Subject: Compound Q; Acyclovir; AZT Resistant Strains Date: May 15 1989 (649 lines) &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& TREATMENT ISSUES -- The GMHC Newsletter of Experimental AIDS Therapies &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& Volume III, Number 3: May 15, 1989 [Footnotes are enclosed in triple quotation marks: ((( )))] Contents: [items are separated by "*****" for this display] Compound Q Acyclovir AZT Resistant Strains Licensing Update New Studies In Brief ***** Compound Q GLQ 223 (Compound Q) is a highly purified preparation of Trichosanthin, a drug extracted from the root of a Chinese cucumber plant. Test tube experiments with the drug show extraordinary anti-HIV activity in cells susceptible to HIV. The drug has also been well tolerated by animals in doses much higher than those planned for the administration to humans. Recently, the FDA announced that Genelabs, the pharmaceutical company that holds the patent to Compound Q, will be allowed to conduct toxi- city and dosage trials of the drug in people. Selectivity in the Test Tube Antivirals work against HIV through a variety of mechanisms. Some, like AL721 and CD4, may prevent HIV from encoding itself onto the genetic information of the infected T4 cell. Still oth- ers, like Dextran sulfate, may break up clumps of cells that facilitate cell to cell transmission of the virus. Compound Q seems to work by entering infected cells and eradicating the virus. In addition to destroying HIV in T4 cells, Compound Q kills chronically infected macrophages, which are white blood cells that harbor HIV. No other antiviral accomplishes this. Finally, Compound Q is able to penetrate the brain -- a crucial property of any anti-HIV treatment. In Vitro Work Compound Q was tested in two types of immune system cells (((McGrath MS et al. GLQ223: an inhibitor of HIV replication in acutely and chronically infected cells of lymphocyte and mononu- clear phagocyte lineage. Proc Natl Acad Sci 86, 1989.))) T4 cells from uninfected donors were inoculated with HIV, then exposed to Compound Q. The effect of the drug was measured by the level of a protein manufactured by HIV called p24. Production of p24 in these T4 cells was almost eliminated when exposed to low concentration of the drug for three hours. The level of viral RNA (genetic code for the virus) also decreased. Other T4s con- tinuously exposed to higher concentrations of compound Q for three days sustained some damage to the cells. While this find- ing may have dosage implication when administered in people, the lower dose of Compound Q used in the test tube was sufficient to neutralize virus. Perhaps the most encouraging activity observed in compound Q is its ability to penetrate and eventually kill HIV-infected macrophages. These were conducted with macrophages infected with HIV in the test tube and with blood samples drown from PWAs and PWARCs. Cells infected in the test tube were exposed both to Compound Q and AZT. Four days after treatment, cells exposed to Compound Q had no detectable levels of p24, in contrast to cells exposed to AZT, which contained measurable levels of p24 after 4 days. Furthermore, in blood samples drawn from 8 HIV-infected persons, a single low-dose eliminated p24 from macrophages in 5 cases. This finding is particularly encouraging because freshly drawn blood typically does not have detectable p24. Yet Compound Q was able to prevent p24 production in these macrophages, sug- gesting that the drug is effective during the latent (asymp- tomatic) stages of HIV infection. Extensive animal toxicity studies have been done. Compound Q has been administered to 5 species of animals with no toxicity observed at dose levels planned for human trials. Trials in People FDA recently awarded Investigational new Drug (IND) status to Compound Q, allowing Genelabs to proceed with human trials of the drug. This decision is commendable, and we hope that other promising drugs will enter clinical testing with as much speed. The only Phase I trial in the country will be at San Francisco General Hospital under the direction of lead investigator Dr. Paul Volberding. Approximately 20 AIDS patients with advanced but stable (no active infections) disease will be recruited for a dose escalation study. The main purpose of this study is to see if subjects can tolerate the drug. Estimates are that this trial will require between 6 and 9 months to complete. Nine months seems like a long time to wait for larger, multicenter trials