Subject: AIDS Treatment News #176 Date: Jun 04 1993 (935 lines) &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& J O H N J A M E S writes on A I D S &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& Copyright 1993 by John S. James; permission granted for non-commercial use. AIDS TREATMENT NEWS Issue #176, June 4, 1993 phone 800/TREAT-1-2, or 415/255-0588 CONTENTS: [items are separated by "*****" for this display] Curcumin Update: Could Food Spice Be Low-Cost Antiviral? The FDA and Buyers' Clubs Report on the recent letter by the FDA to AIDS buyers' clubs Interview with Randy Wykoff, M. D., Director of the FDA's Office of AIDS Coordination and signer of the letter Editorial Fusion Toxin, New Kind of Potential AIDS Treatment, in Early Clinical Trial Action Alert: San Francisco AIDS Care in Jeopardy ***** Curcumin Update: Could Food Spice Be Low-Cost Antiviral? by John S. James In March 1993, researchers at Harvard Medical School published results of laboratory tests of a new method of screening for potential AIDS drugs.(1) They used genetically engineered cells to test for inhibitors of the "LTR" (long terminal repeat) sequence in HIV; the LTR is important for viral activation. The new test found three inhibitors; one of them is curcumin, a chemical found in the food spice turmeric. Curcumin is the ingredient which gives curry its yellow color. It was effective against HIV in both acutely and chronically infected cells. On May 7, 1993, AIDS TREATMENT NEWS published a short review of the Harvard article. Since then, our readers have brought new information about curcumin to our attention: * In Trinidad, about 40 percent of the population is of Indian descent, and uses curry extensively in their diet. Another 40 percent of the population is of African descent, and seldom uses curry. Several years ago, studies of AIDS in Trinidad found that persons of African descent were more than 10 times as likely to have the disease as persons of Indian descent.(2) (We do not have recent data; however, a new report on AIDS epidemiology in Trinidad, by F. Cleghorn, W. Blattner, and others, is expected at the Berlin conference.) * One reader of AIDS TREATMENT NEWS started using a turmeric extract with a very high concentration of curcumin -- about 100 times the concentration in ordinary turmeric -- which he obtained from a San Francisco health-food store. He started using it on May 7, 1993. A week later his regularly scheduled blood tests showed a substantial drop in p24 antigen (a measure of viral activity). This unexpected change impressed his physician, a leading AIDS specialist in San Francisco. The product he used was supplied in capsules, each containing "300 mg. turmeric extract concentrated and standardized for a minimum of preferred 95% curcumin" in a base of whole turmeric, according to the label on the bottle. He took three capsules three times a day -- about 2.5 grams of curcumin per day, for a person who weighs about 100 kg. This dose was chosen arbitrarily; it is considerably greater than the amount of curcumin one would ordinarily get by eating curry, and we do not know whether or not it is safe. Even for this large dose the cost was low, about $2 per day retail in the U. S. We mention this single case because it may be the first time that anyone has taken curcumin as a potential treatment for HIV, and compared viral-activity measurements before and after starting. Pharmacology Curcumin is not soluble in water,(3) and animal tests have found very little of it in the bloodstream after it is eaten.(4) Therefore, it would seem that this chemical could not work as an oral drug. But other researchers have reported much higher absorption -- as much as 60 percent or more.(5,6) And in laboratory studies curcumin is often given to animals in the diet, and various effects are noted. This apparent contradiction is resolved by results of animal tests, some with radioactive curcumin. Much of the radioactivity does reach the blood and organs, even though the curcumin doesn't(4) -- meaning that the curcumin must have been changed into something else and absorbed in a different form. The same team had earlier reported that about 60 percent of the curcumin was absorbed, since only about 40 percent of the quantity administered was found remaining in the gut -- although only traces were found in the blood.(5) Another paper by the same group concluded that "curcumin undergoes transformation during absorption from the intestine," and noted an unidentified compound that it was changed into.(6) So the fact that chemists do not find curcumin in the blood when they look for it does not rule out the possibility that oral use could have biological effects. Curcumin is being studied as an anti-inflammatory,(7) as a possible cancer inhibitor,(8) and for other potential medical uses. It is a strong anti-oxidant. A recent search of the Excerpta Medica database found citations to 149 papers, abstracts, etc. which mention curcumin; the word "curcumin" appears in the title of 74 of these. A review of some possible medicinal uses of curcumin(9) was published in 1991. Turmeric is a mild spice. When curry is hot, that is due to other spices. A recent paper listed the curcumin content of turmeric powder as about 0.6 percent.