Subject: Treatment Issues Vol. 4 No. 6 Date: Aug 30 1990 (648 lines) &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& T R E A T M E N T I S S U E S Newsletter from Gay Men's Health Crisis &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& This display has 648 lines. You can't back up, it has to come in sequence. Copyright 1990 Gay Men's Health Crisis, Inc. All rights reserved. Permission granted for non-commercial use. Non-commercial reproduction is encouraged. Treatment Issues, Volume 4 No. 6 August 30, 1990 Contents: [items are separated by "*****" for this display] AZT Update from San Francisco AZT Resistance PML Vaccine Development In Brief ***** News from San Francisco: AZT Update Kevin Armington By June 1990, tens of thousands of people had taken AZT, many for several years. Such extensive experience will help clinicians use AZT in the most useful and least harmful way. In San Francisco, clinical trials from around the world yielded results that, taken together, demonstrate some important trends concerning dosing, when to begin taking AZT and development of resistance. [Ed. note: In the following articles, we have referenced material that was presented at the VIth International Conference by abstract number in parentheses rather than using our full footnote form.] Why is AZT Still in Clinical Trials? Even though AZT has been approved in the U.S. and other countries, studies that measure the drug's efficacy continue. The original study that led to the approval of AZT only provided six months of data (1). In fact, the majority (152 out of 282) had only completed four months of the study when the paper was written. This study also found that, after three months of treatment, T4 counts started to fall again in people with AIDS, but not in people with ARC. Looking back over these results, two things that have become clear in later studies were also in evidence in this original study: AZT has limited efficacy and it seems to work better at earlier stages of HIV infection. The many AZT studies presented in San Francisco support these two observations. Further study helps define the best dose and the optimal point in HIV illness to begin intervention with AZT. Efficacy and Effect on Overall Survival It is clear that the beneficial effects of AZT are time-limited in late stages of HIV infection (SB.422, SB.447). At the same time, AZT use has had a significant impact on the natural history of the disease. The original American double-blind study reported a 90% survival rate in trial participants who received the drug for one year. In the same trial, only 61% of those who originally received placebo, but were switched to AZT after six months, were alive nine months after the trial began. Without treatment, the one-year survival rate for patients with such severe disease is about 50%. Another review of 783 AIDS patients at Johns Hopkins Medical School showed that 86% of those diagnosed with PCP who took AZT were alive one year after diagnosis. In contrast, only 45% of those diagnosed with AIDS who did not take AZT were alive one year later (3132). Since mid-1987, the number of AIDS diagnoses in the U.S. has been about 15% lower than had been projected (ThC.623). One compelling explanation for this fortuitous "deficit" is the initiation of treatment, specifically AZT and PCP prophylaxis, among others. Researchers involved in the Multi-Center AIDS Cohort Study (MACS) believe there is a link between the diagnosis deficit and AZT (ThC.623). Better management and earlier diagnosis of opportunistic infections also have undoubtedly had an effect on the number of diagnoses. A number of studies compared overall survival in patients who have taken AZT and those who haven't. Physicians at St. Mary's Hospital in London compared two groups of patients who were diagnosed with AIDS between April and December 1987 (ThC.696). Forty seven took AZT, sixteen did not and five died within one month of the study and were not evaluated. The average survival time for those on AZT was over 24 months; for those not on AZT, seven months. One complicating factor in this study is that 47% of those on AZT took PCP prophylaxis while only 11% of those who didn't take AZT received PCP prophylaxis. Retrospective attempts to distinguish whether AZT or PCP prophylaxis provides greater protection have been unsuccessful. What's the Best Dose? It is now clear that 1200 mg/day is too much for most HIV-infected persons. This high dose is the result of clinical trials designed to find the maximum tolerated dose (MTD) of an experimental drug. As trials continually scale back the amount of AZT used, we are now in pursuit of the minimum effective dose. Studies presented in San Francisco used a broad spectrum of doses, ranging from 150 