AIDS TREATMENT NEWS Issue # 185, 10/15/93 phone 800/TREAT-1-2, or 415/255-05888 CONTENTS: Vaccine Controversies at San Francisco Conference Vaccine (gp160) Controversy Update Flu Season Warning Vitamin A Deficiency Associated with Increased Death Rate Antisense: "GEM 91" Human Trial Started in France Announcements: Recent Clinical Trials Recruiting HIV: Alpha Interferon, T-Helper Above 500 HIV: ddI Plus d4T Combination, T-Helper 200-500, No Prior Antiretrovirals HIV: Nevirapine+AZT, T-Helper 200-500, 4-12 Months Prior AZT HIV: ddC Plus AZT, T-Helper Count 100-500, No Prior Antiretrovirals Kaposi's Sarcoma: Recombinant Platelet Factor 4 (rPF4), San Francisco Only Kaposi's Sarcoma: Pentoxifylline Announcements San Francisco: Senator Wellstone Speaks on Single Payer Health Care Reform California: "Day of the Dead" Political Funeral, Sacramento, October 29. In Memoriam: Andrew Zysman, M.D. ***** Vaccine Controversies at San Francisco Conference by Dave Gilden The First International Conference on Engineered Vaccines for Cancer and AIDS, which was held in San Francisco at the beginning of the month, was a study in contrasts. On the one hand, increasing skills in genetic engineering allow complex manipulations of micro-organisms that result in a wide array of immune-stimulating products. On the other, there was no agreement on how to choose the promising HIV-vaccine strategies from among this wide array. Both types of anti-HIV vaccines, preventive and therapeutic, were under consideration. A preventive vaccine would protect people from becoming infected, whereas a therapeutic vaccine would enhance the immune response of those who already are living with HIV. The disagreements did not prevent polio vaccine discoverer Jonas Salk, M.D., from delivering an impassioned plea for rapid steps forward. Addressing representatives of the various vaccine developers gathered for a panel discussion, Salk said, "We risk investigating to exhaustionI People in need are waiting impatientlyI The time has come to move forward. We need to decide now to do something cooperatively." Salk appeared with a group from the Immune Response Corporation of San Diego, which is investigating his therapeutic vaccine concept, which involves inoculating with virus particles that have been both killed and stripped of their outer coat. The idea is to stimulate an immune response to HIV's inner protein appearing on the surface of HIV- infected cells. This therapeutic vaccine has been in human trials since 1987. The notion of a therapeutic vaccine has always been saddled with doubts. Unfortunately, Salk's presentation of his data early in the conference was not clear-cut enough to dispel those doubts and demonstrate that we have "enough clues and indications to go forward," as he put it. In the hallways, Salk privately commented to us that his talk at the conference was, in part, an attempt to reverse the poor impression his associates made earlier this year at Berlin's Ninth International Conference on AIDS. Once again, though, obscure slides slipped by one after another, purporting to show that the "responders" to the vaccine did better than the "nonresponders." Responders are defined as those who develop skin reactions when HIV proteins are applied in a manner similar to a TB skin test. The percent responding seems to increase with higher doses of inoculant. Responders fared better than nonresponders, in that they had slightly higher CD4 levels, fewer clinical symptoms, slight weight increases, and, for some people, reduced HIV levels in the blood. When asked by this writer if his slides were available in some form that allowed more thorough review, Dr. Salk demurred, saying the data were very preliminary. The doctor then grew philosophical: "But this is just information. What is important is the knowledge. Tell your readers that the knowledge is there. We know how to make an effective vaccine." Is that knowledge really there? Another conference speaker, Robert Schooley, M.D., of the University of Colorado, reviewed the state of research on therapeutic vaccines and made it clear there are still plenty of gaps. "Why should this approach work?" Schooley asked, noting that the amount of HIV envelope protein constantly present in the blood is frequently 100 to 1,000 times greater than the amount in any vaccine now being injected at periodic intervals during treatment trials. Vaccine-induced reductions in HIV remain to be definitely established. Also, it is not known whether HIV can mutate to escape the protective antibodies engendered by the vaccine. HIV certainly escapes the defenses the body naturally sets up against the virus, after all. Although Salk's colleagues have been testing their vaccine for six years, they have been unable to resolve such doubts. Dr. Schooley noted a fundamental problem when comparing therapeutic vaccine responders to nonresponders, as the Salk group and other vaccine developers are doing. If responders, that is those who broaden their anti-HIV immune activity after vaccination, tend to stay healthier longer than nonresponders, maybe it is because their immune systems were superior in the first place. That is what enabled them to be