Date: Mon, 09 Jan 1995 14:55:44 -0800 (PST) From: "John S. James" AIDS TREATMENT NEWS Issue #214, January 6, 1995 phone 800/TREAT-1-2, or 415/255-0588 CONTENTS: Oral Ganciclovir Approved FDA Advisory Committees Meet January 26 on Salk HIV-1 Immunogen Women and AIDS -- Unexplained Higher Risk of Death Some Vitamins Associated with Decreased Risk of AIDS and Death 1995: Politics 1995: Business AIDS-Related Research Meetings, January and February 1995 ***** Oral Ganciclovir Approved On January 5, Syntex (a Palo Alto, California pharmaceutical company recently acquired by Hoffmann-La Roche) announced that the U.S. Food and Drug Administration had approved oral ganciclovir for marketing. Ganciclovir (Cytovene() has long been an approved drug widely used for treating CMV retinitis, which if untreated causes blindness in persons with advanced AIDS. A major disadvantage of ganciclovir has been that it had to be given intravenously every day. In addition to the expense and inconvenience, the intravenous administration can increase certain side effects, including serious infections. Treatment with ganciclovir involves two stages: induction therapy (usually twice-daily intravenous infusions for two to three weeks), followed by maintenance therapy, usually one infusion per day. Eventually the maintenance therapy is likely to fail; then the induction may be repeated, or the patient may be treated with another intravenous drug, foscarnet. The newly-approved oral drug can be used for maintenance in some patients; however, intravenous treatment is still necessary for induction. Maintenance with the oral drug is somewhat less effective than with the intravenous; in clinical trials, the average time to disease progression was five to twelve days faster with the oral drug. Therefore the FDA indicated oral ganciclovir only for those "for whom the risk of more rapid disease progression is balanced by the benefit associated with avoiding daily IV infusions." And many of the side effects of intravenous ganciclovir are still present with the oral drug, especially hematological toxicities; therefore blood tests are necessary with the oral as with the intravenous treatment. Oral ganciclovir is taken either three times a day or six times a day, with food. ***** FDA Advisory Committees Meet January 26 on Salk HIV-1 Immunogen On January 26, two advisory committees of the FDA (the Antiviral Drugs Advisory Committee, which considers most AIDS drugs, and the Vaccines and Related Biological Products Advisory Committee) will meet jointly to consider future clinical trials of the HIV-1 Immunogen, a potential AIDS treatment developed by Jonas Salk, M.D. The Immune Response Corporation (IRC), of Carlsbad, California, has already conducted a number of clinical trials of the immunogen; 235 patients have received it in clinical trials since 1987, with no drug-related serious adverse events and no patients dropping out of trials due to adverse events. Now IRC plans to run three larger trials, involving a total of almost 5,000 volunteers. These trials, which will last from two to four years, will test the treatment in three groups of patients: those with T-helper count under 300, those with 300-549, and those with 550 and above. The HIV Immunogen is made with killed HIV, much like killed- virus vaccines for other diseases. The current and proposed trials are not testing it as a preventive vaccine, however, but as a treatment for existing HIV infection. Previous trials have shown evidence of improvement in various immunological and other blood tests; however, they have not been large enough to show conclusively that the treatment has clinical benefit in delaying disease progression. The new studies are intended to determine that, and also to validate the use of blood-test "markers" of disease progression for studying an immune-based treatment such as the immunogen. Volunteers in the previous trials have shown much interest in continuing their treatment. Those in California have long been able to do so (due to California approval by the state's Food and Drug Branch), but those in other states have not. The FDA has already approved a continuation protocol, which applies to volunteers in all states, but supplies of the Immunogen have been limited due to manufacturing issues which are currently being overcome. The joint meeting will be held at the Holiday Inn, Bethesda, Maryland, Versailles Ballrooms I through III, starting at 8 a.m. The first session, from 8:00 a.m. to 10:45 a.m. on January 26, will be closed to the public, apparently to deal with manufacturing issues; the rest of the meeting is expected to be open to the public, with a public hearing from 10:45 to 11:30; persons wishing to speak should make arrangements in advance, if possible before January 19. [Note: the advisory committee meeting will continue on January 27, to deal with other matters.] For more information, contact Judy Rappaport, Salk Immunogen Working Group of ACT UP/Philadelphia, 215/972-1454. ***** Women and AIDS -- Unexplained Higher Risk of Death A study of 768 women and 3779 men with HIV found that the women had a one-third higher risk of death then the men -- and yet no higher risk of progressing to AIDS -- after statistical adjustment for stage of illness. The cause of the difference is unknown. The study was