that would measure efficacy. Rumors that investigators are really expecting this trial to last one year have been reported to Treatment Issues. The PWA community will not tolerate a 12 month delay before larger efficacy trials are begun. We hope this exciting drug is put on a genuine fast track and, if proven safe and effective, made available as quickly as possible. Summary Compound Q has shown remarkable specificity for HIV-infected cells in the test tube. It initially suppresses production of viral proteins and viral RNA in T4 cells and macrophages and eventually kill HIV-infected macrophages. No other potentially safe substance has demonstrated such versatile and potent anti- HIV activity in the text tube. However, we have been disap- pointed before (remember Fusidic acid?). We do not yet know how humans will react when they take the drug systemically. We must be cautious until more is know about Compound Q. People should be extremely careful if they are considering using an underground supply of the drug. A few individuals have already experimented with version of Compound Q that was not pure, and suffered some side effects. Potential users should also be aware that fraudulent version of the drug are being sold. Any powder, pill or other substance marketed as "Compound Q", Chinese cucumber plant extract" or "trichosanthin" should be avoided. Some of these products may actually be harmful. Chinese cucumbers themselves are not thought to have any anti-HIV effect. Compound Q is only available in liquid form, for injection. We will closely follow and report developments on this drug. ***** Acylovir and the Herpes Family of Viruses by Craig-Steven Chin In AIDS patients, viral infections, particularly herpes viruses account for about one-sixth of all infections. Since its release for clinical use in 1982, the Burroughs Welcome antiviral drug acyclovir has been shown in numerous controlled studies to be the safest and most effective drug available in the treatment of certain herpesvirus infections (((Dorsky DI et al. "Drugs Five Years Later: Acyclovir." Ann Intern Med 107: 859- 874, 1987. King H. "History, Pharmacokinetiks and Pharmacology of Acyclovir." J Am Acad Dermatol 18: 176-179, 1988))) The Herpesviruses The herpes family included six human viruses: herpes sim- plex virus type 1 (HSV1), herpes simplex virus type 2 (HSV2), varicella- zoster virus (VZV), cytomegalovirus (CMV), Epstein- Barr virus (EBV), and human herpesvirus type 6. All her- pesviruses share the ability to lie dormant within host cells. In the dormant period, herpes viruses may be detected but viral reproduction does not occur. Patients are generally free of symptoms and latency may last for years. All herpesviruses may be reactivated into a reproducing phase in which infectious virus is produced and host cells are killed. Reactivation of VZV (in the form of shingles) can indicate immune suppression; in HIV positive individuals, shingles sometime is predictive of progres- sion to AIDS (((Melbye M et al. "Risk of AIDS after Herpes Zoster." Lancet 1: 728-731))). Shingles by itself does not indicate HIV infection. Clinical Use Acyclovir is most active against HSV and VZV. Acyclovir is also recommended to prevent reactivation of HSV during latency or to treat active HSV or VZV in immunocompromised patients. Herpes Simplex Viruses HSV episodes in immunocompromised patients can be lengthy, producing extensive lesions. Intravenous acyclovir is the drug of choice for HSV respiratory disease, esophagitis, sever perirectal ulcers, retinitis, and encephalitis. Acyclovir has proved superior to vidarabine (adenosine arabinoside, Ara-A) for the treatment of HSV encephalitis in several randomized trials. Aggressive intravenous therapy is recommended for encephalitis. For severe or resistant HSV encephalitis a combined therapy of acyclovir and vidarabine has been suggested (((Besser R et al. combines therapy with acyclovir and adenosine arabinoside in herpes simplex encephalitis. eur neurol 27: 197, 1987))). Varicella-Zoster Virus Intravenous acyclovir is effective in treating local and disseminated VZV infections in immunocompromised patients (((Straus SE et al. "HIH conference: Varicella-Zoster Infec- tions: Biology, Natural History, Treatment, and Prevention." Ann Intern Med 108: 221-237, 1988))) In a randomized trial of patients with suppressed immune systems, intravenous acyclovir proved superior to vidarabine for VZV infections. Because VZV is less sensitive to acyclovir than to HSV, higher