&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& J O H N J A M E S writes on A I D S &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& Copyright 1992 by John S. James; permission granted for non-commercial use AIDS TREATMENT NEWS Issue #149, April 17, 1992 phone 800/TREAT-1-2, or 415/255-0588 CONTENTS: [items are separated by "*****" for this display] Antivirals, Vaccines, Passive Immunotherapy: Talk by Marcus Conant, M. D. Passive Hyperimmune Therapy: Letter from Abraham Karpas CMV: Long-Awaited Trial of HPMPC CMV: Laboratory Study of Etoposide Rifabutin Available to Prevent MAC FDA Antiviral Advisory Committee Meeting to Consider ddC, ddI, Markers International AIDS Conference: Record Registration California Demonstration for Prisoners with AIDS San Francisco: Health Care Workers' Respiratory Hazards Conference, May 1 and 2 San Francisco Area Clinical Trials Directory ***** Antivirals, Vaccines, Passive Immunotherapy: Talk by Marcus Conant, M. D. Marcus Conant, M. D., is one of the early discoverers of AIDS, and now runs one of the largest private HIV practices in the United States; his San Francisco office also participates in clinical trials of a number of experimental treatments. For several years Dr. Conant and his staff have held monthly talks on AIDS treatments, intended primarily for their patients but also open to the public without charge. The April 6 meeting was especially informative; with Dr. Conant's permission we transcribed parts of it here. [Our own explanatory comments are in brackets.] To be added to the mailing list for notification of future talks, which are usually on the first Monday of each month from 6 to 7 p.m., call Dr. Conant's office at 415/923-1333. For more information about volunteering for any of the studies described below, see the note at the end of this article. International Research Dr. Conant: "The Germans and the French, unlike the Americans, have national AIDS meetings each year, as well as the major international conference; there is a European meeting as well. In the U. S. there are many meetings, including the AIDS Clinical Trials Group (ACTG) meetings; there isn't anything like that in Europe. In Germany, researchers get together once a year, in a meeting sponsored by the German government, and talk about what they're doing, including clinical trials. They ended the conference this year with a panel discussing research findings and social issues; I was invited to talk about our treatment guidelines [Dr. Conant's recommendations on when to start AZT, opportunistic-infection prophylaxis, combination antivirals, and other treatment]. They had a fairly good attendance, 700 or 800 people, and they broadcast that panel throughout Germany. "I was hoping to bring back some information from that meeting to say, 'The Germans are doing this, and it really looks good.' But I didn't see anything that they were doing in Germany that we weren't doing two years ago. The bottom line is that what is happening in the leading U. S. AIDS centers probably still is the cutting edge of what's occurring in AIDS research around the world. Even in terms of potential treatments like iscador, which we call "alternative" treatments here, there were no hard results showing that anything was beneficial. TP5 (Thymopentin) "The TP5 study -- this work's been going for years now -- is up for another review at the end of May. We have some 200 patients in that study; there are another 150 or so around the country. We hope the drug is going to show benefit stabilizing T-helper cell levels in the people on TP5 and AZT together -- but we don't know that until the code is broken [telling which volunteers are getting TP5 plus AZT, and which are getting placebo plus AZT]. If the drug looks good, my guess is that approval could come quickly, because TP5 has been widely used in Europe now for almost ten years. It's very expensive in Europe, but is being used not only for AIDS but for herpes, and for other diseases where an immune modulator might help. With the safety data from Europe, there should be little trouble getting FDA approval if the drug is efficacious. For those of you on the study, after efficacy is shown the sponsor will probably roll everybody over to open label at least until the drug is available on the market. Antivirals: N-Butyl-DNJ Trial "What we really need in AIDS treatment is another place to attack the virus. The three drugs we have that are most widely accepted as effective -- AZT, ddI, and ddC -- block the reverse- transcriptase step in viral replication. There's some recent data that AZT, and ddI/ddC, are actually working at different places on the reverse transcriptase. It is not known yet, but it is likely that there will be cross resistance between ddI and ddC; but resistance to AZT is clearly by different mutations than resistance to ddI. "We still don't know all the things that AZT and these other drugs do. One of the major