conducted by the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA), through analysis of the records of volunteers already enrolled in existing CPCRA studies. In this way, it studied the largest cohort of women with HIV yet reported. It did find gender differences in opportunistic infections and conditions (for example, about a one-third higher risk of bacterial pneumonia in women, and a much-lower risk of Kaposi's sarcoma, which occurred in only two women). But these differences could not explain the overall survival and disease-progression results. The researchers also found that, "Among patients without a history of disease progression at entry, death was the first event reported for more women than men (27.5% vs. 12.2%)." The researchers could not offer a definitive reason for poorer survival of women, but suggested looking at differences in access to healthcare, and at effects of "lower socioeconomic status, homelessness, domestic violence, substance abuse, and lack of social support." The study was published in JAMA (JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION), December 28, 1994. Comment This important study raises questions it does not answer. Why do women have an overall increased risk of death, yet no increased risk of progression to AIDS? And why is death more often the first AIDS-defining event? These findings suggest problems with the 1987 definitions of AIDS-indicating events -- based almost entirely on the disease in men -- but that was not the conclusion of the study. One difficulty in interpreting the data is that the cause of death was often unknown. Another mystery is that women had a considerably higher T- helper count at entry -- a median of 240, vs. a median of 137 for the men. This difference was not explained in the published paper. We would have expected a difference in the opposite direction, since women often receive worse health care than men, due to economic reasons, and are often not diagnosed with HIV until a later stage of the illness. AIDS in women has increased more than 20 times since 1981; it is now one of the five leading causes of death among women aged 25 to 44 nationally, and the leading cause of death in that age group in New York City. ***** Some Vitamins Associated with Decreased Risk of AIDS and Death by John S. James In December 1993, researchers at Johns Hopkins University published results from a study (funded by the U.S. National Institutes of Health) of 280 volunteers, who were studied for an average followup of 6.8 years, which found that dietary intake of certain vitamins was associated with substantially reduced risk of progression to AIDS.(1) In the second half of 1994, they reported on the association of the same micronutrients with survival, in posters presented at the International Conference on AIDS (Yokohama, August 1994)(2) and at the annual meeting of the American Public Health Association (Washington, October-November 1994).(3) Both results are important because the differences are large; for certain micronutrients, persons who used appropriate amounts had as little as half the risk of progression to AIDS -- and half the risk of dying -- compared to others who used too little (or, in some cases, too much). These results must be interpreted with caution, for several reasons: (1) First, they are not from clinical trials which randomly assign people to take particular treatments or foods. Instead, they are from an observational study which asked people what they were eating and what supplements they were taking, then followed up to see how well they did during the following years. This kind of study can only show an association -- it cannot prove a cause and effect relationship -- between the nutrient and the result. In particular, the nutrients studied were in large part obtained from foods, which also contains many other substances which were not looked at in this research. Therefore, it is not certain that taking supplements of the individual nutrients alone would automatically provide the same advantage. (2) Also, the food questionnaire was given at the beginning of the study, in 1984, and that data was used throughout; if people changed their dietary habits or use of supplements over the years, the change was not considered. (Random changes in food intake or supplement use would tend to reduce the differences found in this study, however, not to increase them. Therefore, we do not think that such changes in food usage could be used to argue that the results of the study are not real.) Note: the food questionnaire was repeated on certain later visits, but the newer food data has not yet been analyzed (3) A third reason for caution is that people might misinterpret the results of the Johns Hopkins study and take megadoses of certain vitamins. Not only could this be dangerous, it is also unnecessary, since the improved outcomes seen in this study were associated with modest doses. Despite these cautions, the findings on micronutrients and AIDS progression urgently need more attention. We may not have fundamentally better information for many years, since conclusive proof might require clinical trials with survival or AIDS-progression endpoints, which would take years to run; it is possible that such trials will never be conducted, due to increasing uncertainty of