Subject: Treatment Issues Vol. 5 No. 5 Date: Jun 20 1991 (780 lines) &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& TREATMENT ISSUES -- The GMHC Newsletter of Experimental AIDS Therapies &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& Treatment Issues 55 Volume 5 Number 5 -- June 20, 1991 Contents: [items are separated by "*****" for this display] TREATMENT ISSUES: ddC Update NEUROPATHIES IN HIV PATIENTS POLICY: MONITORING THE ACTG IN BRIEF NEW STUDIES ***** TREATMENT ISSUES ddC Update by Gabriel Torres, M. D. Dideoxycytidine (ddC), an alternative antiviral drug to AZT, has now been used by thousands of patients for several months. People who are intolerant to or failing AZT have started taking ddC through clinical trials or through an expanded access program. Expanded access allows patients who meet certain requirements to take the unapproved drug. Physicians monitor patients on expanded access and report data about the patient's response to the drug to Hoffmann-La Roche, the manufacturer of ddC. From this program and the federally-funded clinical studies, some very early data about ddC are now being analyzed. ddC VS. AZT IN PATIENTS WITHOUT PRIOR AZT USE Hoffmann-La Roche is analyzing data from an on-going major study, which compares ddC to AZT in patients with AIDS or advanced ARC. The study is sponsored by the federally-funded AIDS Clinical Trials Group (ACTG). Early data suggest that in patients who have never used AZT or have taken it for less than three months, ddC might not be as effective as AZT. In the study, 600 patients were treated with either AZT or ddC for an average of 19 weeks. There was no significant difference in survival between patients taking ddC and patients taking AZT. It is notable, however, that more opportunistic infections (OIs) and cancers occurred in patients taking AZT. Not surprisingly, more cancers and OIs were found in ddC patients who entered the study with T4 cell counts under 100. Additionally, patients on ddC with T4 cell counts under 100 had no increase in T cell counts. Those with counts over 100 had only a limited rise. Patients in both treatment groups, who had experienced rises in T4 cell counts, saw them decline back to original levels after 20 weeks of therapy. Similarly, neither drug had a more pronounced effect on p24 antigen levels (a measurement of the amount of HIV reproduction in the body). Some patients needed to interrupt treatment due to toxicity. Treatment was stopped for 18 patients on ddC who experienced peripheral neuropathies. Eleven patients on AZT experienced anemia and neutropenia (low white and red blood cell counts) for which interruption of treatment was required. Other toxicities, which required the discontinuation of ddC, included oral ulcers, anemia, neutropenia and low platelet counts. Additionally, increased liver enzymes caused discontinuation in two patients on ddC and two patients on AZT. ddC VS. AZT IN PATIENTS WITH PRIOR AZT USE Another study compared ddC to AZT in patients with AIDS or ARC who had previously used AZT for one year. One-hundred-and- two patients who were treated for an average of 16 weeks were evaluated. Interestingly, an early analysis of this study has shown a trend for fewer OIs and cancers in patients taking ddC, than in patients taking AZT. This trend may suggest that ddC is more effective as a second-line therapy for people who have already taken AZT for more than a year. These are very early evaluations from small trials. It should be noted that until all the data from these trials are available and analyzed, it is impossible to draw conclusions about who might benefit most from which drug. EXPANDED ACCESS NEWS By the end of March 1991, the ddC expanded access program had enrolled 1,921 patients. Data from the first 833 patients, who were followed for eight weeks, showed that 25 patients had to discontinue ddC due to toxicity. Thirteen of these patients had peripheral neuropathy, and three had pancreatitis (inflammation of the pancreas). Physicians continue to enroll people with AIDS or ARC who are ineligible, intolerant, or are failing AZT. Unfortunately, the paperwork for such enrollment and follow-up is voluminous. Various activist groups (mostly ACT-UP) and physicians (including ACTG researchers and community doctors) have been writing letters in support of curtailing the paperwork. According to a Hoffmann-La Roche representative, the paperwork will be trimmed to two pages within the next few months. OTHER DRUGS AND ddC TOGETHER Physicians have received warnings about the combination of ddC and other commonly used drugs. It is recommended that patients needing radiation therapy, amphotericin B, pyrimethamine, sulfadiazine, and intravenous (IV) formulations of Bactrim (Septra), ganciclovir, pentamidine, and acyclovir (or oral acyclovir in doses over 1000 mg/day) stop taking ddC until they become stable on a maintenance dose of the above medications. Only then should ddC be restarted. Patients