(10) Safety Curcumin and turmeric have long been in daily human use, and are believed to have little toxicity in moderate doses.(1) However, one group found that large doses caused stomach ulcers in rats.(11) A thorough literature review is needed before large doses are used. What Does This Mean? The information above is only suggestive, and does not show that curcumin will have any use in treating AIDS. Most new drug or treatment ideas fail, after later information shows that they are not useful. For curcumin as for any new treatment, the odds are that it, too, will be one of the failures. But the possibility that curcumin or turmeric might be useful in treating HIV or AIDS is so important that it must be studied further without delay. Curcumin is known to be safe, at least in low and moderate doses, and could be available to everyone. Also, in the laboratory tests it was active against HIV not only in acutely infected but also in chronically infected cells -- where the currently approved drugs such as AZT are ineffective. The next step in research should be to give a high but safe dose to 10 to 20 people for several weeks, and measure changes in viral activity, either with the readily available p24 test, or with sophisticated research tests such as quantitative PCR, or the branched DNA assay. Both natural turmeric and concentrated curcumin should be tested. If there is a dramatic decrease in viral activity in people (like that seen in the single case so far), then this potential treatment will receive plenty of attention. If there is little or no decrease, then we can forget about curcumin (except as a possible lead compound for drug development) and move on. We do not know of anybody anywhere in the world doing such a study, or making plans to do so, or otherwise following up on curcumin as a possible AIDS treatment. This is not unusual; there has never been a serious institutional effort to test such treatment leads in early human trials. Medical research is expensive, and requires considerable effort and resources to make anything happen. Those with the resources -- mainly large pharmaceutical companies -- have little commercial or professional incentive to test low-cost, non- proprietary treatments. And government and non-profit research organizations have usually failed to focus on the critical need for getting safe, inexpensive treatment possibilities into small but credible tests for biological activity in humans. We hope this article will help bring this treatment possibility to wider attention, so that the appropriate research can be organized. References 1. Li CJ, Zhang LJ, Dezube BJ, Crumpacker CS, and Pardee AB. Three inhibitors of type 1 human immunodeficiency virus long terminal repeat-directed gene expression and virus replication. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, USA. March 1993; volume 90, pages 1839-1842. 2. Cleghorn F, Battoo K, Diaz C, Balbosa S, Jack N, Blattner W, and Bartholomew C. Update on the epidemiology of AIDS in Trinidad. International Conference on AIDS, San Francisco, June 20-23, 1990 [abstract #Th.C. 718]. 3. The Merck Index, 1989. 4. Ravindranath V. and Chandrasekhara N. Metabolism of curcumin -- studies with (sup 3H)curcumin. Toxicology (Ireland). 1982; volume 22, number 4, pages 337-344. 5. Ravindranath V, and Chandrasekhara N. Absorption and tissue distribution of curcumin in rats. TOXICOLOGY (Ireland). 1980; volume 16, number 3, pages 259-265. 6. Ravindranath V, and Chandrasekhara N. In vitro studies on the intestinal absorption of curcumin in rats. TOXICOLOGY (Ireland). 1981; volume 20, pages 251-257. 7. Satoskar RR, Shah SJ, and Shenoy SG. Evaluation of anti- inflammatory property of curcumin (diferuloyl methane) in patients with postoperative inflammation. INT. J. CLIN. PHARMACOL. THER. TOXICOL. 1986; volume 24, number 12, pages 651- 654. 8. Nagabhushan M and Bhide SV. Curcumin as an Inhibitor of Cancer. JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION. 1992; volume 11, number 2, pages 192-198. 9. Ammon HPT, and Wahl MA. Pharmacology of Curcuma longa. PLANTA MEDICA. February 1991; volume 57, pages 1-7. 10. Mukhopadhyay A, Basu N, Ghatak N, and Gujral PK. Anti- inflammatory and irritant activities of curcumin analogues in rats. AGENTS ACTIONS. October 1982; volume 12, number 4, pages 508- 515. 