responders. The data, therefore, may merely reflect the natural variation in response to HIV -- some people progress faster than others to AIDS -- rather than show that the vaccinations produce any benefit. The controversy over results from Army researchers' trials of the therapeutic vaccine developed by MicroGeneSys Corp. of Meriden, CT [see AIDS TREATMENT NEWS #164 and #183] reflects this uncertainty. Quick, definitive documentation of a vaccine's benefit requires an accepted way to evaluate changes in immunity triggered by vaccines. The lack of consensus continues, though, for preventive as well as for therapeutic vaccines. Dr. Salk acknowledged at the conference that "the correlates of immunity question is holding the effort up. The moment we have something to measure, the game's over." Trials could proceed rapidly and decisively by tracking accepted signs of immune improvement. Dr. Salk thinks that cell-mediated immunity -- as signified by his skin test for response to HIV antigens -- is the appropriate standard (in addition to T-helper cell count, weight gain, and clinical symptoms). The killer lymphocytes associated with cell-mediated immunity specialize in destroying cells infected by virus. Salk thinks that absolute, complete prevention of HIV transmission from person to person will not be possible with a vaccine. Rather, cell- mediated immunity must be primed to immediately isolate the virus contained within cells and snuff out an incipient infection. In a sense, preventive and therapeutic vaccines have a similar role -- controlling HIV after it has already entered the body -- although the timing of these two vaccines is different. But in a presentation at the conference, Susan Zolla-Pazner, M.D., of New York University indicated that antibodies are important, too. "Antibodies play a major role in preventing viral infection," she said. "They play a minor role in controlling infection." Dr. Zolla-Pazner's research concerns monoclonal antibodies, which are laboratory products containing a single specific antibody. She has found an antibody that seems to neutralize all the HIV strains common in North America and Europe (including wild strains, not just laboratory isolates). The antibody reacts to a section of the V3 loop on HIV's envelope molecule (gp120). The V3 loop is a part of the virus that is "out there waving in the breeze," as Dr. Zolla-Pazner describes it. It is easily accessible to antibody recognition and attack. Researchers now plan to try out monoclonal antibodies as a means of preventing HIV transmission during a few special circumstances -- in babies, to prevent transmission from HIV-infected mothers at birth, and then in health care workers exposed to HIV through accidents on the job. A cocktail of these antibodies may also be useful as a treatment, Dr. Zolla-Pazner noted. Another conference participant, Ron Desrosiers, Ph.D., described a novel approach to a vaccine for preventing SIV, the monkey version of HIV. He told AIDS TREATMENT NEWS, "We tried protecting monkeys from SIV with altered vaccinia virus plus subunit booster [genetically engineered smallpox-vaccine virus containing SIV coat proteins plus later inoculations of pure SIV protein fragments]. It resulted in great antibody production, but the protection was minimal. So we started out on a new strategy." Dr. Desrosiers' new strategy was actually a standard one for vaccines in other diseases -- a live but weakened, or attenuated, SIV strain. The SIV was weakened by deleting its "nef" gene, whose function is poorly understood. The attenuated virus produced an extremely low-level, benign, persistent infection instead of a rapidly fatal one. When the vaccine's effectiveness was tested in four monkeys more than two years after vaccination, protection was complete against two closely related SIV strains. Dr. Desrosiers is now experimenting with SIV strains weakened by removing three to five minor genes including nef. Last month, his team started an experiment in chimpanzees using a multiply deleted version of HIV. "All the [existing] HIV vaccines have been tested only under idealized conditions," Dr. Desrosiers said in our interview. "It's likely they will fail in the field. We need to gather some basic safety data on our type of vaccine in humans now." Linda Gritz, Ph.D., of the Therion Biologics Corporation in Cambridge, MA reports that her company has licensed Desrosiers' method and is considering doing just that. "But we hope we don't have to, that one of the other vaccines we're trying works," she told ATN. "There are tremendous fears about using a live, attenuated HIV vaccine on uninfected people. It could take us twenty years to tell whether we're using a strain of HIV that produces no disease progression or only slow progression." Gritz mentioned that Therion is also considering testing a gene-deleted HIV vaccine for treatment purposes. Because of all the doubts, Patricia Fast, M.D., Ph.D., who helps direct AIDS vaccine development at the National Institutes of Health, told the conference, "It is unlikely we have the perfect vaccine but we will continue to push on with every strategy." Her colleague, Dale S. Lawrence, M.D., M.P.H., outlined