on combination therapy with ddC and one or more of these drugs should have frequent (weekly, if possible) laboratory assessments. Drugs that have potential for causing neuropathy (such as Dilantin, vincristine, and Dapsone) should be avoided by patients on ddC, if possible. In all patients in ddC studies through May 31, 1991, there have been a total of 17 cases of pancreatitis. Nine of these cases were considered to be possibly or probably related to ddC. Patients on ddC should be advised to avoid excessive use of alcohol or other drugs that can cause serious damage to the pancreas. Eleven additional cases of esophagitis (inflammation of the esophagus) or esophogeal ulcers were reported to be possibly related to ddC use. In cases of esophagitis that does not respond to acyclovir or antifungal drugs, ddC should be stopped. COMBINATION ANTIVIRAL THERAPY Two treatment regimens that look promising are switching back and forth between ddC and AZT (alternate weeks or months) or taking the two drugs together. Early data indicate that ddC and AZT taken together sustain increases in T4 cell counts better than AZT alone. The doses which are shown to have the best effects are 2.25 mg of ddC (.75 mg/three times daily). Combination therapy with ddC and AZT may be less toxic, and may delay development of resistant strains of HIV. One interesting report in the Journal of AIDS described a patient who developed severe neuropathy after 16 weeks of alternating therapy between ddC and AZT. Two weeks after stopping ddC, but continuing AZT alone, the patient's symptoms resolved. The patient then began a treatment regimen with ddI, and began to experience a worsening case of neuropathy, which manifested as a shooting pain from the balls of his feet. This is a common symptom of ddI neuropathy. Stopping ddI resolved the symptoms within a month. This case suggests that patients may be more susceptible to ddI toxicity if they have previous nerve damage due to ddC. It is possible that once neuropathy develops with one drug, other drugs with similar side effects should not be used. Self-experimentation with combinations of ddC, AZT, and ddI are not recommended and may prove to be harmful. One final piece of news from Hoffmann-La Roche is worthy of note. The company will be submitting a New Drug Application (NDA) in the near future. If the application is approved by the FDA, ddC will become available by physician prescription. It is expected that the drug will be approved for use in patients who are ineligible, intolerant to, or failing on AZT. Rumor has it that new data on the combination of AZT and ddC will be published soon, showing an advantage of combination use over the use of AZT alone. If so, it is conceivable that Hoffman-La Roche would pursue licensing for the use of AZT and ddC together, as first- line therapy, or therapy for people who have no prior use of AZT. ***** NEUROPATHIES IN HIV PATIENTS by Don Shewey Peripheral neuropathy is usually characterized by a sensation of pins and needles, burning, stiffness, or numbness in the feet and toes. It is a common, sometimes painful, condition in HIV-positive patients, affecting up to 30% of people with AIDS. It is perhaps most common in people with a history of multiple opportunistic infections (OIs) and low T4 cell counts. The range of severity among patients with neuropathy is dramatic, from a minor nuisance to a disabling weakness. Additionally, the kinds of neuropathies occurring in people with AIDS are numerous and must be identified before appropriate treatment can be prescribed. The underlying cause of the most common type of peripheral neuropathy remains elusive and possibly attributable to a number of factors. Most definitely, neuropathy has been a continuous problem for patients throughout the AIDS epidemic. The course of this elusive nerve damage has had its twists and turns. What was a common complaint early in HIV infection of severe neuropathy -- usually, burning feet, causing patients to walk on their heels -- has greatly diminished, according to practicing physicians. The decrease in such complaints may be attributable to the antiviral effects of AZT. On the other hand, new varieties of drug-induced nerve damage have been recognized in the use of antivirals like ddI and ddC. Underlying some of these changes are the commonly reported, sometimes overlooked neuropathies whose origins remain mysterious and are generally believed to be caused by HIV itself or by immunosuppression. Researchers have also identified cytomegalovirus (CMV) as a contributing factor in some kinds of neuropathy. This article overviews the different kinds of neuropathies in HIV disease and some of the treatment options available. SENSORY NEUROPATHIES The most common type of neuropathy associated with AIDS is called distal symmetrical polyneuropathy (DSPN). This syndrome is a result of the degeneration of the nerves responsible for conducting impulses, and is characterized by numbness and a