questions that may be answered in the Amsterdam meeting this year is, "What is AZT doing?" How much of its effect is in blocking reverse transcriptase, how much is mediated through stabilizing T-helper counts, and how much of the effect may be in some other area entirely -- and if so, what else is this drug doing? Until we have better answers, it is hard to rationally advise patients -- for example, should they continue taking AZT after they have started ddI [because the AZT appeared to be no longer working]. How long have we had AZT? It has been approved for five years now -- and two years before that, Burroughs-Wellcome was saying they had a drug they thought was going to work. It took two years to get it to market, which is a record time; so it's been seven years without another major AIDS drug. We have the "son of AZT" in ddI and ddC, based on the same mechanism of action. "But clearly we would like to have something that blocked the virus at some other stage in its life cycle. As in tuberculosis, combination therapy is best if you combine drugs that work at different sites. "We are lucky enough to be running a study of N-butyl-DNJ [also called butyl-DNJ, or deoxynojirimycin]. This drug blocks glycosylation of the virus (adding sugars to some of its proteins) as new virus particles emerge from the cell wall. This study is exciting because if you look at what is coming for AIDS treatments, the ones which show great promise, such as the protease inhibitors and the tat inhibitors, are likely to be years away from general availability. But N-butyl-DNJ is well along in trials; the safety data is in. Now if we can demonstrate that it has efficacy in humans, we could probably get the FDA to approve this drug fairly quickly. The drug is exciting not because it will be the greatest AIDS treatment, but because it could be available in a year or two, so we could block the virus at two different points in its life cycle. "We are looking for volunteers for that study. But note that this trial presents difficulties to volunteers. For example, on one day you need to lie on a table for five hours and be bled every hour; sometimes there has been a problem with the lab, and volunteers have had to go through the whole process again. Another problem is that the initial formulation of this drug causes severe diarrhea if you eat carbohydrates, so a special diet is necessary. The good news is that the company, G. D. Searle & Co., has developed a new formulation of the drug which does not cause the diarrhea. So if the drug shows the efficacy that we expect, then we will move to the second compound which does not have the same side effects. We cannot use the second drug now because it does not have all the testing required for use in the trial; the company wants to know that the drug can be effective before it spends the money to get the new version approved. Volunteers for this study must have T-helper counts between 200 and 500, and no AIDS diagnosis [under the "old" definition of AIDS, which is still in effect]. They must have taken AZT for at least 12 weeks. Some people will come off AZT for a short time while we measure the effect of this drug on the virus. Note that this is a phase II study; the phase I [dosage and safety] study has already been done. Vaccines: gp 120 Trial "You could also try to block viral entry. One way is to use a vaccine as a therapeutic, which Jonas Salk proposed in 1987. With AIDS, when someone is first infected, the viral titers [blood levels] go up very quickly. Then the immune system controls the infection; antibodies against several different viral proteins are created. The person goes for years without getting sick. Later, when illness does occur, the antibody titers go down and the viral titers go up. "Dr. Salk suggested stimulating the antibody level to keep patients in the latent, asymptomatic stage for much longer. Some scientists criticized this idea, saying that these people already had plenty of virus in their bloodstream [to make antibodies against], so what good would it do to give a vaccine at that time? But research has shown that you can stimulate HIV-positive people to make more antibody by giving them vaccines to gp 160, or to gp 120, or whole viral extract. [gp 160 and gp 120 are glycoproteins (hence the abbreviation 'gp') made by the virus. Glycoproteins are made up of amino acids (like ordinary proteins), but in addition they include sugars.] "Dr. Robert Redfield [at the Walter Reed Army Institute of Research] gave HIV-positive volunteers gp 160. Some of them made antibodies against gp 160, and some did not. In those who did, the T-helper counts stabilized; in those who did not make antibodies, the counts declined like those of untreated patients. "In one trial, a gp 120 vaccine worked even better. Genentech innoculated a chimpanzee several times with the gp 120 vaccine; then ten times the infectious dose of HIV did not cause an