11. Gupta B, Kulshrestha VK, Srivastava RK, and Prasad DN. Mechanism of curcumin induced gastric ulcer in rats. INDIAN J. MED. RES. 1980; volume 71, number 5, pages 806-814. ***** The FDA and Buyers' Clubs by John S. James [Note: This article consists of three sections: a report on the recent letter by the FDA to AIDS buyers' clubs, an interview with Randy Wykoff, M. D., Director of the FDA's Office of AIDS Coordination and signer of the letter, and an editorial. The first two report on the FDA and its viewpoint; community reaction and our views are reserved for the editorial.] Report: Letter to Buyers' Clubs On May 25, the U. S. Food and Drug Administration wrote, in a two and a half page letter to its list of AIDS-related buyers' clubs, that "FDA has become increasingly concerned about certain potential threats to the health of people with AIDS and advanced HIV disease posed by the activities of some groups." The letter received immediate public attention, with coverage the next day in both The Washington Post and The New York Times. The letter focused mostly but not entirely on the FDA's personal-use import policy, which allows patients to import small quantities of medicines available abroad for their own use, under certain conditions. This policy is not AIDS specific, but applies to other diseases as well. The letter explains that the FDA is undertaking two courses of action: "First, the FDA will intensify its communications with various interested groups: physicians with expertise in treating HIV-infected patients; patient advocacy organizations with experience in therapeutic issues; and other federal, state and local bodies with broad HIV-related medical experience. FDA will initiate an intensive dialogue with these individuals and groups in an attempt to catalog those products that are reported to have the greatest medical promise for HIV-infected individuals and are not yet legally available in the United States. FDA will then explore appropriate mechanisms to help make these products more widely available as scientific data are gathered. We would like to begin this process in the very near future, and would appreciate your thoughts and suggestions in this matter. "Second, in this letter, FDA is reiterating and emphasizing the significance of several aspects of the personal use importation policy. " 1) According to the policy: 'The individual seeking to import the product affirms in writing that it is for the patient's own use (generally not more than a 3 month supply) and provides the name and address of the doctor licensed in the U. S. responsible for his or her treatment with the product or provides evidence that the product is for the continuation of a treatment begun in a foreign country.' "Documentary evidence should be available for immediate review onsite, demonstrating that any patient importing products for personal use has a licensed physician who is accepting responsibility for the patient's care, including the administration of the imported product. FDA does not believe that the best interests of any individual are served by having access to drugs for serious conditions without adequate physician oversight. " 2) According to the policy: 'There is no known commercialization or promotion to persons residing in the U. S. by those involved in the distribution of the product at issue.' "Commercialization or promotion may include meetings, mailings, media advertising, media discussions or similar activities regarding particular therapies. Promotion and commercialization are frequently characteristics of the kinds of deception and health fraud that expose people with life-threatening conditions to ineffective and dangerous products. Promotion and commercialization of unapproved new drugs are violations of the Federal Food, Drug and Cosmetic Act. " 3) According to the policy: 'The product is considered not to represent an unreasonable risk.' "This statement includes products manufactured by unknown sources or under unknown manufacturing conditions as well as products that carry inherent safety risks regardless of manufacturing concerns. These products' increased risk of contamination, variable potency and lack of quality assurance represent a substantial hazard for individuals with serious diseases, particularly those with suppression of their immune systems." ***** Buyers' Clubs and the FDA: Interview with Randy Wykoff, M. D. by John S. James Note: Randy Wykoff, M. D., is Director of the FDA's Office of AIDS Coordination, in charge of coordinating all of FDA's AIDS-related activities, including communicating with the public on AIDS issues. The following interview took place on May 5, as a continuation of our interview with David Feigal, M. D., Director of the Division of Antiviral Drug Products, which was published in our last issue. RW: As the Commissioner Kessler has said, the FDA is committed to identifying products that hold promise, and to make them available under an expanded access program. One thing the community needs to think about is what is the best mechanism to identify those potential treatments. There may be products that many people, including some physicians, believe have some merit. For those people who have no other options, we think that there are ways the FDA can participate in making those products available through legal means, and we'd like to do that. The challenge lies in finding the mechanisms to identify those products. We have also discussed some of our concerns about products through the underground -- including the medical information which is lost when products are taken without medical supervision, the potential risks to the people taking these drugs, and so on. We are sensitive to the fact that people with AIDS and other diseases want to have