Subject: AIDS Treatment News #113 Date: Oct 19 1990 (921 lines) &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& J O H N J A M E S writes on A I D S &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& copyright 1990 by John S. James; permission granted for non-commercial use. AIDS TREATMENT NEWS Issue #113, October 19, 1990 phone 415/861-2432 CONTENTS: [items are separated by "*****" for this display] Azithromycin, Clarithromycin: Broad Potential Receiving Serious Attention AZT: 300 mg Dose May Be Equally Effective ddC: Expanded Access Eligibility Criteria Primaquine Supply Problem: How to Get the Drug Immune-Based Therapies Meeting, Chicago, November 8 BETA: Food Precautions, Oral Problems of HIV Good Intentions: New Book Attacks Conflict of Interest in Medical Research ***** AZITHROMYCIN, CLARITHROMYCIN: BROAD POTENTIAL RECEIVING SERIOUS ATTENTION by Denny Smith For some time, laboratory studies of two relatively new drugs related to the antibiotic erythromycin suggest they might be very useful for treating a number of major and minor infections, including toxoplasmosis, MAI (also known as MAC), and cryptosporidiosis. A few reports of clinical experience which seem to support the animal or test tube results have come to us recently, and there are calls for wider access to both drugs. They are azithromycin and clarithromycin, and the tantalizing potential to treat three opportunistic infections would logically give them the highest priority in AIDS research. Until now that has not been the case, and the plodding momentum of human trials of the drugs threatened to squander their value for thousands of people. Following is the clearest picture we could assemble of their current status, based on conversations with the commercial developers of the drugs, with members of the community, and with the Treatment and Data Committee of ACT UP/New York, which has posed a number of well-formulated questions to the manufacturers regarding the pace and efficiency of their investigations. These two agents appear to be the strongest candidates for treating AIDS-related infections yet to emerge from a growing class of compounds called macrolide antibiotics. Other macrolides under study in AIDS research are roxithromycin and spiramycin. An article in AIDS TREATMENT NEWS #75, March 10, 1989, reported with optimism the potential of azithromycin and roxithromycin to treat toxoplasmosis and cryptosporidiosis. But the following June 16, 1989, issue #81 reported the failure of roxithromycin to treat advanced toxoplasmosis in humans. Spiramycin has been tested as a treatment for cryptosporidiosis, with mixed results; an oral formulation was not useful, but intravenously the drug has helped some people. Spiramycin has also been tried to prevent transmission of Toxoplasma from mothers to fetuses.1 None of these drugs was listed by study title in the abstracts published for the Sixth International Conference on AIDS last June, although we heard them discussed in some contexts with other treatments or infections. They will be discussed in various studies to be presented this month at the 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, October 21-24 in Atlanta. Some of the abstracts from these studies and a few other previously published reports are referenced at the end of this article. We contacted the manufacturers of azithromycin and clarithromycin to ask about their plans for clinical trials and any other avenues of access until their products are proven and licensed. Both drugs are well into phase III trials in the U. S. ; both manufacturers have already applied for the NDA (New Drug Application, meaning permission to market the drug for prescription use). But the companies are pursuing Food and Drug Administration (FDA) approval for label indications not specifically related to treating AIDS. A newly approved drug, however, would be available to physicians treating AIDS infections, because an M. D. can administer a licensed treatment at his or her discretion for any diagnosis, whether named or not in the product labeling. In recent years, however, some health insurance carriers have been refusing to pay for many "off- label" uses of drugs, no matter how convincing the situation. So in spite of a physician's judgment, the exact labeling may ultimately determine who will or will not get the drug. Both drugs also have Investigational New Drug (IND) status, for use in trials against MAI and toxoplasmosis. Azithromycin has been studied in European trials, and is in Phase III trials in the U. S. to treat chlamydia, gonorrhea, and certain other infections not strictly associated with AIDS. It is marketed in Yugoslavia and Czechoslovakia under the brand name Sumamed, manufactured by Pliva. The pharmaceutical firm of Pfizer, Inc., holds the rights to develop azithromycin elsewhere, using the trade name Zithromax. In the U. S., the FDA is due to consider the NDA for azithromycin early next year. An advantage of macrolides is their fat solubility, which increases concentrations of the drugs in body tissues. Azithromycin