infection. This also worked on a second chimp. The gp 160 vaccine did not similarly protect chimps. We do not know how long the immunity will last. "Genentech is interested in looking at its gp 120 vaccine as an HIV treatment. They set up a study at San Francisco General Hospital, the University of California in Los Angeles, and the Deaconess Hospital in Boston. Last month they also asked us to be a site. So we are recruiting for this study at the present time, and expect to be vaccinating people within three weeks with the gp 120 vaccine. We are looking for 15 volunteers with T- helper counts over 500; they will be vaccinated seven times in a year, and have extensive measurements of blood functions. These volunteers cannot be using recreational drugs, especially marijuana, and cannot be using AZT; they will be tested from time to time to assure compliance with study restrictions. "There are six arms of this study, including a placebo arm, so there is one chance in six of getting a placebo. Two different vaccines are being tested. The strain of the AIDS virus which Gallo isolated was the 3B strain. This turned out to be common in Europe; but in the U. S., most patients have the MN strain. Genentech has made a vaccine against both. One group of volunteers will get the 3B vaccine, another will get MN, and a third will get low-dose MN. A fourth group will get 3B and MN simultaneously, another will get them sequentially, and the sixth group will get the placebo. "If this study works -- if one or more of the treatments prove beneficial -- the next step would be to give the vaccine(s) to patients with lower T-helper counts who are on AZT or ddI as well. Passive Immunotherapy "I'm pleased with how we have been able to put together the different studies we are doing. We are looking at a new antiretroviral, N-butyl-DNJ, and we are looking at a new way to stimulate the immune response. But the next question is, what do you do for patients who have very low T-helper counts, who will not have an immune response to the vaccine. "That is when you try passive immunotherapy [also called passive hyperimmune therapy], the approach of taking effective antibodies from healthy HIV-positive people and giving them to somebody else. We [physicians and medical staff in this office] have been talking about this for years, but it looks like we will finally be able to at least start a few patients; and there is some new data as well. "Plasma is taken from several patients and pooled to get a variety of antibodies. Then the plasma is sterilized with a chemical called beta-propriolactone, which has been used for years to sterilize vaccines, to kill HIV and any other viruses or other micro-organisms which may be present. Then the plasma is infused into people with advanced HIV infection, who can no longer make their own antibodies against HIV. "Abraham Karpas in England, who started using this technique as an AIDS treatment, tried it with ten patients several years ago and then quit, because at that time he could not contact enough suitable donors with over 500 T-helper cells in London. A study was started at the Veterans Hospital in the Bronx, but no results have been published. There is a small study in Paris. And a few physicians in private practice in the U. S. are using this treatment. And recently HemaCare, a company in Southern California which has been doing a study, released some of its results [see "Passive Hyperimmune Therapy (Passive Immunotherapy): New Data Released, California Approval Possible," AIDS TREATMENT NEWS #148, April 3, 1992]. "Our office is now making preparations to treat some patients, as well as to apply to the State of California for approval to do some truly innovative studies. For example, assume that the gp 120 vaccine is found to work, and boosts the immune system of HIV-positive people who are vaccinated. Then a possible study would be to have persons who were successfully vaccinated donate plasma for passive immunotherapy -- to get plasma from people with T-helper counts who not only had good antibodies to start with, but also were vaccinated to increase their antibodies still further. "If that works and is safe, a further step would be to vaccinate HIV-negative volunteers, who would make antibodies and could then donate plasma for passive immunotherapy. This approach could help to relieve any possible shortage of HIV- positive donors. All of this is feasible now. "The final step, which would require time to develop the technology, would be to isolate the effective antibody or antibodies and manufacture them, to provide an unlimited supply. "The hope is that this research we are doing will lead to therapies that will give us something which will last from now until we have better treatments, which I don't think will happen until 1996 or 1997." Note: Dr. Conant's office is looking for several special groups of potential volunteers for ongoing research studies: (1) People