Subject: Treatment Issues Vol. 4 No. 7 Date: Oct 12 1990 (734 lines) &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& TREATMENT ISSUES -- The GMHC Newsletter of Experimental AIDS Therapies &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& Treatment Issues 47 Volume 4 Number 7 -- October 12, 1990 Contents: [items are separated by "*****" for this display] ddI Update 556c80 Tacrine Photopheresis Kemron (Oral Alpha Interferon) Drug Availability Update In Brief New Studies ***** ddI: Long-Term Effects Gabriel Torres, M.D. The first report of long-term therapy with ddI in persons with AIDS or ARC was published in the British medical journal, Lancet on September 1, 1990 (1). Fifty-eight patients (22 AIDS and 36 ARC) who have taken ddI for up to 21 months (average: 8.9 months) were studied to determine the long-term effects of the drug on T4 cell counts and p24 antigen levels (a measurement of viral activity), as well as on survival and toxicity. The median number of T4 cell counts at entry for the entire group was 47. The initial phase I dose-escalating study and two subsequent phase I studies had shown increasing T4 cell counts and T4/T8 ratio as well as decreases in p24 antigen levels during the first several months of treatment with ddI at doses of 3.2-51.2 mg/kg (2,3,4). Side effects were more frequent in patients receiving more than 9.6 mg/kg per day. Some interesting efficacy data were reported for a subset of 13 patients who initially received ddI at lower doses (3.2-9.6 mg/kg/day). These patients have received ddI for a median of 17 months and 10 remain on drug. From an average T4 cell count of 157 at entry, they had an increase of 78 cells which persisted for at least nine months. Of the six patients with detectable p24 antigen levels, three have undetectable antigen after 15 months of ddI therapy, and none developed detectable p24 antigen. The patients who received AZT for four months or less prior to starting ddI had greater increases in T4 cell counts than those who had received AZT for more than four months. Four patients who had problems with memory, attention or concentration improved after 6-12 weeks of ddI therapy as measured by neuropsychological tests. Measurement of ddI levels in the cerebrospinal fluid (CSF) showed that approximately 21% of the drug present in the blood penetrated into the CSF, accounting for the neurological improvements. The major toxic effects of ddI were experienced by those patients who received high daily doses (more than 9.6 mg/kg), with 12 cases of peripheral neuropathy (painful sensation in the legs and feet), 5 cases of pancreatic inflammation, 2 cases of liver inflammation (hepatitis) and 3 cases of seizures. No patient died of these side effects. Only three patients who received lower doses (3.2-9.6 mg/kg/day) for up to 21 months experienced toxic reactions. Other mild reactions reported included anxiety, insomnia, irritability, headaches, abdominal pain and rashes. During the course of therapy some patients developed opportunistic infections but no patient developed lymphoma. The most encouraging piece of information in the Lancet report was the overall 88% survival rate after 21 months of ddI therapy. The 21-month survival rate for patients with AIDS was 80%; for patients with ARC, 93%. While the results of this long-term follow-up study are positive they do not tell us what the best dose is or if ddI will prevent progression at earlier stages of HIV disease. In addition, this study does not determine if ddI or AZT is better in prolonging survival. These questions are being addressed by the ACTG clinical trials 116 and 117, which compare AZT and ddI in a double-blind randomized study in patients who have been on AZT for less than one year (trial 116) or more than one year (trial 117). ddI use in patients with AZT resistance A group at the Maine Medical Center reported on six patients with AIDS who were clinically failing on AZT. These patients' virus had test tube evidence of AZT-resistance (5). All the patients had high levels of p24 antigen, and worsening symptoms of fatigue, loss of appetite and sweating. After five months of ddI therapy the p24 antigen levels had fallen in four patients and all had experienced improvement in energy level and appetite, with resolution of fevers, sweats and diarrhea. This report suggests that patients who are clinically failing on AZT have resistant virus and are likely to respond to ddI. Unfortunately, laboratory tests to measure AZT resistance are not readily available, and the exact time to switch from AZT to ddI may vary from individual to individual. Presently, clinical signs or symptoms of