in particular surpasses the other macrolides in its "targeted delivery." Of great therapeutic value in some infections, this describes the capacity to penetrate the walls of some immune cells and remain inside for several hours; as the cells naturally migrate to sites of infections, so does their passenger, spilling out in the attack and enhancing the cell's fight against the infection.2,3 Azithromycin is considered the prototype for developing a macrolide subclass called azalides. Our recent report on MAI therapies in issue #109, August 17, 1990, referred to a San Francisco pilot study of azithromycin for treating MAI infections. Lowell Young, M. D., is the principal investigator of the study, conducted at Pacific Presbyterian Hospital in San Francisco; he has authored some of the past reports of in vitro macrolide studies.4 He told us that the drug has been well tolerated in patients so far. This small, open- label study is still open to recruits because the entry criteria are strict. Interested persons can call 415/923-3262. Pfizer researcher Scott J. Hopkins, M. D., explained to us the current status of other azithromycin studies for AIDS opportunistic infections. Pilot efforts to try azithromycin for cryptosporidiosis are being developed in the U. S. and the U. K., and for toxoplasmosis in France. The most welcome event now is the release of azithromycin through a compassionate use protocol for treating toxoplasmic brain infections in people who have failed the standard therapies, or are known to have a history of intolerance to those drugs. The protocol involves 600 mg of azithromycin daily for one month, then decreased to 600 mg weekly. The physician requesting azithromycin must obtain at least verbal approval from an Institutional Review Board (IRB) for initial doses of the drug, and written approval for continuing access. Case report forms must be returned to Pfizer, so useful information can be compiled through this experience. Effective October 21, physicians can call Michael DeBruin, M. D., at 203/441-5701, or FAX 203/441-5702, to seek enrollment in this protocol for their patients. Clarithromycin is a product of Abbott Laboratories, and has been approved for use in Ireland and Italy, under the trade names Klacid and Claricid. Abbott has submitted an NDA to the FDA for clarithromycin as a treatment for some skin and respiratory infections. Based on results of past studies, Abbott has plans to test clarithromycin in the treatment of toxoplasmosis and MAI, as well as for prophylaxis to suppress latent infections of the same.5,6,7 These plans are apparently less developed than are Pfizer's for azithromycin, described above. A recent trial with 14 patients found a 99.98 percent reduction in MAI blood levels after six weeks' treatment with clarithromycin, compared to an increase in levels in patients receiving a placebo5; a second phase of the trial found a 99.65 percent decrease with the drug. At the dosage used, toxicities required discontinuation of the drug by three patients.. We have heard anecdotal reports of several people who found some improvement in MAI symtptoms after trying a combination of clarithromycin and clofazimine, one of the standard MAI drugs. Azithromycin Anecdotal Experience In response to articles in recent issues of AIDS TREATMENT NEWS which raised the question of azithromycin's untapped potential, two readers called us to share first-hand experience with this drug. The first report was offered by someone who began experiencing neurologic symptoms several months ago, and was diagnosed with toxoplasmic encephalitis after a computerized tomography (CT) scan revealed a brain lesion. These scans are not reliable for distinguishing lesions caused by Toxoplasma from those of cerebral lymphoma, and in fact this person had been diagnosed with lymphoma once before. His response to lymphoma treatment was complete, and the new lesion was not judged to be lymphoma by his physician or the consulting neurologist. So they initiated the standard treatment for toxoplasmosis -- pyrimethamine with leucovorin and a sulfonamide. When our friend developed a serious rash, the sulfa component was replaced by clindamycin, a frequent "next" choice. Unfortunately, this was followed by severe diarrhea, one of the side effects associated with clindamycin, and the treatment was discontinued. By the time our friend could no longer tolerate either combination therapy, he had received about one month of treatment. Pyrimethamine alone is not considered adequate against active toxoplasmosis, and another CT scan showed the lesion persisting, although reduced in size by the treatments. Our friend's doctor then offered to treat the infection with azithromycin. Upon signing an informed consent for using an investigational drug, our friend was given a loading dose of oral capsules totalling one gram of azithromycin, and then a maintenance dosage of 500 mg daily. After one week of treatment, a new CT scan showed no evidence of the lesion; another scan was performed at a different institution and verified the