the reasons for moving quickly to efficacy trials: Vaccines represent an "exquisite weapon" compared to the "sandbag protection" we now have against HIV. Lawrence envisions trials requiring thousands of volunteers. He would be happy to get a 60 percent reduction in HIV transmission with the present crop of vaccines. For the vaccine failures (the volunteers who later become infected with HIV, despite having received the vaccine -- and there are already rumors of one such failure in a small preliminary trial of one vaccine), Lawrence foresees a prolonged period of followup to see whether the vaccine slowed down or enhanced disease progression. The community of course desperately needs new forms of HIV treatment and prevention. Community support will be essential for the large trials, including the mass testing of therapeutic vaccines now under consideration by the Army (see below, and see AIDS TREATMENT NEWS #184). It is also important not to squander the community's trust by rushing into mass testing too early, with crudely conceived vaccines that still resemble "sandbags" more than they do "exquisite weapons." Loss of public confidence due to the inevitable failures will make it all the more difficult to test more promising vaccines in the future. ***** Vaccine (gp160) Controversy Update by Dave Gilden The controversy over Army researchers' plans to conduct a massive trial of therapeutic vaccines (reported in AIDS TREATMENT NEWS #183) continues on its apparently unstoppable course, exhausting everyone involved. The controversy started a year ago when lobbyists hired by MicroGeneSys Corp. convinced Congress to allocate $20 million dollars for the Walter Reed Army Institute of Research to further test the company's therapeutic vaccine. (Therapeutic vaccines are supposed to strengthen the anti-HIV immune defenses in people already infected by the virus -- see the article in this issue on the First International Conference on Engineered Vaccines for Cancer and AIDS.) The original appropriation was reviewed by a panel created by the National Institutes of Health. Nine months ago, this blue-ribbon panel urged that a multiproduct comparison trial be carried out, rather than testing a single vaccine alone (see AIDS TREATMENT NEWS #164, December 4, 1992). But on September 27, 1993, many of the non-NIH members of the panel signed a statement arguing that "the scientific evidence to date does not yet justify Federal support for a large phase III [efficacy] study of either one or several candidate HIV therapeutic vaccines." The statement's signers want the $20 million disbursed as a grant program, underwriting a broad range of AIDS research. Proposals would be judged by an expert review panel set up by the Department of Defense. White House AIDS policy coordinator Kristine Gebbie, M.N., took a similar position on September 28, in a letter to Rep. Henry Waxman (D-CA), the chair of the House Subcommittee on Health and the Environment. Gregg Gonsalves, of the Treatment Action Group in New York, reports that spending the $20 million on peer-reviewed, investigator-initiated AIDS research is also the favored course of the vast majority of the respondents to a TAG survey among activists and scientists. (That survey was published in ATN #183.) He notes that this course does not preclude a large trial of one or more therapeutic vaccines. It just makes the Army researchers get in line like everyone else to justify their proposal. Back at Walter Reed, Deborah Birx, M.D., has been working since the spring to get a large comparative trial off the ground. (The idea of testing the MicroGeneSys vaccine alone seems to have fallen by the wayside. Her concept is now similar to that originally floated by the NIH panel.) She has managed to convince MicroGeneSys to agree to donate its vaccine on a year to year basis for such a trial, something the company was previously unwilling to do. Dr. Birx is now trying to get other therapeutic vaccine developers to similarly aid the study -- at a cost to the companies of $2 million per year. Birx envisions conducting a three-year, placebo-controlled trial with several thousand people per vaccine arm. People with a wide range of helper T-cell counts would be observed, and everyone could take whatever other drugs they wanted, except for experimental antiviral medications. Dr. Birx contends there are hints that therapeutic vaccines are useful for treating HIV. But, she told AIDS TREATMENT NEWS, "Either you buy into this trial as something that doesn't follow the normal scientific steps orI we'll be seven years from the answer [of how effective therapeutic vaccines are] according to usual procedure." Dr. Birx does have a certain amount of support among community-based researchers, who would be included in the trial, and among people with HIV searching for new treatment options. Interestingly, she is close to her opponents' position in that she supports a kind of massive roundtable of scientific and community representatives to reach a consensus about her project. A consensus-building process of one sort or another may get a chance to work if an amendment to the 1994 Defense budget is passed. That