dosages should be used for VZV disease: 10 mg/kg IV every eight hours or oral doses of 800 mg 5 times a day. High-dose acyclovir does not appear useful for lingering pain after VZV infection. Epstein-Barr Virus EBV is only partly sensitive to acyclovir. In the most com- mon Epstein-Barr virus disease, infectious mononucleosis, acyclo- vir has been shown to inhibit oral Epstein-Barr infections, such as oral hairy leukoplakia in HIV positive individuals. This infection appears as white spots on the side of the tongue. Oral hairy leukoplakia accompanying HIV infection, can be predictive of future AIDS development (((Greenspan D et al. Relation of Oral Hairy Leukoplakia to Infection with Human Immunodeficiency Virus and the Risk for Developing AIDS. J Infect Dis 155: 475-481, 1987))). Cytomegalovirus CMV does not respond to acyclovir. But a related drug, gan- ciclovir (DHPG), has proved useful for some CMV disease and retinitis. Ganciclovir treatment failures have occurred in cytomegalovirus disease of the central nervous system and respiratory system. A comprehensive article on CMV appeared in Treatment Issues, Vol. II, No. 8. Resistance Acyclovir-resistant herpes viruses have been isolated from immunosuppressed patients have received repeated or prolonged courses of the drug. Clinical disease with acyclovir resistant virus, notably ulcers, is appearing with increasing frequency in AIDS patients (((Erlich KS et al. "Acyclovir-Resistant Herpes Simplex Virus Infections in Patients with the Acquired Immunode- ficiency Syndrome." N Engl J Med 320: 293-296, 1988))). No proven therapy is yet available for these resistant viruses; however, vidarabine and foscarnet (an experimental drug) (((Youle MM et al. Acyclovir-resistant herpes and AIDS treated with forscarnet. Lancet 2: 341, 1988))) have shown some bene- fit. In one small study of 4 patients with AIDS who had acyclo- vir resistant HSV2 infections, 60 mg/kg body weight of foscarnet were administered every 8 hours. All patients experienced dramatic improvements in their skin lesions (((Erlich KS et al. Foscarnet therapy for severe acyclivir resistant herpes simplex virus 2 infection in patients with AIDS. Ann Intern Med 100(9): 710, 1989))). Administration Acyclovir is available in three formulation: 5% ointment is used for skin lesions; oral and intravenous forms are used for systemic therapy. All three forms have been shown to decrease viral reproduction, diminish pain and accelerate healing in severely immunosuppressed patients with HSV and HZV. Intravenous and oral therapy are equally effective, but intravenous adminis- tration is used in cases where there is disseminated disease or the patient has problems taking oral drugs. A 3% ointment can be used for eye disease. This latter formulation, which is avail- able is Britain, is not yet licensed in the United States. For systemic therapy in AIDS patients with normal kidney function, the intravenous dosage for extensive disease is 5 mg/kg for HSV or 10 mg/kg for VZV every 8 hours. The length of treat- ment will depend on various factor, but HSV, it is generally 5-10 day; for VZV 7-10 days (((Melamed AJ et al. "Drug-Use Criteria for Acyclovir Sodium Injection." Am J Hsp Pharm 45: 382-383, 1988))) The oral dosage of acyclovir for herpes simplex in AIDS patients is 400 mg orally, five time a day for 5 days or until the skin lesions clear. Concurrent use of acyclovir ointment may also decrease discomfort and shorten the disease course. The dosage suggested for oral suppressive therapy for HSV varies, but 200 mg 3 times daily is commonly cited (((Conant MA. "Prophylatic and Suppressive Treatment with Acyclovir and the Management of Herpes in Patients with Acquired Immunodeficiency Syndrome." J Am Acad Dermatol 18: 186-188, 1988))). Toxicity Toxic effects of acyclovir at normal therapeutic levels are minimal (((Arndt KA. "Adverse Reactions to Acyclovir: Topical, Oral and Intravenous." J Am Acad Dermatol 18: 188-190, 1988))). Local irritation can occur with topical and ophthalmic use. The most frequent reactions with short term oral acyclovir are nausea and vomiting. With six months continuous oral use, frequent reactions are headache, diarrhea, nausea and vomiting. But these symptoms were reported almost as frequently by subjects receiving placebos. The most frequent reaction after intravenous acyclovir is skin and vein inflammation at the injection site. Adequate drug dilution and slow administration will usually prevent this prob- lem. In the event of