government financial support, and lack of pharmaceutical interest in research which does not sell a product. Meanwhile, failure to consider safe, simple strategies which might reduce the risk of AIDS and of death by 40 to 50 percent or more would be tragic. The Johns Hopkins study is similar in some ways to a major San Francisco study of micronutrients and AIDS,(4) which was reported in 1993 (see summary in AIDS TREATMENT NEWS #181, August 20, 1993). This study also reported that higher intake of certain nutrients may delay the development of AIDS. The Zinc Controversy There is much disagreement and confusion among experts as to whether zinc supplements may be harmful or helpful for persons with HIV (or possibly harmful in some cases and helpful in others). The Johns Hopkins data suggests that even small amounts of zinc -- close to the U.S. Recommended Daily Allowance of 15 mg -- might be harmful. The researchers did not suggest a possible mechanism. But many other nutrition experts are skeptical. They cite other studies which found different results -- or which found widespread zinc deficiencies in people with HIV, deficiencies which might interfere with immune functioning. In this article on the Johns Hopkins results, we will report the findings for zinc along with the other findings, but leave our analysis for later. We may report about zinc in a separate article, based on interviews with experts. However, we suspect that clinical trials might be necessary for resolving this important issue and making an appropriate nutritional recommendation -- trials which may never be done. (One trial we would like to see, which could be run quickly and inexpensively, would be to see if viral load changes when people with HIV start using zinc supplements.) In any event, the confusion about zinc should not distract from the other study results. Background: The Study Methodology The Johns Hopkins data on micronutrients and AIDS progression came from about 280 patients who enrolled in a major, ongoing national study -- the Multicenter AIDS Cohort Study (MACS), funded by the National Institute of Allergy and Infectious Diseases (NIAID). This study enrolled about 5,000 gay men (both HIV positive and HIV negative) by early 1985, and conducts followup visits every six months for blood tests, physical examinations, and interviews. The 5,000 volunteers are in four cohorts, in Baltimore, Chicago, Los Angeles, and Pittsburgh. The Baltimore cohort has over 1,000 men, but only those who were HIV positive at their first (baseline) visit, and completed an extensive food questionnaire on their second visit, were included. (Also, anyone who had AIDS by their third visit -- a year after they entered the study -- was excluded. The reason for this is that the researchers wanted to learn how diet influenced the progression of early HIV disease. They did not want their results to be complicated by changes in diet that people may have made as a result of their illness.) Micronutrient data was obtained by asking the men what supplements (vitamin pills, etc.) they used, and also by a food questionnaire. The questionnaire listed 116 foods, and asked participants to rate how often they ate each (choosing one of nine categories from "Never, or less than once per month" to "6+ per day") on the average over the last year. Then special software developed for use with this questionnaire estimated the total amount of each nutrient in the diet, based on those answers. For each nutrient, data was analyzed by grouping the volunteers into four equal groups based on their total intake of that nutrient (both from foods and from supplements). Usually the top "quartile" (the 25 percent of the volunteers who used the most of the particular nutrient) was compared with the other three quartiles averaged together. But vitamin A/beta carotene was handled differently, because it has shown a U-shaped curve in other studies, with those taking moderate amounts doing better than those taking either too much or too little; for vitamin A, therefore, the two middle quartiles were compared with the two extreme ones. And zinc was also handled differently, with each quartile being compared to the lowest, in order to show the dose response. The differences in progression to AIDS, or in death, between high and low users of particular supplements was given as "relative hazard." For example, a relative hazard of 0.60 means that one group had only 60 percent of the risk of the other group of progressing to AIDS (or death) within the time frame of the study (6.8 years or more). All the results given below are statistically significant, unless otherwise stated. This means that it is unlikely that they would have occurred by chance alone. We report the results in two separate sections, one on the risk of AIDS prevention, the other on survival. Results: Risk of AIDS Progression The work on micronutrients and AIDS progression was reported in a 14-page paper published a year ago.