amendment, proposed by Rep. Waxman and now approved by the House of Representatives, would give the government another six months to review the need for a large vaccine trial. So the saga of the Army's and MicroGeneSys's $20 million continues to unroll. "We're seeing the best and the worst of the democratic process," complained Joseph Camarado of Wyeth- Ayerst Laboratories, MicroGeneSys's corporate backer. But while arguments re-flared over this $20 million, Congress on October 5 passed a $227 million increase in AIDS research funding without any controversy. That money will be distributed through the National Institutes of Health's regular grant award process involving independent scientific review committees. The NIH process has plenty of critics, but it is still more orderly than having Congress earmark funds for specific projects on a political basis. Commented Terry Beswick, who, at the time of interview, was set to become a temporary advisor to Kristine Gebbie on research policy, "This is a lesson in the bad management in science." Finally, if the groups working on the therapeutic vaccine trial issue cannot come to an agreement, there is an almost completely unnoticed measure before Congress to take back the money. H.R. 1392 (S. 1090 in the Senate) is a general bill to erase a wide range of mistaken appropriations in last year's budget. Included in the 3,000 lines of text is a short clause canceling funding for the large-scale vaccine trial on the grounds that the proposed trial has not been subject to competitive bidding. ***** Flu Season Warning by Dave Gilden This winter's flu season is likely to be particularly severe, the U.S. Public Health Service warns. Three to five times the usual 10,000 to 20,000 flu-related deaths may occur. Worse yet, the harsh "Beijing" strain of influenza that first appeared in February mutated at the end of last year's flu season, and no one is immune to it unless they came down with flu in April or May. The U.S. Public Health Service is recommending that all persons at special risk for flu complications get the updated version of the flu vaccine by November 15. Among these "at risk" groups are people with HIV. A poster presentation (#2249) at Berlin's International Conference on AIDS found that flu vaccine coverage in the U.S. is "sub optimal," with only about a third of people with HIV receiving the vaccine. Also in Berlin, three posters described a low response rate to the vaccine, especially among people with greatly reduced helper T-cell counts (posters 500, 1264 and 1276). Stephen Follansbee, M.D., a San Francisco AIDS specialist who is following the issue, nevertheless urges anyone with HIV to be vaccinated. Complications from infection with the influenza virus include bacterial pneumonia, which can be fatal. For people with low T-helper cell counts, Dr. Follansbee suggests that all housemates also have themselves vaccinated. This would create a kind of sanitary wall around the person most in danger. However, those with a history of allergic reactions to flu shots or to eggs should not be inoculated; and those with fevers should wait until the fevers subside. The vaccine consists of killed influenza virus that was grown in egg cells. Two posters (209, 1929) in Berlin also dealt with the question of whether flu vaccination increases the level of HIV in the body, due to the immune stimulation the inoculant provokes. Increased HIV replication might spark a further decline in the immune system. One of the posters said the vaccine does increase viral load for several months; the other found no change. To look at the question further, Dr. Follansbee and a group of associates are planning a short, 30-person trial involving HIV-infected volunteers at different helper T-cell counts. HIV levels and immune function will be measured for 28 days after vaccination. The trial is now completely enrolled, and a full analysis of the data will not be completed until December at the earliest, well after the recommended vaccination period is over. But Dr. Follansbee says, "I don't want the study to undermine people getting shots." Any negative effect of the flu vaccine is probably minor, compared to the damage the flu could cause. ***** Vitamin A Deficiency Associated with Increased Death Rate A study of HIV-positive intravenous drug users found that those with a vitamin A deficiency (about 15 percent of the HIV-positive persons studied) had a death rate several times as high as those who did not have a vitamin A deficiency. While this study does not prove that correcting the deficiency will improve survival, it strongly suggests that conclusion. Other studies (unrelated to HIV) have shown that vitamin A deficiency does impair both cellular and humoral immunity. Also, vitamin A supplementation in developing countries has been found to reduce childhood mortality by 20 percent to 54 percent. And vitamin A stores in the body may be reduced by infection, suggesting that a vicious circle can develop, with infection depleting vitamin A, and the deficiency causing more infection. But on the other hand, recent studies have found that retinoic acid, which is the active form of vitamin A in the body, can