mg/day up to 2000 mg/day. In general, 500-600 mg/day have been shown to be as effective as 1200 mg/day in terms of viral suppression and increases in T4 counts (ThB.21, SB.447). In fact, one study hinted that the lower dose may be more effective (ThB.20). It was speculated that improved survival on the lower dose was due to the fact that patients did not have to interrupt treatment because of toxicity as often as those on full dose. One short study demonstrated that 300 mg/day has the same effect on viral replication as 600 mg (ThB.24). The 300 mg dose was not administered three times a day in 100 mg capsules, as might be expected; trial participants were given 50 mg AZT every four hours. This dose is difficult to self-administer, since AZT capsules are only available currently in 100 mg capsules. However, AZT is available in syrup form for children and a 50 mg dose can be approximated from this preparation. The rationale for spreading out the dose is to maintain a blood level of AZT. AZT clears quickly from the bloodstream after an oral dose. It is not known for sure, however, if it is important to maintain a consistent blood level of AZT or if it is as beneficial to take the whole daily dose at once. At least one study showed viral suppression at a dose as low as 150 mg/day. On the other hand, the National Institutes of Health are conducting trials with doses as high as 2000 mg/day in patients with AIDS Dementia Complex. Some neurologists feel that such a high dose is necessary to counter neurological complications. One Italian study did report positive effects of AZT in neurological disease at both 1000 mg/day and 500 mg/day (FB.30). Early Intervention: Improved Efficacy vs. Long-Term Toxicity As clinical trials provide more guidelines about the best way to use AZT, one trend is clearly emerging from the majority of studies done to date: the efficacy of the drug is greater when used at earlier stages of HIV infection. This information needs to be balanced with the uncertainty of possible toxicity after long-term use by people with stronger immune systems. The lower doses being explored, however, should diminish the risk of long-term toxicity. Perhaps the boldest statement made at the Sixth International AIDS Conference was by Dr. Margaret Fischl, a researcher at the University of Miami. Based on results from a placebo-controlled trial of AZT in people who were slightly symptomatic (ACTG #016), she stated that the greatest benefit of AZT was associated with the earliest use. The trial recruited 711 participants who were followed for an average of 11 months (2). When trial participants who had originally received placebo were switched over to AZT, their rate of disease progression was still faster than those who received drug from the beginning. Another multicenter American study found no difference between AZT and placebo in preventing progression to Walter Reed Stage 6 of HIV illness (i.e. diagnosis of an AIDS-defining opportunistic infection) (SB.446). Trial participants had T4 counts below 500 and received 800 mg AZT/day or placebo. The authors of this study did notice that trial participants with T4 counts between 400-500 benefited from treatment with AZT. This was a relatively small study (172 participants) and only provided data on 100 days of follow-up. In contrast to mounting evidence that "early is better", one small Canadian study did not show a difference between 1200 mg AZT/day and placebo in asymptomatic individuals (SB.439). This trial is ongoing and has followed some participants for up to 42 weeks. Researchers did note that those on drug had a slower rate of decline in T4 counts than those on placebo. These results certainly differ from those of other studies but with only 74 participants, this trial is dwarfed by much larger ones showing a significant difference between drug and placebo. What does all this Mean? It is difficult to extract a take-home message from this vast array of trials using different doses, looking at different populations, some lasting for weeks while others endure for years, etc. But the largest studies seem to agree on a couple of points: at earlier stages of HIV infection, the efficacy of AZT is enhanced and the toxic side effects are much better tolerated, especially at lower doses. In addition, development of resistance, which is discussed at length in a separate article in this issue, occurs less frequently when the drug is begun sooner. The best T4 level at which to start AZT is still a matter of debate. However, we await the results of a large, multicenter study being done at several VA hospitals that should yield some hard data on beginning AZT at T4 levels below 500 vs. below 200. ***** AZT Resistance Gabriel Torres, M.D. The phenomenon of AZT