response. We considered the question of whether the entire effort was applied to an incorrect diagnosis. But if the lesion had been lymphoma, it would not have been affected by any of the drugs tried, and symptoms would have lingered or worsened. There is also the dilemma of understanding anecdotal successes -- how to know which drugs in a multiple-drug regimen obtained the response. In this case, was azithromycin effective enough to replace the established treatment, or did it only play a complementary role after those drugs brought the infection under control? It is very improbable that the lesion would regress independently after the drug combinations were stopped, given the usual course of AIDS-related toxoplasmosis. Both our friend and his physician are convinced that azithromycin controlled the infection. They saw no obvious toxicities, and in line with the established treatment regimen, a suppressive maintenance dose will be continued indefinitely. The other report came from Larry Bruni, M. D., who treats HIV in his Washington, D. C., practice, and who has advocated for investigations of both drugs for some time. He decided to offer azithromycin to two of his patients whose bloodwork revealed past exposure to Toxoplasma, and in whom high titers pointed to an increased risk for a reactivated infection. The titers were decreased in both patients on the drug, and Dr. Bruni feels it has been effective so far in preventing active toxoplasmosis. He also tried azithromycin with three patients diagnosed with cryptosporidiosis. One of the patients said that he doubted the drug was helping, and he was lost to follow-up early in the experiment. The other two reported good responses to the drug, and they continue to use it. Comment Regarding Access Unfortunately, the differences in healthcare systems and drug licensing among various countries have led to uneven access to many important drugs. In our reports of investigational treatments, we try not to take for granted the approval status of experimental drugs in countries outside the U. S., or the economic limits imposed on countless people who need AIDS treatments urgently. Where drugs are not licensed, or affordable, clinical trials may provide access to a treatment for some people. If participation in a trial is not feasible, physicians can sometimes secure an experimental drug by petitioning the manufacturer on behalf of patients in need, especially those who have failed standard treatments, or who have no other options. We have not heard of any access to azithromycin outside of Yugoslavia, Czechoslovakia, or release by Pfizer. Dr. Bruni speculated that since they are quite close in structure, clarithromycin might be used to treat infections which are reported to have responded to azithromycin. Clarithromycin is available in the U. S. through the PWA Health Group in New York City; the drug is expensive, and two to four weeks are required to obtain it from abroad. Requests must include a doctor's prescription; interested people can call 212/532-0280 to ask for a mail-order form. Clarithromycin may be available immediately from a new buyers club in Los Angeles, called LABC/Staying Alive; their number is 213/748-1295. Both of these groups are non-profit organizations, run by people well known in the community. One aspect of the clarithromycin research plans challenged by ACT UP/New York's Treatment and Data Committee is the decision of Abbott Laboratories to test clarithromycin alone against MAI, since clinical experience with treating mycobacterial infections generally has concluded that a multiple drug approach is necessary. Proprietary interests could explain the single-agent focus, and yet if an effective drug fails to win results because of an ineffective application, no one's interests will be served. Trials implementing different approaches could be conducted at the same time, and should be soon, given the critical passage of time for people now ill. On the other hand, high marks were given to Abbott's plans to design a trial of clarithromycin as a possible prophylaxis against several infections at once. The compassionate release of azithromycin for toxoplasmosis is a welcome gesture from Pfizer. Both Abbott and Pfizer have in their possession substances which at the moment may be the best, or only, options for treating many people. Whether these drugs are approved for lesser infections or continue on to larger studies, the only appropriate pace is one of urgency. References 1. McCabe RE and Oster S. Current recommendations and future prospects in the treatment of toxoplasmosis. Drugs, volume 38, number 6, pages 973-987, December 1989. 2. Girard AE, Cimochowski CR, and Faiella JA. Correlation of increased azithromycin levels with phagocyte infiltration into sites of infection [abstract 762]. 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, October 21-24, 1990, Atlanta. 3. Wildfeur A, Laufen H, Muller-Wening D, and Haferkamp O. Interaction of azithromycin and human phagocytic cells. Uptake of the antibiotic and the effect on the survival of ingested bacteria in phagocytes. Arzneimittelfurschung, volume 39, number 7, pages 755-758, July 1989. 