Subject: AIDS Treatment News #103 Date: May 24 1990 (775 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 # 103, May 18, 1990 CONTENTS: [items are separated by "*****" for this display] ddI Early Results Glycyrrhizin: Research Still Promising, Still Limited ACT UP, Senator Helms, and Tobacco: A Proposal In Memoriam: Skip Harris; Don Gorman News Notes: Senate vote; Fluconazole; AZT; WHO Sixth International Conference News: Public radio coverage; Treatment activist meeting Announcements: Nationwide ddC trials; San Francisco MAI study; Subscription price ***** DDI EARLY RESULTS by John S. James Two separate reports of small trials of ddI appeared in the May 10 New England Journal of Medicine. These papers are unrelated to the current trials of ddI, and to the expanded access program under which several thousand people have been treated with the drug. Instead these papers describe earlier "phase I" studies: one at New York University, the University of Rochester, and the National Institutes of Health, the other at two medical centers in Boston (in order to distinguish, we will call them "the New York study" and "the Boston study" in this article). The results of these studies have already been used (before they were formally published) in the design of the current phase II trials and the expanded access program; therefore there are no big surprises. But some of the information now published may be useful to persons taking or considering ddI. In the same issue of the Journal, an editorial by Anthony Fauci, M. D., director of the National Institute of Allergy and Infectious Diseases (NIAID), compares and evaluates the studies. Both of them reported a number of different indications that the drug was working: T-helper increases, p24 antigen decreases, improved hematological measures, and substantial weight gain and energy level increases. In the Boston study, which used less ddI and gave the drug only once a day, 11 patients had had mild peripheral neuropathy before they started the ddI; this symptom resolved for eight of the 11 while they were using the drug. (Since peripheral neuropathy can be a side effect of ddI, it is interesting that peripheral neuropathy due to HIV infection would improve during treatment with the drug.) P24 and T-helper improvements were seen even at the lowest doses -- adding to the increasing suspicion that the doses of ddI now generally used (in the clinical trials and in the expanded-access program) might be too high. The most serious side effect of ddI is pancreatitis, which has caused several deaths among the several thousand patients who have used the drug. In the New York study, which gave the larger total doses of ddI, five of 37 patients developed pancreatitis. In the Boston study, only two of 34 developed pancreatitis. But the New York study had better p24 results. Dr. Fauci speculated that since the active form of ddI inside the cells has a half- life of 12 hours, the best regimen might be lower doses twice a day; but he noted that more trials are necessary to determine if this is true. Both studies were short-term, giving ddI for a mean of 17 weeks in New York and 15.8 weeks in Boston -- another reason why the ongoing trials are necessary. Symptoms of Toxicity Some of the descriptions of the more common side effects published in the report of the New York study might help patients who are using ddI recognize them if they occur. It is very important to notify one's physician immediately in case of side effects, so that the dose can be reduced or the drug discontinued. In the latter case, it is often possible to restart later, at a lower dose. The neuropathy "consisted of a tingling, burning, or aching in the lower extremities, particularly in the soles of the feet. The pain was particularly prominent at night but was also present throughout the day. Initially, the discomfort was noted in walking, but in more advanced cases pain interfered with sleep and routine daily activities... The onset of neuropathy occurred from 55 to 201 days after the initiation of therapy." Pancreatitis was "manifested by abdominal pain and elevated amylase levels. The episodes began with vague abdominal pain, nausea, and vomiting and progressed to moderate or severe epigastric pain, which required narcotic analgesics in three of the five patients... The symptoms resolved within one to three weeks after the cessation of ddI therapy." There have also been other side effects, such as seizures in a few patients. Physicians who are using ddI under the expanded-access program receive updates from the sponsor, Bristol-Myers Squibb Co., and from other doctors, as new information becomes available. Some patients in the expanded-access program have decided to reduce their doses of ddI, often by taking only one of the two daily