resistance received a lot of attention in San Francisco, since the practical implications for patients who are deteriorating despite long-term therapy with AZT are crucial. Resistance to antibiotics has been seen in common bacterial infections like gonorrhea, staphylococcus aureus and mycobacterium tuberculosis, as well as viral infections such as herpes simplex and influenza. The likelihood of resistance increases with the amount of virus present in the body, the length of infection and the degree of immunosuppresion. AZT resistance can be defined as the reduced ability of AZT to inhibit HIV replication in the test tube. This is determined in the laboratory by obtaining viral isolates from patients and testing the ability of AZT to inhibit replication. The first report of AZT resistance was by Larder et al., which showed that virus obtained from patients with AIDS or ARC who had received AZT for periods of approximately six months or longer frequently showed reduced susceptibility to AZT inhibition in the test tube (3). In a recent study viral isolates obtained from patients in ACTG studies 019 and 016 (asymptomatic and early ARC patients treated with AZT versus placebo) were compared to viral isolates obtained from patients with AIDS and advanced ARC (4). Patients with late stage HIV infection developed resistance significantly sooner than those with early stage disease. By 12 months after initiation of AZT therapy, an estimated 89% of persons with AIDS or ARCok had developed resistance compared to 31% of those with early-stage infection. All the patients who developed highly resistant virus had late-stage infection. A low T4 cell count was strongly associated with resistance; for example the rates of resistance at one year for baseline T4 cell counts were as follows: Baseline T4 cell count % Resistant after 12 months of AZT less than 100 63-99% 100-400 18-75% more than 400 11-59% Stage of Disease and Its Effect on Resistance Development of resistance occurred somewhat sooner among patients who received higher daily doses of AZT (1200-1500 mg/day) compared to those who received lower doses (500-600 mg/day). Resistance was not associated with the presence of p24 antigen in the blood. The 41 viral isolates obtained from patients who had never received AZT were uniformly sensitive to the drug. In San Francisco, Drs. David Ho and Hiroshi Mohri reported cases of resistant HIV isolates obtained from 10 patients who had received AZT. Six were highly resistant and four were moderately resistant; in some patients 100% of their total HIV burden was AZT resistant. In addition, two of five patients who had never received AZT also had resistant virus. It was theorized that these individuals may have been infected by a strain of HIV that was already AZT resistant (SB.81). A controversial report from the investigators of the Canadian Multicenter AIDS Trials showed a significant difference in the rate of progression to AIDS and ARC in those who developed AZT-resistant strains, yet the subjects who progressed had lower T4 cell percentages, which may cause earlier development of resistance as well as faster progression of disease (SB.84). Are Others Drugs Useful after Development of Resistance to AZT? In the laboratory, cross-resistance to other nucleoside analogues (drugs that are closely related to AZT) has been demonstrated with AZdU, AZA and AZG but not with ddI, ddC, d4T or foscarnet (5). CDC researchers reported HIV resistance to alpha interferon in patients with AIDS and suggested that testing for interferon susceptibility may predict who will benefit from AZT and interferon combinations (SB. 86). One report from the National Cancer Institute (ThA. 236) showed that resistance did not develop in two patients treated with alternating AZT and ddC after one year of therapy, suggesting that combination antiretroviral therapy may be the solution to the problem of AZT resistance. The other alternative is switching to another agent such as ddI or ddC after one year of therapy with AZT. One report of seven patients with AZT resistant HIV strains who were clinically failing while on AZT showed impressive reductions in p24 antigen levels and improvement in clinical status following three to six months of ddI therapy (2178). With expanded use of AZT in early HIV infection, concern has arisen about the potential consequences of resistance after prolonged AZT use. The potential for transmission of resistant strains of HIV via sexual intercourse, intravenous drug use or transfusion of blood products can be catastrophic. For the HIV-infected asymptomatic individual, the dilemma exists of postponing AZT therapy and risking disease progression or taking AZT and risking not having an effective therapy at the time of symptomatic