access to the most promising products. JJ: What are your concerns about the buyers' clubs? RW: As you know, we have been communicating regularly with the clubs over the past year and a half, and we have some increasing concerns, not just about the self-identified clubs, but about other groups that are purporting to act like buyers' clubs. From the FDA standpoint, we do not recognize a legal entity called a "buyers' club." So basically anybody doing almost anything can call themselves a buyers' club. The areas where we have most concerns generally fall into three categories. We are very concerned about the lack of physician involvement in the care of people getting products through alternative mechanisms. We don't believe that the best interest of any patient is served by having products without their physicians' involvement. So we certainly want to move in the direction of increasing physician involvement. Secondly, we are concerned about the growing promotion and commercialization of products. I'm referring not just to those groups the AIDS-affected communities might recognize as a buyers' club, but to anybody who purports to be acting as a club. Clearly promotion and commercialization provide a framework by which individuals can begin to conduct health scams and frauds, and other related activities. JJ: The community is leaning toward asking that a buyers' club be a legally registered non-profit organization, with a board composed of patients or people close to patients making the decisions in an open way, under the tax laws that require some public reporting and accountability. That wouldn't answer all of your concerns, but at least it would narrow the scope of potential conflict. RW: As we've said in the past, access to unapproved products is not a single thing, it's a broad spectrum. At one end you have the involvement of a physician and a knowledgeable patient, and a legitimate desire to the get the most promising product. At the other end of that same spectrum is the classic snake-oil salesman who is profiting on the desperation of the terminally ill. Our challenge is to make sure that we take those actions that are in the best interest of the public health. Promotion and commercialization are problems to us. Our third area of major concern is products from unknown sources. While this is particularly true of injectables, it is true of any product. When the personal-use import policy was put into place, as an exercise of the Agency's enforcement discretion, the sense was that this would be under limited circumstances and for people who would gain access to a legitimate product in another country that just wasn't available in the U. S. There are many risks to people with HIV from taking products from bathtub laboratories or unknown sources in other countries. Those are our three areas of major concern, all of which are related to protecting the public health, which is our main motivation in this. In the next month or so, we will be communicating with leaders of the AIDS-affected communities and the buyers' clubs and others, and expressing these general points to them. At the same time, we will ask them for input into ways in which promising products really can be identified, to be made available through legal means. This really needs to be a dialog process. We're all moving towards the same outcome together. If your readers have comments on what Dr. Feigal said [see AIDS TREATMENT NEWS #175], or what I said, they can contact me, and we can either respond directly or take them into consideration. [Note: If you have any comments or information concerning the subjects covered in this interview, you can send them to: Randy Wykoff, M. D., Office of AIDS Coordination, U. S. Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857. Dr. Wykoff can also be reached by fax at 301/443-4555, or by phone at 301/443-0104. AIDS TREATMENT NEWS would also appreciate hearing about these issues from our readers.] ***** Editorial In the short time between the FDA's letter and going to press for this issue, and with the ongoing preparations and people leaving for the IX International Conference on AIDS next week in Berlin, we could only begin talking with representatives of buyer's clubs and others about issues relevant to the FDA's letter. This editorial outlines some of the concerns we have heard, and some of our own. We are publishing this preliminary outline because it is important that persons who are interested in treatment access move quickly to decide what we want, explore areas of consensus, and explain any concerns about current policy directions of the FDA. (1) While no figures are available, everything we know suggests that the great majority of persons who obtain medicines from abroad with the help of AIDS buyers' clubs are using them in consultation with a physician. In fact, in the historical examples of ddC and probably of clarithromycin, both obtained through buyers' clubs before their U. S. approval, the common pattern, in San Francisco at least, was for patients to go to the buyers' clubs at the suggestion of their physician. Few patients make such