Subject: AZT-Acyclovir, New book: Strategies Date: Dec 4 1987 (533 lines) &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& J O H N J A M E S writes on A I D S &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& copyright 1987 by John S. James; permission granted for non-commercial use. AIDS TREATMENT NEWS Issue Number 46 December 4, 1987 CONTENTS: [items are separated by "*****" for this display] Good News On Treatments and Survival AZT and Acyclovir Combination Paying for AZT Fansidar Danger, Again Important Articles From Project Inform New Book: Strategies for Survival Columbia Symposium Tapes, Transcript Available Holiday Schedule: Next Issue January 1 ***** Good News on AIDS Survival, and Treatments by John S. James Recent studies in San Francisco and New York have found major, unexpected improvement in median survival after an AIDS diagnosis, and in long-term survival. And many physicians with large AIDS caseloads are having far fewer deaths this year than last, and fewer complications serious enough to require hospital- ization, even though they have more patients. This article examines the statistical evidence on survival in San Francisco and New York, and in the United States as a whole. It looks at why the improved survival figures may be even more important than they first seem. We also interviewed Nathaniel Pier, M.D., a New York physi- cian in private practice with about 300 AIDS/ARC patients, on the much lower death rate he and his colleagues are seeing this year, on current ethical issues in AIDS, and on what medical approaches seem to be making a difference. (More on this interview will appear in a later issue.) And we asked Michael Callen, a found- ing member of the PWA Coalition in New York, about his current interview study of long-term survivors diagnosed with AIDS for over three years. San Francisco Survival Study Since 1981 the San Francisco Department of Public Health has kept track of the median length of survival of persons diagnosed with AIDS each year. (The median is not the average, but the middle of the range of length of life after diagnosis.) For the first five years median survival was unchanged, about ten months. But in 1986 it unexpectedly jumped to about 14 months. This improved survival resulted from better outlook for per- sons with diagnosed with pneumocystis. Survival for KS did not improve last year, but it has always been much better than for pneumocystis. The San Francisco Examiner interviewed Dr. George Lemp, an epidemiologist with the Department of Public Health, and reported this increasing survival on November 6 (page A4); so far there has been little notice of these results outside of San Francisco. No one knows for sure why persons are suddenly living longer after an AIDS diagnosis, but San Francisco epidemiologists suspect that it may be due to prevention and better treatment of pneumocystis, and/or to use of AZT. We asked Dr. Lemp for more details on the new findings, and on how the research was conducted. Information on what treat- ments people used was not recorded. This is an epidemiological study not a clinical one, and keeping track of all the different diagnoses and treatments would have been difficult. In June of this year the epidemiologists did start asking what antiviral drugs each person used, so by early to mid 1988 they will be able to start checking on correlation of survival with use of AZT. How were the annual medians derived? Dr. Lemp explained that, for purposes of analysis only, all patients diagnosed with AIDS within a given calendar year were followed as a cohort. Because persons with AIDS often survive for a long time, the median survival cannot be estimated accurately until well after the year has ended. For example, the "1986" data includes follow up through August of 1987. For this reason it is too early to know 1987 results yet. But very early indications are that 1987 looks better than 1986. No one knows for sure why the median survival time increased in 1986, when it had not done so before. But it seems reasonable to guess that the improved survival is due to treatments. We do not have scientific proof But it is hard to devise any other plausible explanation. Few new treatments were widely used in 1986, the year of diagnosis for the cohort which survived longer; AZT, aerosol pen- tamidine, and AL 721, for example, had only reached a few. But since the 1986 survival data actually includes what happened as late as August 1987, treatments received in 1987 could also have had an effect. Before August 1987, both AZT and aerosol pentamidine had become widely used in San Francisco. Less publicized improve- ments in clinical treatment for pneumocystis and other infections were also being used on enough patients that they might have affected the survival statistics. What about alternative treatments? On AL 721, the all-egg generic versions arrived here in late summer, probably too late to affect the 1986 survival median; the soy-based "home formula" arrived in January 1986, however, so it might have had an effect. It would be worth checking whether other treatments, such as ribavirin, DNCB, megadose vitamin C, or certain herbal treat- ments, first became widely used during the time when they might have contributed to improved survival of the 1986 San Francisco cohort. If it is true that one or more treatments are responsible for the 1986 improvement, they would probably be adding much more than the four months of additional survival seen in the median figures. For only a minority of persons in San Francisco had access to new treatments and chose to use them by early 1987. And those diagnosed in early 1986 were largely affected by 1986 treatment anyway. For both