disease. This risk is diminishing with expanded access to drugs like ddI and ddC. Until the clinical implications of AZT resistance in the test tube are clearly demonstrated however, the recommendations for early intervention with low dose AZT (500 mg per day) cannot be altered. Further research correlating AZT resistance with clinical disease is imperative, as well as the effect of combining or alternating other antiretroviral agents like ddC and ddI with AZT in an attempt to circumvent AZT resistance (for a detailed discussion of progress in combination trials, see Treatment Issues Vol 4 No 5). ***** Progressive Multifocal Leukoencephalopathy (PML) Richard Dunne Carole Lemens PML is a brain infection caused by reactivation of the JC virus, a member of the papovavirus family. Approximately 80-90% of adults are infected with JC virus, but it is controlled by an intact immune system. Immunosuppression by HIV can lead to spread of the virus through the blood stream into the brain, usually from the kidney which harbors the virus during the asymptomatic stage of the infection. Virus can be detected in the urine when it is actively reproducing. Recent studies have shown that the JC virus is found in the white blood cells in the bone marrow, which presumably carry the virus to the brain (6). The JC virus infects brain cells called oligodendroglial cells, which produce myelin, a spongy white matter that surrounds and protects the nerves. Destruction of myelin leads to death of nerve cells. This causes lesions in the brain and symptoms of neurological dysfunction. The lesions grow and multiply rapidly and can, in a period of weeks or months, destroy areas of the brain that control several boy functions. The most common symptoms of PML are mental deterioration such as confusion, disorientation or lethargy, weakness in one or more limbs, difficulties in coordination or movement, and visual problems such as blurriness, double vision and even blindness (7). PML was first identified as a disease in the 1950's in patients with cancer such as lymphoma and leukemia. PML also has been seen in transplant patients receiving immunosuppressive therapy and, since the early 80's, in people with HIV infection. Even so, PML is exceedingly rare. Prevalence To date, fewer than 1,000 AIDS-related cases of PML have been reported to the Centers for Disease Control (CDC). One study found the incidence of the infection to be approximately 4% among AIDS patients. There is reason to believe that there are considerably more cases however. PML is apt to be misdiagnosed as a more common opportunistic illness such as AIDS Dementia Complex or toxoplasmosis. Also PML may not appear until the late stages of AIDS and hence not be reported to CDC. Several autopsy surveys in Italy and Switzerland suggest that PML is more prevalent than is generally thought. In 385 consecutive AIDS autopsies performed at an Italian hospital over a five year period, PML was confirmed in 8% of the AIDS-related deaths (8). The incidence of PML is likely to increase in the future because of the increased number of people with advanced HIV disease and reduced mortality from PCP and other more common infections. Diagnosis and Treatment When suspected, PML can be diagnosed by CT scan of the head. MRI (Magnetic Resonance Image) however, is a more sensitive test and can show lesions not seen on CT scan. The only conclusive method for diagnosis is by brain biopsy which is usually only performed after an abnormal CT or MRI (9). PML has traditionally been associated with a very high mortality rate. In one study, the mean survival time after the onset of neurologic symptoms was four months. There have been scattered reports, however, both of spontaneous remission and possibly successful treatment. Some case studies seem to show that early and aggressive treatment can prolong life. PML progresses so rapidly that treatment decisions need to be made very quickly. Although extremely serious, a diagnosis of PML is not hopeless and there are survivors. There are two general and complementary theories on how best to treat PML. The first is to restore the immune system through antiviral therapies such as AZT (higher doses may be necessary), ddI or ddC. The hope is that an enhanced immune system will once again be able to keep the JC virus in check providing symptomatic improvement and perhaps remission of PML. In addition, treatments that attack the JC virus itself should be considered although at present there are no standard therapies. Some of the symptoms of PML can be controlled with readily available drugs. The oldest treatments for PML are two antiviral drugs: ARA-A known as adenine arabinoside or vidarabine and ARA-C also known as cytosine arabinoside or cytarabine. ARA-C