doses. There is some confusion on whether it is possible to do this with the knowledge of Bristol-Myers, or whether the drug would be cut off in such a case. We do not know the answer. In order to assure the accuracy of the safety information being collected from the expanded-access program, Bristol-Myers should make it clear that patients can reduce their doses and report that fact, without threatening access to the drug which some have found to be a lifeline. ***** GLYCYRRHIZIN: RESEARCH STILL PROMISING, STILL LIMITED by Denny Smith An extract from the root of Glycyrrhiza, the licorice plant, has been studied for several years by Japanese researchers for anti-viral and immunomodulatory activity against HIV, and for therapeutic effects on liver disease. The extracted substance, glycyrrhizin sulfate, has been observed in laboratory tests to inhibit HIV replication, interfere with virus-to-cell binding and cell-to-cell infection, suppress the clumping of infected cells and induce interferon activity. Of related interest, glycyrrhizin also inactivated herpes simplex virus and varicella zoster virus, both of which can become serious opportunistic infections. Among existing applications it is used in Europe and China to treat stomach ulcers and in Japan to treat hepatitis. Botanic and medical literature refer to two species of Glycyrrhiza as a source for the component: G. radix and G. glabra. Most of the articles discussing HIV refer to the first species. Glycyrrhizin is one of several members of a chemical group called sulfated polysaccharides which have demonstrated varying degrees of anti-HIV activity. These include lentinan, Carrisyn, heparin and dextran sulfate. Glycyrrhizin's potential as an HIV therapy is not confirmed to be stronger or weaker than any of its chemical relatives, but anti-inflammatory characteristics and protective action against liver damage may make it useful for many people with HIV or hemophilia who must cope with chronic hepatitis or drug-related liver toxicity. Over three years ago AIDS TREATMENT NEWS reported at length on glycyrrhizin (issue #17, November 7, 1986). Since then, the other sulfated polysaccharides have captured more media and research attention. However work on glycyrrhizin continued, and within the last year several studies in Japan reported promising results with oral and intravenous formulations given to people with HIV or AIDS. At least two of the studies involved people who also have hemophilia. One study of twenty asymptomatic seropositives at Osaka National Hospital was reported at the V International Conference on AIDS in Montreal last June. Of ten participants in this study who were given daily oral doses of glycyrrhizin, ranging from 150 to 225 mg, none progressed to symptoms over periods of one to two years. In the control group of ten who were not treated, one developed lymphadenopathy, and two others were diagnosed with AIDS and subsequently have died (Ikegami and others, 1989). Another study was sponsored by Tohoku University, Fukushima Medical College, and Akita University. Nine patients with hemophilia who were HIV+ but asymptomatic were given 200-800 mg of intravenous glycyrrhizin daily for over eight weeks. Eight patients experienced an average 88.9% increase in T4-helper cells, and six experienced an average 66.7% improvement in their T4/T8 ratio. Liver dysfunction noted in four patients improved, and no serious side effects were observed (Mori and others, 1989). A study conducted at Kumamoto University Medical School and Tokyo Medical College involved glycyrrhizin administered intravenously to three hemophiliac patients with AIDS. Six different courses of treatment were reported, usin mg daily (adjusted by body weight) for at least one month. p24 antigenemia was detectable at the beginning of five of the six treatment episodes, but undetectable by the end of three of those five; for the other two, the levels decreased. The authors suggest that glycyrrhizin might inhibit HIV replication (Hattori and others, 1989). Glycyrrhizin appears relatively nontoxic, but is capable of causing some side effects, including hypokalemia (low potassium levels), myopathy (muscle soreness or fatigue), high blood pressure, and sodium and fluid retention. Persons currently experiencing these symptoms are advised against using glycyrrhizin. Even in the absence of these conditions, we advocate supervision by an HIV-knowledgeable health provider for people considering a new treatment. A friend of AIDS TREATMENT NEWS has been using Glycyron 2, a Japanese pharmaceutical preparation of glycyrrhizin for oral use, since last October. He shared with us these impressions so far: For several years prior, his helper cells had remained very stable, in the 500 range. Then, last summer they began to decline rapidly in