inflammation, warm soaks and alternate IV sites will help. Overly rapid intravenous administration of acy- clovir can also cause temporary kidney dysfunction. This may be prevented by slow intravenous administration, adequate water intake, maintenance of urine output and adjustment of the dosing interval so as to not exceed the kidney's excretion rate. Acyclovir is primarily eliminated by the kidneys. This fact is especially important for AIDS patients, of whom 10-30% may have kidney disease. Patients with kidney impairment or failure are more susceptible to central nervous system toxicity due to acyclovir accumulation. This buildup of the drug causes the most serious adverse effects associated with acyclovir: neurotoxicity (abnormal encephalogram, lethargy, tremors, confusion, hallucina- tions, agitation, seizures, and coma). The incidence of neurolo- gic side effects correlates with high plasma levels of acyclovir (((Feldman S et al. "Excessive Serum Concentrations of Acyclovir and Neurotoxicity." J Infect Dis 157: 385-388, 1988.))) Human Immunodeficiency Virus (HIV) Acyclovir has been shown to augment the anti-HIV activity of AZT in the text tube. Some trials of this combination have also been conducted in people. A ten-week Phase I trial of acyclovir and AZT (100 mg AZT and 800 mg acyclovir every four hours) in 8 AIDS patients suggested good tolerance of this drug combination with continued anti-HIV activity (((Surbone A et al. "Treatment of the Acquired Immunodeficiency Syndrome (AIDS) and AIDS Related Complex with a Regimen of 3'-Azido-2',3'-Dideoxythymidine (Aziodothymidine or Zidovudine) and Acyclovir: A Pilot Study." Ann Intern Med 108: 534-540, 1988))). Another report of 397 patients with AIDS or ARC had encouraging results (((Fiddian AP et al. Preliminary report of a multicenter study of zidovudine plus or minus acyclovir in patients with AIDS or ARC. Jour Infect Dis 18(1,S-1): 79, 1989))). Patients were randomized to 1000 mg daily of AZT alone, 1000 mg of AZT plus 3200 mg acyclovir or pla- cebo. No justification was stated for subjecting AIDS or ARC to placebo. A significant difference in survival was noted in AIDS patients: after 48 weeks, 66% of patients who received AZT alone were alive vs. 85% receiving AZT plus acyclovir. Also, fewer and less severe opportunistic infections were seen among partici- pants who received the combination. This study strongly suggests a heightened antiviral effect for AZT when taken with acyclovir. Summary Acyclovir has been shown in numerous, controlled studies to be both extremely effective and very safe (when properly admin- istered) for active HSV and VZV infections. Acyclovir is also useful for suppressive prophylaxis of herpes simplex. The prin- cipal problems with prophylactic use are the emergence of acy- clovir resistant herpesviruses and the high cost of oral suppres- sive therapy, which can range from $1.50 to $2.50 a day for an indefinite period. Some evidence suggests that acyclovir in com- bination with AZT may act against HIV better than AZT alone. If these finding are confirmed, patients who take AZT may be able to take less drug for greater effect and lowered toxicity. ***** AZT Resistant Strains William Byne, Ph.D. In a highly publicized study, HIV with reduced sensitivity to AZT was isolated from the blood of several patients who had been taking AZT for six months or more (((Larder BA et al. HIV with reduced sensitivity to zidovudine (AZT) isolated during pro- long therapy. Science 243: 1731, 1989))). Resistance to AZT was demonstrated in the test tube but was not linked to any deterioration in the patients' health. The researcher concluded that it would be premature to alter any treatment protocols for HIV-infected patients on the basis of their findings. Because of the attention given to this study by the media, it is reviewed here in an attempt to dispel any confusion or undue alarm that may have been generated. Briefly, Larder et al attempted to isolate HIV from the blood of 101 patients, about half of whom had received AZT. Virus was successfully isolated from only 33 patients, 21 of whom had received AZT. The isolated viruses were then added to cells in lab dishes and their interaction with AZt was observed. In these experiments, HIV caused the cells to clump together, making viral activity easy to monitor. Isolates from patients who had taken AZT for less than 6 months and isolated from untreated patients were equally affected by the drug. But most of the 15 isolates from patients