these reasons, the four-month figure includes the majority which was not treated and presumably did not survive longer than those diagnosed in previous years. Therefore, the minority which did get new treatments and presum- ably accounted for the four-month increase in the median survival must have had much more than a four-month improvement. New York Survival Study The most detailed study yet on AIDS survival was published in the New England Journal of Medicine, November 19, 1987, and widely reported in the press at that time. This study by the U.S. Centers for Disease Control of over five thousand persons diagnosed with AIDS in New York City found as many as 15 percent surviving up to five years. Although the researchers admitted that they may have missed some deaths, they concluded that the general impression that AIDS is always fatal cannot be supported. The existing evidence does not rule out the possibility that some people could live indefinitely with AIDS, or could recover. This New York study included only patients diagnosed through December 1985. Therefore its findings would not reflect the improvement (presumably due to new treatments) shown in the 1986 San Francisco cohort discussed above. National Survival Study Seemingly contradictory and much more pessimistic results of a smaller study at the Centers for Disease Control (CDC) were released at a conference on October 5, 1987 and widely reported in the press the next day. This study, by researcher Ann Hardy, was designed to check the reliability of the official CDC estimate that 15 percent of persons with AIDS survive three years, by verifying that the peo- ple on whom that statistic was based were indeed still alive. Only two to five percent had been determined to be alive, and the news stories which went out listed the three-year U.S. survival rate as only two to five percent. This figure differs greatly from the New York and San Francisco findings. We spoke with Ms. Hardy, who pointed out that San Francisco might have longer survival times than elsewhere in the country because more persons with AIDS here have KS, and those with only KS survive much longer than others, on the average. She did not know why the New York results differed so greatly from hers, and referred us to the researchers who conducted that study. We reached one of the researchers, but were unable to get the per- mission required for an interview by press time. Ms. Hardy's study only involved persons diagnosed with AIDS in December 1983 or before. Therefore it has no bearing on the major San Francisco result, the large increase in survival for those diagnosed in 1986 compared to any previous time. Long-Term Survivor Interviews Michael Callen, a founding member of the PWA Coalition in New York and himself a long-term survivor diagnosed in 1982, is interviewing persons who have survived with an AIDS diagnosis for over three years. So far he has interviewed 17 persons. Results will appear in an article and probably in a book. Meanwhile, Mr. Callen told us of some of the early, often surprising findings so far. Here are some of his preliminary observations. Be careful in interpreting them. The fact that these survivors made certain choices three or more years ago, when their options were very different from the options today, does not necessarily imply that people should make the same choices today. * Persons can survive far longer with KS than many have been led to believe. Persons can lead a long and happy life with KS. * Only three of the 17 used aggressive chemotherapy. One of these was in a suramin trial, and almost died. The other used HPA-23. A third is now on AZT (see below). * Mr. Callen at first had trouble finding persons who had survived three years after a pneumocystis diagnosis (a diagnosis made three or more years ago, before improved treatments were available). But eventually he did find persons who have survived for four years, and for four and a half years, after the diag- nosis. * Only one of the long-term survivors is on AZT. Others said if it wasn't broke, don't fix it. They had done well before AZT became available, and didn't want to rock the boat. * All of them had dabbled in alternative approaches. With KS, there were several striking stories of success with macrobi- otic or vegetarian diets. About half of the long-term survivors had made major diet changes. And the rest paid more attention to their diets. * Most or all had used approaches such as shiatsu massage, acupuncture, or visualization. A clear majority were involved with groups such as Louise Hay, or AIDS Mastery. * All but two found solace in religion--about half in the religion of their childhood. Others did not seek organized reli- gion, but spoke of spirituality, or a sense of oneness. None became Bible-thumping fundamentalists. All who did become involved in churches were critical of some aspects of organized religion. * All said they needed hope to survive. Each had to deal in some way with the media's repeated message that everyone dies. Some found it important to know survivors; many knew each other. All but two are aggressively involved in the AIDS movement, or working with PWAs; many are in the forefront. * They are fighters, often difficult patients, not passive. Most used a group of physicians to coordinate their care, not just one. A majority have fired a physician, or ordered one out of their hospital room. * Several had moving, near-death experiences. * There was no magic bullet, no single treatment used by all the survivors. Not all of them used lipids, or macrobiotics, or ribavirin, or anything else. Their experience suggests that AIDS is not one disease, with one substance which will work for every- one. Mr. Callen