4. Bermudez LE, Young LS. Activities of amikacin, roxithromycin, and azithromycin alone or in combination with tumor necrosis factor against Mycobacterium avium complex. Antimicrobial Agents and Chemotherapy, volume 32, number 8, pages 1149-1153, August, 1988. 5. Dautzenberg B, Legris S, Truffot C, and others. Clarithromycin clears Mycobacterium Avium Intracellulare (MAIC) from blood of AIDS patients. A randomized trial [abstract 1264]. 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, October 21-24, 1990, Atlanta. 6. Prokocimer P, Dellerson M, Craft C, Pernet A, Ruff B, and Grosset J. Effect of clarithromycin on blood cultures positive for Mycobacterium Avium Complex in HIV+ patients [abstract 634]. 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, October 21-24, 1990, Atlanta. 7. Pichotta P, Gupta S, Prokocimer P, and Pernet A. The overall safety of oral clarithromycin in comparative clinical studies [abstract 1332]. 30th Interscience Conference on Antimicrobial Agents and Chemotherapy, October 21-24, 1990, Atlanta. ***** AZT: 300 MG DOSE MAY BE EQUALLY EFFECTIVE by John S. James A study published October 11, 1990, in The New England Journal of Medicine compared three different doses of AZT (also called zidovudine, or Retrovir) and found all three equally effective, according to several different measures.1 The doses were 300, 600, or 1500 mg per day; as expected, the low doses had less toxicity. This phase II, unblinded, "pilot" study enrolled a total of 67 volunteers, all of whom had symptomatic HIV infection, but not AIDS. All had T-helper counts of 200 to 500, and were either p24 positive or had plasma viremia, when they began the trial. (For the viremia measure, this study used a quantitative test for the amount of virus present, not the older viral cultures which were only positive or negative but did not indicate an amount.) Those randomly assigned to the 300-mg dose had the greatest T-helper improvement, from an average of 321 to 412 during the first 12 weeks of treatment. Several other measurements -- the proportion who became p24 negative, the decrease in p24 levels in the others, and the reduction in plasma viremia -- were the same in all dosage groups. Clinical improvement, measured by weight gain, Karnofsky performance scores, and reduced fatigue, was better in the low and medium doses (300 and 600 mg) than in the 1500-mg dose. After the 12th week, patients continued in a second phase of the trial for a median of 28 additional weeks. None of the 22 who were p24 positive at the 12th week became p24 negative later -- suggesting the limited effectiveness of AZT. In fact, the p24 levels increased 14 percent during this second phase (the median of 28 weeks after the 12th week of treatment). This increase was comparable in all three dosage groups. As an additional test to see whether the different doses worked equally well, some patients were crossed over from 300 or 600 mg to 1500, or from 1500 to 300. This change in the dose of AZT had no effect on p24 levels. This study also tested acyclovir (Zovirax) in combination with AZT, by randomly assigning some of the patients in each of the AZT dosage groups to 4.8 grams of acyclovir per day. There was no evidence that the combination had any more antiretroviral effect than AZT alone. But the authors pointed out that their study could not rule out the possibility that acyclovir might increase survival, as one study2 suggested. Only additional trials could determine if suppressing certain herpes viruses with acyclovir would have clinical benefit. No toxicity was seen from the acyclovir, when combined with any dose of AZT. The researchers concluded, "The consistency of the clinical and laboratory data...suggests that 300 mg of zidovudine a day has antiviral and CD4-lymphocyte-enhancing effects similar to those of a 600-mg dose, with less toxicity than higher doses." However, "Our findings must be corroborated before this dosage is routinely adopted." They also conclude that "The minimal effective dose of zidovudine for the treatment of HIV infection has yet to be determined, and further studies of very low daily doses are warranted." This study was supported by grants from the National Institutes of Health and the AIDS Clinical Trials Group (ACTG) of the National Institute of Allergy and Infectious Diseases. The principal investigator was Lawrence Corey, M. D., of the University of Washington in Seattle. Comment The fact that a small study was finding that 300 mg of AZT seemed to work as well as 600 mg had become widely known in the AIDS community. But formal publication provides the details which make the result more useful. At this time the usual dose of AZT is 500 or 600 mg per day. It is unlikely that this standard will change just because of one relatively small study. But the new results should make physicians and patients more confident about lowering the dose when necessary, or when they are already inclined to do so. This trial was