Subject: ddI; CMV Prevention; Imuthiol; DHEA Date: Apr 6 1990 (738 lines) &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& TREATMENT ISSUES -- The GMHC Newsletter of Experimental AIDS Therapies &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& Treatment Issues Volume 4 no. 2 April 6, 1990 Contents: [items are separated by "*****" for this display] ddI Update An Ounce of Prevention: CMV Imuthiol Treatment-IND Denied DHEA- Potential Immunomodulator In Brief New Studies ***** ddI: Experience to Date Gabriel Torres, M. D. On March 12, 1990, The New York Times reported that 290 patients receiving ddI through the expanded access program had died, as compared to two patients in the controlled clinical trials. These two patient groups were inappropriately compared. As a result, many people taking ddI reacted badly to this irresponsible reporting. Little emphasis was given to the fact that patients in the expanded access program were more advanced in their HIV disease, with poorer performance status, lower T4 cell counts, more opportunistic infections and were probably taking a greater number of other medications than patients in the clinical trials. Patients who qualified for the trials included persons with AIDS and ARC with fewer than 300 T4 cell counts, most of whom had a much greater probability of living longer than the patients in the expanded access program. Toxicity to Date ddI (dideoxyinosine) was made available in September 1989 by Bristol-Myers Squibb Company as part of an expanded access program to persons with AIDS and ARC who are intolerant of AZT (Treatment-IND protocol) and to persons with AIDS who are clinically deteriorating on AZT (open safety protocol). The latter includes patients with neurological deterioration, weight loss, three opportunistic infections within the previous six months, low performance scores (totally disabled and bedridden), or T4 cell count of 50 or less on two measurements. The patients are monitored on a monthly basis by their personal physicians for signs of toxicity with physical examinations and laboratory tests. In the Phase I trials, the most common toxicities seen were peripheral neuropathy and pancreatitis, which occurred more frequently at the higher doses. For example, at doses of 1400- 3500 mg/day, peripheral neuropathy occurred in 58% of patients and pancreatitis in 12.5% of patients. At doses of 800-1400 mg/day, neuropathy occurred in 18% and pancreatitis in 14%. At the lower doses of 500-800 mg/day, no patients developed neuropathy, and only two (6.4%) developed pancreatitis. The highest dose used in the expanded access program is 750 mg/day, and is based on body weight and adjusted for any conditions predisposing patients to either pancreatitis or peripheral neuropathy. Neuropathy ddI neuropathy manifests itself as numbness, burning or pain in the feet, which can last for hours, yet is reversible if the drug is discontinued. If patients develop symptoms suggestive of neuropathy, they are instructed to discontinue the drug and are followed closely until all the symptoms disappear. ddI has been restarted successfully at a lower dose, without recurrence of neuropathy in several patients. When symptoms of neuropathy occur, various other possible causes must be ruled out. These include vitamin deficiencies (especially vitamin B12), toxic neuropathies due to other drugs frequently used by HIV-infected persons or direct damage by HIV. Pancreatitis Seven deaths related to pancreatitis were also reported in The New York Times article of March 12. Five deaths occurred in the expanded access protocols and two patients in the clinical trials died. Unfortunately no details were given about the circumstances surrounding these deaths, including other opportunistic infections or malignancies, concomitant medications or temporal relationship between intake of ddI and death. Pancreatitis refers to inflammation of the pancreas, which is an organ whose enzymes metabolize fats, carbohydrates and proteins. The condition is characterized by nausea, vomiting and constant abdominal pain, which is worsened by eating. In addition, the pancreas regulates the production and release of insulin in response to the blood sugar level. Toxins such as alcohol can produce severe pancreatic inflammation. Drinking alcoholic beverages should be avoided while taking ddI since the combination may result in cumulative toxicity. Other commonly used drugs which can cause pancreatitis include steroids, pentamidine, sulfa drugs (Bactrim, Septra, sulfadiazine), cimetidine (Tagamet), tetracycline, opiates, metronidazole (Flagyl), Lomotil, acetaminophen (Tylenol, Anacin, etc.) and diuretics. Since the contributuion of these drugs to the effect of ddI on the pancreas is unknown, persons on both should be monitored closely for this toxicity. Drugs which decrease stomach acidity, such as those used for gastritis and peptic ulcers (antacids, Tagamet, Zantac and Pepcid), substantially increase ddI absorption. Physicians participating in the expanded access program are kept informed of new adverse effects which are reported to the pharmaceutical company. Three letters have been sent to physicians reporting new side effects which seem related to use of ddI. The side effects reported so far include: -Diarrhea reported in less than 1% of patients according to Bristol-Myers, seems to be related to the citrate-phosphate buffer and can be usually controlled with antidiarrheal medications such as Immodium. -Changes in mental status, ranging from confusion to disorientation, were reported in three patients one to two weeks after starting ddI. Normal mental status was restored between one and 36 hours after discontinuation of the drug. In one case, the change in mental status recurred after ddI was restarted at a lower dose. -Low levels of potassium, calcium and magnesium have been associated with five seizures and three cases of cardiac arrest. A summary of adverse drug experiences reported to Bristol- Myers from January 1, 1989 to January 5, 1990 was made available in mid-March to community physicians. It describes the side effects reported from 208 of the 5890 patients who had received ddI in both the expanded access program and the AIDS Clinical Trials Group (ACTG) clinical trials up to that point. The 208 patients reported 267 serious adverse effects, including 111 deaths which occurred predominantly in patients in the expanded access program. Most deaths seemed to be related to progression of HIV disease. Neurologic complaints including both the central and peripheral nervous system occurred in 50 patients. Conversely agitation-hyperactivity-anxiety also occurred in five patients. None of the patients reporting symptoms of peripheral neuropathy was receiving less than 750 mg/day of ddI, the highest dose in the expanded access program. The report also describes reports of elevation in amylase levels, which occurs vbefore pancreatitis without accompanying symptoms. There were also nine reports of seizures (convulsions). Two of the patients had HIV- demential, and two had toxoplasmosis. In the others the cause could not be determined. Anemia was reported by three patients; low white blood cell counts, by eight patients; and low platelet counts, by five patients. Yet some of these patients had a history of decreasing cell counts with AZT, and others received other drugs which could have caused the low cell counts. Rashes and allergic reactions were reported by 11 patients, which could represent allergic reactions to ddI. However two cases may have been food allergies. Miscellaneous adverse effects, which occurred in very few patients, include elevation in liver function tests, uric acid and triglyceride levels. The most recent report from Bristol-Myers, on March 28, 1990, described a total of 78 cases of pancreatitis. Seven of these cases progressed rapidly to death. With approximately 8300 patients currently under treatment with ddI in the U. S., this constitutes an apparent incidence rate of 0.9% of pancreatitis. There is no current evidence, however, that the proportion of patients with pancreatitis is increasing with expanded access. Careful screening of patients for a history of pancreatitis or recent alcohol abuse is strongly encouraged. Avoidance of other drugs which may also cause pancreatitis is strongly recommended, especially sulfa drugs or intravenous pentamidine, which require discontinuation of ddI therapy. Early symptoms of pancreatitis require immediate attention. Blood levels of amylase and triglycerides should be monitored closely, since they may be early signs of pancreatitis. Despite the new information on ddI toxicity, patients who cannot take AZT or are deteriorating despite AZT have few options, and the benefit of ddI for many may outweigh the possible risk. Access to the drug through early release programs should continue for those eligible, with emphasis on closer supervision and awareness of early symptoms associated with toxicity. ***** An Ounce of Prevention: CMV Howard Rubin Cytomegalovirus (CMV), a member of the herpes virus family, can cause severe infections in PWAs. The virus is quite widespread among adults. Up to 50% of people over the age of 40 have antibodies to CMV although most never develop signs of infection. Among gay men, CMV is much more prevalent. CMV can be transmitted through sexual contact, from mother to fetus and via organ transplants. The virus has also been found in about 5% of donated blood. Like oral or genital herpes (herpes simplex 1 and 2), CMV can reproduce in people with normally functioning immune systems and establish a latent infection. When the immune system controls CMV, the infected individual may have no symptoms or just have lymphadenopathy or a mononucleosis-like illness. CMV can be reactivated when someone becomes