sensation of pins and needles. DSPN causes few serious abnormalities and mostly results in numbness or tingling of the feet and slowed reflexes at the ankles. It generally occurs with more severe immunosuppression and is steadily progressive. Treatment with tricyclic antidepressants, such as Elavil, relieves symptoms but does not affect the underlying nerve damage. Side effects to note when using Elavil include dry mouth, difficulty urinating, sweating, and drowsiness. Taking Elavil at night may offer relief and is a way for patients to sleep through these effects. MORE SERIOUS NERVE DAMAGE A less frequent, but more severe type of neuropathy is known as acute or chronic inflammatory demyelinating polyneuropathy (AIDP/CIDP). In AIDP/CIDP there is damage to the fatty membrane covering the nerve impulses. This kind of neuropathy involves inflammation and resembles the muscle deterioration often identified with long-term use of AZT. It is sometimes the first manifestation of HIV infection, where the patient may not complain of pain, but fails to respond to standard reflex tests, such as vibrations or pin pricks on the toepads. This kind of neuropathy may be associated with seroconversion, in which case it can sometimes resolve spontaneously. It can serve as a sign of HIV infection and indicate that it might be time to consider antiviral therapy. AIDP/CIDP may be an auto-immune phenomenon, which means the body launches a kind of misguided attack on itself with disease-fighting antibodies. AIDP/CIDP responds to treatment with steroids or plasmapheresis, a procedure in which blood is removed from a patient's body and returned again without antibodies. Physicians are often reluctant, however, to subject patients to plasmapheresis, which is time-consuming, potentially hazardous, and expensive. Additionally, the chronic use of steroids in immunosuppressed patients has well-known hazards, including aggravation of thrush and Kaposi's sarcoma (KS). DRUG-INDUCED NEUROPATHIES Drug-induced, or toxic, neuropathies can be very painful. Antiviral drugs like ddI and ddC commonly cause peripheral neuropathy, as do vincristine (a drug frequently used to treat KS), Dilantin (an anti-seizure medication), high-dose vitamins, isoniazid (INH), and folic acid antagonists. Peripheral neuropathy is often used in clinical trials for ddI and ddC as a dose-limiting side effect, which means that more drugs should not be administered. Additionally, the use of ddI, ddC, and vincristine can exacerbate otherwise minor neuropathies. Usually, these drug-induced neuropathies are reversible with the discontinuation of the drug. CMV-RELATED NEUROPATHIES CMV causes several neurological syndromes in AIDS, including encephalitis, myelitis, and polyradiculopathy. Polyradiculopathy, a rapidly developing, ascending paralysis that affects both hands and feet, is difficult to treat. Fuller et al have hypothesized that recognition of painful peripheral neuropathy (PPN) may help in the diagnosis of CMV infection, and allow for earlier initiation of treatment. TREATMENT NOTES Neuropathy-related symptoms are very difficult to treat, since often the underlying cause of the neuropathy is not known. Two physicians with considerable experience in treating neuropathy spoke with Treatment Issues about practical approaches to treatment. General practitioner Dr. Dan Williams finds that Tylenol or Tylenol with codeine is clinically helpful for minor complaints. For neuropathies which are not controllable by mild pain relievers, he prescribes tricyclic antidepressants, and has had the most success with low-dose Elavil in gradually increasing doses. He has also tried anti-seizure drugs, such as Dilantin, but has had mixed results. A neurologist, Dr. Josh Torgovnick prescribes treatment according to specific complaints. For burning he prescribes tricyclics, and for shooting pain, anticonvulsants, like Tegretol. For stiffness or pain in the calves, he uses Lioresal. He has tried topical preparations such as Zostrix, without success. Sometimes he prescribes opiates. Unlike Dr. Williams, Dr. Torgovnick does not hesitate to prescribe steroids for more sever neuropathy, specifically, AIDP/CIDP. He is also in favor of plasmapheresis. Torgovnick points out that sometimes what appears to be neuropathy may turn out to be standard tension- related muscular pain, which responds to antidepressants, massage, and sleep. Essential to treating neuropathies is eliminating the possibility of other causes such as syphilis, vitamin B-12 deficiency, myelopathy, and neuropathies caused by drugs or drug interactions. Many patients with severe neuropathy require narcotics, such as codeine, Percocet, Dilaudid or morphine to relieve the pain. Physicians should not be reluctant to prescribe narcotics to these patients, since in most cases it is the only treatment that will relieve the pain. Problems to watch out for in these patients are narcotic dependence and the development of tolerance. RESEARCH