decisions on their own without medical assistance, and the AIDS treatment community strongly discourages people from doing so. But for physicians, monitoring the use of an unapproved drug when no other therapy is satisfactory, or even suggesting its use to patients, is different from allowing themselves to be listed on an official form used to grant their patients access to drugs not approved in the U. S. The perceived problem is not with the FDA, and probably not with state medical authorities, but with malpractice insurance. Requiring the name on the form could put physicians in the difficult position of having to balance professional risks to themselves against the welfare of their patients. There is also a burden of paperwork, including (in practice) extra trips to pick up and deliver forms, which comes on top of the fact that the patients and physicians involved are trying to balance many things in their lives already. This turn toward greater enforcement of the documentation requirement (including the physician's name) does not seem to have resulted from any problem which actually occurred in the context of the AIDS buyers' clubs. It seems more likely that the real target is elsewhere -- especially offshore operations which make a business of selling unapproved drugs to Americans (usually not for AIDS). The FDA strongly opposes these businesses, which often cite the personal-import policy as legal grounds to protect what they are doing. The FDA has been accused of uneven enforcement of the law, giving special privileges to people with AIDS. In the continuing atmosphere of substantial public hostility against AIDS, such charges may carry weight in some circles, even though the FDA clearly knows the difference between a fast-buck operation on the borderline of the laws, and a nonprofit self-help group with no other purpose than providing access to rational and legitimate treatment options for persons with life-threatening diseases. The FDA has the enforcement discretion to make this distinction, and we suspect that were it not for the stigma around AIDS, it would not be embarrassed about using it. What happens in the future will depend on what the FDA intends. In the worst case, if they want to shut down much of the personal-use import policy, they have positioned themselves well to do so. For in the ongoing emergencies and stress of major illness, with hundreds of patients receiving drugs, there will certainly be cases where documentation is not in order. As a result, the FDA could successfully raise the issue at any time, presenting itself to the press and public as protecting patients from unscrupulous organizations which sold them unapproved drugs without their physicians' involvement. We do not believe that the FDA's intent is to make the import policy unworkable. But we do remember that back in the clarithromycin days, the ongoing battle was with bureaucrats who wanted to require a separate shipment from abroad for each patient, despite the fact that the drug was often needed urgently. The recent letter lays the groundwork for similar problems in the future, by expressing a policy which, if fully enforced, is likely to be unworkable for the reasons cited above. This is why the community is concerned. (2) The "drugs from unknown sources" warning is also a cause for concern, in that most new treatments are likely to start that way. This issue was set to arise next with the "tat drug," the only tat inhibitor in human trials, which has been developed slowly by Hoffmann-La Roche. As of this writing, the word in the community is that the Roche tat drug is not working well. If the current rumors are confirmed, there will be little or no market for the drug, so it will not be a potential source of dispute between the FDA and the AIDS community. But the issue will likely arise with other drugs. (3) The area addressed by the FDA's letter where there is least concern in the AIDS community is commercialization or promotion. There is a sense that if something is truly important, people will learn about it without being prompted -- and that it is wrong to create markets for unapproved products for serious illnesses. People want the freedom of access after they have made their own decisions; they don't want exploitation of the desperate, nor additional confusion introduced by commercial campaigns. (4) The basic thrust of the FDA's approach is to substitute legally recognized means of access to potentially useful unapproved treatments -- such as the expanded access programs for drugs in development -- for the AIDS treatment underground that has now existed for several years. No one disputes that the recognized means are better, in that anyone would choose to use a drug manufactured to FDA-approved standards of quality control over a version of the drug that was not. But at the same time, we cannot find anybody who believes that the currently available means of making experimental treatments available will always meet the need. Because of fundamental problems in the U. S. medical and drug- development systems, there will always be legitimate, significant