who had received AZT for 76 months or longer required more AZT to reduce viral activity by 50%. In some cases, this increase was small, but one third needed at least 100-fold increasing the amount of AZT required to inhibit viral activity by half. Resistance to AZT was not accompanied by resistance to some other antiviral drugs, including foscarnet (reviewed in Treatment Issues Vol. II, No. 8) In considering the possible implications of this study, it is important to bear in mind that only one-third of the attempts at virus isolation form the original 101 were successful. Thus, the isolated studied may have been unusual to begin with. More- over, the 5 patients whose isolated demonstrated dramatic resis- tance to AZT represented less than 5 percent of the total sub- jects int he study who had received the drug. Additionally, most of the subjects had badly damaged immune systems as evidenced by low T4 cells counts. According to Larder et al, experience with the herpes simplex virus has shown that drug resistance is more likely to develop in immunosuppressed patients. Thus, one cannot assume resistance will develop in asymptomatic seropositive with higher T4 counts. The critical issue is whether reduced sensitivity in the test tube also results in clinical resistance to AZT therapy. One potential indicator f viral activity in a patient is the amount of p24 antigen in the blood (p24 antigen is a protein made by the virus and is thought in most cases to increase in the blood as the virus multiplies). Larder et al did not observe a consistent increase in p24 antigen is patients with dramatic AZT-resistance. This finding suggests that the resistance demon- strated in the test tube may have little clinical significance. However, the p24 test may not accurately reflect viral replica- tion in some cases McHugh TM et al. Relation of circulating lev- els of human immunodeficiency virus (HIV) antigen, antibody to p24, and HIV-containing immune complexes in HIV-infected patients. (((Inf Dis. 158: 1088, 1988))). A further question is whether resistance to AZT would have any relationship to HIV's ability to cause disease. Larder et al emphasized that resistance did not signal an accompanying sudden deterioration of health. They also noted that in the case of another virus (herpes simplex), all isolates that have developed resistance to standard therapy have also demonstrated decreased ability to cause disease (((Larder BA et al. Selection and char- acterization of acyclovir-resistant herpes simplex virus type 1 mutants inducing altered DNA polymerase activities. Virology 146: 262, 1985.))). Only time will tell if a similar picture will emerge for HIV. In summary, the study by Larder et al demonstrated the emer- gence of AZT-resistant HIV in a small percentage of severely immunosuppressed patients who had taken AZT for at least 6 months. The clinical significance of this observation in the test tube is not know even for patients with full blown AIDS, let alone asymptomatic seropositive. As is the case with the herpes simplex virus, drug resistance might even go hand in hand with less potent virus. While the finding of Larder et al raise several questions for further research, they do not warrant modification of any existing HIV treatment protocols. Clinical trials of AZT have been reviewed in two previous editions of Treatment Issues (Vol. II, No. 1 and Vol. III, No. 1). The evidence to date shows that while AZT does not eliminate HIV from the body, it clearly increases life expectancy and improves the quality of life for patients with AIDS and advanced ARC who can tolerate the drug. Consequently, AZT has been approved by the Food and Drug Adminis- tration for AIDS patients and for ARC patients with significantly depressed T4 cell counts. One of the biggest questions today is when and if to start AZT in asymptomatic patients infected with HIV. Although the NIH trials of AZT in asymptomatic seropositive are still in progress, more physicians are prescribing the drug for asymptomatic patients in the hope that AZT will delay the onset of symptoms. The largest of these trials is scheduled to run another 2 years, but is evaluated every 6 months. Until we have conclusive evidence, the risk/benefit ration of starting AZT in symptomatic patients will be unknown. ***** Licensing Update Greg Lugliani Having navigated the drug approval bureaucracy for some time now, three experimental drugs have recently received judgement from FDA advisory committees -- panels which carry great