is being used experimentally and is administered intrathecally through a shunt in the skull (10,11,12). Other possible and highly experimental treatments include acyclovir in high doses and alpha or beta interferon. N-acetylcysteine (NAC) has been proposed as a drug that may be worth investigating for this infection. Anecdotal reports are that AZT has improved survival in PML. Heparin, a commonly prescribed blood thinner is currently being studied in low doses as a potential PML treatment. The theory is that heparin somehow interferes with the mechanism by which B cells carry the JC virus to the brain. Its use may be contraindicated in hemophiliacs with PML. ***** Vaccine Development Michael Thorn, R.N. In San Francisco, there were reports on several fronts in the area of vaccine development. There are three potential roles for a vaccine against HIV: protection of those uninfected from primary infection, prevention of perinatal transmission from mother to fetus or prevention of disease progression in people already infected (FA.1, ThA.330). While it has been estimated that a vaccine to prevent primary infection is still a decade away, vaccines that can be used therapeutically in individuals who are HIV-positive may be available much sooner. Various Vaccine Candidates Many different approaches are being taken to develop a safe and effective vaccine against HIV. Some vaccine preparations use a portion of HIV, such as a protein from the envelope or core of the virus. Others use whole killed virus or killed virus with a portion removed. Both types have their potential drawbacks: there is some concern that vaccines using whole virus may stimulate HIV production, and that vaccines composed of portions of the viral coat may not protect against all strains of HIV. Certain vaccines incorporate an adjuvant, a compound that would improve the body's response to the vaccine. The major goal of a vaccine is to elicit a response from the immune system that will enable it to control or inhibit the disease-causing microorganism. This response could be a humoral response, i.e. production of antibodies to control or neutralize the virus or a cellular response, which would mobilize white blood cells such as macrophages and natural killer cells that directly attack foreign particles. Animal Research Vaccine research is complicated because of the difficulties in conducting HIV-related research in animals. "Animal models" have been difficult to come by: only chimpanzees can be infected with HIV, but few are available. Chimps are scarce and very expensive and they do not develop full-blown AIDS after infection with HIV. On the other hand, rhesus macaques (monkeys) can be infected with simian immunodeficiency virus (SIV), a retrovirus similar to HIV which can be used as a model for human HIV infection. Work with chimpanzees and HIV at a number of sites show mixed results. While protection of infected chimps from a second infection has been demonstrated by injecting portions of gp120, a protein from the virus envelope, other sites report testing 13 vaccine preparations that failed to protect chimpanzees from infection (ThA.338, FA.4). One preparation given to chimps caused signs of infection to appear twice as fast in the vaccinated animals compared to the controls (13). Dr. Michael Murphy-Corb, a researcher affiliated with a primate research center at Tulane University, presented results from three centers conducting SIV vaccine research on rhesus macaques with whole, inactivated virus. Several of the immunized macaques did not become infected when subsequently exposed to SIV and the vaccine also delayed progression of disease in a large majority of macaques who were already infected (FA.5). A more recent development in animal models is the creation of an immunodeficient mouse, called the SCID-hu (Severe Combined Immune Deficient) mouse, that will not reject human white blood cells, and can therefore be infected with HIV. These altered mice can be used as efficient animal models to test potential antiviral drugs or vaccines against HIV. This animal model has vastly improved the pace of vaccine research. Experiments on SCID mice evaluated combinations of two vaccine preparations using the gp160 envelope protein. Both are recombinant, one using a vaccine (HIVAC-1e, Oncogen) made with the vaccinia preparation used by Dr. Jonas Salk. It was found that giving both vaccines, with the vaccinia preparation first, provided the best response (ThA.343). Vaccine Research in People A number of different vaccine preparations have already been used in experiments with people. A vaccine to prevent primary infection will take much longer to test due to the difficulties in establishing efficacy and the long latency period of HIV. Therapeutic