immunocompromised. In PWAs, the organs most commonly affected are the eyes, lungs, nervous system and intestinal tract. (A more detailed description of CMV can be found in Treatment Issues, Volume 2, Number 8). Maintenance Therapy Ganciclovir (DHPG) has been shown to have some efficacy in controlling active CMV disease. After an initial course of high- dose ganciclovir, patients must go on a maintenance dose, usually 6 mg/kg for five days a week, to suppress CMV. In one study of 18 PWAs with CMV retinitis in one eye, ganciclovir prevented development of disease in the unaffected eye. However, 60% of a similar group who did not receive ganciclovir developed retinitis in the other eye. Thus, secondary prevention with ganciclovir is necessary to prevent total blindness in most PWAs with CMV retinitis (1). Similarly in gastrointestinal disease, maintenance ganciclovir has prevented recurrence of esophagitis, colitis and rectal ulcers, and improved survival (2). For maintenance ganciclovir, patients need to have a catheter implanted, which allows direct access to the bloodstream. Syntex, ganciclovir's manufacturer, has developed an oral form of the drug which is in clinical trials in San Diego and San Francisco. Both ganciclovir and AZT are bone marrow suppressive, so the two are not usually given together. Some patients have been able to tolerate low doses of both drugs. An experimental drug called GM-CSF is being used in trials to stimulate production of the white blood cells that ganciclovir and AZT suppress. GM-CSF may allow patients to stay on AZT and ganciclovir together and for longer periods of time. (For information about trials using these drugs in combination, consult the AIDS Treatment Registry, the AmFAR Directory or call 1-800-TRIALS-A). There is not much experience with long-term use of ganciclovir as suppressive therapy. One problem that has begun to emerge is that some strains of CMV have developed resistance to ganciclovir. Another drug in development as a treatment for CMV is Foscarnet, which also is active against other herpes viruses. Daily intravenous treatment with Foscarnet must also continue indefinitely. Although Foscarnet does not suppress the bone marrow, allowing patients to take it with AZT, it does cause kidney toxicity in about 15% of patients. Primary Prophylaxis It would be better, of course, to prevent any manifestation of CMV disease in patients at high risk. A couple of strategies look promising. Researchers are now testing acyclovir (an antiviral drug that is currently used to treat other herpes infections) as a preventative treatment for CMV in PWAs who do not have active infections. Test-tube studies indicate that it inhibits the replication of CMV, but at much higher doses than are required to suppress herpes simplex or zoster viruses. Toxicity and side effects, which are dose-related, can include nausea, vomiting and headache. Drs. Craig Metroka and H. Josefberg at St. Luke's/Roosevelt Hospital in New York City are conducting a study of the efficacy of high-dose oral acyclovir in the prevention of CMV in PWAs. From December 1987 to January 1989, they followed 60 patients who were at a high risk for CMV, based on low T4 cell counts. All were under 150 and the mean count was 75 (3). The regimen was 800 mg of acyclovir every four hours. Nineteen of the 51 patients on acyclovir were also on AZT. None of those taking acyclovir developed evidence of CMV. In contrast, three of nine patients who chose not to take the acyclovir developed CMV disease. Dr. Metroka has continued his study through January 1990, enrolling 120 patients with T4 counts under 150 (mean count: 64) (4). The duration of follow-up ranges from 15.5 to 24 months. Only two out of 120 patients on acyclovir developed CMV disease; none developed signs of herpes infection, and 16 recovered from oral hairy leukoplakia. Dr. Metroka's results have important implications. Given that a large number of PWAs develop CMV disease, trials combining acyclovir and AZT may have renewed importance. In addition, some studies have provided hints of synergism (increased anti-HIV effect) when AZT and acyclovir are combined. Dr. Metroka's work represents an extension of recent studies on the use of acyclovir as CMV prophylaxis in people receiving organ transplants. Like PWAs, donor organ recipients are at increased risk for developing CMV disease, since medication taken to avoid organ rejection renders them immunodeficient. In the first study, fewer instances of CMV reactivation were observed in transplant patients given intravenous acyclovir than in those not on the drug, although 18 patients experienced kidney toxicity (5). Another randomized trial was conducted with oral acyclovir for transplant patients (6). During the first year after transplant, a significantly smaller number in the acyclovir group developed CMV (4 out of 53) than in the control group (15 out of 51). In June 