with T-helper counts over 500; (2) Those who had an opportunistic infection over three years ago; (3) Those who have been HIV infected less than two years; and (4) Anyone who has been on AZT for more than four years. If you fall into any of those groups and would consider volunteering, call Dr. Conant's office, 415/923-0555, and leave your name and number for a return call. ***** Passive Hyperimmune Therapy: Letter from Abraham Karpas A leading developer of passive hyperimmune therapy, Abraham Karpas, Sc. D., of the University of Cambridge in England, wrote to AIDS TREATMENT NEWS about our article on this treatment in our last issue (#148, April 3, 1992): "I read with interest your excellent write-up about passive hyperimmune therapy. I trust you will not mind a few additional comments? "Firstly you ought to emphasize that plasma donation does not do any harm and, from the results of several studies, could be beneficial. In March last year Cummins et al. reported in BLOOD (volume 77, pages 1111-1117, 1991) a study of a large number of patients who gave numerous transfusions -- up to 105 donations in 17 months by one donor. They came to the conclusion that "13 of 14 donors had actual cell counts significantly higher than the predicted value" and that plasmapheresis is not detrimental to HIV-infected individuals. It is important to disseminate this information because, as you know, the bottleneck to passive immunization is the availability of hyperimmune plasma. "As to patients, you ought to correct the comment about the questionable neutralization of free virus from the circulation (p24 antigen). Our paper, entitled "Polymerase Chain Reaction Evidence for HIV-1 Neutralization by Passive Immunization in Patients with AIDS and ARC," published in the PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, USA in 1990 (volume 87, pages 7613-1717) confirmed the disappearance of free virus from the circulation. (The PCR assays were done by Dr. I Hewlett at the FDA laboratory in Bethesda.) " [Editor's note: We were discussing the HemaCare report, which provided p24 antigen data, but not results of polymerase chain reaction tests.] "Our 1988/89 trial did not include a control group, but I have never had any doubt in my mind about the beneficial effects of this non-toxic form of treatment. Although it is not a cure it appeared to improve the quality of life of even our advanced AIDS patients. On the basis of our uncontrolled studies, I will venture to predict that passive immunization will prolong the life of early AIDS (ARC) patients by years rather than months. "We are about to start a trial on the effects of passive immunization in pre-AIDS; namely as soon as the helper T-cell count drops to below 400. We would expect to delay the onset of the disease by years with a far lower amount of hyperimmune plasma (150 ml to start with). "Last, but not least, we started not only publishing data about the beneficial effects of neutralizing antibodies in 1985 but also using passive immunization in four patients at Addenbrooke's Hospital, Cambridge (LANCET, pages 695-697, 1985). Even the Economist of 16 November 1985 wrote about our work (page 89)." ***** CMV: Long-Awaited Trial of HPMPC Mt. Zion Medical Center of the University of California San Francisco is initiating the first human study of HPMPC, a nucleotide analog which is more potent against CMV, in laboratory tests, than ganciclovir or foscarnet. (AIDS TREATMENT NEWS first reported on HPMPC as a potential treatment for CMV infection over three years ago, in issue #76, March 24, 1989). The Mt. Zion protocol is a phase I/II study which will administer the drug intravenously once a week. It is open to people who are culture-positive for CMV, but who have not been treated before with ganciclovir or foscarnet, and who are not showing symptoms of active infection. The work-up and monitoring for this study are intensive, involving two overnight hospital stays; participants will be reimbursed $400. For more information, interested persons should call Eileen Glutzer, RN, or Jay Lalezari, M. D., at 415/476-6356. ***** CMV: Laboratory Study of Etoposide Etoposide (also called VP-16, or Vespid) is an approved drug used in cancer chemotherapy; it can be taken orally. Now a laboratory study has suggested that the drug might also be useful in the treatment of CMV. ("Irreversible Inhibition of Human Cytomegalovirus Replication by Topoisomerase II Inhibitor, Etoposide: A New Strategy for the Treatment of Human Cytomegalovirus Infection," by Eng-Shang Huang and others, Antiviral Research 1992: volume 17, pages 17-32.) The researchers reported that etoposide "can irreversibly inhibit CMV replication at the drug concentration (2.5 micrograms/ml) greatly below toxic levels to stationary phase cells...Because of their irreversible inhibitory effects and approval usage in clinical oncology, it is suggested that this group of compounds, particularly