deterioration along with falling T4 cell counts and rising p24 antigen levels are the most practical factors to consider in deciding if and when to switch antivirals. Expanded Access Program Bristol-Myers Squibb, the company which sponsors the expanded access program of ddI, recently issued a Quarterly Safety Summary of serious adverse effects. Greater attention is being paid to serious side effects (pancreatitis and peripheral neuropathy) so these conditions are being diagnosed more frequently. Yet the overall severity is less because the drug is being stopped earlier when the first symptoms of neuropathy or pancreatitis occur (6). Diarrhea related to the sucrose and citrate/phosphate buffer continues to be the most frequently reported side effect, occurring in approximately 15%. This diarrhea often requires treatment with antidiarrheal medication. In the expanded access program certain factors have been identified which appear to be associated with a higher risk of pancreatitis. These include a prior history of pancreatitis, more advanced HIV disease, elevated amylase or liver function tests or concurrent treatment for CMV or MAI infections. Other toxic reactions reported in the expanded access program include 51 cases of seizures, of which 25 were not related to other HIV-associated brain abnormalities. Finally, deaths continue to be reported in the expanded access program, yet in 97.5% of cases they are due to progressive HIV-related disease or miscellaneous causes (cardiac failure, lung disease, strokes and suicides), and not due to ddI side effects. Seven deaths due to pancreatitis and three deaths from liver disease have been reported. ddI may have contributed to these deaths, but its role remains unclear. Conclusion ddI has now been in use for almost two years by patients in the original phase I studies and for more than one year by patients who are intolerant to AZT or who are clinically deteriorating while on AZT, through the expanded access program. The Lancet report indicates that the drug is effective and well-tolerated for up to 21 months at doses of 9.6 mg/kg or less, with improved long-term survival in patients with AIDS or advanced ARC. The toxicities (pancreatitis, neuropathy and hepatitis) seem to be related to higher doses and are reversible when the drug is discontinued at the first sign of a toxic reaction. The expanded access program continues to provide data on toxicity in very advanced patients. There are indications that certain medications commonly used for MAI or CMV may not be used with ddI. Signs of clinical deterioration may indicate AZT-resistance and justify switching to ddI, although the best time to switch drugs is unknown, and requires further investigation. ***** 566c80: A New PCP Therapy Darren J. Britton A study published in February by Walter Hughes and Winston Gutteridge, from St. Jude's Research Children's Hospital in Memphis, Tennessee, indicates that an investigational drug called 566c80 (566), may be more effective than Bactrim or pentamidine for treatment and prevention of PCP. 566 may in fact kill the cysts, the tiny "shelter" spaces that harbor the organism causing PCP. These cysts often remain after the parasites outside of the cysts have been eradicated (7). Killing the cysts would give 566 an advantage over Bactrim (or Septra) or pentamidine, the standard treatments for PCP. Background 566 belongs to a class of drugs called napthoquinones which were discovered in 1946 by Wellcome Research Labs. The drug was first found to inihibit a malarial parasite (8). Research then resurged in 1978 (9), and a variety of similar drugs were found to have activity in the test tube against other protozoa (10), including the organisms that cause toxoplasmosis and PCP. Since PCP is susceptible to broad-spectrum anti-protozoal drugs, 566 seemed like a good candidate for PCP treatment. 566 is the first napthoquinone to enter large-scale clinical trials in people. Animal Studies: Hughes et al. found that PCP was prevented in 90% of rats with induced immunosuppression at an oral dosage of about 100 mg/kg of body weight. All untreated control rats developed PCP. Lower doses (50 mg/kg) were less effective and doses of 25 mg/kg were essentially ineffective. In one group of animals with PCP, the drug was administered for three weeks at 100 mg/kg per day to determine its effectiveness as a treatment. An 80% cure rate was achieved when the drug was administered during an advanced stage of PCP. In a study in Memphis, treatment was begun 2 weeks earlier at a less advanced stage of illness. All of the animals receiving 100 mg/kg per day were cured (as determined by lung