Subject: GMHC Treatment Issues Vol. 6 No. 11 Date: Dec 1992 (1462 lines) &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& && T R E A T M E N T I S S U E S && &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& TREATMENT ISSUES The Gay Men's Health Crisis Newsletter of Experimental AIDS Therapies Volume 6, Number 11 -- December 1992 CONTENTS: [items are separated by "*****" for this display] Depression and HIV Tobacco Smoking Pentoxifylline Update CDC Defintion Update Drug Company Watch Treatment Briefs More on Nutrition Support Services Glossary ***** DEPRESSION and HIV by Judith G. Rabkin, Ph.D., MPH and George Gewirtz, M. D. The term "depression" is used to describe various conditions, including transient moods, mild but persistent sadness, and clinical illness. Clinical depression is defined as a cluster of symptoms that occur together daily for a certain period of time. The main forms of depressive disorder are major depression, which is often episodic, and "dysthymia," which is a milder chronic condition. This review will focus on the clinical disorders. Depression and HIV Although clinical depression is the most commonly observed psychiatric disorder among people with HIV illness, rates are no higher in HIV-infected gay men than in the general population. Early reports of psychiatric illness among those with HIV were described up until 1987 as widespread depressive and anxiety symptoms. However, these studies relied primarily on self-report symptom rating scales. More recent and more extensive studies of community samples and research volunteers have been conducted.[1] These studies used structured diagnostic instruments and trained clinicians as interviewers. They found rates of current depressive disorders among HIV-positive gay men to be approximately the same as those found in HIV-negative gay men and general population samples that had been matched for age and gender.[2] In a study of gay men who had an AIDS defining diagnosis for at least three years ("long-term survivors"), only three of 53 (6%) were depressed.[3] Similarly low rates for gay men using self-report symptom checklists were reported.[4] The same has been found in nondrug-using women.[5] It should be noted, though, that some investigators have found higher rates in HIV- positive men.[6] In general, about 4%-14% of HIV-positive men and HIV- positive nondrug-using women are found to have current depressive disorders. The prevalence rate in the general population is 5%. It is important, of course, to recognize that the majority of HIV-positive people who do not have clinical depressive disorders are nevertheless likely to experience periods of sadness and distress from time to time. For example, in the "long term survivor" study mentioned above, participants were asked, "How has your mood been recently? Have you felt pretty cheerful or depressed!" Forty-two percent answered "cheerful," and another 42% described transient sad feelings. An additional 11% had some depressive symptoms. These transient states are not routinely reported in epidemiological studies, and therefore no comparison group exists. However, the absence of a current depressive disorder does not necessarily signify a persistently "cheerful" mood or a total absence of distress. HIV and Suicide A recent study published in the Journal of the American Medical Association reported on the risk of suicide among persons with AIDS. The study found that while people with AIDS have an increased risk of suicide, a recent trend in rates shows a decline in AIDS-related suicide between 1987-1989. The authors find the declining suicide rates to be encouraging and possibly due to greater optimism among PWAs about both quality of life and long survival, emerging potential therapies for HIV, better psychiatric care, and a perceived lessened social stigma against people with HIV disease. Health care providers, nonetheless should consider assessment of suicide risk as an integral part of standard HIV care. Causes of Depression It has been suggested but not demonstrated that HIV itself causes mood changes and that AIDS related dementia induces depression. As Markowitz et al. note, there is little evidence to support either of these hypotheses.[8] Stern and colleagues did not find depressed mood associated with early, subtle cognitive changes in HIV-positive men.[9] Their findings are that apathy rather than sadness appears to be the predominant effect in AIDS-related dementia. Another important question is whether HIV drugs such as AZT induce mood changes. Isolated cases of AZT-associated mania have been reported in the literature.[10] Some patients report feeling depressed after starting to take AZT, but there is little systematic documentation of such effects, if indeed they exist. In an interview of 15 leading AIDS specialists in 1992, each of whom had a current caseload of an average of 500 HIV-positive patients, Rabkin and colleagues (unpublished) found none who had observed consistent mood effects from HIV medication. In practice, it is extremely difficult to distinguish between the symbolic effects of starting antiretroviral treatment with its direct chemical effects. In later stages of HIV illness it becomes even more difficult to identify effects of any one medication on mood (such as alpha interferon and INH), since as a rule many are taken simultaneously. Overall, while individual patients may experience mood changes in association with an HIV medication, no major impact on mood has been documented to date. Diagnosis The diagnosis of major depression, as defined in current psychiatry, requires the presence of at least five of nine specific symptoms during the same two-week period.