well designed, in several ways. It used relatively few patients, and therefore could be conducted quickly, cleanly, and economically. It made good use of laboratory endpoints, including quantitative plasma viremia, and also used clinical endpoints such as weight gain and fatigue scores. While none of these measurements is by itself definitive, the consistency between them is convincing. The researchers tabulated results at 12 weeks (known to be long enough for AZT to show benefits), but then continued the study to obtain longer-term data. These aspects of this trial illustrate current developments in clinical-trial design. References 1. Collier AC, Bozzette S, Coombs RW, and others. A pilot study of low-dose zidovudine in human immunodeficiency virus infection. The New England Journal of Medicine, October 11, 1990, volume 323, number 15, pages 1015-1021. 2. Fiddian AP. [Wellcome Research Laboratories, Beckenhham, Kent, U. K.] Preliminary report of a multicentre study of zidovudine plus or minus acyclovir in patients with acquired immune deficiency syndrome or acquired immune deficiency syndrome-related complex. J. Infect., January 1989, volume 18 [supplement 1], pages 79-80. ***** DDC: EXPANDED ACCESS ELIGIBILITY CRITERIA On September 10 Hoffmann-La Roche announced that it planned to make ddC available through a compassionate access program for persons with AIDS or related conditions who could not effectively use other treatments. A number of patients are already on the program. This article summarizes the entry criteria now in use; the intent is to let patients and physicians know who is likely to qualify. * To obtain ddC under this program, patients can qualify by AZT treatment failure, or AZT intolerance, or AZT ineligibility. * To qualify under AZT treatment failure, patients must have received at least 500 mg/day of AZT for at least six months, and not been off of the drug for more than 30 days during that six- month period. They must have had at least one of the following: - Three opportunistic infections or cancers in the last six months; or - Drop of 50 T-helper cells, and a T-helper count of less than 50 on two occasions one month apart; or - Sustained or increasing p24; or - Involuntary weight loss of 2-2.5 pounds per week for at least four weeks; or - Significant neurologic deterioration; or - Karnofsky score less than or equal to 40 for at least one month, as a result of AIDS. * To qualify under AZT intolerance, patients must have remained intolerant to AZT although the dose was reduced to 500 mg per day or less. Intolerance is defined as one or more of the following: - Decrease in hemoglobin by 2 gm/month; or - ANC less than 750; or - Severe vomiting or intractable nausea due to AZT; or - Severe headaches not treatable by analgesics; or - Acute psychosis; or - Severe agitation; or - Declining muscle strength, such as inability to climb stairs, with CPK greater than 1000. These toxicities must have required discontinuation of AZT, and must resolve to Grade 2 or better within 45 days after discontinuing AZT, and before entry into this ddC protocol. * To qualify under AZT ineligibility, patients must: - Be taking necessary treatment with drugs which cannot safely be given with AZT and could be given with ddC (e.g., ganciclovir for life-threatening or sight-threatening CMV infections); or - Have baseline ANC less than 1000, and no prior use of AZT; or - Have baseline hemoglobin less than 8.5. * The protocol also defines ddI intolerance and ineligibility. Originally, patients could receive ddC only if they had failed both AZT and ddI. After protests by activists, who objected to patients being required to fail other than standard therapies, this "ddI loop" was eliminated. ddI intolerance or ineligibility are no longer required for access to ddC, but the information is still being collected, for research purposes. * The AZT toxicities described above "would be considered met: - Logical time course following drug administration; - A known toxicity of the drug; - Improvement after discontinuation of the drug; - Recurrence with rechallenge with the drug." (Note that these criteria do not necessarily require rechallenge, which would be dangerous in some circumstances.) * Patients must also meet all of the following conditions: - Hemoglobin at least 8.0 and not transfusion dependent; - ANC at least 750; - Platelet count at least 80,000; - Estimated creatinine clearance greater than 50 ml/minute (a formula is given for making the estimate); - SGOT and SGPT less then five times upper limit of normal (in some cases, a hepatitis B surface antigen test should be done); - Both men and women must practice birth control, and women must have a negative serum beta HCG pregnancy test within seven days of entry into the protocol; - Patients must be at least 12 years old, with consent of parent or guardian for those under 18. * Exclusion criteria. Patients must not have any of the following: - A history of peripheral neuropathy due to any cause -- or any finding suggestive of peripheral neuropathy found at baseline