vaccines for those who are already infected are much further along in development, however. At Johns Hopkins, the VaxSyn HIV-1 vaccine produced by MicroGeneSys of West Haven, Connecticut, was given to eight volunteers in four doses over an 18-month period (FA.2). The vaccine is composed of gp160, a protein from the envelope of the virus. Three of the volunteers developed T cells that killed the virus in the test tube. These killer or cytotoxic T cells are activated T4 or T8 cells that are capable of finding and destroying other cells infected with HIV. In further studies with this vaccine, eight of eleven subjects with early HIV infection showed an increase in anti-HIV activity with T4 cell counts remaining stable over the eight months of the study. Three of the eleven had the usual T4 cell decline that is seen with progressive HIV disease. The National Institute of Allergy and Infectious Diseases study ACTG 003, also using the VaxSyn HIV-1, enrolled 18 low-risk HIV-negative volunteers. One of two doses of the vaccine was given to each subject with a booster dose in six months. No adverse effects were noted. After six months some of the subjects had developed HIV antibodies, but these results were only found after several attempts at testing. This vaccine showed a strong immune response to specific regions of the virus outer protein envelope. The next step in the testing of VaxSyn is to study higher doses for toxicity and efficacy. Salk's Vaccine Research has been underway in human volunteers since November 1987 with the Salk HIV-Immunogen vaccine (FA.3). This preparation is made from whole killed virus with the envelope protein gp120 removed. Results in chimps have been very encouraging. Two early trials that followed a total of about 20 people for over two years showed that the vaccine is well tolerated. In another larger trial, no harmful effects were noted in 19 people with ARC, 50 asymptomatic persons, or 13 asymptomatic and symptomatic persons who also were given AZT for three months. Approximately 60% showed an improved response to skin testing. Some minor toxicity was seen in this trial. It should be noted that vaccination was not associated with the development of an antibody response to HIV. Also, one patient developed PCP 18 weeks after vaccination, three developed Kaposi's sarcoma after one and a half to two years and one was diagnosed with herpes zoster retinitis at 16 weeks. A progression rate of 4% in two and a half years was noted, which the researchers claimed was lower than would be expected in this population of patients. Dr. Alexander Levine, who presented these results, seemed very enthusiastic about the potential of this vaccine in combination with AZT. V3 Loop Vaccine: Recent research has pointed to a possible connection between some maternal antibodies and transmission to the fetus. A vaccine utilizing an area of the virus coat called the V3 loop may cause formation of neutralizing antibodies to 85% of HIV viral strains. This area seems to be remarkably constant and holds a great deal of promise for future research efforts. Since the V3 loop is constant in multiple strains of HIV, a vaccine which triggers antibodies that recognize this protein on the virus coat may protect against different strains and be more effective when given to a large population (14,15). HGP-30 Vaccine from CEL-SCI Corporation/Viral Technologies, Inc. is developing a vaccine from a synthetic form of the p17 protein found in the core of the virus. This protein is common to all strains of the virus and would not be vulnerable to the usual genetic mutation that effects the usefulness of other vaccines. Studies with monkeys and humans have shown no toxicity and an increased production of CD8 cells in four human recipients. Summary Greater than expected strides have been made in vaccine development over the last two years. Unfortunately, a vaccine to prevent primary infection is probably far in the future and some important issues, such as long-term efficacy, will take many years to resolve. The most encouraging news is for those already infected. A number of potentially therapeutic vaccines have been shown to be safe in the short-term and there are some preliminary indications of efficacy. It is likely that some of these vaccines will be used together in new clinical trials to hopefully induce a greater immuno-protective response. ***** In Brief Hyperthermia: This blood-heating technique caused a sensation when the first patient treated took to the talk shows and championed hyperthermia as a cure for Kaposi's sarcoma, if not for HIV infection. Very little meaningful information has been made public since the first media barrage. GMHC conducted a survey of 300 physicians to learn their impressions