. ***** AIDS Research Meetings, May 1995 and Later The following list is mainly for conferences and meetings with substantial information about research and development of treatments for AIDS-related conditions. However, we have also included some others which may interest our readers. Because of the many changes in arrangements, we did not list events unless we could contact the organizers to confirm this information. Please let us know about meetings we missed. Second Seminar on HIV Infection and AIDS in Cuba. May 3-5, Havana. Contact Cuba Information Project, 212/227-3422, fax 212/227-4859. (Note: Cuba is a leader in biomedical research -- which is not widely known in the U.S., due to political problems.) Rapid Utilization of Natural Products -- Sources for Drug Discovery and Development. May 15-16, San Francisco. Registration: academic $595 conference only, $395 workshop only, $790 for both; commercial 895 conference only, 595 workshop only, 1190 for both. Contact IBC (International Business Communications) USA Conferences, 508/481-6400, fax 508/481-7911. BIO Ninth International Biotechnology Meeting & Exhibition. May 20-25, San Francisco. Exhibit hall only, $30 member, $60 nonmember; full conference, $875 member, $1395 nonmember. Half-day and one-day rates are also available. Contact BIO Meetings Department, 202/857-0244, fax 202/331-8132. 95th American Society for Microbiology General Meeting. May 21-25, Washington D.C. Registration, $150 member, $225 nonmember. Contact American Society for Microbiology meetings department, 202/942-9248, fax 202/942-9340. First Annual International Congress on Alternative and Complementary Medicine. May 22-25, Arlington, Virginia. Sponsored by Mary Ann Liebert, Inc. Nonprofit/student, $545 ($495 before May 12); other $695 ($645 before May 12). Contact BioConferences International, 301/652-3072, fax 301/652-4951. Clinical Trials: Strategies for the Design and Management of Efficient Studies. May 22-23, McLean, Virginia. Registration: academic until May 19, $350, later $395; commercial until May 19, $679, later $795. Contact Cambridge Healthtech Institute, 617/487-7989, fax 617/487-7937, email chi@world.std.com, World Wide Web http://www.healthtech.com/conferences. Cord Blood Stem Cells -- Banking, Expansion & Transplants. May 22-24, Martha's Vineyard, Massachusetts. Sponsored by Tufts University School of Medicine, and Cambridge Healthtech Institute. Registration: academic $395, commercial $795. Note: This conference is sold out; only seats available are in video overflow room, for same price. Contact Cambridge Healthtech Institute, 617/487-7989, fax 617/487-7937, email chi@world.std.com, World Wide Web http://www.healthtech.com/conferences. AIDS, Medicine, & Miracles. June 1-4, Rhinebeck, New York. Contact 303/447-8777, 303/447-3902. (Not a research meeting.) HIV Infection of the Brain. June 2-4, Stockholm. Sponsored by the European Community, the Swedish Medical Research Council, the Swedish National Board of Health and Welfare, Pharmacia, and the Wellcome Foundation. No registration fee -- but few places are left in this meeting. Contact Dr. Francesca Chiodi, +46 (8) 728 63 15, fax +46 (8) 33 13 99. NIAID Council: AIDS Research Advisory Committee and Subcommittee of Council. June 6-7, Bethesda, Maryland. Sponsored by the U.S. National Institute of Allergy and Infectious Diseases. Contact Anne Claysmith, 301/402-0755. Core Program on Early Intervention. June 7, Chicago. Contact Midwest AIDS Training Center of the University of Illinois at Chicago, 312/996-1071. (This is a one-day seminar for primary- care physicians.) 5th Annual Canadian Conference on HIV/AIDS Research. June 8- 11, Winnipeg, Manitoba. Registration: member $75, nonmember $125, PWA $25. Contact Ms. Julie Knight, 204/789-3376, fax 204/789-3489, email knight@bldghsc.lan1.umanitoba.ca. Clinical Care Options for HIV. June 8-11, Laguna Niguel, California. Registration $225. until May 24, then $300. Contact, 818/752-9396. Note: This meeting is for front-line primary care physicians. The Endocrine Society, 77th Annual Meeting. June 14-17, Washington D.C. Registration: member $245, nonmember $390 Contact The Endocrine Society, 301/941-0200, fax 301/941-0259. Development and Applications of Vaccines and Gene Therapy in AIDS: An International Workshop. June 15-16, Naples. Program directors: Dani Bolognesi, M.D., Gaetano Giraldo, M.D., Marco Salvatore, M.D. Registration: deadline May 1. Contact (phone and fax) 39-81-545-1276. HIV/AIDS and Chinese Medicine, Third International Conference. June 16-18, New York City. Sponsored by 26 Chinese medicine clinics, colleges, and other sponsors. Contact AIDS and Chinese Medicine Institute, 415/282-4028, 415/282-2935. International Congress on Drug Therapy in HIV Infection. Had been scheduled for June 19-23, in Bangkok; now changed to March 1996 in Bangkok, and November 1996 in Birmingham. See listings below. International Conference on New Applications of Emerging Molecular Diagnostics for Infectious Diseases. June 26-27, London. Registration: academic before May 19, $330, later $380; commercial before May 19 $695, later $745. Contact Cambridge Healthtech Institute, 617/487-7989, fax 617/487- 7937, email chi@world.std.com, World Wide Web