is continuing this study. Results will appear in the Village Voice, and probably in book form also. He would like to hear from anyone who has survived with an AIDS diagnosis for over three years. He can be reached in New York at the PWA Coal- ition, (212) 627-1810. To Be Continued Later articles will examine the experience of AIDS physi- cians who have had fewer deaths and serious infections this year than last, despite having more patients. We will examine physi- cians' views of what does and does not work in AIDS treatments and care, and in the development and application of new drugs. ***** AZT and Acyclovir Combination Acyclovir (Zovirax), a readily available prescription drug, appears to work synergistically with AZT, meaning that the combi- nation may be a better AIDS treatment than either one alone. Several studies of this combination are now going on; for a list of the studies, see AmFAR Directory of Experimental Treatments for AIDS and ARC, published by the American Foundation for AIDS Research, (212) 333-3118. Trials are planned or underway in France, Italy, Sweden, Germany, Belgium, Switzerland, United Kingdom, Denmark, Australia, and the U.S. Meanwhile a number of physicians and patients are using this drug combination -- sometimes as a half dose of AZT combined with a full dose of acyclovir -- but few physicians are willing to speak publicly about it, because the combination has not been approved and, according to the October 1987 edition of the AmFAR Directory, no confirmatory data is available. AIDS Treatment News hereby releases what may be the first published data on the use of this combination in the treatment of AIDS and ARC. Project Inform, in San Francisco, CA, filed a Freedom of Information Act request and obtained extensive internal documen- tation of the large double-blind placebo-controlled AZT trial with 282 patients. One paragraph of this documentation concerned the combination of AZT and acyclovir. We reproduce the paragraph here: "Seventy of the 282 patients enrolled in this trial (25%) received acyclovir (ACV) in addition to their study medication. Thirty-four were patients randomized to receive AZT ... no evi- dence of increase hematologic toxicity .... Only 2 of the 34 patients (6%) who received ACV in addition to AZT developed opportunistic infections over the course of the trial compared to 22 of 111 (20%) of the AZT recipients who did not receive ACV during the study." Researchers should consider the possibility that the benefit of including acyclovir with AZT in the treatment of AIDS or ARC may be even greater than the above figures suggest. For the AZT patients who also received acyclovir presumably had an infection which the acyclovir was being used to treat, so as a group they were probably sicker to begin with than the AZT patients who did not receive acyclovir. Even so, they did much better. It is too early to know for sure that the combination is useful. We will report more information as it becomes available. ***** Paying for AZT James Palazzolo, who is writing an article on AZT, brought the following to our attention. (1) Family Pharmaceuticals in South Carolina, a company which specializes in low prices for expensive prescription drugs for chronic diseases, sells AZT at what is reported to be one of the lowest prices in the U.S. On early December 1987 (before the 20 percent price reduction announced in mid December by Burroughs-Wellcome) it quoted $204.85 per 100, about $6000.00 per year for a full dose, two capsules every four hours. For the current price or for more information, call Family Pharmaceuti- cals at (800) 922-3444. (2) The Federal AIDS Drug Reimbursement Program appropriated $30,000,000 to pay for AZT for persons who cannot afford it. Unfortunately, however, some states are not yet ready to disburse the money. This program, traded off in Senate deal-making for AIDS testing of immigrants, pays only for FDA-approved anti-HIV agents, meaning only AZT. Income eligibility is about $11,000 per year for family of one. This program only applies to those who meet the official FDA guidelines for use of AZT. Basically, persons must either have had pneumocystis, or have under 200 T-helper cells and be symp- tomatic. The money is given to each state, based on its number of AIDS patients. The Burroughs-Wellcome AZT Information Hotline, (800) 843-9388, may know whom to contact in your state. In San Francisco, the Health Department will issue a press release when California sets up an office to administer the pro- gram. At that time the San Francisco AIDS Foundation hotline, 863-2437, will have information on how to apply. ***** Fansidar Danger, Again In previous issues (#42, #43) we discussed the dangers and benefits of fansidar, one of several preventive treatments for pneumocystis. Recently we heard of two more cases of serious reactions to this drug. One happened to a friend of this writer, who used fansidar because he was unable to obtain aerosol pentam- idine in San Diego. He had not realized that fansidar must be stopped if a skin rash occurs, and almost died as a result. We repeat the following warning from the Physician's Desk Reference, which also includes other precautions. This part of the warning is printed twice in all caps, and set off in separate boxes for additional emphasis. "FATALITIES ASSOCIATED WITH THE ADMINISTRATION OF FANSIDAR HAVE OCCURRED DUE TO SEVERE REACTIONS, INCLUDING STEVENS-JOHNSON SYNDROME AND TOXIC EPIDERMAL NECROLYSIS. FANSIDAR PROPHYLAXIS SHOULD BE DISCONTINUED AT THE FIRST APPEARANCE OF SKIN RASH, IF A SIGNIFICANT REDUCTION IN THE COUNT OF ANY FORMED BLOOD ELEMENTS IS NOTED, OR UPON THE OCCURRENCE OF ACTIVE BACTERIAL OR FUNGAL INFECTIONS." Persons with