[11] These must include either the first or second of the following: 1. Depressed mood; 2. Markedly diminished interest/pleasure in almost all activities; 3. Significant unintentional weight gain or loss; 4. Insomnia or oversleeping; 5. Fidgetiness or slowed movement or speech; 6. Fatigue or loss of energy; 7. Feelings of worthlessness or excessive/inappropriate guilt; 8. Diminished ability to think or concentrate; 9. Recurrent suicidal thoughts. The task of diagnosis is complicated, since several of the above symptoms could be caused by HIV itself, specific HIV- related conditions, or even HIV medications. Furthermore, the diagnosis is not made if the disturbance is "a normal reaction" to the death of a loved one. However, if focused queries are employed by a clinician with experience in depression and HIV illness, it is possible to obtain a reliable diagnosis in the context of HIV. Clinical Trials Published information on antidepressant treatments for HIV illness is extremely limited. Virtually no data have been released on the use of psychostimulants for depression. To our knowledge, in fact, only three controlled clinical trials of antidepressant medication have been conducted to date. No results have been published. Manning and colleagues at Cornell University conducted a randomized doubleblind comparison of imipramine (brand name Tofranil) and placebo for 40 HIV-positive men and women with major depression.[12] Standard medication doses (up to 250 mg/day of imipramine) were prescribed, with a mean peak dose of 225 mg/day. Response rates were 67% for imipramine-treated patients and 47% for participants taking placebo. The response rate to imipramine was as expected, but the placebo response in this study was unusually high. Rabkin and colleagues reported results for the first 7.7 patients randomized in a study of the same design and with the same drug as described above. Upon entry, 33% of participants had T4 counts under 200. Response rate to imipramine was 69%, for placebo 23%, making a statistically significant difference. The same rate was found in 21 patients with entry T4 counts under 200. Thus the degree of immune suppression in participants was not found to be a factor in response to antidepressant medication. Zisook and colleagues in San Diego are conducting a double-blind trial of fluoxetine (Prozac) and placebo. All patients are invited to a weekly support group. Of the 35 patients studied to date, high rates of response have been found in both treatment groups.[13] Rabkin and colleagues treated with Prozac 31 patients who had failed imipramine or placebo. Twenty-eight patients responded, about half with additional low doses of Dexedrine after partial response of Prozac alone. Fernandez and colleagues are conducting a study in which depressed HIV-positive patients are randomized to either methylphenidate (Ritalin) or desipramine (Norpramin) in a six- week trial. There is no placebo-control group in this study. So far both treatments appear to be effective. Finally, Rabkin and Rabkin are conducting an open pilot study of dextroamphetamine (Dexedrine) as an initial treatment for people with AIDS defining conditions who are depressed, have low T4 counts, and manifest lethargy as a major problem. Of the seven patients treated to date, who at entry had an average of 10 T4 cells, six responded with excellent results. The seventh patient discontinued medication because he felt "wired." Dexedrine to treat depression has to be used selectively, and patients with history of psychostimulant abuse should be excluded. The study needs extension and replication, but appears to offer a promising strategy for a select group of late-stage HIV-positive people. Antidepressants The available research literature indicates that HIV- positive depressed patients can tolerate standard doses of antidepressant medications. These are up to 250-300 mg/day of imipramine, 40 or 60 mg/day of Prozac, and up to 200 mg/day of sertraline, if insufficient clinical effect is obtained at lower doses. Tests of the medication should last at least six weeks (eight weeks for Prozac) before a decision is made that the drug is not effective. Many "treatment" failures are due to inadequate dose and duration of medication. Prozac is safer to use because danger of overdose is limited. Its long half-life is a clear advantage for a patient who is ill or hospitalized. Additionally, discontinuation of the drug seldom causes problems, except for patients taking unusually high doses, in which case five weeks are needed to clear the drug from the system. Several AIDS specialists are prescribing Prozac at 20 mg/day when patients complain of