cases where a necessary treatment is not available through any of the legally recognized means, but is obtainable otherwise. And when these cases do arise, it is the community's consensus that patients working with their physicians should be able to make rational medical decisions and then obtain the treatments they choose. Any organization has two kinds of motivations which guide its policies and actions. One relates to its stated fundamental mission -- in the FDA's case, protecting the public health. The other relates to institutional self-interest and sometimes to unstated missions. These can include: maintaining the appearance of consistency; protecting itself against criticism; positioning itself for favorable publicity; maintaining the medical monopoly of large, well-financed interests, which has done so much to limit the options for practical treatment development and to increase the cost of care; and preventing the development of institutions fundamentally at variance with the existing system (such as offshore businesses to supply unapproved drugs). We do not know the relative strengths of these two basic motivations in this case -- and the FDA itself may not know, either. But both must exist, even though only the former is publicly reported in the FDA's statements above. The reason motivation is important is that, to the extent that public health is primary, the FDA can work together with everyone else involved to increase access to important treatments through legally recognized means, thus automatically shrinking the role of the treatment underground without denying access to patients. But to the extent that the FDA basically wants to get rid of alternative means of treatment access, and develops public-health rationales as justifications or other tools toward that end, there will be conflict, because the interests of the regulators will diverge from those of the patients ostensibly being protected. The ultimate danger of fighting over access to unapproved treatments is that it would distract from the real issue -- improving the drug-development system and working together to find treatments that do work and are approved, which would end the debate over unapproved treatments. But meanwhile we also face an immediate danger. If the communities interested in treatments for AIDS and other diseases are not assertive enough in negotiating to protect their interests, policy directions may be set in a vacuum, in the absence of real examples. Then when important but unrecognized drugs or research opportunities do come into view, the regulatory system will be an obstacle rather than an ally. We must plan for the unexpected, since that is where so many of the most important advances occur. We need expanded access to known promising drugs, and will work with the FDA on this. But we also need regulatory flexibility -- the slack or breathing room that allows people to make the dysfunctional drug- development and access systems work. We have had flexibility in the past; the current unease reflects a fear that there could be less of it in the future. ***** Fusion Toxin, New Kind of Potential AIDS Treatment, in Early Clinical Trial by John S. James A new kind of potential HIV treatment is beginning clinical trials in Boston and Baltimore; the first HIV patient was treated in May 1993. For scientific and safety reasons, this early trial is limited to patients who have T-helper counts between 300 and 600, have not had an opportunistic infection, are not taking antiretrovirals, and also have a positive p24 antigen test -- at least 45 on the new "ICD" ("immune- complex dissociated," also called "acid dissociated") p24 test. But if the treatment is found to work, it would likely be useful for other patients as well. Fusion toxins, developed by Seragen, Inc., a company in which Boston University is a major shareholder, have been tested in people for several other diseases. Promising early results from human trials for rheumatoid arthritis, and for certain lymphomas, were reported in Medical World News, September 1991. The treatment may also be useful for some other cancers, and for additional autoimmune diseases, including insulin-dependent diabetes. A fusion toxin is a single molecule, produced by genetic engineering, with one end designed to selectively attach to certain kinds of cells; the other end is a toxin (poison) to kill those cells. The drug treats autoimmune diseases by targeting and selectively killing activated immune-system cells (including those which are part of the immune system's reaction against tissues of the body itself). For treating cancers, the drug is designed to target cells which have high levels of certain receptors on their surface, as some kinds of cancer cells do. For HIV, the fusion toxin used is designed to target activated immune-system cells, those expressing what are known as high- affinity IL-2 receptors; HIV infection causes the cells to express these receptors. In laboratory tests, the drug does selectively kill HIV-infected cells. The current trial with HIV is the first time a fusion toxin has been tried for treating an