http://www.healthtech.com/conferences. Antiviral Discovery: Response to the Viral Drug Resistance Epidemic. June 27, Philadelphia. (Note: This is a workshop connected to a June 26 antibiotic discovery conference.) Registration: (workshop only): academic $295, commercial $495. For those who cannot attend, the documentation binder is available separately for $$298. Contact IBC (International Business Communications) USA Conferences, 508/481-6400, fax 508/481-7911. National Task Force on AIDS Drug Development. June 29-30, Rockville, Maryland. This meeting will finalize recommendations to Health and Human Services Secretary Donna Shalala on incentives for private investment in drug development for AIDS and other life-threatening diseases. There will be a public comment period; persons wishing to speak should make advance arrangements. Contact Kimberley M. Miles, FDA Office of AIDS and Special Health Issues, 301/443- 0104. Clinical Trials -- Re-Engineering Clinical Research to Maximize Economic Efficiencies. July 19-21, Boston. Registration: $1295. Contact IBC (International Business Communications) USA Conferences, Inc., 508/481-6400, fax 508/481-7911. International Symposium on Clinical Immunology 1995. July 20- 23, San Francisco. Registration: advance, regular $200, trainee $50. Contact registration manager, SLACK, Inc., 609/848-1000. (Note: dates coordinated with 9th International Congress of Immunology, below.) 9th International Congress of Immunology. July 23-29, San Francisco. Sponsor: American Association of Immunologists. Registration: scientist $385, student/post doctoral fellow, $175. Contact 301/530-7010, fax 301/530-7014. (Note: dates coordinated with International Symposium on Clinical Immunology, 1995, above.) Consensus Symposium on Combined Antiviral Therapy. July 25-27, Lisbon. Sponsored by the International Society for Antiviral Research and the U.S. National Institute of Allergy and Infectious Diseases. Registration: $200 student/PWA; member ISAR $400 before May 15, then $450; nonmember $450 before May 15, then $500. Contact Macrae Group, 212/988-7732, 212/717- 1222. Note: This conference will be held again in September 1996; exact date not set yet. USAID Third HIV/AIDS Prevention Conference: Evolving Responses to an Evolving Epidemic. August 7-9, Washington, D.C. Contact Al Nimocks, 703/516-9779, fax 703/516-4489. NIAID-DAIDS Vaccine Working Group. August 16-17, Bethesda, Maryland. Contact Janice Cordell, 301/402-0846. Fifth European Conference on Clinical Aspects and Treatment of HIV Infection. September 27-29, Copenhagen. Sponsored by EACS, the European AIDS Clinical Society. Registration fee 2100 - 3500 Danish. Contact International Conference Services, (+45) 3161 2195, fax (+45) 3161 2068. (Note: both phone numbers will change after July 18, due to phone changes in Copenhagen; instead of 3161, use 3961.) 1995 National Skills Building Conference. October 19-22, Los Angeles. Call 202/546-6119 (voicemail) for further information. (Not a research meeting.) AIDS Education: Interventions in Multi-Cultural Societies -- 9th International Conference. November 26 - December 1, Jerusalem. Sponsored by The International Society for AIDS Education. Contact the secretariat, (972 3) 5140014, fax (972 3) 514077. Infectious Diseases Society of America. September 16-18, San Francisco. Registration: early, member $90, nonmember $110, trainee $40; regular, member $100, nonmember $120, trainee $50; late (final week - at the door) $120. member, $140 nonmember, $70 trainee. (Note: Dates coordinated with ICAAC meeting, below.) ICAAC (The 35th Interscience Conference on Antimicrobial Agents and Chemotherapy). September 17-20, San Francisco. Registration: $225 member, $290 non-member. Contact American Society for Microbiology meetings department, 202/942-9248, fax 202/942-9340. (Note: Dates coordinated with IDSA meeting, above.) 20th ACTG (AIDS Clinical Trials Group) meeting. December 1-7, Washington D.C. Sponsor, U.S. National Institute of Allergy and Infectious Diseases. Contact Technical Resources Inc., 301/770-0160, fax 301/468-2245. 1996 International Congress on Drug Therapy in HIV Infection. March 18-21, 1996, Bangkok. Registration, $350 U.S. Contact Jane Fensome, Conference Coordinator, (+44) 1625 615325, fax (+44) 1625 616563. (Note: the phone and fax numbers are in the UK.) 9th International Symposium on Infections in the Immunocompromised Host. June 23-26, 1996, Assisi, Italy. Sponsor: Immunocompromised Host Society. Contact Warren C. Snow, 616/329-1288, 616/329-1631. XI International Conference on AIDS. July 7-12, 1996, Vancouver, British Columbia. Cosponsoring agencies: Canadian Association for HIV Research, Global Network of People Living with HIV, International AIDS Society, International Council of AIDS Service Organizations, World Health Organization. Registrations fees not set yet. Contact the conference secretariat, 604-668-3225, fax 604/668-3242. International Congress on Drug Therapy in HIV Infection. November 4-7, 1996, Birmingham. Registration #350 (UK). Contact Jane Fensome, Conference Coordinator, (+44) 1625 615325, fax (+44) 1625 616563. (Note: the phone and fax numbers are in the UK.) ***** 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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