neurological exam (An isolated finding of absent Achilles reflex may be allowed.) ; or - Cancer other than KS or basal cell carcinoma; or - Concomitant treatment with any other nucleoside analog (e.g., AZT); or - Concomitant treatment with excluded medications. ("Excluded medications include other experimental drugs, immune modulators, systemic corticosteroids, drugs with known nephrotoxic or hepatotoxic potential, and drugs likely to cause peripheral neuropathy."); or - Pregnancy or breast feeding; or - Being unwilling or deemed unable to sign an informed consent. * Concomitant medications. Most non-experimental medications are permitted when necessary. But any that could cause peripheral neuropathy should be avoided. And other precautions are recommended or required; for example, ddC must be stopped temporarily if certain drugs need to be administered. Disclaimer This article summarizes the eligibility criteria of the ddC expanded-access program; it is not complete. In addition, the criteria will probably change over time. The above summary is for background only. For detailed information about this ddC expanded-access program, physicians only should call 800/ddC-21HIV (800/332- 2144), Monday through Friday, 9 a.m. to 8 p.m. Eastern Time. For more information about ongoing ddC clinical trials, patients or physicians can call the AIDS Clinical Trials Information Service at 800/TRIALS-A (800/874-2572), or Hoffmann-La Roche at 800/526-6367. ***** PRIMAQUINE SUPPLY PROBLEM: HOW TO GET THE DRUG Primaquine, a drug which is vitally important for a few people with AIDS, has been unavailable at pharmacies in the United States for about three months, and could remain unavailable for months longer. Affected patients and their physicians must be informed that it is possible to get the drug. Primaquine is usually used to treat or prevent certain kinds of malaria. In AIDS it is used in combination with clindamycin to treat or prevent pneumocystis -- but only for patients who cannot tolerate or do not benefit from all three of the preferred treatment regimens -- Bactrim (Septra), pentamidine, and dapsone. The supply was cut off because the sole U. S. manufacturer of primaquine, Winthrop Pharmaceuticals, has been unable to obtain a chemical precursor needed to make the drug. The U. S. Centers for Disease Control obtained an emergency supply, which it will provide free to physicians for treatment of certain kinds of malaria (but not for malaria prophylaxis, because the supply is limited). Apparently no provision was made for persons with AIDS, for whom use of the drug is "off label," as primaquine has not been officially approved specifically for pneumocystis. What is not widely known is that this shortage exists only in the United States. Elsewhere, primaquine is cheap and plentiful. Apparently the foreign manufacturers are unwilling to invest the money required to obtain generic approval for their preparations, since there is little malaria here, few other patients need the drug, and the profit margin is low because primaquine is generic. In response to this emergency, the PWA Health Group in New York has obtained primaquine from England. (Individuals can legally import small quantities of foreign pharmaceuticals for personal use.) A bottle of 1,000 tablets (7.5 mg) costs $34; a prescription is required. For more information, call the PWA Health Group at 212/532-0280. Note: An article on the primaquine supply problem appears in the excellent September, 1990, issue of Notes from the Underground, the newsletter of the PWA Health Group. For a copy, call them at the number above. An article in the July 20, 1990, Morbidity and Mortality Weekly Report, published by the U. S. Centers for Disease Control, alerted the medical community to the supply problem, and explained the arrangements made for patients with malaria. California note: The California legislature recently passed a law to add clindamycin (the drug used with primaquine) to the Medi-Cal (Medicaid) formulary, allowing it to be prescribed to Medi-Cal patients. State authorities had previously refused to pay for the drug. ***** IMMUNE-BASED THERAPIES MEETING: CHICAGO, NOV. 8 A one-day meeting on "The Status of Immune-Based Therapies in HIV Infection and AIDS" will take place on November 8 in Chicago, in association with the 5th Annual Conference on Clinical Immunology, which is November 9-11. Topics include interleukin-2, alpha interferon, other cytokines, DTC (Imuthiol), isoprinosine, levamisole, immune serum, anti-gp 160 monoclonal antibodies, CD4 blocking, CD4 adhesin, vaccines for HIV-infected individuals (gp 160 vaccine and others), and laboratory evaluation of immune-based therapies. Registration is $55 for the one-day meeting. For more information, call 800/257-8290, or 609/848-1000. ***** BETA: FOOD PRECAUTIONS, ORAL PROBLEMS OF HIV The sixth and current issue of the Bulletin of Experimental Treatments for AIDS (BETA), published by the San Francisco AIDS Foundation, contains an excellent survey of food- preparation precautions which could prevent certain