(1) The last paragraph summarized the findings: "In summary, we have found that high intake of several nutrients (niacin, vitamin C, and vitamin B1) were associated with slower progression to AIDS, after adjustment for confounding variables. Vitamin A may have a U-shaped relation with risk of AIDS, and increasing zinc intake was associated with more rapid disease progression. These results need to be replicated before any firm conclusions can be drawn about their relevance to the natural history of HIV-1 infection." We discuss some of the numbers below. Note that the nutrient amounts given in this article are NOT recommendations, for many reasons. One is that these figures for nutrient intake include both food and supplements, not supplements alone. Also, there is no adjustment for body weight, or for individual medical conditions. And the situation with vitamin A is more complex, because the amounts are given in international units of vitamin A, while in fact, the relation found was between beta carotene intake and AIDS (beta carotene is converted to vitamin A in the body, and is safer to take than vitamin A itself); no relation was found between vitamin A intake and AIDS. Professional assistance will be required to develop recommendations for individuals, or to prepare general guidelines, based on this micronutrient study and other information. For vitamin C, the volunteers in the highest quartile had a relative hazard of 0.55 of progression to AIDS -- meaning that they were scarcely more than half as likely as those who used less vitamin C to progress during the study. Those in this upper quartile took 715 mg (0.715 grams) or more of vitamin C per day, in food and supplements combined. For vitamin B1, those in the highest quartile had a relative hazard of 0.60 of progression to AIDS, compared to those who took less. Those in this quartile took greater than 4.9 mg of vitamin B1 per day, in food and supplements combined. For niacin, those in the highest quartile had a relative hazard of 0.52. Those in this quartile took greater than 61 mg of niacin per day total (in their food and supplements combined). For vitamin A, those who did best were in the two middle quartiles, with total intake (mostly from beta carotene) from food and supplements combined being equivalent to between 9,062 IU (international units) and 20,268 IU. Their relative hazard of progression to AIDS was 0.55, compared to the those in the lower quartile (who consumed less than 9,062 IU per day). The upper quartile (who consumed a total of more than 20,268 IU) had a relative hazard of 0.94 (not statistically significant), compared to the lower quartile -- meaning that the risk of progression for these two groups was about equal. For zinc, those in the highest quartile (consuming more than 20.2 mg per day in food and supplements combined) had a relative hazard of 2.06 of progression to AIDS, compared to those in the lowest quartile (less than 11.7 mg per day). [This is a cause for concern in that the U.S. RDA is only 15 mg per day -- and many, probably most, of the multivitamin/mineral pills in common use contain the 15 mg RDA. Yet taking only 20.2 mg of zinc per day, from food and supplements combined, was found to be associated with double the risk of progression to AIDS, compared to those who used less zinc.] These particular numbers depended on how the statistics were analyzed. The numbers above were from the analysis which the researchers chose to use in their abstract. These numbers (a "single nutrient model") look at each nutrient alone, statistically adjusted for age, symptoms, T-helper count, lymphocyte count, energy intake, use of antiretrovirals, and use of pneumocystis prophylaxis. A different analysis -- which statistically adjusted with some of the nutrients together, not alone -- did not change the relative hazards much, except for zinc, where the relative hazard increased, from 2.06 to 2.97 for the highest quartile (those consuming over 20.2 mg per day). Two other nutrients barely missed being statistically significant for risk of AIDS progression. They are vitamin B2 (relative hazard 0.61, for those consuming more than 5.9 mg in food and supplements together, vs. those consuming less), vitamin B6 (relative hazard 0.60 for those consuming greater than 5.7 mg per day, vs. those consuming less then 2.0 mg). However, both of these were significant in the analysis of relative hazard of death, below. Results: Survival The full results on micronutrient intake and probability of survival have not yet been published. The most complete data made public so far was presented at a poster at the annual meeting of the American Public Health Association, October- November 1994 in Washington. D.C.(3) For beta carotene, the third quartile of intake was associated with increased survival (relative hazard of death, 0.58), and increasing amounts of zinc were associated with poorer survival. After the data was statistically adjusted for beta carotene and zinc (as well as for age, symptoms, T- helper count, lymphocyte count, energy intake, and treatment), the following were statistically significant: vitamin B1 (relative hazard 0.62), vitamin B2 (relative hazard 0.61), vitamin B6 (relative hazard 0.47), and niacin (relative hazard 0.59). The above relative hazards relate to total intake of the nutrient, from both foods and supplements. If one looks at supplements alone, the results are sometimes different. Those who took vitamin B6 in supplements at more than twice the RDA had improved survival (relative hazard of death, 0.63). Any intake of zinc supplements was associated with poorer survival (relative hazard, 1.52, meaning