a trend apparent over consecutive tests. By October they registered 320, and he began taking glycyrrhizin in daily doses of 500 mg. After a month his helper cell count rose to 420, liver enzymes which had been slightly elevated were decreased, and he noticed an increase in energy. Of course, helper cells fluctuate notoriously in many people, even without HIV involvement, and no one would claim that T-cell counts alone are predictive of illness or the efficacy of a given treatment. But together with symptom improvement, they are a first step toward more intensive monitoring of a trend. Our friend is always careful to have his bloodwork sent to the same lab. In November he began treatments with Compound Q, and has continued since then with both Q and glycyrrhizin, with good results in his bloodwork. His p24 antigen tests were negative before starting either treatment, but in January his p24 antibodies registered 400, compared to a pre-treatment count of 50. (Do not confuse p24 antibodies with p24 antigen. For the antibodies, a high value is desirable; for antigen, the reverse is true.) Attributing the improvements to one treatment or the other is not possible for certain; he feels that they complement each other. Glycyrrhizin is available over the counter in Japan, where it costs about 10 cents per one 25 mg tablet. Depending on the desired dose, which varied widely in the above studies, glycyrrhizin could be an inexpensive complement in an HIV treatment program. Licorice root is the natural source and is widely available as a tea in health food stores in the U. S. Apparently, glycyrrhizin components comprise from 8 to 12% of licorice root, and they are available simply by drinking the tea. But obviously, this would be a haphazard and not a methodical way to obtain measured, standard amounts of glycyrrhizin. Chinese medicine often employs licorice root, but usually in small amounts combined with other therapeutic plants. We do not know of any U. S. source of the Japanese tablets at this time, but some buyers' clubs are considering carrying them. References Ikegami, N and others. Clinical Evaluation of Glycyrrhizin on HIV-Infected Asymptomatic Hemophiliac Patients in Japan. V International Conference on AIDS. Abstract W. B. P. 298, June, 1989. Mori, K and others. Effects of Glycyrrhizin (SNMC: Stronger Neo-Minophagen C) in Hemophilia Patients with HIV Infection. Tohoku Journal of Experimental Medicine, volume 158, pages 25-35, 1989. Hattori, T and others. Preliminary evidence for inhibitory effect of glycyrrhizin on HIV replication in patients with AIDS. Antiviral Research, volume 11, pages 255-262, 1989. Tochikura, TS and others. Antiviral Agents with Activity Against Human Retroviruses. Journal of Acquired Immune Deficiency Syndromes, volume 2, number 5, pages 442-447, 1989. Tochikura, TS and others. Human Immunodeficiency Virus (HIV)- Induced Cell Fusion: Quantification and Its Application for the Simple and Rapid Screening of Anti-HIV Substances in Vitro. Virology, volume 164, pages 542-546, June, 1988. Ito, M and others. Mechanism of inhibitory effect of glycyrrhizin on replication of human immunodeficiency virus (HIV). Antiviral Research, volume 10, number 6, pages 289-298, December 1988. ***** ACT UP, SENATOR HELMS, AND TOBACCO: A PROPOSAL by John S. James ACT UP groups and others have called for a boycott of Marlboro cigarettes, because Philip Morris is a major corporate contributor to the election campaigns of Senator Jesse Helms, Republican of North Carolina, who has consistently sabotaged U. S. AIDS policy and impeded Federal efforts against the epidemic. The boycott is now supported by ACT UP chapters in Washington DC, New York, Boston, Provincetown, Atlanta, Shreveport, Indianapolis, San Francisco, Seattle, Portland, and Paris, France. (For more information on the Marlboro boycott, call Michael Petrelis or Carl Goodman of ACT UP/DC, 202/543-1070.) This article proposes another tactic which we believe could be effective against Helms, and also valuable in its own right in building national and international health coalitions. Recently, public opinion and government policies in the United States have turned strongly against smoking. But as smoking declines here, it is increasing in the rest of the world. Export to other countries has become a life-or-death issue to the tobacco industry, since its future may rest on international sales. So while U. S. health officials are strongly discouraging smoking at home, U. S trade officials are forcing other countries to accept U. S. tobacco, and to allow U. S. -based multinationals to aggressively promote smoking within their domestic populations, even to children -- under threat of trade sanctions which can amount to sabotage of those countries' economies. South Korea, Taiwan, and Japan