tissue exam), compared to an 80% cure rate in those animals treated with Bactrim. The design of the trial allowed researchers to gain some insight into whether the treatment is also effective in killing the cysts that harbor the parasites, or whether it just kills free parasites, leaving the cysts untouched. To date, there is no known treatment for either PCP, toxoplasmosis or most of the other related parasites, which actually eliminates the cysts. This is why initial ("induction") treatment is not sufficient for these infections in people with suppressed immune systems and indefinite maintenance therapy (prophylaxis) is necessary to prevent recurrence. In studies conducted in both rats and dogs with doses up to 500 mg/kg for six months, no clinical or laboratory signs of toxicity related to 566 have been noted. In preliminary dose-ranging studies for toxicity on developing fetuses in the rat, no effect on fetal body weight and embryo mortality have been found at a maximum dose of 100 mg/kg/day. Human Studies In an early pilot study of five volunteers with no illness, only one adverse reaction was seen. One volunteer experienced headache and vomiting nine hours after first administration of the lowest dose, which recurred after trying again 14 days later, and he was withdrawn from the study. This is the only reported adverse reaction attributable to 566 so far. Other studies to evaluate the drug's safety and absorption in humans have indicated that 566 stays in the bloodstream for a long time (half-life: about 72 hours). At doses of 750 mg every four hours, three times more drug is absorbed with all doses when a standard breakfast is eaten. In a Phase I trial in HIV-infected asymptomatic patients with T4 cell counts of under 250, very little drug was absorbed above a single dose of 750 mg. This study will continue to determine how many doses of 750 mg can be administered per day and how well this amount is tolerated. So far, no patients have complained of significant headache, nausea, or vomiting, as had been reported in the earlier case. Furthermore, no significant effect on white or red blood cell counts or platelets have been noted in any of the different dosings, up to 3000 mg four times per day. Finally, a phase I/II study of 566 for the treatment of mild to moderate PCP is under way at the National Institutes of Health, and will enroll a total of 50 patients. Patients will be asked to keep a food diary immediately before and after medication, and blood will be drawn two to three times per week. A protocol for a phase II/III study of PCP treatment has just been written and submitted for approval by Dr. Judith Falloon. For enrollment information, contact Barbara Baird at 301-496-9320. Additionally, a PCP prophylaxis study will be ready for accrual this month, and the contact person at the NIH for this study is Kristin Ownby at 301-402-0980. Burroughs-Wellcome is said to be aggressively pursuing its own well-designed studies at an apparently unprecedented speed, having identified some 22 sites nation-wide, including New York and San Juan, Puerto Rico, for its own upcoming phase II/III PCP treatment studies. Toxoplasmosis At least one pilot study is currently underway for treatment of toxoplasmic encephalitis, also at the NIH, for those who have failed pyrimethamine-sulfadiazine (standard treatment). Accrual is temporarily on hold. For more information on this trial contact Donna O'Neill at 301-496-9320. Some of the earlier relatives of 566 have been indicated for use against other parasites, most importantly toxoplasma and cryptosporidium. Conclusion 566 is a new type of antibiotic which has been shown in rats to be effective for both the prevention and treatment of PCP. In phase I studies in humans it seems to be well-tolerated without significant toxicity. Phase II/III trials are underway under the sponsorship of the NIH and the drug sponsor, Burroughs Wellcome to assess its role in the treatment of mild to moderate PCP. ***** Tacrine in HIV Infection Mike Barr Tacrine is an orally administered drug discovered in 1909 and first used to treat intestinal parasites. In the United States it is currently being tested for use in fighting the debilitating effects of Alzheimer's disease. Recent studies from France have shown it to be hopeful in the treatment of HIV infection. At the Sixth International Conference on AIDS this past June, two French studies reported possible immunomodulatory and antiretroviral effects in people with AIDS. The larger of these studies was detailed in a conference abstract which compared Tacrine to AZT in 70 AIDS and ARC patients. (This abstract was not published in