Research and treatment studies of neuropathy have traditionally taken a back seat to more pressing, life- threatening AIDS infections. Recently, however, that has begun to change. Researchers have looked to the medical literature concerning experimental treatments of painful neuropathy experienced by diabetes. Among the medications already licensed to treat neuropathy in diabetics are: piroxicam (Feldene), calcitonin (nasal spray), capsaicin (which is, by the way, the ingredient in hot peppers which makes them hot), the anticonvulsant phenytoin (Dilantin), antidepressants such as imipramine, desipramine, and fluoxetine (Prozac). Also drugs for cardiac patients, such as intravenous lidocaine and mexiletine seem to have some effect. Mexiletine is the focus of a controlled clinical trial sponsored by the AIDS Community Research Consortium (ACRC) in Northern California, funded by American Foundation for AIDS Research (AmFAR). A derivative of lidocaine, originally an anticonvulsant and now used to treat an irregular heartbeat, mexiletine caught the attention of medical researchers when it appeared to resolve neuropathies occurring in cardiac patients. Among diabetics, mexiletine significantly relieved the symptoms of chronic, painful neuropathy. In addition to conducting basic research on the interaction of mexiletine and AZT, ACRC is running a phase I, 13-week, placebo-controlled crossover study of HIV-related neuropathy. Patients in one arm of the trial will take drug for six weeks and then, after a one-week washout period (time off of the drug), will switch to placebo. The other group of participants will first take placebo and then switch over to drug. This study, conducted by Dr. Ari Ganer and Dr. Stanley Deresinski, is still seeking to enroll participants. Fifteen to 17 patients with moderate to severe neuropathy have been enrolled so far. Brian Camp is the coordinator of the study for ACRC and can be reached at (415) 364-6563. Community Research Initiative (CRI), New England, meanwhile, is conducting a study of acupuncture as a treatment for HIV- related neuropathy. Also funded by AmFAR, the protocol excludes patients with ddI-or ddC-related neuropathy, unless they have been off the drug for more than two months. Those suffering from chemotherapy-related neuropathies are eligible. All participants will receive free acupuncture treatments twice weekly for up to six months. A neurologist will screen all participants upon entry, at six weeks, and again at six months. More than 25 people have been enrolled so far, and the maximum enrollment will be 40. Preliminary reports on the first ten to 12 people who have completed six weeks of therapy describe patients as having a subjective sense of improvement. One of the goals of this study is to convince doctors to consider acupuncture for treatment of chronic pain and to persuade insurance companies to reimburse patients for acupuncture. The coordinator is Dr. Cal Cohen who can be contacted at (617) 424- 1524. CONCLUSION There is no question that neuropathy is one of the major problems in treating AIDS. It is an undeniable contributor to physical weakness, difficulty standing and walking, and overall disability. Long overshadowed by more serious and acute medical problems, neuropathy continues to assert a nagging need for attention to its elusive cause and a sure-fire treatment. ***** POLICY: MONITORING THE ACTG by David Barr Most AIDS clinical research is conducted through the AIDS Clinical Trial Group (ACTG), a network of about 50 medical centers, where studies about potential treatments for HIV and its complications take place. The ACTG is supported by the National Institute of Allergy and Infectious Diseases (NIAID), which is an agency of the National Institutes of Health (NIH). Other research in the United States may be conducted by pharmaceutical companies, government agencies, private or community research organizations or by another NIAID program called Community Programs for Clinical Research on AIDS (CPCRA), which conducts studies on AIDS drugs at hospitals and clinics in communities where the impact of the AIDS epidemic is severe. This article will focus on ACTG sponsored research sites which have recently established Community Advisory Boards (CABs) to represent community points of view, review study protocols, and address enrollment problems. BACKGROUND The ACTG is divided up into committees that develop the blueprints for the trials (protocols), recruit patients, make sure that standard care is delivered, and collect data. The committees are further divided according to scientific areas, such as opportunistic infections, pediatrics, patient care, data management, immunology, neurology, oncology, pharmacology/ pharmacokinetics, primary infection, and virology. The stated goals of the ACTG are "to conduct clinical trials that will (1) provide timely information to guide physicians in the selection of appropriate therapies for their patients, and (2) lead