have already been forced to accept U. S. tobacco imports and advertising, and now the pressure is on Thailand. If Thailand refuses, all its imports to the United States could be stopped in retaliation, under the Trade Act of 1974, according to a New York Times article of May 18. How do tobacco companies promote their products abroad, after the U. S. government has used its economic clout to prevent sovereign nations from implementing antismoking policies to protect their citizens? "In Kuwait the companies take photos of children next to Formula One race cars and hand out the photo, cigarettes, a lighter, and T-shirts to the children; in Thailand, where cigarette advertising is outlawed, Marlboro and Winston logos appear on schoolbook covers, kites, and T-shirts in anticipation of a favorable trade ruling; in Germany, citizens were handed packs of Camels as they came through the Berlin Wall," according to a recent issue of Cancer News, published by the American Cancer Society. After Taiwan and South Korea gave in to U. S. pressure, "cigarette promotion surged in these markets, and for the first time, advertising has been directly targeted to women who traditionally had very low smoking rates in these countries," according to the same source. If present trends continue, smoking will become a leading cause of death worldwide, especially in Third World countries; it is projected to kill 12 million people each year by 2050. U. S. officials have argued that tobacco export is a trade issue, not a health issue -- that under the law it does not matter that smoking is dangerous to health, all that matters is that tobacco is a product. Last week Congressman Henry A. Waxman (Democrat of California) and others were outraged when Dr. James O. Mason, Assistant Secretary for Health, cancelled a May 17 appearance before Waxman's subcommittee on the tobacco-export issue. Dr. Mason had strongly criticized tobacco export last month at the World Conference on Tobacco and Health, but later he was apparently silenced by the Bush Administration. How can the United States continue to protect its own citizens while forbidding other countries from protecting theirs? The answer is that those who suffer from these unconscionable export policies have no voice in them because they are not citizens here. It has been much harder to raise U. S. grassroots opposition to the export policies than to issues which affect millions of Americans directly (like secondhand smoke in public buildings and vehicles). This situation presents a special opportunity for AIDS activists and groups like ACT UP -- and also for the arts community, which has its own problems with Senator Helms -- to have a disproportionately large impact. Tobacco is widely grown in North Carolina, and tobacco companies are among Helms' leading supporters. Exports are the future of the tobacco industry, because of the strong turn against smoking by the U. S. public. No country wants future deaths and huge medical bills, so exports depend on U. S. policies which force other countries to take the product. These reprehensible policies, opposed by the countries affected, by international organizations, and by U. S. organizations like the American Cancer Society, continue because it is hard to personalize export policy as a grassroots issue. But Senator Helms could be the key to personalizing this issue as it could never be personalized before. For example, actions by AIDS activists or by artists at the offices of the U. S. trade negotiators, or directed at members of Congress who support the unconscionable policies, could force the press to explain the issue, amplifying the testimony of anti-smoking experts and mobilizing public revulsion at the hypocrisy and national dishonor of discouraging cigarettes at home while forcing them abroad. Endless grassroots projects are possible. Groups like ACT UP, or arts activists, could contribute unique visibility to the campaign against tobacco exports, which otherwise consists largely of testimony by experts to august bodies. Helms himself provides the motivation to bring a colorful, ongoing, and permanent grassroots presence into an issue of vital importance to his biggest supporters. Such a campaign could change him from an asset to the tobacco industry into a central threat to its future. And the same campaign would also help to build coalitions between AIDS activists and those of other diseases, in the U. S. and internationally. Last week the American Cancer Society launched its "Trade for Life" plan against the tobacco-export policies. Developed earlier in the year at a consensus conference of international tobacco control experts from 16 countries, the Trade for Life Global Plan was overwhelmingly adopted by nearly 700 delegates representing 67 countries at the Seventh