etoposide (VP-16), can be used to control life- threatening CMV infections, such as CMV pneumonitis and CMV retinitis, in cancer and immunocompromised patients or patients with AIDS. " The paper suggests that the toxicity of etoposide in this use might be comparable to that of ganciclovir. But since its suppression of CMV is irreversible (at least in the laboratory tests) prolonged treatment might not be needed. Note: Etoposide is also used for treating Kaposi's sarcoma, and for some AIDS-related lymphomas. ***** Rifabutin Available to Prevent MAC Under a "Treatment IND" approved last month by the U. S. Food and Drug Administration, Adria Laboratories will provide rifabutin to certain patients for prevention of MAC (mycobacterium avium complex, also called MAI), before the drug is regularly approved for U. S. marketing. In a major controlled trial with over 500 patients, rifabutin reduced the incidence of MAC to about half that of the placebo group. A separate, similar trial is now being analyzed. This program is only for prevention, not treatment; patients must have no history of MAC. They must also have a T-helper count under 200, and meet certain other criteria. Physicians who have patients who might benefit from this program should call the PACT Rifabutin Treatment IND Study Center, 800/552-7228, between 8 a.m. and 5 p.m. Eastern time, for more information. Comment Although not part of this program (and certainly not part of the message from Adria) there is reason to believe that rifabutin may be useful in treatment of MAC, as well as its prevention. It may also be useful in treatment of tuberculosis, including some multi-drug resistant strains. At this time these uses are not proven, however. ***** FDA Antiviral Advisory Committee Meeting to Consider ddC, ddI, Markers by John S. James On April 20 and 21 the Antiviral Drugs Advisory Committee, a panel of outside experts set up by the U. S. Food and Drug Administration (FDA), will meet in Bethesda, Maryland, outside Washington D. C. This meeting, scheduled to begin 8:30 a.m. April 20, and 7:30 a.m. April 21, at the Bethesda Ramada Inn, is open to the public. On the first day the committee is scheduled to discuss: * ddI, now an approved AIDS treatment, which was recommended for approval by the same committee in July 1991, and approved in October; * The use of T-helper cells as a "surrogate marker" to show if a drug for HIV infection is working in a clinical trial; and * Whether to recommend approval of ddC. This issue will also be discussed on April 21. New data on ddI is expected to be released either at the committee meeting, or at the Washington, D. C. meeting of the AIDS Clinical Trials Group (ACTG) the week before. The purpose of the ddI section of the meeting will be to evaluate whether T- helper cell increases have proven reliable as a basis for evaluating efficacy of nucleoside-analog drugs (such as AZT, ddI, and ddC) used for HIV treatment. The committee had previously recommended ddI for approval partly on the basis of T-helper counts seen in a major clinical trial. The most important part of this meeting will of course be the discussion of ddC, since the issue at hand is whether or not ddC should be approved. Comment Although no one knows what will come out of this meeting, the prevailing opinion, unfortunately, is that the committee will not recommend approval of ddC. As a single drug, ddC appears to be inferior to AZT, at least in the short term. And some members of the committee feel that there is less urgency for this approval than there was in the case of ddI, since now there are two antiretroviral drugs approved (AZT and ddI), instead of only AZT. The real interest in ddC is for use in combination with AZT, which has become a de facto standard of care among many leading AIDS physicians. The only published study on this combination use showed extremely good results (see "ddC Background," AIDS TREATMENT NEWS #145, February 21, 1992). But this study, called ACTG 106, was fairly small, and was not designed to test the efficacy of the combination; it was designed to test dosage and safety of this use. What happened is that the combination was found to work much better than anybody had expected. A larger study designed to test the efficacy of the combination (ACTG 155) is ongoing now, but no data has been released. Apparently the advisory committee will not be allowed even a peek at this data -- a very limited look so that they can see whether or not the results of ACTG 106 are being confirmed -- which was allowed earlier for the same committee's evaluation of ddI. (Researchers are almost always unwilling to release release results while a trial is going on, for fear that volunteers would conclude too early that one treatment looked better than another, and drop out of the trial before conclusive evidence was obtained.) Two other issues may be involved: * A new trial, ACTG 175, is testing this combination