to the approval of new drugs." The Executive Committee oversees the entire operation. FORMALIZATION OF COMMUNITY INPUT In November, 1990, after repeated demands by AIDS activists, NIAID agreed that it would be useful to include people with AIDS and their advocates in the development and implementation of clinical research programs. As a direct solution, the Community Constituency Group (CCG) was formed. The CCG is made up of 24 people from around the country for broad-based representation of patient advocates and HIV-infected persons from a spectrum of affected communities. Its purpose is to represent community interests within the ACTG. Each CCG member represents a community or communities affected by AIDS. Members are chosen by the CCG itself, taking into account an individual's expertise in treatment issues and the communities from which he or she comes. Every CCG member also sits on an ACTG committee. In this way, community interests are represented throughout the ACTG, including the Executive Committee, which now includes two CCG members. Substantively, the CCG focuses on a variety of issues, including clinical trial design, equal access to clinical trials and dissemination of information regarding research developments. One of the first acts of the CCG was to propose the creation of Community Advisory Boards at each site where ACTG trials are conducted. The CCG believes that community input is necessary on both national and local levels. CABs will be particularly useful for overseeing the diversity of trial accrual, ensuring that the needs of patients are met, and for helping to educate communities about treatments and clinical research. The Executive Committee accepted the CCG's proposal and now requires that every ACTG site establish and maintain a CAB. CABs IN NEW YORK In New York, there has been considerable difficulty getting the CABs up and running. New York has over seven ACTG sites, more than any other city. Establishing boards at each site is time-consuming and requires enough people willing to put in the effort. Recently, a meeting of people involved in the ACTG, including researchers, physicians,ACTG staff and activists was convened. The formation of the CABs was discussed at length. It was decided, despite the difficulties, that each site needed its own board to deal with specific problems within the individual institution. However, it was also felt that a central board, made up of members from the individual boards would also be useful to address citywide problems, such as trial accrual. In order to get more people involved in the ACTG and the CABs, forums are being planned at various ACTG and other sites which will educate people about AIDS clinical trials and the CABs. Another work group is meeting to discuss CAB structure and membership. For more information, or to register interest in joining a local CAB, please contact David Barr at (212) 337-3569. [Editor's note: This is the first in a series of policy articles which will appear in forthcoming Treatment Issues.] ***** IN BRIEF MORE DATA ON LOW-DOSE AZT Preliminary data from a European trial comparing AZT at doses of 1200 mg versus 600 mg in 76 persons with AIDS or ARC were reported in an early May edition of Lancet. These data underscore U. S. findings, which now recommend 600 mg of AZT daily. The European study found that 46% of patients in the full-dose group and in 44% of patients in the half-dose group progressed to AIDS, demonstrating equal efficacy for both doses. Survival rates and differences in T4 counts and p24 antigen measurements were not observed between the two groups. The 600 mg regimen was also better tolerated. These results are further proof that 600 mg AZT/day should now be considered "full dose." However, some physicians feel that higher doses are more effective for lymphoma and HIV-related neurological problems. ADVANCED NOTES FROM THE INTERNATIONAL CONFERENCE ON AIDS A review of the advanced program for the VII International Conference on AIDS in Florence, shows a strong bias for presentations on basic research. This means that the majority of the medical presentations will have little or no practical clinical value for people with symptomatic HIV infection. A distressingly small number of presentations will focus on treatments that have been tested in people. Very few sessions deal with treatment or prevention of opportunistic infections. Six presentations will be made on cancers: two of those deal with non-HIV related KS. The most relevant clinical information from this conference will most likely be found in the published abstracts and posters that were not accepted as oral presentations. It is our hope that reviewers for future International AIDS conferences will weigh the needs and interests of researchers and clinicians in a more equal manner. MARIJUANA THERAPY IN HIV Dronabinol is a pill containing cannabis and sesame oil made by Roxane Laboratories, and marketed under the name Marinol. Marinol is