depression. This is often helpful and sufficient. Some patients may need a lower dose initially (10 mg/day). During the first four to six weeks, clinical improvement may not be noticeable, and patients also need encouragement and support during this time. Higher doses (up to 60 mg/day) are sometimes in order. Adding another medication, such as a low dose of a tricyclic or psychostimulant, may be helpful. Psychostimulants In clinical practice methylphenidate (Ritalin) is more often prescribed than Dexedrine because it is a more "acceptable" treatment to both physicians and patients. Starting doses of Dexedrine, which is more potent, are 2.5 to 5 mg/day, taken at least eight hours before bedtime. Occasionally, 30 or 40 mg/day is necessary to affect energy and mood. Cautioning patients not to discontinue medication abruptly is necessary for people taking doses in this higher range. Dexedrine has a very rapid action, and a ten-day trial is often sufficient to assess efficacy. Ritalin is usually started at 15 mg/day, increasing as needed up to 60 mg/day in three divided doses. Side effects In the available research literature and our own clinical experience, depressed HIV-positive patients respond well to tricyclic antidepressants. The most common side effects include dry mouth, constipation, postural hypotension, and drowsiness. Additionally, drugs like Prozac and Zoloft that inhibit a neurotransmitter called serotonin are effective and often preferred because the side effects are milder. Side effects to these drugs include overstimulation, upset stomach, and headache. Psychotherapy Several clinical studies reports that therapy and group therapy can be of benefit to patients with depression.[14] [See side bar for resources.] An encouraging pilot study by Markowitz and Perry observed that 20 of 23 HIV- positive patients improved after an average of four months of interpersonal psychotherapy.[15] The authors are conducting a comparative clinical trial with two forms of structured psychotherapy: cognitive behavioral therapy and interpersonal psychotherapy, each of which comes with a detailed training manual for therapists. In the study, imipramine and additional clinical management are used. It is the impression of the authors that psycho- therapeutic methods are effective in alleviating clinical depression and general distress.[16] Testosterone Replacement Therapy Hormones originate in the thyroid, adrenal, testes, or ovaries and travel by the bloodstream to places in the body in order to regulate various functions. Testosterone is the naturally occurring male hormone that is produced in the testicles and adrenal glands. Its function is to build muscles and masculinize. Synthetic versions of the hormone have been used to stimulate the bone marrow to produce red and white cells in certain autoimmune diseases in men and women. Some HIV-positive men have been found to have low levels of testosterone at a wide range of T-cell levels. The condition is associated with sexual dysfunction in men, muscle loss, and a lack of energy, including mild depression. Some doctors have begun to offer patients testosterone in monthly injections. The effect of testosterone replacement has not been documented in HIV-positive people. It is not being offered to or tested in women. But to date there have been no reports of adverse effects in HIV-positive men from injections of testosterone. Columbia Presbyterian Medical Center, Department of Psychiatry, is currently conducting a free pilot trial of injectable testosterone. The study is limited to men with under 400 T4 cells with diminished sexual desire or function and low mood. Associated problems may include low energy, low appetite, and weight loss. Testosterone blood levels are assessed at the initial visit to determine eligibility. Subjects are asked to monitor mood, sexual interest, activity, energy, and weight. To enroll or find out more about the trial, call (212) 960-5762. Conclusion The limited experience to date indicates that people with HIV illness respond like anyone else to standard treatment, and treating depression has been one of psychiatry's success stories. The overall message has two components: first, most people with HIV disease are not depressed. Second, those who have clinical depressive disorders respond well to treatment. Two trials in New York City are enrolling. For more information contact Dr. Perry of Cornell Medical College at 746- 3921 and Dr. Rabkin of Columbia Presbyterian Medical Center at 960-5762. References 1. Williams et al. Multidisciplinary baseline assessment of homosexual men with and without HIV infection: II. standardized clinical assessment of current and lifetime psychopathology. Archives of Gen Psych 48:124-130, 1991 and Perry SW et al. Severity of psychiatric symptoms after HIV testing. Amer Journ Psych, in press, 1992. 2. Robins L & Regier D. Psychiatric Disorders in America: The Epidemiologic Catchment Area Study. New York, Free Press,1991. 3. Rabkin IG et al. Suicidality in AIDS long term survivors: What is the evidence? Presented at 144th Ann Meeting of American Psychiatric Association, New Orleans, May, 1991. 