increase HIV replication in laboratory tests. This raises the concern that vitamin A supplementation might not always be helpful in HIV disease. In addition, the association found in the study does not prove causality, because patients who were sicker (and more likely to die anyway) may have therefore developed nutritional deficiencies, due to malabsorption or other causes. Reference: Semba RD, Graham NMH, Caiaffa WT, Margolick JB, Clement L, and Vlahov D. Increased Mortality Associated With Vitamin A Deficiency During Human Immunodeficiency Virus Type 1 Infection. Archives of Internal Medicine. September 27, 1993; volume 153, pages 2149-2154. Comment The studies needed to get definite answers about use of vitamin A in HIV disease have not been done and may never be done. In the meantime, people must make decisions on the information available. The usual recommendation for vitamin A supplementation is to use beta carotene, not vitamin A itself. Vitamin A is toxic in overdose; beta carotene is safer because the body only converts what it needs to vitamin A. Also, beta carotene is an antioxidant (vitamin A itself is not), and there are indications that antioxidants might help to reduce progression of HIV disease. The scientifically ideal study would give beta carotene, and/or vitamin A, to randomly chosen HIV-positive patients within a study group, then follow them for years to see if there was a difference in death rate between those who received the supplementation and those who did not. A more practical study would use modern tests for viral activity or viral load, instead of looking for differences in death rate. This way, results could be obtained in weeks instead of years, and without serious risk of harming volunteers in the trial. These results would not give an ultimate answer of what supplementation is best, but they probably would establish that certain doses could be used without risk of increasing HIV activity. Once that is shown, the clear course of action would be to use the supplements, since there is overwhelming evidence that vitamin A can reduce the risk of other infectious diseases, and beta carotene is safe, readily available, and not expensive. Meanwhile, it appears that people with HIV should be using at least some beta carotene (unless their physician recommends otherwise) to prevent possible vitamin A deficiencies. Even more importantly, this study re-emphasizes the need for good overall nutrititional support in AIDS treatment. ***** Antisense: "GEM 91" Human Trial Started in France The first human trial of an antisense compound for HIV has started in France. On October 13, Hybridon, Inc. of Worcester, Massachusetts, announced that it has begun a single-dose safety study which will test escalating doses of its compound GEM 91 in up to 24 patients. Hybridon is working in collaboration with ANRS, the French Agency for AIDS Research. In the laboratory, the drug is active against all strains of HIV which have been tested so far. Resistance is expected to be less of a problem with antisense compounds than with other classes of drugs. Animal studies have found that antisense drugs can work comparably in animals as in the laboratory. An antisense drug targets specific genetic information in viruses, other infectious organisms, cancer cells, or human cells, to prevent one selected gene from working. The drug targets what is called mRNA (messenger RNA), to prevent the production of the particular protein which is specified by the gene. The importance of antisense is that, once a technology to make one antisense drug has been developed, other potential drugs can be designed just by changing the code, as long as there is a known sequence to be targeted (which is often the case). Therefore, it may be possible to quickly develop drugs against a wide variety of diseases. Each drug should be highly specific against a particular disease, by targeting sequences which do not normally occur in the body. Therefore, it should be possible to give effective doses with few side effects. An early laboratory study of an antisense compound against HIV was published in 1986 (see AIDS TREATMENT NEWS #58, June 3, 1988). But developing the basic technology of antisense has been difficult, since it is necessary not only to code for specific sequences, but also to do so in a way that can work as a drug in the body. Now that the technology is advanced enough for human testing to begin, further progress may be rapid. ***** Announcements: Recent Clinical Trials Recruiting Mark Jacobson, M.D., at San Francisco General Hospital, brought several trials for HIV, and for KS, to our attention. All but one of these trials is recruiting in several cities (not only in San Francisco). None of these trials is listed by the AIDS Clinical Trials Information Service (at phone number 800/TRIALS-A). This is because 800/TRIALS-A, a Federally-sponsored service, lists all Federally-sponsored AIDS trials, but only some privately- sponsored ones. Trials sponsored by a pharmaceutical company are only listed if the company agrees, and goes to the trouble to provide the information. [When trials are not listed, it can be difficult to find information by