the official book of abstracts, but appeared in the Conference Bulletin on June 23, 1990.) According to the data presented in the report, Tacrine's performance was superior to AZT's by every parameter measured. Dr. Gille Fredj, principal author of the study, reported that Tacrine (150-250 mg/day) had a stronger positive effect on the immune system, a greater antiviral effect and was more effective at preventing development of opportunistic infections than was AZT (600-1200 mg/day). The 18 trial participants receiving Tacrine experienced an average T4 cell rise of 75% over 24 weeks, while the 19 taking AZT showed an average decline of 30% during the same period. Additionally, blood levels of HIV viral protein p24 fell an average of 59% for those in the Tacrine group. Blood levels of p24 rose an average of 160% in those taking AZT. Side effects reported by the patients receiving Tacrine were largely limited to nausea, although elevated liver enzymes have been reported in many of the Alzheimer studies (11). The other French study also reported encouraging results, but they were less dramatic than the larger one (SB.458). Dr. Fredj was the prinicipal investigator of this study as well. Fifteen patients who discontinued AZT due to toxicity after an average period of 24 weeks were given Tacrine (150-250 mg/day) for an average of 18 weeks. While on AZT, patients had an average decline in T4 counts of 52% and an increase in p24 antigen levels of 51%. After switching to Tacrine, these same trial participants had an average gain of 22% in T4 counts and a decline of 35% in p24 levels. It should be noted, however, that this was a small sample and the study was very short. In a London study which tested Tacrine at lower doses (150 mg/day) in a much smaller group of seven trial participants, Dr. Michael Youle concluded that Tacrine had no effect on the immunologic function of HIV-infected patients and produced no improvement in their overall clinical state (abstract # SB.457). Research into treatment with Tacrine for HIV-infected patients, particularly those intolerant to or failing on AZT, has produced some initial encouraging results. However, studies of potential immunomodulators are difficult to interpret due to lack of agreement among researchers and regulators about the significance of various surrogate markers (measurable values like T4 and p24 levels). Dr. Fredj's studies offer an opportunity to examine both clinical and so-called surrogate markers in assessing the efficacy of Tacrine therapy. It is important that his data be objectively reviewed. A public relations representative for Parke-Davis, the company which manufactures Tacrine, reacted with considerable skepticism to Dr. Fredj's findings and indicated that researchers at the company are not currently investigating Tacrine's reputed anti-HIV action. ***** Photopheresis Gabriel Torres, M.D. A report in the Annals of Internal Medicine about a new potential treatment for HIV infection called photopheresis has received some media attention and raised questions by patients and physicians about its efficacy and safety. A small study of five patients was done at Morristown Memorial Hospital in New Jersey. The treatment consists of administering a drug called psoralens, which becomes active when exposed to ultraviolet (UV) light. White blood cells are separated from the blood of the patient who has received psoralens, and are exposed to UV light and then reinfused into the patient. This therapy has been successful in the treatment of a skin cancer called cutaneous T cell lymphoma, and is FDA licensed for this purpose. The experiments at Morristown involved five patients with ARC who received between 10-12 photopheresis treatments during a six-month period. None of the patients had received previous therapy for HIV infection. Four had resolution of HIV-related symptoms (fever, night sweats, low energy) and lymphadenopathy (swollen lymph nodes) disappeared in all five. Four patients regained the ability to respond to skin tests. T4 cell percentages increased in four patients, yet absolute T4 cell counts decreased in two patients. There was insufficient data on p24 antigen levels to assess an effect. Blood cultures for HIV became negative in two patients and remained positive in three patients after 15 months of follow-up. None of the patients developed opportunistic infections or cancers and no toxicity was observed. Despite the small number of patients and the lack of a control group, objective reviewers felt that the report had sufficient scientific merit to warrant further study. A phase II clinical trial of 20 people with ARC has been underway