infections for people with HIV. The article is authored by Irene Baucom and traces the origin of various infections associated with compromised immunity, as well as reasons and measures for minimizing exposure to food-borne microbes. In the same issue Caroline L. Dodd, B. D. S., and Deborah Greenspan, B. D. S., report on a spectrum of oral infections and lesions associated with HIV disease. Treatments as well as diagnoses are discussed. To ask for this edition, or to subscribe to BETA, call 800/327-9893 or 415/863-2437. ***** GOOD INTENTIONS: NEW BOOK ATTACKS CONFLICT OF INTEREST IN MEDICAL RESEARCH by John S. James Good Intentions -- subtitled How Big Business and the Medical Establishment are Corrupting the Fight Against AIDS, a sure-to- be-controversial book by Bruce Nussbaum, a senior writer at Business Week, appeared in bookstores this month. It is published by Atlantic Monthly Press. Good Intentions is based on over 100 interviews between 1988 and 1990 with key figures in AIDS research, mostly in the Washington, DC, New York City, and Raleigh, North Carolina, areas; only one scientist refused to be interviewed. The author approached the subject without preconceptions: "I didn't begin the book angry but I did finish it that way." A quote from the introduction gives a better sense of the message than our description could: "Despite my twenty years as a journalist, much of it covering business and finance for Business Week, I was not prepared for the behind-the-scenes realities of big-time medical research. Even after the wild and woolly eighties, where greed became a Wall Street theology, the corruption was startling. "On Wall Street, the financial crooks, the insider traders, knew for the most part that they were cheating, breaking the law. The games they played were new -- the LBOs, the hostile takeovers, the greenmail. But the corruption itself was as old-fashioned as embezzlement. "Nothing of the sort exists in medical science. In that arena, people have good intentions. They believe they are doing good works for the general health of the nation. Indeed, personal corruption is still rare, although faking experimental data appears to be on the rise. "The corruption in medical science goes much deeper. It derives from the very way the Food and Drug Administration, the National Institutes of Health, and the dozens or so elite academic biomedical research centers work with private drug companies. "An old-boy network of powerful medical researchers dominates in every disease field, from AIDS to Alzheimer's. They control the major committees, they run the most important trials, they determine what gets published and who gets promoted. They are accountable to no one. Despite the billions of taxpayer dollars that go to them every year, there is no public oversight. Medical scientists have convinced society that only they can police themselves. "Yet behind the closed doors of 'peer review,' conflicts of interest abound. These are not perceived as conflicts of interest by the scientists themselves. The researchers are convinced that they have only good intentions. This book will show that medical science is the graveyard of good intentions. It will indicate how medical science, in its own unique way, may turn out to be the Wall Street of the nineties. "Good Intentions is about AIDS. It could be about cancer or heart disease or any other major disease. The social, political, and financial structure of the biomedical research behind each one is similar. Acquired Immune Deficiency Syndrome is relatively new. The deals, the arrangements, the conflicts of interest are therefore more open to the observer. They are only just now being constructed. "AIDS is also a killer. It strikes young people in the prime of their lives. The AIDS virus is infectious. Anything that gets in the way of quickly developing safe and effective treatments is monstrous. Against this background, the behavior of medical science is thrown into stark relief. A long history of cancer would illustrate the same issues and problems." (Copyright 1990 by Bruce Nussbaum, reproduced by permission.) Comment Good Intentions seldom attacks individual researchers. Some emerge as heroes, and most did the jobs they were supposed to do. The problems arise more from the system than from the people. This is not the first book to allege that medical/scientific monopolies or conflicts of interest have grossly harmed research in AIDS and other diseases. But it may be the first to make the message accessible and credible to non-specialists -- media people, politicians and their staffs, business and foundation leaders, and anybody else interested in current affairs. Why is this book important? You can see for yourself by visiting any book or magazine store with a good public-affairs section. Shelves are loaded with general-interest books and articles on science and government, and on almost every national problem. But AIDS is strangely absent from this world of discourse -- not mentioned at all, for example, in books on the Federal government during the Reagan