World Congress on Tobacco and Health last month in Australia. A key element in the plan is an international computer network of the American Cancer Society -- ACS Globalink -- to provide tobacco control information and expert assistance throughout the world. Over 100 healthcare leaders, representing all major international health groups, have agreed to join this computer network. Organizations or individuals who would like more information about the Trade for Life program, and how they might join in this effort, can call John Madigan at the American Cancer Society, 202/546-4011. ***** IN MEMORIAM: SKIP HARRIS Hemophilia/HIV activist Skip Harris died on May 17. His death is a serious loss to both the AIDS and hemophilia communities in the San Francisco Bay Area. AIDS TREATMENT NEWS had interviewed Mr. Harris and published his remarks in our last issue, in an article addressing the challenges faced by people with both hemophilia and HIV. When asked what he would like to see in the future for each community, Skip responded: "I'd want much more education disseminated through all the local chapters of the Hemophilia Council ... secondly, the government needs to fulfill a commitment to make treatment available. This year treatment was finally the recipient of some of the giant fundraising benefits. For a long time I found it very disturbing that AIDS prevention was the only idea addressed by those benefits, never AIDS treatment. The Reagan administration's policy toward AIDS very deliberately was to write off those who were already infected ... Bush has talked more about treatment but hasn't put his money where his mouth is. I really think the value of coalitions will grow in the future, coalitions of all the communities affected by HIV ... what happens with health care will make or break this country." Skip also worked with us as a board member of the Community Research Alliance. IN MEMORIAM: DON GORMAN Don Gorman's name has not appeared in AIDS TREATMENT NEWS, but without him there would have been no newsletter. Over five years ago John James approached the newly formed Mobilization Against AIDS, and asked how he could help by researching and writing articles. Mobilization suggested calling the Documentation of AIDS Issues and Research Foundation, Inc. (DAIR) -- a group which had evolved from a documentation and library committee within Mobilization. Don Gorman, the president of DAIR, suggested writing articles about experimental treatments -- and provided the names of about a dozen treatments of interest. He published our first article in April 1986 in the newsletter DAIR Update, then introduced us to the San Francisco Sentinel, where our articles appeared every two weeks. AIDS TREATMENT NEWS began several months later; the DAIR Update article, on AL 721, appears today as issue #1. Don's DAIR Foundation also provided critical support for the early development of Project Inform. As a registered nurse, Don approached AIDS information as a person with AIDS, an activist, and one trained in medical management. He published articles about medical management, especially about pneumocystis and the availability of aerosol pentamidine, early in the epidemic. The DAIR Foundation, which maintains AIDS archives open to the public and prepares reports to support AIDS organizations, continues today in San Francisco; it can be reached at 415/552- 1665. Anyone who could volunteer time to help continue Don's work is encouraged to get in touch. ***** NEWS NOTES Senate Votes Overwhelmingly for AIDS Care On May 15 the U. S. Senate voted 95 to 3 to override objections by Senator Jesse Helms, Republican of North Carolina, and vote on a bill to provide emergency disaster relief to cities and states with many AIDS cases. The next day, the Senate passed the bill by a vote of 95 to 4. The bill had been introduced by Senators Edward M. Kennedy, Democrat of Massachusetts, and Orrin Hatch, Republican of Utah; it has 65 other co-sponsors. Much more is necessary before the bill becomes law -- especially the separate appropriations process in Congress. But the degree of consensus signals a welcome change in Washington on dealing with AIDS. Most observers see two reasons for the change. First, more members of Congress now know someone with AIDS, or someone who has died of it. The second factor is the excellent work of the AIDS Action Council and other lobbying groups. They drafted solid, practical legislation representing a consensus on AIDS by dozens of major, mainstream health and medical organizations. NIAID Recommends Fluconazole for Cryptococcal Meningitis Maintenance Therapy On May 11 the U. S. Public Health Service announced preliminary results of a clinical trial of fluconazole vs. amphotericin B for preventing recurrence of cryptococcal meningitis. All 205 