4. Ostrow D et al. HIV-related symptoms and psychological functioning in a cohort of homosexual men. Amer Journ Psych 146:737-742, 1989 and Janssen RS et al. Neurological and neuropsychological manifestations of HIV-1. Arch Gen Psych 45:859-864, 1989. 5. Brown GR & Rundall IR Prospective study of psychiatric morbidity in HIV-seropositive women without AIDS. Gen Hospital Psychiatry 12:1-6, 1990. 6. Atkinson IH et al. Prevalence of psychiatric disorders among men infected with HIV: A controlled study. Arch of Gen Psychiatry 45:859-864, 1989. 7. Cote T et al. Risk of suicide among persons with AIDS: A national assessment. JAMA 268:2066-2068, 1992. 8. Markowitz J et al. Treating depression in HIV-positive patients. AIDS, in press, 1992. 9. Stern et al. Multidisciplinary baseline assessment of homosexual men with and without HIV:III Neurologic and neuropsychological findings. Arch Gen Psychiatry 48:131-138, 1991. 10. Perkins D et al. HIV-related major depression: Response to zidovudine treatment. Psychosomatics 32:451-454, 1991. 11. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition Revised (DMS-III-R). Washington, D. C.: American Psychiatric Association, 1987. 12. VI Int'l Conf on AIDS, Abstract #Th.B. 32, San Francisco, June, 1990. 13. Personal communication, Zisook S., August, 1992. 14. Levine A et al. Group psychotherapy for HIV-seropositive patients with major depression. Amer J Psychother 45 (3): 413- 24, 1991 and Schaffner B. Psychotherapy with HIV-infected patients. New Directions for Mental Health Services 48:5-20, 1990. 15. Markowitz I et al. Interpersonal psychotherapy of depressed HIV seropositive patients. Hospital and Community Psychiatry 43:885-890, 1992. 16. Personal Communication, Markowitz J. August 28, 1992. ***** TOBACCO SMOKING and HIV DISEASE by Garance Franke-Ruta Smoking and HIV Infection People who smoke tobacco are more likely to become HIV- infected or participate in high-risk behaviors that facilitate HIV transmission than those who do not. This has been shown in groups as diverse as Haitian women, Californian gay men, and teenagers from Oregon.[1] Often attributed to people ignoring prevention messages, the association between smoking and HIV infection may in fact have a biological basis. In many, smoking degrades the lining of the oral cavity or leads to minuscule ulcerations that could facilitate HIV transmission. Smoking has a number ot known negative biological effects that may affect the progression of HIV disease. These include decreased lung function, chronic inflammatory disease of the lower airways, gum and oral diseases such as periodontis, various cancers, and a lowered ability to heal wounds. Along with the chronic inflammation of the lungs, which can lead to chronic bronchitis or emphysema, smoking causes an elevation of the body's white blood cell count, a condition known as smoker's leukocytosis. Smoking and Disease Progression Because of smoking's general effects on the immune system and the body, some researchers have hypothesized that smoking in early HIV disease may increase risk of progression to AIDS by activating T4 cells, thus facilitating HIV replication.[2] A study from the Food and Drug Administration (FDA) provides preliminary evidence that, at least in the test tube, constituents of cigarette smoke induce HIV production in chronically-infected cells.[3] A British group of researchers retrospectively reviewed the smoking status of people with AIDS in a lung study they were conducting. They saw a more rapid progression to AIDS and a higher risk of developing Pneumocystis carinii pneumonia (PCP) in those who were smokers than in nonsmokers (a group that included former smokers). Further analysis showed no difference between smokers and nonsmokers in progression to non-PCP AIDS. The authors recommend that, in addition to T4 count, the effects of smoking on lung function be taken into account when prescribing PCP prophylaxis, since smokers' decreased lung function seems to place them at a higher risk of developing PCP than their nonsmoking counterparts.[4] Other studies have found little or no effect of smoking on disease progression. A study of Haitian men and women found that smoking status was not associated with changes in T4 cell percentages or beta-2-microglobulin (a measure of immune system activation).[5] A long-term follow-up study of 202 gay men found that T4 counts and serum beta-2-microglobulin levels were elevated in smokers compared to nonsmokers following seroconversion. However, this difference in immune parameters disappeared after two years and had no impact on clinical outcomes such as AIDS or the development of PCP. [6] Another study of 249 men in Canada with HIV found no association between smoking and the development of AIDS.[7] A long-term study of HIV-infected and uninfected men found that, across the board, smokers had higher T4 counts; however, this difference was less marked for those who were HIV-infected. The authors also found that of those participants who seroconverted, smokers' T4 counts fell faster than nonsmokers' counts.