1988, Dr. Maxime Seligmann, of Hopital St. Louis in Paris, presented results from a study of acyclovir plus AZT vs. AZT alone at the Fourth International AIDS Conference. His results for the combination were encouraging although they still have not been published. For 48 weeks, 132 patients received a daily dose of 1000 mg AZT alone or in combination with 3200 mg acyclovir. A lower incidence of CMV was reported for patients on the combination (7). Monoclonal Antibodies At the University of Arizona, researchers have been pursuing a novel approach to controlling CMV with doses of anti-CMV antibodies produced outside of the body (8). This technique involves mass producing antibodies capable of suppressing CMV and giving them to patients as treatment. A Japanese firm called Teijin Unlimited is sponsoring the research. The treatment has been used with success in Japan for bone marrow transplant patients. In a small pilot study, 12 HIV-positive patients with CMV antibodies received a single dose of the drug, which was well tolerated. Patients with stable CMV disease are now being recruited for a multiple-dose study. Encouraging results have been seen so far: one patient with positive culture at entry became buffy coat-negative (a laboratory test for CMV) after one dose and has remained negative for eight weeks. However, the possibility remains that patients will develop antibodies that may neutralize these "foreign" anti-CMV antibodies although this has not yet been seen. Patients in the Tucson, Arizona area who are interested in this study should call the University of Arizona clinical trials information nunmber (602) 626-6887. At New York University, Dr. Susan Zolla-Pasner is trying to develop monoclonal antibodies to CMV. To date, her lab has succeeded in reproducing a few antbodies, but they have not yet been used in people. Other Possibilities Attempts to find other agents for treatment and maintenance of CMV are currently under investigation. Dr. Douglas Dieterich has submitted protocols for trials of oral ganciclovir and FIAC, another oral drug being investigated for CMV, at NYU. It is much too early, he says, to indicate whether the drug will prove useful or not. FIAC is currently in trials in Seattle, San Diego, Bethesda and Birmingham. Intravitreal injections of ganciclovir (injections directly into the eye) have been successful in both treatment and prevention of recurrence of CMV retinitis, without any of the systemic side effects of intravenous ganciclovir (9). Finally, Burroughs-Wellcome, maker of acyclovir, also is investigating a similar drug called desciclovir. Desciclovir is a "prodrug" of acyclovir, meaning that it is metabolized into acyclovir after absorption (10). The advantage of this drug is that it is much more efficiently absorbed, so patients might be able to take less and achieve the same results as high-dose acyclovir (11). Nothing has appeared in the medical literature about this drug since 1987, despite the fact that desciclovir was found to be as effective as acyclovir in the treatment of herpes zoster in doses of only 125 mg three times a day (12). Acyclovir is by no means a cheap drug. Interestingly, its price has increased twice in the last few years, both times soon after AZT's price was lowered. For New York residents who have trouble paying for acyclovir, financial assistance is now available for those who qualify. The AIDS Drug Assistance Program (ADAP) has added acyclovir to the list of drugs it will cover. For more information, call 1-800-542-2437. ***** FDA Denies Treatment-IND for Imuthiol Kevin Armington Several placebo-controlled studies since 1985 have provided evidence that this drug slows progression of HIV-related disease (13,14). The French have been treating AIDS patients with Imuthiol (DTC) since 1983, with encouraging results. Upon completion of a multicenter American study, sponsored by the French pharmaceutical company, Institut Merieux, data were presented to the FDA in support of a Treatment-IND (for early release) and full licensing of Imuthiol. Despite promising results from controlled trials, the FDA turned down Merieux's request, denying HIV-infected individuals access to this drug. In the American study, 387 patients with AIDS or ARC were randomized to placebo or 10 mg/kg Imuthiol a week. Patients were evaluated after an average treatment period of 18.5 weeks. Those who responded best were people with AIDS, who had fewer that 200 T4 cells (15). The most significant finding was a difference in numbers of opportunistic infections (OIs): 25 OIs occurred in patients on placebo as opposed to 10 in those on drug. (In a recently completed study [ACTG #019], a similar finding persuaded FDA to approve AZT for patients with T4 cell counts under 500.) In addition, patients on drug had a reduction in thrush, oral hairy leukoplakia (white ridges or lesions on the side of the tongue) and certain clinical