since June at Morristown Memorial Hospital, sponsored by Johnson and Johnson. Researchers at Morristown hope to have enough data to present to the FDA in early 1991. The next goal, however, is not licensing, but larger clinical trials. The number at Morristown is 201-540-5401. ***** Kemron (Oral Alpha Interferon) Update Dave Roche Kemron is the brand name given to the version of oral alpha interferon used in the Kenyan study that has generated so much excitement. Anecdotal reports, assumptions, and personal opinions abound on the use of oral alpha interferon to treat HIV infection; unfortunately, conclusive results on its effectiveness are still non-existent. Since so many people are trying -- or have tried -- so many brands of oral interferon in different ways (liquid preparations, wafers, etc.) it is not surprising that a singular voice on this substance has not emerged. For example, of three different buyers clubs surveyed (Dallas Buyers Club, 214-826-7455; PWA Health Group in New York 212-532-0280; and PWA Health Alliance, Ft. Lauderdale, 305-763-7723), each offers a different brand of oral alpha interferon, with each brand administered somewhat differently. Such a wide variety of different products is another factor contributing to the confusion surrounding this drug. Moreover, the one "official" trial of oral alpha interferon in the United States at Mt. Sinai Hospital in New York is not expected to yield practical results before year end 1990. This delay is, of course, extremely frustrating in light of the Kenyan announcement of startlingly positive results in people only 2-4 weeks after commencing treatment. This placebo-controlled trial is still accepting patients and plans are in place to start a second clinical trial at Mt. Sinai (non-placebo-controlled, recruiting both ARC and AIDS patients) later this fall. Additional information can be obtained by calling the office of Dr. Joseph Hassett at 212-241-6331. It should be noted that the rigid study criteria have made it difficult to fill the trial quickly. The World Health Organization (WHO) recently completed a brief trial that recruited over 100 patients. Results are being analyzed now, but it is clear that the miraculous improvement reported from Kenya has not been duplicated in this trial. One rumor has it that WHO was mistakenly provided placebo preparations, but this has not been substantiated. Why isn't anyone covering Kemron? There is some feeling that this treatment has been ignored by the media. This is far from the truth as far as grass-roots AIDS treatment publications are concerned. Soon after the initial report in Biotechnology Newswatch, articles on oral alpha interferon appeared in: Publication Date AIDS Treatment News 2/16/90 4/20/90 BETA 8/90 Critical Path AIDS Project 5/90 6/90 Notes From The Underground 7/90 Project Inform Bulletin 6/07/90 Treatment Issues 5/22/90 These and other community publications consistently print accurate, up-to-date information about experimental treatments. Articles on experimental AIDS treatments that appear in the lay media (daily newspapers, television news magazines, etc.), are usually reported with a great deal of sensationalism. The lay media in general should not be considered a reliable source of information on experimental AIDS treatments. In summary, the more one looks for answers to the questions raised by oral alpha interferon, the more confusion one finds. Oral alpha interferon is still an untested drug and for now, it is not recommended to place undue hope in the substance. An excellent article on oral alpha interferon appears in the September issue of Notes From the Underground, a treatment publication produced by the PWA Health Group. This article is the most comprehensive piece on the oral alpha interferon controversy that has come to the attention of Treatment Issues staff to date. ***** Drug Availability Update Kevin Armington Foscarnet: This drug has been in clinical trials in the United States for several years and has already been approved in a number of European countries. In clinical trials, foscarnet has demonstrated efficacy in treating CMV and other herpes viruses. Evidence to date shows that it is about equally effective as ganciclovir (DHPG), the only treatment approved for CMV retinitis. Foscarnet is also, unfortunately, as difficult to take as ganciclovir. Long-term therapy for CMV retinitis involves frequent intravenous infusions, usually through a catheter surgically implanted in the chest. (For more information about about catheters, see Treatment Issues, vol. 3 no. 6.) Unlike ganciclovir, foscarnet can be taken in conjunction with AZT. On September 