FDA-approved to control nausea and vomiting in cancer patients receiving chemotherapy. A study from San Francisco General Hospital found that the drug increased appetite and wight gain in asymptomatic HIV-positive men. The authors also hypothesize that Marinol may counteract the side effects of antiviral therapy. The doses range from 2.5 mg/2-to-3 times daily to 10 mg, and the price of Marinol can cost from $227 to $911 a month. On a similar note, marijuana (Cannabis sativa) is available to threat nausea, vomiting, and loss of appetite through a Compassionate Use Program. Doctors must set up a "one person trial" with the FDA for each patient who wishes to use this drug. Both doctor and patient will be investigated by the Drug Enforcement Agency for past drug use. The marijuana, administered as an herb to be smoked, will be provided by the National Institute of Drug Abuse, which operates its own farm. For more information, contact Corrine Moody at (301) 443-3741. ORAL ALPHA INTERFERON AT MT. SINAI Mt. Sinai continues to recruit patients for its two studies with oral alpha interferon (a drug similar to Kemron). The first study is for patients with ARC, who have T4 cell counts between 100-350. The study has places for ten more patients. For the first ten weeks, patients will be randomized to drug or placebo. For the following 48 weeks, every participant will receive 150 international units (IU) of oral alpha interferon daily, an extremely low dose. The second study is for people with AIDS and T4 cell counts under 300. This study is a dose-ranging double- blinded study (no one knows who is taking what dose of drug). Patients will receive either 75, 150 or 500 IU of drug a day. The study will last 36 weeks. Early word from both studies is that no patient has experienced any toxicity from oral alpha interferon. Side effects which were observed did not seem to be directly related to the drug. Because these are early results, there is no conclusive information about the drug's efficacy or the best dose. On a positive note, many patients report subjective improvement of symptoms, more energy and increased appetite. No word yet as to the laboratory results, but there have been no major changes in T4 cell counts. To enroll in either of the Mt. Sinai Medical Center trials, contact Dr. Joseph Hassett at (212) 241-6331. The PWA Health Group, which has been selling a version of oral alpha interferon for over a year, reports that sales of the drug are down. APPROVAL RECOMMENDED FOR FOSCARNET On June 12, the Antiviral Drugs Advisory Committee of the FDA recommended that the agency grant marketing approval for foscarnet (brand name Foscavir). This drug has been in clinical trials as a treatment for cytomegalovirus (CMV) for a number of years. In addition, foscarnet has some limited effect against HIV, at least in the test tube. It has also shown some efficacy in treating herpes simplex virus that has developed resistance to acyclovir (Zovirax), a drug approved to treat the condition. If the FDA follows the committee's recommendation, foscarnet will join ganciclovir (DHPG) as a licensed treatment for CMV. Foscarnet has its share of limitations. Unfortunately, like ganciclovir, foscarnet does not cure CMV. People with CMV who are immunosuppressed must continue to take maintenance doses of foscarnet indefinitely. Otherwise, the infection will rebound. Since the drug can only be administered intravenously, regular dosing requires the surgical implantation of a catheter, a device providing direct access to the bloodstream. Foscarnet is a toxic drug, causing kidney problems and anemia. Recently, another serious toxicity has come to light -- foscarnet also causes severe calcium deficiencies. Foscarnet- associated calcium deficiencies are not detectable by ordinary lab tests which measure calcium levels. However, the symptoms are quite evident to anyone experiencing them. People taking foscarnet should report to their physician any numbness or tingling in their fingers, toes, or lips, as well as nausea and dizziness. There is an easy solution to this problem: calcium can be administered intravenously before foscarnet treatments. The tubing must be flushed with saline after the infusion of calcium and before the infusion of foscarnet. Despite the shortcomings of foscarnet, it is a welcome addition to the arsenal of drugs available to treat HIV-related opportunistic infections. Foscarnet is compatible with AZT, unlike ganciclovir. In addition, the drug has been shown to be effective in people with CMV who have developed resistance to ganciclovir. IVIG MAY KEEP CHILDREN WITH SYMPTOMATIC HIV OUT OF THE HOSPITAL LONGER The National Institute of Child Health and Human Development (NICHD) has found that monthly administration of intravenous immunoglobulin (IVIG) results in fewer hospitalizations for children with symptomatic HIV infection. IVIG, a solution of concentrated antibodies, which kills bacteria and various other infections, is infused