symptoms (fever, fatigue, night sweats). A slight rise in T4 cell counts was seen in those on drug after 24 weeks of treatment. Aside from a metallic taste and gastrointestinal upset, no toxicity was seen. Results from a German study of Imuthiol were published in the March 24, 1990 Lancet (16). This group's findings were similar to earlier data in terms of toxicity and efficacy. Sixty patients with ARC were randomized to oral Imuthiol, intravenous Imuthiol or placebo. After 24 weeks of treatment, six patients on placebo versus none on drug progressed to AIDS. Although T4 cell counts did not rise significantly in patients on drug, Imuthiol appears to stabilize T4 levels, according to these researchers. This study also noted that Imuthiol has activity against a number of microbes that are commonly seen in HIV- infected individuals. Why did the FDA Say No? According to representatives of Institut Merieux, the FDA raised objections about the limited survival data. In addition, there was some concern about the methaline chloride content of the coating on the capsule, which preserves the drug from digestion in the stomach. Finally, the FDA argued that the availability of AZT in this country makes access to Imuthiol unnecessary. Officials at the FDA disputed that the Treatment-IND was rejected on such rigid grounds. In general, regulators who reviewed the data are not convinced that Imuthiol slows progression of HIV illness or that there is "significant" evidence of efficacy. The most common infection reported in the placebo group was PCP, and the data were re-examined after Merieux specified who received prophylaxis, which was optional in the study. Treatment Issues was unable to obtain these data. Excluding PCP, however, ten OIs were reported in those on placebo, while only three OIs were seen in those on drug. Officials at the FDA asserted, however, there was some disagreement about these numbers. It appears that the availability of AZT did have an impact on the FDA's decision to deny the Treatment-IND, which is difficult to understand from a scientific point of view. AZT is approved as an antiviral treatment; Imuthiol appears to work through immunomodulatory mechanisms. The two drugs appear to be perfectly safe when used together and could be effective complementary therapy. The FDA's unfortunate decision is yet another example of an overly cautious regulatory process which errs on the side of blocking access to potential treatments. If Imuthiol is compared to ddI, it is especially baffling that the Treatment-IND was denied. Seven years of clinical experience have demonstrated Imuthiol's safety, and more than one placebo-controlled trial have provided evidence of efficacy. Treatment-INDs were envisioned to allow very ill patients with no other treatment options early access to promising drugs. In this case, it seems that the standard the FDA is using is equivalent to the standard for full approval and licensing of a new drug. ***** DHEA-Possible Immunomodulator Wayne Kawadler Dehydroepiandrosterone (DHEA) is a hormone which originates in the adrenal gland and causes the release of both testosterone and cortisol. DHEA is found almost everywhere in the body incuding the testes, ovaries, lungs, and brain. Large amounts are concentrated in the urine. The amount of DHEA in the body peaks at 25 to 30 years of age and then decreases. Exercise does not change DHEA levels, but vegetarian diets result in lower levels. DHEA has been shown to have immunoregulatory, anti-diabetic, anti-cancer and anti-stress activity. A test tube study has shown that DHEA inhibits Epstein-Barr virus. This same study provided hints that DHEA may play a role in the maturation process of T cells (17). In mice, DHEA has been shown to prevent obesity, prolong life, and fight cancer causing agents (18). Another study in mice showed that DHEA improved the immune response to viral infection (19). In patients with AIDS, it has been noted that DHEA levels are dramatically lower than normal (20). A small double-blind, placebo-controlled study of DHEA, administered orally, has been done in Amsterdam. All 12 participants were p24 antigen positive, and received either a daily dose of powdered DHEA (750mg) or placebo. The results from this study, which were recently published, showed that DHEA may have no clear anti-HIV effect, but it may have had a positive effect on the immune system. Improvement in T cell performance and some evidence of immunomodulation were noted. In five of eight patients on drug, there was evidence of T cell activation and proliferation. No significant changes in p24 levels occurred in this group. This study suggests that the lower dose may be more effective. More trials of this sugbstance at differing doses may be useful (21). Community Research Initiative (CRI) is continuing to enroll participants in a Phase I dose-escalating trial of DHEA to obtain initial information