weight with FDA policy makers. Two of these drugs, aerosolized pentami- dine and ganciclovir (DHPG), have secured recommendation for approval, and thus verge on clearing the FDA process. The immu- nomodulator Imreg- 1, however, has been sent back to the clinical trials drawing board, as Phase III test results have left FDA unconvinced that the drug works. Imreg-1: Responding to FDA's encouragement of pharmaceuti- cal companies to seek early release under the Treatment IND pro- gram for AIDS drugs, Imreg-1's manufacturer, Imreg Inc., applied for that designation in October, 1988. FDA refused the request, maintaining that the data was insufficient, the trial was not adequately blinded, and that inclusion criteria were not properly observed. FDA itself bluntly argued that the drug was no better than a placebo. However, in April, 1989, the same advisory com- mittee unanimously urged Imreg and FDA to work together to design and conduct new tests for Imreg-1's efficacy, stating "there is a feeling that there may be some effects from this drug." At present, FDA has officially denied Imreg's request for Treatment IND status, but is offering to work with the manufacturer "if they [Imreg] want to meet for further clinical studies." Apparently, Imreg, Inc., is taking FDA at its word: SAid an Imreg spokesman, "We are still, despite the debate, knocking at the FDA door." Aerosolized Pentamidine: Although commonly used to prevent PCP for some time, not until early 1989 did FDA loosen the re- striction no aerosolized pentamidine by granting Treatment IND status. Two pharmaceutical companies, LyphoMed Inc. and Fisons produce the drug. Since the company that secures approval first has exclusive marketing rights for seven years under the Orphan Drug Act (which applies to drugs that will be used by fewer than 200,000 people), a heated race to complete tests has been underway between the two companies. On May 1, 1989, FDA's Anti-Infective Advisory Committee held a public hearing on the safety and effi- cacy of aerosolized pentamidine, during which both LyphoMed and Fisons presented trial results. LyphoMed's data supports a dose of 300 mg monthly for most effective prophylaxis. On the other hand, Fisons presented data from ta Canadian trial that yielded impressive results with a lower dose (60 mg twice monthly). At this point it is unclear which company will win the license, but the panel unanimously recommended approval the drug for both primary and secondary prophylaxis against PCP for people with T4 counts of 200 or below. The recommendation hastens the rating of aerosolized pentamidine's New Drug Application (NDA), and full licensing is expected in weeks. Ganciclovir (DHPG): Manufactured by Syntex for use against CMV retinitis, ganciclovir has also received its share of mixed signal from FDA. Although available liberally on a compassionate use basis and generally regarded as effective in preventing AIDS- related blindness, FDA's Anti-Infective Advisory Committee denied Syntex's request for a license in October, 11987, stating that more data on long-term use of the drug were needed. In December, 1988, FDA, NIAID and Syntex restricted the availability of ganci- clovir in order to gather acceptable clinical data. Persons whose eyesight was not immediately treated were ushered into a delayed treatment trial in order to receive the drug; those with threatened sight were allowed immediate access to ganciclovir. An outcry from activists caused FDA in early March to allow peo- ple with CMV retinitis access to the drug, even though they were not enrolled int he trial. At that time, FDA asked to the Anti- Infective Advisory Committee to reconsider its earlier decision on approving ganciclovir. Therefore, on May 2, the committee held another hearing to assess the safety and efficacy of the drug. Test results from recent studies conducted in the U. S. and France by Syntex and independent researchers convinced the advisory committee to vote 8 to 0 for recommending the drug's approval. The committee also called for extensive post-marketing studies, particularly research on whether the drug can be used concomitantly with AZT, and suggested further comparison studies between ganciclovir and foscarnet, another experimental drug for CMV retinitis. Full licensing of ganciclovir is expected this summer. Erythropoietin: Another drug that is no the verge of being licensing has been mired in a legal battle. Erythropoietin (EPO) has been shown to stimulate the production of red blood