patients in the trial had first been treated successfully with amphotericin B for the acute phase of the disease. Then they were randomly assigned to either fluconazole or amphotericin B for continuing treatment to prevent relapses. Of 106 patients who received fluconazole (200 mg by mouth daily), only two developed recurrent cryptococcal meningitis, in a median time of 212 days. But of the 77 who received intravenous amphotericin B, 13 had relapses. (These numbers do not add up to the 205 patients total, because some could not be evaluated in the analysis.) Because of these results, the trial was ended, and all participants were offered fluconazole, which has far less toxicity than amphotericin B. As a result of this study, the National Institute of Allergy and Infectious Diseases now recommends that fluconazole replace amphotericin B for maintenance therapy of cryptococcal meningitis. NOTE: AIDS TREATMENT NEWS covered fluconazole treatment for cryptococcal meningitis in a five-page article almost three years ago, on September 25, 1987 (issue #41). At that time the drug had been used to treat over 2,000 people in Europe, mostly for less serious fungal infections; it had also worked well in the few cases in which it had been tried for cryptococcal meningitis. However, fluconazole was not approved in the United States until January 29 of this year. It is very expensive, and some people are using itraconazole instead. Itraconazole is not approved in the United States but is available in Mexico, and perhaps other countries, at a fraction of the U. S. fluconazole price. More information about itraconazole may be obtained from buyers' clubs; also see "Itraconazole: Affordable Fluconazole Substitute," AIDS TREATMENT NEWS #80, June 2, 1989. AZT Early-Intervention Study Published On May 15 the Annals of Internal Medicine published a formal report of ACTG 016, the major national study of persons with mildly symptomatic HIV and T-helper counts over 200. The results of this trial have already been incorporated into the recommendations concerning treatment of persons with T- helper counts between 200 and 500. While the conclusions are not new, the 11-page report includes many details which may be helpful to physicians in refining treatment strategies. Reference Fischl, M. D., Richman, D. D., Hansen, N. and others. The safety and efficacy of zidovudine (AZT) in the treatment of patients with mildly symptomatic human immunodeficiency virus type 1 (HIV) infection. A double-blind, placebo-controlled trial. Annals of Internal Medicine vol. 112, pages 727-737, May 15, 1990. WHO Names New AIDS Program Director On May 14 the World Health Organization (WHO) appointed Michael Merson, M. D., as head of the Global Programme on AIDS. He had been temporary head since March 26, when Dr. Jonathan Mann was forced out (see AIDS TREATMENT NEWS #99, March 16, 1990). Dr. Merson, a WHO employee for 12 years, directed its Control of Diarrheal Diseases Programme. He had also worked for the U. S. Centers for Disease Control (CDC). WHO also appointed the deputy director of the CDC, Walter Dowdle, M. D., as consultant to Dr. Merson, when the latter assumed the interim position. ***** SIXTH INTERNATIONAL CONFERENCE NEWS Live Coverage on Public Radio Those who cannot attend the Conference should be able to receive coverage for two hours each day through a local public radio station. KPFA in the San Francisco area, WBAI in New York, KPFK in Los Angeles, KPFT in Houston, WPFW in Washington, DC, and dozens of other stations are expected to carry the live broadcast, and/or use use modular segments of it in news programming. The schedule for the live coverage, produced by Pacifica Foundation and distributed to other stations through satellite, is 9-10 AM (all times are Pacific Time) on Wednesday June 20, 9- 11 AM on June 21-23, and 11 AM to 1 PM on Sunday June 24 for the closing ceremonies. Broadcasts will include interviews, and parts of the major plenary sessions. Treatment Activist Meeting in San Francisco On June 19 the Treatment Issues Committee of ACT UP/San Francisco will host a Treatment Activist Roundtable at Project Inform, 347 Dolores Street (at 16th Street) in San Francisco. The purpose is "to allow for the exchange of treatment information and the development of a registry of activists who are primarily concerned with fighting to make treatments for HIV real and accessible NOW. .. Please remember that this is not an educational meeting, but a chance for activists committed to work in the area of HIV treatments to exchange information." The agenda will be loose, with introductions, discussions, and brainstorming. If you want to attend, write to: Jesse Dobson, 385-61st Street, Oakland, CA 94618; for more information, phone 415/547- 7414. You can also reply by fax to Jesse