infectious disease. There is a risk that the drug might kill not only HIV-infected cells, but also activated cells which are part of the body's response to infection, thereby reducing the immune response to HIV itself, or to opportunistic infections. No one knows if this problem in theory will occur in practice; but anyone volunteering for the trial should understand the possibility. To reduce the risk, this trial is being limited to persons at an early stage of HIV infection (with high T-helper counts); and the drug will only be given for five days at a time, with a two-week rest in between, with blood work carefully monitored so that problems can be detected if they occur, and the trial stopped if necessary. It has been hard to recruit volunteers for this trial for several reasons. First, people must have high T-helper counts, and also have a positive p24 antigen test (showing viral activity), a somewhat unlikely combination. (The p24 test is required so that there will be something to measure to show whether the drug is working or not.) Second, persons at an early stage of HIV disease have other treatment options, such as AZT. Third, the trial sites are geographically limited. And fourth, the literature explaining this trial to physicians and potential volunteers did not include practical information such as how long the study will last, how many visits are required, whether any travel expenses can be paid, what test results the volunteers will receive, the fact that no placebo will be used, and whether it will be possible to continue receiving the drug after the trial, if the drug appears to be successful. This trial is important, because if the fusion toxin works, it could provide a new kind of HIV treatment, opening doors to different therapeutic approaches. New treatment options are certainly needed. Whether or not the trial benefits the patients who enroll, it will benefit the AIDS community by providing information which might save many lives, if it turns out that the treatment works. Study Details The first three visits are for screening, baseline, and entry. If volunteers are on antiretrovirals, they will need to go off for a four- week washout period before beginning the study. Volunteers are randomized to one of three doses of the study drug (which is named DAB389IL-2). They will receive five daily intravenous infusions, and then be off the drug for the next two weeks. They will receive a second and third five-day course of infusions, again with a two-week gap between them. After the third course, and a followup period of just over two weeks, the study is over. It lasts for ten weeks overall (not counting the four-week washout required for those currently on antiretrovirals before they enter). Tests for T-helper count, p24 antigen, and viral cultures are checked before and after each course of treatment. Because the study is blinded, most lab results will not be given to volunteers until the end of the study. This fusion toxin trial for HIV is only being conducted at the three sites below. For more information, physicians or patients interested in enrollment in the trial can call the contact person at one of these sites: * Mary Anne Lee, R. N., Beth Israel Hospital, Boston, 617/735- 5098. * Beverly Byam, R. N., Boston City Hospital, 617/534-5404. * Denise Jones or Donna Brown, Johns Hopkins Hospital, 410/955- 3422. ***** Action Alert: San Francisco AIDS Care in Jeopardy by Dave Gilden San Francisco's budget crisis has reached a point at which the public health department's model AIDS care program is seriously threatened. City officials at the mayor's office have insisted all along that preserving AIDS services was a high priority. But even maintaining AIDS services at their current level would be insufficient given the increasing numbers of people living with AIDS. Needed services also are becoming more complex as the population affected by the epidemic becomes poorer and less educated. City officials do not seem to understand the extent to which AIDS care is integrated with health care service as a whole. The city's Public Health Department has been struggling all year to cope with first $32 million and then $57 million in lost appropriations from the city's general fund. Last week the department was suddenly asked to provide a plan within 24 hours to make up for a further $32 million reduction in general fund donation. As usual, the demand, from the city's chief administrative officer, included a stipulation that AIDS services were to be protected. Even before this latest reduction, AIDS services were being nibbled away. Two weeks ago, the staff of the well-regarded AIDS clinic at the county hospital (San Francisco General) were chagrined to learn that they would lose at least one part-time doctor or full-time nurse practitioner. In considering the cut, the head of the hospital's Department of Medicine, Merle Sande, M. D., argued, "Hospital outpatient clinics have to reduce their capacity by 80,000 visits a year. There are attempts to preserve AIDS, but I can't possibly do that. Everything comes out of the same pot. I have to cut across the