cells in anemic patients. Versions of the drug have been tested by three pharmaceutical companies: Ortho Pharmaceuticals, Amgen, Inc. and Chugai-Upjohn, a joint Japanese-American venture. Ortho and Amgen entered into an agreement by which Amgen would attempt to secure licensing to sell the drug, under the Orphan Drug Act, to patients with chronic kidney failure. When Amgen presented its data to the FDA, Ortho insisted that its own data on the use of EPO in pre-dialysis patients be included. Amgen balked and a lawsuit ensued which eventually forced Amgen to submit Ortho's data. In the meantime, Chugai-Upjohn has submitted data to the FDA for license to sell the drug to the same patient population. Ortho, presumably, is pursuing a license to sell EPO to other anemic patients, including PWAs. All that this maneuvering means for PWA is that the financial interests of pharmaceutical com- panies are eclipsing the needs of patients. Fortunately, FDA has hinted that the drug is close to licensing. EPO will first be licensed for kidney patients, but that will enable doctors to prescribe the drug for other indications such as AZT -- induced anemia. For more detailed information on this promising drug, see Treatment Issues, Vol. III, No. 2. ***** New Studies Dr. Murray Wittner at the Albert Einstein College of Medi- cine is conducting a Phase III trial of Somatostatin in HIV- infected individuals with chronic diarrhea. Participants will be hospitalized for tow weeks, then will continue the trial as out- patients. This trial will examine efficacy and attempt to find the optimal dose. Participants will guaranteed a free lifetime supply of the drug, which very expensive. At a conference last fall, Dr. Donald Kotler, a specialist in gastrointestinal disease, mentions that, in several cases, this drug caused a "virtual cessation" of diarrhea. For more information, call Dr. Wittner at (212) 430-3342. The New York Hospital is recruiting for a study of gamma interferon in MAI infections. Some patients who are receiving other medications for MAI may be included in the study, but it is preferred that candidates not be taking other MAI drugs. Gamma interferon is a naturally occurring secretion of the immune sys- tem that has been synthesized. Earlier trials of the drug as a treatment for Kapsosi's sarcoma were disappointing, but research- ers are hopeful about the drug's prospects in treating mycobac- terial infections (for more information on mycobacteria, see Treatment Issues Vol. III, No. 2). The hospital will also be recruiting for a dosage and safety trial of gamma interferon in PWAs who are on AZT. Researchers hope to activate certain white blood cells, enhancing the immune system. For more information about these or other trials at New York Hospital, call Walter Weirs, R. N. at (212) 746-4181. ***** In Brief GMHC sponsors an ongoing series of public health seminars addressing the following issues: medical, clinical trials, nutrition, legal/insurance and complementary health care. The seminars, which are open to the public, take place on Thursday evenings, from 7:00-9:00; one topic is covered per evening. The schedule for June is: Medical Update, 6/1; Clinical Trials Issues, 6/8; Legal and Insurance Issues, 6/15; Nutrition; etc. The seminars will take place at GMHC, 129 West 20th St., 3rd floor classroom. The National Institutes of Health have opened a toll-free hotline to provide information on HIV-related clinical trials run by the federal government. According to an NIH press release, operators are trained to provide specific details about trials throughout the country. The information is updated weekly. Call- ers may request a Spanish speaking operator. The lines are open Monday through Friday from 9:00 a.m. to 7:00 p.m., eastern time. The number is 1-800-TRIALS-A. It may take a while to get through, but keep trying. 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 1989 Gay Men's Health Crisis, Inc. All rights reserved. Non- commercial reproduction is encouraged. Subscription list is kept confidential. Editor: Kevin Armington Technical Assistance: Howard Welsh We Need Your Support Your contribution will help GMHC to continue Treatment Issues and is tax-deductible. Mail to GMHC, Department of Medical Informa- tion, 129 West 20th St., New York NY 10011. A $20/year donation is suggested for a yearly subscription ($40/year foreign). All back issues are available for a suggested $10 donation. &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& End of display