vs. other treatments (AZT plus ddI, AZT alone, and ddI alone) for a different group of patients -- those with T-helper counts between 200 and 500. This study, expected to enroll over two thousand volunteers, will use a substantial fraction of the resources available for clinical trials of AIDS treatments, and will probably take over two years to produce any results. But it is likely to be a cash cow for the participating institutions. If AZT plus ddC becomes a generally accepted standard of care for HIV infection, ACTG 175 might need to be discontinued. Could institutional self-interest have contributed to the unusual resistance to this combination treatment? * Hoffmann-La Roche, the developer of ddC, has announced that it will modify its expanded-access program for this drug, to allow it to be used in combination with AZT, for some patients. Since the drug will be more available than before through this program, the advisory committee may conclude that approval is less urgent. But expanded-access programs, while a great advance over no drug at all, do have drawbacks. They are not really "free," even if the drug is free; requirements for medical care and laboratory work usually exclude public clinics and uninsured patients. And such programs almost always have strings attached, taking control of treatment decisions away from patients and their physicians. Expanded access developed as an alternative to drug approval because a number of leaders who are influential on this issue consider it immoral to sell a drug without full proof of efficacy. But they have less problem with giving the same drug to the same patients for free. The resulting politics has led to a dysfunctional system, with no vision for its improvement. What should be done? We believe that ddC should be approved quickly, with appropriate documentation ("labeling"), provided that the currently-existing data from ACTG 155 confirms the results of ACTG 106. Let patients and their physicians decide whether or when to use the combination treatment. There is already enough information to support rational decision-making under uncertainty, which is what physicians normally do. And little is lost if we "never know" for sure if the combination treatment is best, since even this combination leaves much to be desired, and will become obsolete as soon as a truly good treatment becomes available. For the long term, we need to start now with proper planning and management of the whole HIV treatment-development effort. Do we really need to have each new drug tested two or three times because of arbitrary dividing lines of T-helper counts under 200, 200 to 500, and over 500? Should we spend much of the money and other resources available for AIDS clinical trials over the next several years for developing treatments which everybody knows are mediocre at best? It is already clear that ACTG 175 will show that the combination therapies are better than the single-drug treatments The main question this study will answer is how long it will take to get the required statistical proof. We should approve ddC now and move on, to develop better drugs for the future. ***** International AIDS Conference: Record Registration Despite the late move of the Eighth International Conference on AIDS, rescheduled from Boston to Amsterdam because of continued U. S. restrictions on entry of HIV-positive persons, more than 6,000 people have registered so far -- more than any previous International AIDS Conferences at comparable dates, according to an April 7 press release from Harvard AIDS Institute, which is co-sponsoring the Conference with The Dutch Foundation AIDS Conference 1992, the International AIDS Society, and the World Health Organization. Forty percent of the registrants are from the U. S. Also, more abstracts have been submitted to this conference than to last year's conference in Florence "We've received more than 1,100 abstracts from researchers in developing countries -- an 80 percent increase over the past three AIDS Conferences," said Jonathan Mann, chair of the conference. "With 85 percent of new infections occurring in the developing world, it is crucial that those working in and affected by HIV/AIDS in these regions participate in this meeting." ***** California Demonstration for Prisoners With AIDS ACT UP CHAIN, the California HIV Activist & Inmate Network, is holding a demonstration on May 4, 1992 in Sacramento, CA, to support prisoners with HIV/AIDS and demand that the California Department of Corrections implement a comprehensive and humane treatment plan for them. The demonstration will begin with a rally at the State Capitol at 10th St. & Capitol Mall at 11 am. ACT UP is organizing carpools from San Francisco, Los Angeles and Santa Barbara. For more information contact ACT UP/Los Angeles (phone: 213/669-7301; address: PO Box 26601, Los Angeles, CA 90026), ACT UP/San Francisco (phone: 415/563-0724; address: Box 14844, San