21, Astra, the Swedish pharmaceutical company that makes foscarnet, announced that they had submitted data to the FDA to obtain a license to market the drug in the United States. Astra is also considering applying for a Treatment-IND, which would allow the company to supply the drug (possibly at a cost) to qualifying patients before full licensing. If Astra applies for a Treatment-IND that could indicate that they are not confident that FDA will approve foscarnet soon. In the meantime, Astra has announced an expanded access program for people who are intolerant to or have failed ganciclovir. This program will provide foscarnet on a case-by-case basis, through a "compassionate-use" protocol. Intolerance to ganciclovir is defined as having a seriously low neutrophil count (a type of white blood cell necessary for fighting infections) or a low platelet count. In addition, people who have herpes infections that no longer respond to acyclovir (Zovirax), a condition usually referred to as "acyclovir-resistant herpes," are eligible for foscarnet. For acyclovir-resistant herpes, the criteria are more strict: patients must have had their viral isolates tested and found to be acyclovir-resistant or they must have attempted a 10-day course of intravenous acyclovir, with no improvement. Neither of these criteria are easy to meet. According to physicians who have tried to obtain foscarnet, it is initially easy to get the drug to treat an acute case of CMV or herpes. However, it is necessary to go on chronic maintenance therapy to avoid recurrence. Astra has made it very difficult to keep getting drug for maintenance therapy. In addition, it is necessary for physicians to complete a 76-page case report form for each patient to continue getting the drug. However, a shorter, less labor-intensive case report form is being prepared. An Astra spokesperson denied any responsibility for rigid restrictions and laid the blame squarely on the FDA. Another important roadblock for physicians wishing to use foscarnet is the requirement that hospital Institutional Review Boards (IRBs) approve use of an experimental drug in the hospital on a case-by-case basis. Sometimes IRBs meet infrequently, and the process for obtaining permission to use an experimental drug may drag on for some time. For very sick patients, this time may be a luxury they do not have. In the case of ddI, another experimental drug that is available through an expanded access program, many IRBs have given blanket approval for all patients wishing to use the drug in a given hospital. This arrangement required the cooperation of Bristol-Myers Squibb, the company that makes ddI. Perhaps Astra could consider approving a similar arrangement to expedite access to foscarnet for those who need it. Some foscarnet clinical trials are open to people who cannot take ganciclovir and company representatives will try to fit people into the trials before providing the drug on expanded access. One trial evaluating the use of a lower maintenance dose (90 mg/kg daily) after initial treatment is being conducted in Houston at the Park Plaza Hospital. foscarnet, call Astra at 1-800-388-4148. ddC: Hoffman-La Roche is taking a second stab at an expanded access program for ddC, and this time, it seems like they mean business. The first program, announced last June, provided access for people who could no longer take AZT and ddI. New York's ACT UP chapter, in consort with other activist groups, convinced Hoffman that requiring intolerance to two drugs served no one's purpose. The new program will make ddC available to people who can no longer take AZT regardless of ddI experience. This sensible approach is a triumph for everyone: Hoffman-La Roche, activists and people with AIDS. For more information about ddC expanded access, call 1-800-ddC-21-HIV (1-800-332-21448). Operators will first try and fit callers into clinical trials of ddC. ***** In Brief Lower-Dose AZT! A pilot study comparing different doses of AZT (300, 600 or 1500 mg/day) alone or in combination with acyclovir has shown better effects with the low-dose as compared to the higher doses. The study included 67 patients with ARC with T4 cell counts between 200-500 and detectable p24 antigen or plasma viremia. Patients on 300 mg AZT per day gained more weight and had more sustained rises in T4 cell counts with similar suppression of viral activity than patients on higher doses of AZT. Bone marrow toxicity was lowest at the 300 mg dose. Acyclovir did not enhance AZT's antiviral efffect. This preliminary report suggests that 300 mg may be just as effective and less toxic than higher doses. Cryptosporidiosis Treatment? Anecdotal