that those who took zinc supplements had a .52 greater chance of dying; the median amount of zinc supplement taken was 15 mg per day, which is the same amount as the RDA). Use of vitamins B1 and B2 at five times the RDA or more was associated with better survival, but this result was not statistically significant. Information on niacin from supplements alone is not available, because the software did not break out this number. And while total vitamin C may have been associated with increased survival, no relationship was found between vitamin C from supplements alone and survival. Comment This observational study cannot prove that the supplements are causing the changes in progression to AIDS and in survival. To get definitive proof will require clinical trials -- a different large trial for each nutrient -- which, as we pointed out before, will take a long time, if they are done at all. It might be possible to get some insights into what is happening by doing small, short, exploratory trials, which randomize patients to nutritional supplements and look at changes in viral load, T-cell subsets, tests of immune functioning, and other markers. If the results of these trials parallel the results of the observational study -- for example, if the optimal amount of vitamin A leads to improvement in the markers, while too much leads to worsening -- this would help to confirm the observational results, and open doors to further rapid testing of combinations of nutrients, and to the use of nutrients to enhance drug therapy. But no one knows in advance which markers, if any, would be appropriate, since we do not know the possible mechanisms of action of the various nutrients. Still, the fact remains that certain safe, inexpensive nutrients may be associated with a greater long-term reduced progression of HIV disease, and improved survival, than that of any known anti-HIV drug. The key question, of course, is whether there is cause and effect -- whether improving nutrient level will improve disease outcome. Or could it be that persons with HIV who tend to take certain levels of nutrients also tend to do better, for other reasons? Perhaps those who eat well and use reasonable levels of supplements also tend to have better access to health care, or take better care of their health in other ways. Or maybe those who are healthier anyway are more likely to eat well. If theories like these account for the associations found in the micronutrient study, then changing one's nutrient intakes to match those associated with favorable outcome might not be of any benefit. But it seems unlikely that these theories could explain the results observed. How would they explain why some nutrients were associated with improvement in the study, while zinc was consistently and unexpectedly associated with worse outcome? How would they explain the U-shaped curve of the response to vitamin A/ beta carotene (also seen in other studies), where a moderate amount seemed to be better than either too much or too little? We will be living with uncertainty about micronutrients and HIV disease for years to come. We need to make the best decisions possible now and at each future time, instead of waiting for perfect information. What we know now strongly suggests that rational strategies for improving micronutrient intake can improve disease outcome. And since the strategies suggested are generally quite safe, the cost of adopting them in error is far less than the cost of ignoring the strategies if, in fact, they do work. For too long the micronutrient work outlined in this article has received little attention, partly because people are afraid to make nutritional recommendations, due to the possibility that they might be wrong. What we need now is for medical and scientific experts to examine all the information available, and develop guidelines (by consensus when possible) for use by physicians and patients. For More Information on HIV and Nutrition IMMUNE POWER, A COMPREHENSIVE TREATMENT PROGRAM FOR HIV: COMBINING HOLISTIC AND STANDARD MEDICAL THERAPIES INTO THE OPTIMAL TREATMENT PROGRAM OR HIV, by Jon D. Kaiser, M.D. (Saint Martin's Press, New York, 1993) It costs $18.95 in bookstores. A new book which should be out this Spring is POSITIVELY WELL: LIVING WITH HIV AS A CHRONIC, MANAGEABLE, SURVIVABLE DISEASE, by Lark Lands (Irvington Publishers Inc., New York, 1995). Copies can be ordered by calling 800/542-8102, 9-5 Eastern time, to be shipped when the book is available. References 1. Tang AM, Graham NMH, Kirby AJ, McCall LD, Willett WC, and Saah, AJ. Dietary micronutrient intake and risk of progression to acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus type 1 (HIV-1)-infected homosexual men. AMERICAN JOURNAL OF EPIDEMIOLOGY December 1993; volume 138, number 11, pages 937-951. 2. Tang AM, Graham NMH, and Saah AJ. The effect of micronutrient intake on survival in HIV-1 Infection. Tenth International Conference on AIDS, Yokohama, August 7-12, 1994 [abstract PB0894]. 3. Tang AM, Graham NMH, and Saah AJ. The effect of micronutrient intake on survival time in HIV-infected gay and bisexual men. American Public Health Association 122nd Annual Meeting, Washington, DC, October 30 - November 3 [abstract book, page 2082]. 