Francisco, CA 94114), or ACT UP/Santa Barbara (phone:805/569-3299; address: PO Box 4899, Santa Barbara, CA 93140). Over 6,000 HIV positive prisoners in California are suffering from discrimination, segregation and substandard or non-existent health care. According to national studies, prisoners with AIDS live half as long as other people with AIDS, yet the California Department of Corrections has refused to take the necessary measures to improve conditions for prisoners with HIV. The demands of the demonstration include: comprehensive standard of care HIV/AIDS treatment; access to clinical trials; equal access to visitation and other prison programs; voluntary and anonymous testing; no forced segregation; compassionate release for health reasons; and HIV prevention and peer education. Comment On behalf of our incarcerated readers and all prisoners with HIV, we encourage Californians who are not in prison to attend this demonstration, or write letters to your representatives about the issue. People with HIV in the state prison system are subjected to unacceptable conditions and inadequate treatment for their medical needs. Because they are incarcerated, there is little room for them to advocate for their needs. This demonstration is important to let the State know that prisoners with HIV/AIDS have the right to live. ***** San Francisco: Health Care Workers' Respiratory Hazards Conference, May 1 & 2 The American Lung Association is sponsoring a two-day conference in San Francisco to address the many respiratory precautions critical to people working in health-care settings. The conference is scheduled for May 1 and 2 at the Laurel Heights Conference Center, 3333 California Street. Session topics include aerosolized medications, the re-emergence of tuberculosis, the ethics of medical surveillance, and the impact of advancing technologies on health care workers. For registration information, interested persons should call 415/543-4410. ***** San Francisco Area Clinical Trials Directory The Spring 1992 edition of the Community Consortium's Directory of HIV Clinical Trials in the Bay Area is now available. It lists 85 trials, for the following conditions: Anal cancer, Bronchitis, Cryptococcal meningitis, Cryptosporidiosis, CMV retinitis, Fungal infections, Herpes, Herpes zoster, Histoplasmosis, HIV, Kaposi's sarcoma, Lymphoma (both Hodgkin's and non-Hodgkin's), MAC, Measles (vaccine), Pain relief (including headache), Peripheral neuropathy, Pneumocystis, Septra (Bactrim) side effects, Syphilis, Thrush, Toxoplasmosis, Tuberculosis, and Weight loss/diarrhea. This directory is excellent in its organization and presentation of the information, and could serve as a model for similar listings of clinical trials. It includes an introduction to clinical trials, brief instructions on how to use the directory, table of contents, trial finder by condition and drug(s) being tested, listings of the trials (including title, purpose, background, requirements, and locations), common questions about clinical trials, how to enroll, women and clinical trials, injection drug users and clinical trials, list of trial sites, Community Consortium site and physician list, resource list for AIDS information, glossary, and index. To obtain a free copy, call 415/476-9554, or write to: Community Consortium, 3180 18th Street, Suite 201, San Francisco, CA 94110. ***** 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 415/255-4659 fax Editor and Publisher: John S. James Medical Reporters: John S. James Michelle Roland Denny Smith Reader Services, Business, and Marketing: Thom Fontaine Keith Griffith Laura Thomas Tadd Tobias Rae Trewartha Statement of Purpose: AIDS TREATMENT NEWS reports on experimental and standard treatments, especially those available now. We interview physicians, scientists, other health professionals, and persons with AIDS or HIV; we also collect information from meetings and conferences, medical journals, and computer databases. Long-term survivors have usually tried many different treatments, and found combinations which work for them. AIDS Treatment News does not recommend particular therapies, but seeks to increase the options available. Subscription Information: Call 800/TREAT-1-2 Businesses, Institutions, Professionals: $230/year. Nonprofit organizations: $115/year. Individuals: $100/year, or $60 for six months. Special discount for persons with financial difficulties: $45/year, or $24 for six months. If you cannot afford a subscription, please write or call. Outside North, Central, or South America, add air mail postage: $20/year, $10 for six months. Back issues available. Canadians add 7% Goods and Services Tax. 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 1992 by John S. James. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used. &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& -- ------------------------------------ Jack Hamilton jfh@netcom.com