calling the companies directly; it took us about two days' work to find and confirm the listings below. One company refused to give us any information, even the names of the cities where the trial would take place, until they had authorization from the investigators at the sites, which would take them ten working days; we got the information elsewhere. Most gave us the information, but usually it took a number of calls to find it, even when we started with a number given out for that purpose. And sometimes the sponsors give different contact numbers than the sites themselves. Only a few companies have, coherently and in one place, all the information potential volunteers will need to find a trial site near them (if there is one). Since recruiting volunteers is the biggest problem for most clinical trials, anyone conducting a trial should at least pay attention to making it easy to find.] Note: Not all of the entry criteria for these trials are listed below. Clinical trials often have many inclusion/exclusion criteria, most of which apply only to a few patients. The notices below only list the requirements which are most likely to exclude potential volunteers, so that readers can get a quick idea of whether or not they might qualify. ** HIV: Alpha Interferon, T-Helper Above 500 This trial is studying whether low or moderate doses of alpha interferon can slow HIV progression in early infection. The theory behind the trial is that there are two kinds of T- helper immune response, Th1 (cellular immunity, with cells attacking and destroying infected cells) and Th2 (which leads to production of antibodies). For HIV, the Th1 response seems to be most important; and the Th2 response, when it occurs, may reduce the Th1 response. Alpha interferon may increase Th1 activity and/or decrease Th2 activity. If these theories are correct, it might help to prevent progression of HIV disease. (AIDS TREATMENT NEWS published an advance notice of this potentially important trial in issue #179, July 23, 1993.) Alpha interferon has been used as a treatment in HIV disease since early in the epidemic, but has not been systematically studied in early infection. There is reason to believe that early use might be most beneficial, since without treatment the Th1 response is lost before a major decline in T-helper cell count occurs. Volunteers must be HIV positive, with T-helper count over 500, and must never have used AZT or other antiretrovirals. They will be tested and must be deficient in one or more of three measures of Th1 response (recall antigens, alloantigens, or PHA) -- apparently so that the trial will have some way to measure treatment success. There are a number of other inclusion/exclusion criteria. Those accepted will be randomly assigned to one of three groups: 0.2 million units of interferon (Intron A) three times a week, 2.0 million units three times a week, or an untreated control group. The drug is given by subcutaneous injection. The treatment will be continued for 12 weeks, and there will be two later followup visits. This trial is sponsored by Schering Corporation. The sites are: Denver (University of Colorado, contact Virginia Waite, B.S.N., 303/270-8340; the trial should begin at the Denver site within the next few weeks); Durham (Duke University, contact Robert Dodge, R.N., 919/684-5260); and San Francisco (San Francisco General Hospital, contact Linda Johnson, R.N., 415/476-9296 x84099). Comment Alpha interferon is an approved drug, and any physician can prescribe it. The doses being tested in this trial are low to moderate. The disadvantage of using the drug outside of the trial is that until the study is done, nobody knows if this treatment will be useful. Also, the drug is expensive, and does have side effects. ** HIV: ddI Plus d4T Combination, T-Helper 200-500, No Prior Antiretrovirals This trial, sponsored by Bristol-Myers Squibb, will test five different combination regimens of two anti-HIV drugs: ddI (didanosine), which is approved; and d4T (stavudine), which is in late stages of human testing and also currently in use through parallel track. This study will look first at the safety of the combination, since both drugs can cause peripheral neuropathy. But it will also measure antiviral activity using a number of tests: acid-dissociated p24 antigen, beta-2 microglobulin, PBMC viral titers, and HIV RNA and DNA PCR. Development of resistant viruses will also be measured. Volunteers must have T-helper counts from 200-500, and must never have received AZT, ddI, ddC, or d4T. This is a pilot study, which will only enroll a total of 75 volunteers. This study will require approximately 12 visits to the clinic over a period of one year. The four study sites are: Galveston (the University of Texas, contact Bernadette Montgomery, 409/772-3991); Los Angeles (UCLA, contact Suzette Chafey, 310/206-6414); New York (Cornell Medical Center, contact Jim Mahoney, 212/746-4177); and San Francisco (San Francisco General Hospital, contact Ted Bush, R.N., 415/476-9296 ext. 84098). ** HIV: Nevirapine+AZT, T-Helper 200-500, 4-12 Months Prior AZT This study will compare the combination of AZT plus nevirapine (formerly called BI-RG-587) with