years, or getting at best a few sentences of the most superficial comment. Many books have been published on AIDS, but few include anything about treatment research, and fewer still are ever seen by the general public. Why has AIDS research suffered this neglect in the intellectual life of the nation? We believe the major reason is that non-specialists were afraid of the difficulty and complexity of the issue. They do not want to say anything about AIDS research, because they fear getting it wrong. Until now, any non-specialists who wanted to know what really was happening in AIDS treatment development would have needed to undertake an extensive personal research project, finding information in newsletters, in Congressional hearings, through interviews with experts, etc., and then deciding what is relevant and what is credible. No wonder it was easier to accept the "mantram" that everything possible was being done, we're moving as fast as we can, good science takes time. Good Intentions is far from the last word on AIDS research; no single book could tell the whole story. Many legitimate questions and criticisms will be raised. Some of those who appear in the book may have good reason to question how they are portrayed. But while not the last word, it is in a sense a first word, opening research issues for the first time to the normal process of public discussion and debate. Some may say this book appears at the wrong time. For AIDS activists and researchers are now working together better than ever before; the spirit of cooperation calls for defending rather than attacking each other. Many believe there are too many personal attacks already. We should remember that the book is not accusing individuals of wrongdoing; instead it shows problems in the system, problems no one could have foretold and which few have imagined until now. It provides a first glimpse of the enormous inefficiencies and lost opportunities everywhere in medical research. We can only guess what progress could be made if these problems can be corrected. Some may fear that the book is ill-timed because of the growing dangers to Congressional funding due to Federal financial problems. But a recent nationwide survey found that one American in five personally knows someone who has AIDS or is HIV positive (Boston Globe, July 17, 1990, page 1). Congress cannot walk away forever. We can and must address alleged problems openly, and correct them to make research more efficient and productive. Good Intentions suggests that the fundamental problem in medical research, not just in AIDS, is that the real decisions are made for the benefit of powerful interests, not for the benefit of current and future patients, on whose behalf the whole enterprise is ostensibly being run. The best corrective may be the development of patient advocacy movements (like ACT UP and Project Inform), which do their homework on research, learn what really happens there, and represent the public interest in a way it has not been represented before. These movements are not always adversarial; they increasingly work together with professional, industrial, and regulatory interests. They provide a voice at the table for those who have had no voice until now. In many areas of U. S. public life, most real power rests with what is called the "iron triangle," consisting of an industry, the Federal regulators of that industry, and the Congressional committees and staffs which oversee the regulators. In medical research the traditional structure might be called an iron quadrangle, including not only the usual three, but also the relevant professions (medicine and science), which have rules, independence, and interests of their own. The AIDS activist movement is adding a fifth group, as patients demand and win a place at the bargaining table, too. A potential problem for this patient movement is that most of the public-affairs constituency has had no understanding of its issues. Groups in the liberal, public-interest, good- government, consumer-protection spirit should be allies of patient advocates, not opponents. It is easy for well-intended reformers, intimidated by the complexity of science, to uncritically accept the opinions of authorities, without realizing that these authorities have interests and agendas of their own. Good Intentions sheds light here; for the first time, it brings the hidden realities of drug development into general public view. ***** STATEMENT OF PURPOSE AIDS TREATMENT NEWS reports on experimental and complementary treatments, especially those available now. It collects information from medical journals, and from interviews with scientists, physicians, and other health practitioners, and persons with AIDS or HIV. 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. We also examine the ethical and public-policy issues around AIDS treatment research and treatment access. [Obsolete subscription information has been removed. See the latest issues for up-to-date information. -- sysop] &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& End of display