about this treatment and the way it has been handled in the media. The return rate was 43%. Although more than 90% of respondents had been asked about hyperthermia by their patients, 82% felt they did not have enough information about its effect on HIV; 79% felt they did not have enough information about its effect on KS. While many respondents have an open mind about the potential of hyperthermia, there was strong criticism of the media for raising unrealistic hopes and of the doctors performing the procedure due to their reluctance to openly discuss their theory or results. In fact, the two doctors who were performing the procedure (Kenneth Alonso and William Logan) are no longer working together. Dr. Logan has moved his research to Mexico City, where local authorities are attempting to stop him, since he has no license to practice in Mexico. At least one death has been reported in an American patient who traveled to Mexico City for hyperthermia. The cost is astronomical: Dr. Alonso is demanding a $50,000 cash payment. Interested patients are charged $250 for a screening interview, with no guarantee that they will receive the therapy. A team of doctors from the NIH have been dispatched to investigate Dr. Alonso's claims and to examine the patients who have undergone hyperthermia. A detailed report was scheduled for release by the time we went to press. Kemron: This is the same drug that burst onto the treatment scene early this year, when Kenyan doctors researching it announced miraculous results. Since then, several thousands of people have experimented with other versions of oral alpha interferon. The Kenyan results have not been duplicated. In fact there are anecdotal reports from California of adverse reactions and T cell drops. Unfortunately, the renewed interest has not been accompanied by any objectively reviewed new data. The clinical trial which is being conducted by Mt. Sinai is having trouble with recruitment because people are taking this drug on their own. It is crucial that the Kenyan results be duplicated and that we learn more about this drug as quickly as possible. A second trial, which will compare various doses, is being planned at Mt. Sinai. This trial will recruit both PWAs and PWArcs. Primaquine Availability: Primaquine, a drug that is approved in the U.S. for treatment of malaria, is also being used experimentally with clindamycin ("off-label") to treat PCP. The American supply of the drug is now very low due to a shortage of an ingredient necessary to produce Primaquine. It is currently being dispensed by the Centers for Disease Control, only for malaria. To fill the void, PWA Health Group has come to the rescue and will import Primaquine from England, cheaply, for anyone with a prescription. For more information, call the Health Group at (212) 532-0280. ***** Footnotes: 1 Fischl MA et al. The efficacy of AZT in the treatment of patients with AIDS and AIDS-related complex. NEJM 317(4):185-91, 1987. 2 Fischl MA et al. The safety and efficacy of AZT in the treatment of subjects with mildly symptomatic HIV-1 infection. Ann Int Med 112(10):727-37, 1990. 3 Larder BA et al. Science 243:1731-4, 1989. 4 Richman DD et al. J AIDS 3:743-6, 1990. 5 Richman D. Rev Infect Dis 12:S507-512, 1990. 6 Houff SA et al. Involvement of JC infected mononuclear cells from bone marrow and spleen in the pathogenesis of PML. NEJM 318:301-05,1988. 7 Berger JR et al. PML associated with HIV infection: Ann Int Med 107:78-87,1987. 8 VIth Int Conf on AIDS abstract #TH.B.449 San Francisco, June, 1990. 9 Berger JR et al. PML associated with HIV infection: Ann Int Med 107:78-87,1987. 10 Embrey JR et al. Long term survival and late development of bladder cancer in renal transplant patient with PML. J Neuro 139:580-581,1988. 11 Schlitt et al. PML: Three patients diagnosed by brain biopsy, with prolonged survival in two. Neurosurg 18:407-414,1986. 12 Tashiro K et al. PML with magnetic resonance imaging verification and therapeutic trials with interferon. J Neuro 234:427-429,1988. 13 CDC AIDS Weekly, 6/25/90, p.3. 14 Rossi P et al. Presence of maternal antibodies to HIV-1 envelope glycoprotein gp120 epitopes correlates with the uninfected status of children born to seropositive mothers. Proc Natl Acad Sci 86(20):8055-8058, Oct. 1989. 15 Devash Y et al. Vertical transmission of HIV is correlated with the absence of high-affinity/avidity maternal antibodies to the gp120 principal domain. Proc Natl Acad Sci 87(9):3445-3449, May 1990. ***** 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: Richard Dunne Carole Lemens Michael Thorn, R.N. Gabriel Torres, M.D. GMHC, Department of Medical Information, 129 West 20th Street, New York, NY 10011. &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& End of display