AZT alone, to see if the combination can reduce viral measures (HIV RNA, and viral cultures) and increase T-helper cell count and T-helper cell percent, after three and six months of treatment. All patients will continue on AZT throughout the study; and those initially assigned to placebo will be switched to open-label nevirapine during the trial. Volunteers must have T-helper counts of 200-500, and must have used AZT for at least four months, and no more than 12 months, immediately before entering the study. They cannot have CDC-defined AIDS, and also cannot have certain HIV- related conditions. This trial will be conducted in five cities: Baltimore (Johns Hopkins University Hospital, contact Becky Becker, R.N., or Louis Grue, R.N., 410/955-2898); Chicago (Northwestern University Medical School, contact Pam Donath, R.N., 312/908- 9636); Galveston (University of Texas Medical Branch, contact Bernadette Montgomery, R.N., 409/772-0361); San Francisco (San Francisco General Hospital, contact Kathy Dybeck, R.N., 415/476-9296 x84097); and St. Louis (Washington University School of Medicine, contact Mark Myers, 314/454-0058). The trial is sponsored by Boehringer Ingelheim ** HIV: ddC Plus AZT, T-Helper Count 100-500, No Prior Antiretrovirals This large study, enrolling over 500 patients at over 20 sites, is comparing different doses and schedules of AZT and ddC used in combination. There is no placebo, and all volunteers enrolled will get both drugs. The AZT doses are 500 mg per day (100 mg every four hours while awake) vs. 600 mg per day (200 mg every 8 hours); the ddC doses are 0.75 mg every eight hours, and 0.375 mg every eight hours. This trial is sponsored by Hoffmann-La Roche. Volunteers must have a T-helper count between 100 and 500, and not have had any previous treatment with AZT, ddI, ddC, or d4T. They also must not have symptoms of peripheral neuropathy at the time of the trial, or any history of peripheral neuropathy of grade 2 or greater. This trial is being conducted at sites in the following cities: Albuquerque, Boston, Bronx, Brooklyn, Chicago, St. Louis, Columbus, Dallas, Denver, Galveston, Harbor City, CA, Miami (2 sites), Milwaukee, New York, Portland, OR, San Diego, San Francisco, St. Paul, Washington (2 sites), and Wichita. For more information about volunteering, call 800/526-6367 teleprompt 2 to be referred to a site near you. ** Kaposi's Sarcoma: Recombinant Platelet Factor 4 (rPF4), San Francisco Only This phase I/II trial, sponsored by Repligen, is being conducted only at San Francisco General Hospital. In a previous study, shrinkage of KS lesions was found in six out of 12 patients who were treated with rPF4 by direct injection into the lesions. This new trial will test the drug for systemic treatment, giving it in six-hour intravenous infusions. The trial is looking for evidence of safety, and also for activity of the drug on KS, either on the skin or internally. Volunteers must have biopsy-proven KS, and be clinically stable. For more information, contact Carol Arri, R.N., 415/476-9296, ext. 84094. ** Kaposi's Sarcoma: Pentoxifylline There are theoretical reasons to believe that pentoxifylline (Trental), an approved drug, might have some activity against KS. This trial, sponsored by Hoechst-Roussel, is to make sure it is safe to combine pentoxifylline with antiretroviral drugs patients are already using, and to look for evidence of clinical activity of pentoxifylline, either against KS, or against the progression of HIV infection itself. [For background on pentoxifylline as a possible HIV treatment (not focused on KS), see AIDS TREATMENT NEWS # 156, August 7, 1992.] Nausea has been the most common side effect found so far. To enroll in this trial, volunteers must have relatively mild KS, not be likely to need chemotherapy during the study, and have had no KS treatment during the last 30 days. There are separate slots for persons with T-helper counts over 200 and under 200; the latter are almost full, at least at the San Francisco site, so it may be easier for persons with over 200 to enroll. The trial will be conducted at three sites in two cities: Los Angeles (UCLA, contact Ashley at the Care Facility, 310/206- 6414); Los Angeles (Norris Cancer Hospital, contact their clinical-trials information office, 800/5-CANCER); and San Francisco (San Francisco General Hospital, contact Julie Russell, R.N., 415/476-9296 ext. 84100). ***** Announcements ** San Francisco: Senator Wellstone, Oct. 24, Single Payer Healthcare Reform Senator Paul Wellstone (D., Minnesota), principle author in the Senate of the American Health Security Act of 1993, for a Canadian style single payer health care reform -- a leading alternative to the Clinton reform plan -- will address a rally on Sunday, October 24, 1:30 to 2:30 p.m., at the Cathedral Hill Hotel in San Francisco. There is no charge for this event, which is part of a one-day conference by UHCAN! (Universal Health Care Action Network), an organization mobilizing grassroots support for single-payer health care reform. (For more information about the conference, call UHCAN! at 216/241-8422 or 800/634-4442; or call Neighbor to Neighbor at 415/824-3355. Registration