on toxicity and efficacy in PWAs. The 16- week trial will have two arms. One group will receive 1gm DHEA daily to be administered orally. The second group of 12 will receive 2gm daily if no significant toxicity is observed in the first group. For further information about this study, call CRI at 212-481-1050. ***** In Brief Earlier Use of AZT: The FDA formally announced a labeling change for AZT, allowing physicians to prescribe the drug for any HIV-infected individual with fewer than 500 T4 cells. The dosage recommended is 500 mg a day, based on results from a study that recruited over 1300 asymptomatic patients (protocol # 019). Twice as many patients in the placebo arm had disease progression compared to the patients in the treatment arms, who received either 1500 mg or 500 mg AZT daily. Since no significant difference was noted between the two doses, the lower one is recommended. Results from this study were recently published in the April 5, 1990 issue of New England Journal of Medicine. This paper notes that the long-term effects of AZT use in asymptomatic patients is unknown, and that further study is necessary to determine if AZT improves survival in this population. Information already gathered about the drug mostly concerns toxicity. The community-based study is funded in part by a $250,000 grant from Sandoz Pharmaceuticals, maker of ganciclovir. ADAP Expands List of Covered Drugs: The AIDS Drug Assistance Program of New York State recently added the following drugs to the list of those for which they will reimburse: acyclovir (Zovirax), fluconazole, dapsone, leucovorin, Fansidar, Bactrim (Septra), ganciclovir, clotrimazole, ketoconazole, acidilin and nystatin. For more information about this program, call 1-800-542-2437. All information is kept strictly confidential. Medical Forum: GMHC will be co-sponsoring a forum with Beth Israel on the following topics: the design, value and purpose of clinical trials; prophylaxis of PCP and other infections; the value of a "team approach" to coordinating health care and issues surrounding inpatient treatment for acute illness. The intended audience is HIV-infected patients. The forum will be held on Thurday, April 26, 1990 from 7:00 to 9:00 pm in Beth Israel's Dazian Pavilion - Podell Auditorium, 10 Nathan D. Perlman Place (east of Second Ave., between 16th and 17th St.) Space is limited, and seats may be reserved by calling (212) 420-2069. HIV-Positive Forum: On Thursday evening, May 24, Positive Action of New York has invited Dr. Anthony Fauci, Director of the NIH AIDS Program, to address the following topic: Staying Healthy - Propects for People with HIV Infection who do not have AIDS. After his talk, Dr. Fauci will answer questions from a panel representing eight local HIV/AIDS-related service organizations. During the final hour, Dr. Fauci will take questions from the audience. The forum will be held at Fashion Institute of Technology, Haft Auditorium, 227 W. 27th St., New York, N.Y. It will begin at 7:30 pm. Suggested donation is $5.00. Treatment Issues Survey: Many thanks to readers who took the time to fill out the survey that ran in the last issue. This valuable feedback will guide us in our effort to assess and improve Treatment Issues. If you haven't returned the survey yet, it's not too late -- we want to hear from you! ***** New Studies Community Research Initiative in New York is opening a double-blind, pacebo-controlled trial with a drug called Met- Enkephalin. Met-Enkephalin is a naturally occurring endorphin which may play a role in restoring the immune system. The drug will be administered by intravenous infusion once a week. Patients must have between 200-500 T4 cells and at least one symptom of ARC. Concurrent use of AZT or alpha interferon is not permitted. For further information on this study, please contact Heidi Dorow at 212-481-1050. A trial comparing ketoconazole and nystatin in the treatment of candida infections (thrush) of the mouth, pharynx and esophagus is being conducted at Harlem Hospital. The trial is open to anyone with thrush who has not been treated for candida within the last two weeks and is not on medication for tuberculosis. Following completion of the two-week study, participants will be paid $50. For more information, call (212) 491-8554. The North Jersey Community Research Initiative is conducting a study comparing two doses of Bactrim, a drug that is used to prevent (and treat) PCP. The purpose of this study is to see if a lower-than-normal dose will be as effective. Participants will receive two double-strength tablets daily or three times a week. Candidates must have a T4 cell count under 200. For more information, call (201) 648-0350. Hill Health Center, in New Haven, CT, recently joined on the same protocol. Their number is (203) 787-9055. The AIDS Treatment Registry provides up-to-date information on clinical trials of antivirals, immunomodulators, and drugs for HIV-related infections and cancers in New York and New Jersey. Their easily readable guide can be obtained by calling (212) 268-4196. American Foundation for AIDS Research (AmFAR)also publishes a catalog of trials involving experimental drugs. To order the "AIDS/HIV Experimental Treatment Directory", write to AmFAR at 1515 Broadway, Suite 3601, New York, N. Y. 10036, or call (212) 719-0033. The National Institutes of Health operate a toll-free hotline to provide information on HIV-related clinical trials run by the federal government. Callers may request a Spanish speaking operator. The lines are open Mon.