Dobson, 415/558-0684. ***** ANNOUNCEMENTS ddC: Nationwide Trials Recruiting ddC, one of the important potential anti-HIV treatments, is now in nationwide clinical trials sponsored by Hoffmann-La Roche, Inc. Like ddI, ddC does not cause the hematological toxicity of AZT; but unlike ddI, ddC does not cause pancreatitis. Both ddI and ddC can cause peripheral neuropathy, but the current ddC studies are using very small doses, and serious neuropathy appears to be rare. ddC is active in very small amounts; the doses currently used are about 100 times less than those of ddI or AZT. As we pointed out earlier (issue #89, October 20, 1989), this low dose contributes to a low manufacturing cost, about five cents a day, making ddC a potential treatment for Third World nations where cost is a critical problem. (Clearly this low price does not include distribution, physician education, etc., or drug development.) The two major nationwide ddC trials have been filling slowly because they need hundreds of volunteers yet have restrictive entry criteria -- but not because they are unattractive for those who can get in. Below are the most important entry criteria (but not all of them); those who might be eligible can call the numbers below for more information. The two trials are: (1) protocol N3300 (also called ACTG 114), for patients with AIDS or symptomatic HIV infection who have not had more than 90 days treatment with AZT, and (2) protocol N3492 (ACTG 119), for similar patients who have been treated with AZT for at least a year. In both trials, volunteers are randomly assigned to receive either AZT or ddC -- with a "crossover" provision allowing those who become intolerant to AZT to switch to ddC. Both trials provide free drug and laboratory tests (except for aerosol pentamidine, which is required but not paid for by Hoffmann-La Roche). Both men and women are eligible, but women of childbearing age must have a negative pregnancy test and must practice adequate birth control during the trial. Protocol N3300 Criteria and Locations To enter this trial, patients must be at least 18, have less than or equal to 200 T-helper cells per cubic millimeter and either (1) be within 120 days of their first episode of PCP, or (2) have at least one of the following: unexplained weight loss, oral thrush, unexplained diarrhea over 30 days, or a history of unexplained fever. Hemoglobin must be at least 9.5, granulocytes at least 1,200, platelets at least 100,000, and transaminases within three times the upper range of normal. Patients cannot have KS, most kinds of cancer, severe dementia, or peripheral neuropathy. Locations for protocol N3300 (cities, listed alphabetically by state) are: California (Harbor City, Los Angeles, Sacramento, San Francisco 3 sites, San Jose), District of Columbia, Florida (Fort Lauderdale, Fort Myers, Miami), Georgia (Atlanta), Illinois (Chicago 2 sites), Massachusetts (Boston), Michigan (Detroit), New Jersey (New Brunswick, Newark), New York (Albany, Brooklyn), North Carolina (Winston-Salem), Ohio (Cleveland), Pennsylvania (Philadelphia), and Texas (Dallas, Galveston, Houston). Protocol N3492 Criteria and Locations Patients must be at least 13, and have received at least 500 mg of AZT for more than 48 weeks. AZT cannot have been interrupted for more than 30 consecutive days, or for more than 90 days total. When AZT was begun, patients must either have had PCP but no other opportunistic infection, or had less than 200 T-helper cells and at least one of the following symptoms: unexplained weight loss, oral thrush, unexplained diarrhea lasting over 30 days, a history of unexplained fever, hairy leukoplakia, or herpes zoster. Also, patients must currently have hemoglobin at least 9.5, granulocytes at least 750, platelets at least 75,000, and transaminases within five times the upper range of normal. They cannot have progressive KS, most kinds of cancer, or peripheral neuropathy, or have received prior treatment with ddC. Locations for this trial are: California (San Francisco 2 sites), District of Columbia, Florida (Miami), Indiana (Indianapolis), Maryland (Baltimore), New Jersey (New Brunswick), Ohio (Cincinnati), Pennsylvania (Philadelphia), and Texas (Dallas). For more Information More information about either trial is available through the AIDS Clinical Trials Information Service (run by the U. S. Public Health Service), phone 800-TRIALS-A. San Francisco: MAI Treatment Study Now Open San Francisco General Hospital is now recruiting for participants in a study of three combined drugs -- rifampin, ethambutol, and ciprofloxacin -- to treat active infections of Mycobacterium avium intracellulare (MAI), also called M. avium complex (MAC). The protocol designed for the study notes that MAI is the most frequently diagnosed opportunistic infection