AIDS or ARC may be more likely to have these reactions than other people. (Fansidar is usually used as a preventive for malaria.) Use of this drug may be justified in some cases. But patients should make sure to get the warnings from their physicians--or look them up themselves in the Physician's Desk Reference, usually available in public libraries. Fansidar seems to be used infrequently in San Francisco, as aerosol pentamidine prophylaxis is more available here. ***** Important Articles From Project Inform The October 1987 issue of PI Perspectives, the newsletter of Project Inform, has two articles which are proving influential. "Evaluating New Treatment Alternatives" urges a cautious approach to proposed treatments. It provides checklists of ques- tions for rationally evaluating the available evidence of effi- cacy, when there isn't full scientific proof. No available drug, mainstream or alternative, gets a perfect score. The point is not to reject them all, but rather to weigh the evidence prop- erly. "False Hope: Smoke and Mirrors From the FDA" reviews the new rules approved by the FDA in June of this year, rules supposed to provide easier access to experimental treatments which were safe and probably effective, although they had not yet achieved full mass-market approval. The article analyzes why these rules have failed to work. A section titled "Questions for the FDA" caused annoyance at that agency, as reporters from around the county have found that the FDA is indeed unable to answer eight simple questions which Project Inform suggested. Some of the questions are: * What is the procedure by which a physician may apply to receive an experimental drug for a life-threatened AIDS or ARC patient? Where can we get the forms? * Are there any drugs for AIDS or ARC, immunomodulators or antivirals, that the FDA feels would currently be eligible for release under the new regulations? * What criteria will be used to determine the effectiveness of a drug so that it can be released under the new regulations Where are those criteria spelled out? * What, if any, role is there for the private physician under the new regulations? To obtain the October issue of PI Perspectives, and to get on the mailing list for future issues, call Project Inform, (800) 822-7422 U.S. outside of California, (800) 334-7422 in Califor- nia, or (415) 928-0293 from anywhere. [These issues may be seen in full elsewhere on this bbs -- ed.] ***** New Book: Strategies for Survival This book, by three authors including the two founders of Project Inform, gives workbook-like checklists and exercises con- cerning strategies for one's own health, and for the health of the gay community. It also has annotated lists of community ser- vices, as well as relevant books, articles, and videotapes. The authors designed the book not to tell to reader what to do, but to provide information on ways to assess one's situations and make one's own choices. The authors made major efforts to keep the price down; the book has 310 8-1/2 by 11 pages and sells retail for $10.95. It is available in bookstores, or from St. Martin's Press, New York, NY. ***** Columbia Symposium Tapes, Transcript Available Tapes and transcripts are now available from the Columbia Gay Health Advocacy Project panel on treatments for antibody- positive persons, which took place on November 17. The panel included nine medical doctors experienced in treating AIDS, and two other persons including this writer. For more information see AIDS Treatment News #44 (November 6). This panel could only begin in its main purpose: finding consensus among knowledgeable physicians about recommendations for preventing the development of AIDS or ARC by early treatment of antibody-positive persons, even before symptoms appear. The main bottleneck is the reluctance of physicians to recommend treatments without final proof of effectiveness -- proof which will take many years to obtain because of the slow speed with which the disease develops. However, much useful information about treatments in general did come out of the meeting. Tapes and transcripts can be ordered from the Columbia Gay Health Advocacy Project, Columbia University, John Jay Hall, New York, NY 10027, or call 212-280-2878. The videotape is $100., audiotape $25., transcript $20. PWAs with problems paying can call [phone number not given at print time -- ed.] and discuss -- or see if the local AIDS service organization can order the material. ***** Holiday Schedule: Next Issue January 1 AIDS Treatment News will not publish December 19; our next issues will be dated January 1 and mailed soon after that date. All subscriptions will be extended automatically, so subscribers will receive the same number of issues. We will use the breather as a working vacation to catch up on a backlog of uncompleted work, to reorganize our office to handle the rapidly increasing volume of calls and requests, and to plan the changes necessary to help AIDS Treatment News keep up with the rapidly changing situation in AIDS treatments. We plan to send our first bills in January; we have not yet started billing due to our priority to getting the information out. Back issues are still not ready; we are hoping for January. Before reprinting, we are examining the old issues for any obvi- ously outdated information, and we are also creating an index. Starting January 4 AIDS Treatment News will have a full- time office manager and assistant, Denny Smith, as well as several part-time people who have already been working here. ***** [Obsolete subscription information has been removed. See the latest issues for up-to-date information. -- sysop] &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& End of display