4. Abrams B, Duncan D, and Hertz-Picciotto I. A prospective study of dietary intake and acquired immune deficiency syndrome in HIV-seropositive homosexual men. JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES August 1993; volume 6, number 8, pages 949-958. ***** 1995: Politics by John S. James [Note: Each year AIDS TREATMENT NEWS publishes a list of treatments to watch during the coming year. Our list for 1995 was not ready for this issue; it will probably appear in issue #215.] As of this writing (January 6), it is too early to know what threats to AIDS research, care, and prevention will come from the new Republican-controlled Congress. A serious but little- noticed concern is that Congress will spend the next six months debating and passing tax cuts, without telling people what programs will be cut to pay for them. Then, starting around July, programs will suddenly and hastily be cut before the new fiscal year which begins in October. Military programs, social security, and Medicare -- which are the most expensive -- will be spared because they have powerful constituencies, resulting in huge cuts elsewhere (including Medicaid, which unlike Medicare is only for persons with financial difficulties). Exactly where the cuts occur will depend on the strength of political constituencies, not on the national interest. Under this scenario, the reauthorization of the Ryan White CARE Act -- a major priority of AIDS organizations -- could be relatively easy. But reauthorization is only one step in funding; money must also be appropriated later. We will need grassroots public support for both steps. On AIDS prevention, another concern is that funding from the U.S. Centers for Disease Control may be put into block grants to states; then states with conservative administrations may defund AIDS prevention because it is controversial. With block grants, state bureaucrats controlled by the governor and the legislature will make the decisions, eliminating the community involvement which has developed in Federal programs. AIDS should be bipartisan, and there is talk that Washington AIDS organizations over the years have worked mainly with a few Democrats, and not built working relationships with other Democrats, or with moderate Republicans, and their staffs. (The new Congress could be helpful in some ways, such as reducing the vast, legally-required inefficiencies in drug development, allowing small companies to participate effectively.) Both parties should remember a nationwide survey, published by the BOSTON GLOBE on June 17, 1990, page 1, which found that one American in five personally knew someone who had AIDS or was HIV positive; the survey questioned 1,000 adults chosen to be representative of the U.S. population. As far as we know, no similar survey has been done since, so we do not have more recent data. But the percentage is probably higher by now, because there are more cases, and also because there is more openness about AIDS, so the illness is less likely to be concealed. [Incidentally, the same poll which showed that mass organizing in AIDS is possible also showed why it is necessary --the huge "compassion gap" depending on how people were infected. About 88 percent strongly agreed that people who got AIDS from a blood transfusion should be treated with compassion. But the figure fell to about 43 percent for those who got AIDS through a homosexual act, about 42 percent if through IV drug use, and about 45 percent if through sex with a drug user.] Of these 50 million or more people who have a personal connection with the epidemic, a relative, friend, or acquaintance whose life is at risk, probably far fewer than one percent have ever contacted their representatives in Congress, or any other public officials, to let them know of their concern. Many members of Congress -- probably most -- never hear from their constituents that AIDS is important to them. Unless this changes, we are in serious trouble. A central reason for the silence is that AIDS organizations, with very few exceptions, have failed to ask the public (in ways that make sense to those not already heavily involved) to contact their representatives. Most AIDS "action alerts" have been written for AIDS professionals; they take many shared assumptions for granted, and do not explain the rationale of the issue to the general public. Many of the largest AIDS political organizations do not even offer individual memberships, or any other way for non-specialists to be involved. Also, most people will not phone or write public officials alone by themselves, just on the basis of a written document; they also want to hear about the issue from other people. AIDS organizations need to support grassroots groups throughout the country, which could meet frequently and make their concerns known to their representatives. Our representatives must hear from us no matter what their position -- even if they already seem to be committed enemies, or committed friends. They need to know their constituents care. And we will need to include political communication as a regular part of our everyday lives, not only at elections or when AIDS is in the headlines, but at all times. The "AIDS Coffee Klatch," described in the last issue of AIDS TREATMENT NEWS, is one model for small, local groups. We had to start independently, as national AIDS organizations are not doing