board." With the latest budget reduction, the already overcrowded AIDS clinic is targeted for a loss of $500,000. This reduction will mean the loss of three full-time doctors, a principal clerk, a phlebotomist, a pharmacist's assistant, a nurse's aide, and a clinic administrator. The crowded nature of the AIDS clinic has meant that not all AIDS outpatients are seen there. Many go to the hospital's family medicine department, for example. Others go to neighborhood health centers for early HIV care. And all patients go to specialty clinics for conditions requiring their particular expertise. Most of these facilities already require four to eight week waits for appointments. In the most recent scenario, San Francisco General's primary and specialty clinics would be cut by a third of their capacity, and four of the eight district health centers would close. Two of the remaining district health centers are in neighborhoods hard-hit by the AIDS epidemic. Their survival is being purchased by taking $1.2 million away from such AIDS services as home mental health counseling; home health, attendant and hospice services, food bank aid, hospital peer counseling, psychosocial and advocacy services; and media relations and prevention efforts. Then there are all the programs that help people with AIDS or HIV even though city hall does not take them into consideration when claiming to "maintain AIDS services." Consider, for example, the proposed elimination of the methadone detoxification program to help people off heroin. That program serves about 275 HIV-positive San Franciscans per year. Laguna Honda Hospital, the city's chronic care facility, is slated to lose 300 beds. This will mean that some patients at San Francisco General's in-patient AIDS ward will not be discharged as soon as they could be, and a stay at the AIDS ward costs $1500 per day. Lastly, the range of mental health and addiction treatment services administered by the department will lose $27 million in city funds and concentrate mainly on crisis resolution. This will deprive many people with HIV, or at risk for HIV, of the personal resources they need to protect themselves. Behind the city crisis is the looming state deficit of $10 billion. The state budget gap results from failure to plan for the economic realities of the post-Cold War era, especially the shrinkage of California's defense industry. To help bridge the gap, Governor Wilson wants to eliminate local aid paid for by the state sales tax, causing city governments across California to search for ways to downsize their operations. Dramatic trimming of state expenditures also is expected, although last month's vote in a state Senate committee to kill all state AIDS programs was quickly rescinded. It is now expected that funding for AIDS will remain the same next year. Flat-funding has been the case for the last five years; it really amounts to a 30 percent cut because of inflation and the 60 percent growth in the number of people with AIDS. The AIDS Drug Assistance Program, which helps people of moderate income, has had a chronic insufficiency of funds. For this reason, the program rejected a recommendation by its physicians' advisory board that it add ddC, foscarnet and acyclovir to the list of reimbursable drugs. Other parts of Governor Wilson's proposed budget also would affect the AIDS community. At present, about 40 percent of Californians with AIDS receive some of their treatment through Medi-Cal, the state's version of Medicaid. Wilson wants to eliminate several eligibility categories for the medically needy. He also is asking to reduce a number of optional Medi-Cal benefits, including adult dental services, optometry and audiology, and many medical devices. In another area of the budget, those receiving Social Security disability payments would receive no cost of living adjustment this year because the state would reduce its supplemental grants to the program. The uproar over health funding is peaking just as the US Department of Commerce is releasing figures indicating that the San Francisco metropolitan area has the highest per capita income in the country ($30,550). Activist Tab Buckner noted, "The money is there. In a practical way, business and governments have to be more in partnership. When businesses give back to the community, they see a return in terms of improvements in the quality of the social environment." The sentiment is growing that business and the well- to-do should bear their "fair share" of California's financial problems. Buckner is a member of San Francisco's Coalition for Public Health Services, a broad coalition of AIDS, women's and other grassroots groups, political clubs, and unions that has come together to preserve health programs. The Coalition is planning a number of actions to call public attention to the effects of cutting the health budget. Further information on the Coalition's activities can be obtained from Jerry Windley at 415/788-4999 between 9 and 2 on weekdays. ***** 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. &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& End of display