reports abound about the possible role of an approved drug called Humatin to treat cryptosporidiosis, a parasite causing severe diarrhea, for which there is no standard treatment. Humatin (paramomycin) is an anti-parasite drug, which passes through the gastrointestinal tract with little absorption into the bloodstream. It is therefore useful for treating conditions found only in the gastrointestinal tract. At the Sixth International AIDS Conference in San Francisco, a poster was presented (# 2121) which described significant efficacy using Humatin to treat cryptosporidiosis. Of 23 patients with cryptosporidiosis, all responded to treatment with 1500-2000 mg/day of Humatin: 16 had a complete response and 7 had a partial response. During follow-up many of the patients had a recurrance after being taken off the drug, but responded to retreatment. Anecdotal reports from a number of sources are that the drug is being used successfully but that maintenance therapy is necessary. More to follow. Activist Conference: An AIDS Treatment Activist Conference (ATAC) will be held in Washington, D.C. on November 10-11, immediately preceeding the AIDS Clinical Trials Group meeting. For more information, contact Mike Barr at 212-765-7127. Treatment Conference: NMC Infusion Care company is sponsoring another of their PWA Education Lecture Series on Wednesday, October 31. The topic will be a review of highlights from the Sixth International Conference on AIDS in San Francisco last June. The conference will run from 9:00 am until 1:00 pm at NYU Medical Center, 550 First Avenue, in Farkas Auditorium. To reserve a seat, call 718-359-8117. ***** New Studies Proctor and Gamble is sponsoring a phase III clinical trial program to evaluate the safety and efficacy of a substance callled Peridex Oral Rinse. This agent may be used in preventing or delaying oral candidiasis (thrush) in persons with HIV infection. Peridex is currently prescribed to treat bleeding and inflammation of the gums due to gingivitis. Trial participants must have been diagnosed with oral candidiasis within the past three months, but be free of infection upon entry. The trials are being conducted at medical sites in San Francisco,Houston, Los Angeles and Columbus. For further information call 1-800-TRIALS-A. ____________________ Footnotes 1 Yarchoan R et al. Long-term toxicity/activity profile of 2,3'-dideoxyinosine in AIDS or AIDS-related complex. The Lancet 336:526-29, 1990. 2 Yarchoan R et al. The National Cancer Institute Phase I study of 2'3'-dideoxyinosine administration in adults with AIDS or AIDS-related complex: Analysis of activity and toxicity profiles. Rev Infec Dis 12,supplement 5:S522-533, 1990. 3 Lambert JS et al. 2'3'-dideoxyinosine (ddI) in patients with AIDS or ARC. A phase I trial. N Engl J Med 322:1333-40, 1990. 4 Cooley TP et al. Once daily administration of 2'3'-dideoxyinosine in patients with AIDS or ARC. N Engl J Med 322:1430-35, 1990. 5 Bach MC. Clinical Response to dideoxyinosine in patients with HIV infection resistant to zidovudine. N Engl J Med 323:275, 1990. 6 Bristol-Myers Squibb Company. didanosine Quarterly Safety Summary (April 2-June 19, 1990), August 6, 1990. 7 Hughes WT et al. Efficacy of a hydroxynaphthoquinone, 566c80, in experimental PCP. Antimicrob Agents Chemoth 34:225-228, 1990. 8 Wendell WB. Influence of naphthoquinones upon respiratory and carbohydrate metabolism of malarial parasites. Fed Proc. 5:406-407, 1946. 9 Lopes JN et al. In vitro and in vivo evaluation of the toxicity of 1,4-naphthoquinone and 1,2-naphthoquinone derivatives against Typanosome cruzi. Ann Trop Med Parasito. 72:523-531, 1978. 10 Hudson AT et al. Novel anti-malarial hydroxynaphthoquinones with potent broad spectrum anti-protozoal activity. Parasitology 90:45-55, 1985. 11 Summers WK. Long term hepatotoxicity of tacrine. Lancet no. 8640, 4/1/89. ___________________ Other Resources 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. The AIDS Drug Assistance Program provides many free medications used by people with HIV infection to those whose income is under $44,000 for a single person. For more information, call 1-800-542-2437. 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. "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" on experimental treatments with in-depth political analysis. Another excellent resource is their drug hotline: 1-800-822-7422. 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: Mike Barr Darren Britten Dave Roche Gabriel Torres, M.D. GMHC, Department of Medical Information, 129 West 20th Street, New York, NY 10011. &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& End of display