this work. And we had to write our own action alerts, because most of the existing ones proved unusable. Small citizens' groups should not need to do this. The AIDS community is facing disaster if it does not do a better job of grassroots organizing. It must bring together the organizers who can do the work with those who can fund them. And it must support local groups with policy recommendations and action alerts which both activists and the public can fully endorse. And it must develop a "corporate culture" of day-in, day-out mass mobilization of support. ***** 1995: Business Biotechnology investors had a terrible year in 1994. This is bad for people with AIDS, because it makes it hard for companies to raise money to develop new treatments and test them. BioCentury, a weekly fax newsletter which reports on the business of biotechnology, found that only the largest companies, with market capitalization over $500 million, held their own in stock prices during 1994. The 190 smaller companies which BioCentury follows lost an average of 37 percent in shareholder value; the "infectious diseases and AIDS" group of companies lost 42 percent. This is on top of other losses in 1993. BioCentury's analysis showed that the actual performance of the industry was not bad in 1994; the success rate for new drugs was about what would be expected in the pharmaceutical industry. The problem, some experts suggested, may have been the great unpredictability of which drugs will work. Some were expected to do well, but instead failed in clinical trials. Comment In this business climate, advocates for people with AIDS, cancer, and other serious diseases should think carefully before pushing for price-control laws or other mechanisms to hold down the prices of newly-developed pharmaceuticals. The few drugs which do work must pay not only for their own research and development, but also for the many more research and development projects which fail. Otherwise, investors will keep losing money until they stop putting more money in to this high-risk area, and new treatments will not be produced. The impossibility of predicting which new drugs will actually work in people also reinforces the need for many small, screening trials, to see which potential treatments do seem to be working, and to learn more about them as a basis for further development. The danger, in both corporate and government research, is that too much of the available money and other resources will be diverted to a few large projects, because they have more political influence than small ones. [Note: For information about BioCentury, call 415/595-5333.] ***** AIDS-Related Research Meetings, January and February 1995 This incomplete list is in order by starting date. Note that most of these meetings are intended for research specialists (including AIDS treatment activists), or for other healthcare professionals. ** Retroviral Integrase: Molecular Biology and Pharmacology, A Novel Target for the Treatment of AIDS, January 19-20, Lister Hill Auditorium, National Institutes of Health. This meeting, "to bring together academic and industry groups," is sponsored by several institutes/offices at NIH. For a copy of the brochure, call Technical Resources, Inc., 301/770-0610. ** National Task Force on AIDS Drug Development, January 19, Holiday Inn, Bethesda, Maryland. The mission of the National Task Force "is to insure that all aspects of AIDS drug development are rapidly taking place in a creative, coordinated manner, free of unnecessary barriers." So far the group has not done much, but that could change. Note additional listing for the meeting starting February 23, below. The January 19 meeting will review the recommendations made to this point. ** CPCRA (Terry Beirn Community Programs for Clinical Research on AIDS) 16th group meeting, January 25-27, Hyatt Regency Washington, Washington, D.C. The first day is an orientation session for new groups; the regular meeting begins January 26. For more information, call Rii Conference Department, Silver Spring, Maryland, 301/565- 4020. ** FDA advisory committees meeting on Salk Immunogen, January 26. See separate article in this issue of AIDS TREATMENT NEWS, page 1. ** Third International Congress on Biological Response Modifiers, January 26-29, Cancun, Mexico. This meeting is organized by the Inter-American Society for Chemotherapy. For registration information, contact Meetings Manager, CME, Inc., Princeton Junction, New Jersey, 609/799- 2300, fax 609/275-8745. ** HIV Immune-Based Therapies Workshop, January 27-29, Stouffer Harborplace Hotel, Baltimore, Maryland. For information, call Clinical Immunology Society, Thorofare, New Jersey, 609/848-1000 ext. 213. ** The Second National Conference on Human Retroviruses and Related Infections, January 29 - February 2, 1995, Sheraton Washington Hotel, Washington, D.C. This meeting is especially important this year, since there will be no International Conference on AIDS in 1995. Unfortunately it is also expensive (on-site registration $425), and as far as we know there are no scholarships for people with AIDS or HIV. AIDS TREATMENT NEWS and many other AIDS publications will be there and will publish reports. Note: A satellite round-table meeting on protease inhibitors and drug resistance, organized too late to be on the