- Fri. 9:00 am to 7:00 pm eastern time. The number is 1-800-TRIALS-A. "AIDS Treatment News" is a biweekly report which chronicles current developments in experimental and alternative treatments and deals with public policy issues. Contact John S. James at P. O. Box 411256, San Francisco,CA 94141 or call (415) 255-0588. Project Inform publishes a newsletter called "PI Perspective" which deals with experimental treatments. Another resource is their drug hotline: 1-800-822-7422. "PWA Coalition Newsline", published "by and for people with AIDS and AIDS Related Conditions," is a grass-roots news magazine that appears monthly. Write PWA Coalition Inc., 31 West 26th St., New York, N. Y. 10010, or call (212) 532-0290. Body Positive is a organization for people who are HIV- positive. They publish a monthly newsletter called "The Body Positive." Write to: 208 West 13th St., New York, NY 10011 or call 212-633-1782. Also providing services to seropositives is an organization called "Positive Action". For more information, call (212) 727-7768. Treatment Issues is GMHC's newsletter devoted to providing reliable information on experimental AIDS therapies. Describing an experimental therapy should not be construed as recommending it. All new treatments should be done under a physician's care. ***** Treatment Issues is published ten times yearly. Copyright 1990 Gay Men's Health Crisis, Inc. All rights reserved. Non- commercial reproduction is encouraged. Subscription lists are kept confidential. Editor: Kevin Armington Medical Consultant: Gabriel Torres, M. D. Technical Assistance: Wayne Kawadler Writers: Wayne Kawadler Howard Rubin Gabriel Torres, M. D. Proofreader: Roger Cottingham Contributor: Stephen Gum, M. D. GMHC, Department of Medical Information, 129 West 20th Street, New York, NY 10011. Footnotes 1 Jabs DA et al. CMV Retinitis and AIDS. Arch Opth 107:75-80, 1989. 2 Chachova A et al. Ganciclovir in the treatment of CMV gastrointestinal disease in AIDS. Ann Int Med, 107:133-37, 1987. 3 Vth Int Conf on AIDS. Abstract # MBP. 126. June 1989, Montreal. 4 Personal communication, C. Metroka. 5 Meyers JD et al. Acyclovir for prevention of CMV infection and disease after allogeneic marrow transplantation. NEJM 318(2):70-75, 1988. 6 Balfour HH et al. A randomized placebo-controlled trial of oral acyclovir for prevention of CMV disease in recipients of renal allografts. NEJM 320(21):1381-87, 1989. 7 Seligman M. Oral presentation Retrovir Satellite Symposium IV Int Conf on AIDS, Stockholm, Sweden. June 6, 1988. 8 Personal communication. Gray, J. 9 Cantrill HL et al. Treatment of CMV retinitis with intravitreal ganciclovir. Opth 96:367-74, 1989. 10 Krasny HC et al. Metabolism of desciclovir, a prodrug of acyclovir, in humans after multiple oral dosing. J Clin Pharm 27(1):74, 1987. 11 Rees PJ et al. A515U: a prodrug of acyclovir with increased bioavailability. J Antimicro Chemo 18 Suppl. B:215, 1986. 12 Peterslund NA et al. Open study of desciclovir in the treatment of herpes zoster. J Antimicro Chemo 20(5):743, 1987. 13 Brewton GW et al. A pilot study of DTC in patients with AIDS and ARC. Life Sciences 45(26):2509-20, 1989. 14 Lang JM et al. Randomised, double-blind, placebo-controlled trial of ditiocarb sodium ('Imuthiol') in HIV infection. Lancet ii(8613):702-06, 1988. 15 Personal communication, P. Cohen. 16 Reisinger EC et al. Inhibition of HIV progression by dithiocarb. Lancet 335(8691):679-82, 1990. 17 Henderson E et al. DHEA and 16a bromo-epiandrosterone: Inhibitors of Epstein-Barr virus induced transformation of human lymphocytes. Carcino 2:683-86, 1981. 18 Pashko LL et al. DHEA and 3B methylandrost-5-en-17-one: inhibitors of 7,12-dimethylbenz anthracene (DMBA)-initaited and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin papilloma formation in mice. Carcino 5:463-66, 1984. 19 Loria RM et al. Up-Modulation of the Immune Response to Virus Infections with DHEA. Depts of Micro, Immuno, and Patho, Schools of Basic Health Science and Medicine, VA Commonwealth Univ, Richmond VA., 23298-0678. 20 Seaman JD et al. DHEA and DHEAS in AIDS. Submitted Jrnl of Clin Endocrin and Metab, 1988. 21 Mulder JW et al. DHEA Admin in HIV Infection. European AIDS Conference, March 1990. &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& End of display