for the day is $15 without lunch, $30 with lunch). Senator Wellstone will also address a fundraising reception later that day in San Francisco; suggested contribution for this event is $50 to $100, with no contributions over $100 accepted. The reception will be in the Monterey Room of the Sir Francis Drake Hotel, 450 Powell Street, 5:00 to 7:00 p.m. For more information about single-payer health care reform, call Ellen Shaffer in Senator Wellstone's office, 202/224- 5641. ** California: "Day of the Dead" Political Funeral, Sacramento, October 29. A political funeral/demonstration against inadequate AIDS funding in California is being organized by ACT UP chapters in California. The main event will occur Friday October 29 at noon at the State Capitol. State AIDS programs have remained flat or decreased, while the case load has continued to grow. "The demonstration is planned in conjunction with Halloween and the Day of the Dead, and will target the State AIDS budget disaster. ACT UP plans on marching through Sacramento and eulogizing people who have died of AIDS at the State Capitol steps. Ghoulish costumes and visuals are encouraged. "Additionally, if you would like to memorialize a person with enlarged photographs, or by bringing their ashes to the demonstration, we will arrange that. Please call 415/252-9200 for more information." [Note: There are legal concerns about human ashes that need to be considered.] "We are also planning transportation. If you need a ride (from San Francisco) to Sacramento, meet at the Safeway on Market Street in the Castro at 8:30 a.m. on Friday, October 29." "The political funeral is the first of its kind in Sacramento and is being organized by a newly formed coalition of California ACT UP chapters. ACT UP/Golden Gate, ACT UP/San Francisco, ACT UP/East Bay, ACT UP/Sacramento, ACT UP/San Diego, and ACT UP/Los Angeles are the participating chapters. AIDS and health care advocates are involved and endorsing this action." [Note: Shortly before we went to press, the official name of the demonstration was changed to "Bring Out Your Dead," at the request of ACT UP/San Francisco, which feared that the original name might be offensive to some who observed the traditional Day of the Dead.] For more information, call 415/252-9200. Background: Day of the Dead The Day of the Dead is a traditional Mexican holiday with roots going back before the Spanish conquest. It is a playful, festive occasion with food and costumes in honor of the dead. People visit cemeteries on November 1 with offerings for the departed, wait for the spirits of the dead to visit them, which happens at midnight, and then leave at daybreak. In the U.S., the Day of the Dead has been observed in different forms since 1972, when it was introduced as a healing celebration following the East Los Angeles riots; more recently it has come to the attention of communities affected by AIDS. In San Francisco this year, there will be a reception at the Mission Cultural Center on Tuesday, November 2, from 5:00 to 8:00 p.m., then a procession starting at 7:30 p.m. near 24th and Mission. ***** In Memoriam: Andrew Zysman, M.D. by John S. James San Francisco activist Andrew S. Zysman, M.D., died of AIDS complications on October 12. He was 38. We knew Andy's work through the ACT UP/Golden Gate Treatment Issues Committee. He focused on research on new treatments for Kaposi's sarcoma, making many trips to Washington to bring together government and corporate scientists and officials so that important trials could proceed. Andy noticed that Japanese companies, with almost no experience with the U.S. drug-approval system, often teamed up with consultants who had plenty of experience in how the FDA worked five or ten years ago. When mistakes were made, research stopped; the system has no mechanism to identify these problems and overcome them. Andy provided relevant advice, which was often followed. In at least one case, he made important contributions to involving the U.S. National Cancer Institute, which has plenty of FDA experience, in a critical drug development effort, after corporate-FDA communication had bogged down. Scientists and officials relied on Andy and other treatment activists, who -- like bees pollinating flowers -- carried important messages between them when egos and organizational constraints prevented direct communication. Andy was also a leader on other AIDS issues, including getting an annual price cap on acyclovir to protect those who must use large, ongoing doses. As a member of the governing board of the American Association of Physicians for Human Rights, he testified before the Centers for Disease Control and helped to prevent mandatory testing (and de facto dismissal) of HIV-positive healthcare workers. A memorial service will be held in San Francisco in mid November. For more information, call 415/552-1428. ***** 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: Jason Heyman John S. James Nancy Solomon Reader Services and Business: David Keith Thom Fontaine 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. 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 1993 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.