program, is scheduled Feb. 2 at the conference hotel. The working title is, Protease: Resistance, Cross-Resistance, Implications for Monotherapy and Combination use, and Clinical Studies for 1995 and Beyond. Time and location will be announced on bulletin boards at the conference. The Human Retroviruses conference is sponsored by the American Society for Microbiology, in Washington, D.C. For information, call their meeting hotline at 202/942-9356 (24 hours voicemail). [Comment: A philosophical issue about the fight against AIDS in the current era is highlighted by the following, from the preliminary program of the Human Retroviruses conference: "It is hoped that this second conference, conducted in an atmosphere of scientific inquiry and collegiality, will catalyze free exchange of information and ideas and spawn new data and collaborative studies to hasten the understanding of these relatively new agents and their diseases." In other words, a meeting unchallenged by people with AIDS will spawn data and studies, it is hoped.] ** HIV 7th National AIDS Update Conference, January 31 - February 3, Moscone Convention Center, San Francisco. This is not primarily a research meeting, but a major continuing-education meeting for healthcare professionals. For more information, contact Krebs Convention Management Services, San Francisco, phone 415/255-1297, fax 415/255- 2244. ** Gene Therapy & Nucleic Acid Vaccine Strategies, February 16 and17, Hyatt Regency, Bethesda, Maryland. Expensive and highly technical meeting on DNA vaccines, etc. for cancer, AIDS, other viruses. For information, contact IBC USA Conferences Inc., Southborough, Massachusetts, phone 508/481-6400, fax 508/481-7911. ** ACTG (AIDS Clinical Trials Group) 19th meeting, February 18-22, Washington Renaissance Hotel, Washington, D.C. This technical meeting of researchers participating in the largest AIDS clinical-trials network happens twice per year. For more information, call Rii Conference Department, Silver Spring, Maryland, 301/565-4020. ** HIV Infection in Women: Setting a New Agenda, February 22- 24, Sheraton Washington Hotel, Washington, D.C. About 1500 experts are expected for this major conference, which will focus solely on adult and adolescent women with HIV. Sponsors include the U.S. National Institutes of Health, the Centers for Disease Control, the Food and Drug Administration, the Health Resources Services Administration, the Substance Abuse and Mental Health Services Administration, the Agency for Health Care Policy and Research, and the Public Health Service Office on Women's Health. For registration forms and additional information, contact the conference secretariat, phone 703/356-8376, fax 703/790- 7237. ** National Task Force on AIDS Drug Development, February 23- 24, Holiday Inn, Bethesda, Maryland. This meeting of the National Task Force will focus on protease inhibitors. Persons wishing to make a formal presentation should notify Jean H. McKay or Kimberley M. Miles, FDA Office of AIDS and Special Health Issues, 301/443- 0104, by February 9, "and submit a brief statement of the general nature of the evidence or arguments they wish to present, the names and addresses of proposed participants, and an indication of the approximate time required to make their comments." A transcript will be available approximately 15 working days after the meeting. ** Wasting Disorders: Molecular and Clinical Aspects, February 23-26, Bonaventure Resort and Spa, Fort Lauderdale, Florida. For information, contact Serono Symposia, USA, Norwell, Massachusetts, phone 800/283-8088 or 617/982-9000, fax 617/982-9481. ***** AIDS TREATMENT NEWS Published twice monthly Subscription and Editorial Office: P.O. Box 411256 San Francisco, CA 94141 800/TREAT-1-2 toll-free U.S. and Canada 415/255-0588 regular office number fax: 415/255-4659 Internet: aidsnews@igc.apc.org Editor and Publisher: John S. James Reader Services and Business: Richard Copeland Thom Fontaine Tadd Tobias Statement of Purpose: AIDS TREATMENT NEWS reports on experimental and standard treatments, especially those available now. We interview physicians, scientists, other health professionals, and persons with AIDS or HIV; we also collect information from meetings and conferences, medical journals, and computer databases. Long-term survivors have usually tried many different treatments, and found combinations which work for them. AIDS Treatment News does not recommend particular therapies, but seeks to increase the options available. Subscription Information: Call 800/TREAT-1-2 Businesses, Institutions, Professionals: $230/year. Nonprofit organizations: $115/year. Individuals: $100/year, or $60 for six months. Special discount for persons with financial difficulties: $45/year, or $24 for six months. If you cannot afford a subscription, please write or call. Outside North, Central, or South America, add air mail postage: $20/year, $10 for six months. Back issues available. Fax subscriptions, bulk rates, and multiple subscriptions are available; contact our office for details. Please send U.S. funds: personal check or bank draft, international postal money order, or travelers checks. VISA, Mastercard, and purchase orders also accepted. ISSN # 1052-4207 Copyright 1995 by John S. James. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used.