into the blood. In a study to evaluate the effectiveness and safety of IVIG monthly, 372 symptomatic, HIV-infected children between the ages of two months and 12 years were given IVIG. All of the children in the federally- funded ACTG study received an IV preparation, whether or not they were on drug or on placebo. This was a controversial aspect of the trial, and many activists remain opposed to IV placebo, which has no affect in the body, but requires fairly complicated procedures for the children. IVIG was shown to increase the time that children remain free from infection. It also reduced the number of hospitalizations for children with T4 counts over 200. In children, with T4 counts over 200, no significant improvement occurred. There was no difference in the mortality between the placebo and the IVIG group. It is notable, that while on the drug, patients received standard of care of HIV, which means they were taking AZT and PCP prophylaxis. The noted side effects of the treatment are mild, the most common reaction being a brief rash. None of the children from the trial had any reaction to the IV, so the rash was determined to be drug-related. IVIG is made by Cutter Biological, who agreed to provide immunoglobulin free of charge to all study patients on the recommendation of the child's physician and consent of the child's parent or guardian. Results of this trial will be published in New England Journal of Medicine in early July, 1991. AIDS OR DRUG ABUSE RESEARCH FELLOWSHIP The Aaron Diamond Foundation recently launched a Research Fellowship program to support and encourage the training of young M. D.'s and Ph.D's in research areas contributing to the understanding of AIDS or drug abuse. Fellowships will be awarded for three years, administered by the New York State Health Research Council, with guidance from the Aaron Diamond Foundation Fellowship Selection Committee. This year's application deadline is July 31, 1991. For more information contact, Ellen L. Rautenberg, Program Director at (212) 613-2525 or write to the Aaron Diamond Foundation Postdoctoral Research Fellowships, New York State Health Research Council, 5 Penn Plaza, Room 308, New York, NY 10001. TAT GENE INHIBITOR TRIAL REVISITED We reported in our last issue that further studies of the TAT gene inhibitor trial, which were scheduled at Johns Hopkins University were put on hold due to financial considerations of the sponsoring drug company, Hoffmann-La Roche. TAT is one of the most powerful genes on HIV, which aids in the reproduction of new virus particles once HIV has entered a new cell and taken over its DNA. The Tat inhibitor is designed to block the protein made by the TAT gene in hopes that if the protein is unavailable, formation of new virus particles will be halted. This trial was to be the only of its kind. As we go to press, it has come to our attention that this important trial is back on schedule. According to sources at Hoffmann-La Roche was seeking a partner to help shoulder some of that cost. Although, to date, no such partner has been found, the company decided to restart the trial, after much community pressure. The actual protocol of the trial is still in development. For further information contact Linda Nerhood at (301) 955-3224. ***** NEW STUDIES OBSERVATIONAL DATA BASE STUDY A study at Newark Community Health Centers, Inc. in Newark, New Jersey, is seeking individuals to participate in an observational study. No treatment will be administered during this study, but participants may continue pursuing any treatment course they and their physicians choose. The purpose of this study is to compile information on the progression of HIV infection in a broad range of HIV infected persons. For more information call (201) 565-0355 or (201) 483-1300. PROPHYLAXIS FOR CMV AND MAI A study to determine the safety and effectiveness of two drugs in preventing CMV and Mycobacterium avium intracellulare (MAI) is being started at a number of ACTG cites in New York City and New Jersey. The double-blind study is designed to evaluate if acyclovir can prevent people from getting CMV disease and to see if clarithromycin can prevent MAI disease. It will have three arms. In the first arm, participants will receive 800 mg of acyclovir five times daily and an MAI placebo. The second arm will receive 500 mg of clarithromycin twice daily and a CMV placebo. The third arm will be a combination of the two drugs with no placebo. Patients must have T4 cell counts under 150, and must taking and antiviral drug unless they are intolerant. For further information contact Sandi Sledz at New York Hospital -- Cornell Medical Center, (212) 746-4177, or Denise Bundow at Memorial Sloan-Kettering Cancer Center, (212) 639-7426, or Brenda Kolach at Saint Luke's/Roosevelt Hospital, (212) 523-6722. In New Jersey, contact Grace Ouma at the Robert Wood Johnson Medical School in New Brunswick, (201) 937-8571. ***** 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