in people with AIDS, and that in spite of this, very little data exists to advise clinicians treating patients. This particular trial employs a randomized, crossover/placebo design, meaning that for the first eight weeks, half of the participants will receive the drugs and the other half will receive a placebo. Then for the next eight weeks the two groups will be switched, so by the study's end everyone will have received the drugs. All costs related to the trial will be covered. Interested persons can call David Gary, R. N., at 415/821-5089. ***** AIDS TREATMENT NEWS PRICE INCREASE JULY 1 by John S. James On July 1 AIDS TREATMENT NEWS will increase the reduced subscription rate (for persons with AIDS or related conditions who cannot afford the regular rate) from $30 per year to $40. The half-year rate will increase from $16 to $20 All other rates will stay the same. Current subscribers at the reduced rate may voluntarily renew, without waiting for the next billing cycle, at the current rate through July 31. We have been reluctant to raise the reduced rate, and would like to explain why this increase is necessary. AIDS TREATMENT NEWS has a staff of six, and no income besides subscriptions and unsolicited gifts; we accept no advertising, and we are not funded by anybody. The $30 reduced rate has not changed significantly since we started the newsletter over three years ago. We calculated that rate to match the incremental costs of sending out each additional copy -- first-class postage, printing, envelope, labor, order processing, billing, and accounting -- with nothing calculated for rent, phone, research expenses, or salaries for anything except subscription fulfillment. In setting the reduced-rate price, our model was that if on our second day of operation we received thousands of subscriptions, every one of them at the low rate, we must be able to fulfill them and not go out of business. This formula has worked fairly well, but in three and a half years our costs have increased. In addition, we failed to include all of the expenses in computing the incremental cost, especially the costs of answering and returning phone calls, and of providing subscriptions to those who cannot afford the low rate (currently about eight percent of subscribers). Both these expenses increase as circulation grows, and therefore they must be counted as incremental cost if calculations are to accurately reflect the economic viability of the newsletter. Currently 70 percent of our paid subscribers are at the reduced rate. This rate must cover at least the fulfillment costs, especially since research and overhead costs are extra, and we have no other sources of income. The maximum salary at AIDS TREATMENT NEWS is less than people earn for comparable work at other AIDS organizations, which are notoriously underfunded -- and less than the prevailing San Francisco rates for such jobs as word processing, with no other responsibilities. Recently we obtained employee health insurance, after over three years without. Despite the low pay for this expensive city, we have had little turnover, with most people here for two years or more -- a great benefit to our ability to operate smoothly and keep focused on our central mission. For a time it was appropriate to rely on dedication and emergency commitment. But people cannot be asked to make sacrifices forever; as AIDS work continues, it must eventually become more comparable to similar work elsewhere. We know that many people cannot afford to subscribe to AIDS TREATMENT NEWS. We believe that the best way to address this problem is to continue to allow free copying by PWA coalitions, buyers' clubs, and other nonprofit groups, as well as offering liberal terms for reprinting articles to publications like San Francisco Bay Times, or Outweek. We will continue to seek new ways to get the information we publish to people who need it. But we have no income besides subscriptions, and must charge enough to cover all costs and continue to operate effectively. Clarification of Copyright Policy Permission is granted for non-commercial reproduction of AIDS TREATMENT NEWS, for example to give away copies or sell them at cost at PWA organizations or buyers' clubs, or to reproduce articles in free newsletters of nonprofit organizations. You do not need to ask us in advance. We do request: (1) Contact us before reprinting anything more than several months old, so that we can tell you if we know that the information has changed. (2) Make sure that our address and phone number is included with any reprint, so that readers can contact us. (3) Send a copy of the reprint to us at AIDS TREATMENT NEWS, attn: copyright file. ***** 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 ARC. 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