[8] Smoking and Opportunistic Infections At the VIIIth International Conference on AIDS in Amsterdam last July, a few abstracts associated smoking with the development of certain opportunistic infections and poor outcomes. A group from California found that people diagnosed with cryptococcal meningitis were four times more likely to have smoked within the last 30 days than people diagnosed with other opportunistic infections. The organism that causes the meningeal infection (inflammation of the lining of the brain), Cryptococcus neoformans, is believed to enter the body through the lungs. The authors postulate that smoking-impaired lung defenses might allow the organism to colonize the lungs, which precedes its spread to the central nervous system.[9] In an abstract dealing with oral lesions in smokers and nonsmokers, another California group found that smoking was associated with a higher risk of developing oral thrush, but a lower risk of developing oral ulcers.[10] And in a second study to explore the association of smoking with the development of PCP, heavy smokers were found to be over three times more likely than light smokers to develop the infection. Intermediate smokers were also found to have an increased risk of PCP, regardless of T4 count, gender, ethnicity, or use of PCP prophylaxis.[11] Smoking and Healing Cigarette smoking has been observed to impair the healing of wounds, although few studies have been done to confirm this conclusion. Smoking has been associated with slower healing of ulcers, oral injuries, mastectomies, and facelifts, as well as increased scar formation, postoperative complications and recovery time.[12] Proposed reasons for this finding are the constriction of blood vessels induced by cigarette smoke and the reduced proliferation of red blood cells (which carry oxygen), macrophages, and fibroblasts (which are involved in the healing of wounds). At the same time that there is less oxygen and blood flow, smoking increases the heart rate and the oxygen demands of tissues. It also interferes with enzymes crucial to healing and inhibits the growth of new skin cells (epithelial cells). The combined effects of these processes lead to a recommendation that "smokers should be advised to stop smoking prior to elective surgery or when recovering from wounds resulting from trauma, disease, or emergent surgery for at least two weeks."[13] Smoking and HPV-Related Anogenital Cancers People with HIV are at increased risk for developing anogenital cancers and precancerous abnormalities due to their suppressed immunity and high incidence of infection with the human papilloma virus (HPV). HPV is thought to cause most genital warts, lesions, and cervical or anal cancers. However, the development of anogenital cancers and lesions, especially cervical cancer, is associated with factors other than just HPV infection. Suppressed immunity is one of them, but so is poor nutrition. Vitamin C and beta- carotene seem especially important.[14] Smoking dramatically reduces the body's stores of vitamin C, and smoking has been associated with the development of precancerous cervical lesions and cervical cancer.[15] Tobacco products (like nicotine) are also found in high concentrations in cervical secretions, where they may act as carcinogens or suppress local immunity.[16] Former smokers do not have as high a risk of cervical cancer as current smokers. While there is no study that shows that quitting smoking decreases the risk of anogenital cancer or lesions in people with HIV, quitting smoking is known to reduce the risk of cervical cancer in women in general, especially in women who have precancerous lesions. The same would very likely hold true for men with HPV-related anal or penile lesions. Quitting smoking is something that people with HPV and HIV who are concerned about anogenital cancer can do to reduce their risk of cancer.[17] One abstract presented at the VIIIth International Conference on AIDS found an association between abnormal anal cell growth (running the spectrum from lesions to warts to cancer) and smoking in men with late-stage HIV disease.[18] Joel Palefsky, M. D. found that in addition to HIV infection and T4 counts of under 200, current smoking was associated with a 13- fold higher risk of developing anal cellular abnormalities in men.[19] Conclusion Tobacco smoking is harmful not only to smokers but also to those who live or work with them, regardless of HIV status. It has been associated with a higher risk of HIV infection. There are conflicting data on the effects of smoking on HIV disease progression, and the effects of preexisting smoker's leucocytosis do not seem to be protective. Although some recent studies point to increased risks for certain opportunistic infections in smokers, especially PCP, the only infection in which this association has been proved is in the case of anogenital abnormalities and cancers. Despite the long time it takes many smoking-related problems to develop, smoking is by no means without health risks for the immunocompromised person. For information about smoking cessation support in your area contact the American Cancer Society Stop Smoking Office at (212) 582-2118, or ask your physician about the new Nicotine Transdermal Patch. References 1. Halsey NA, Coberly JS, Holt E, et al. Sexual behavior, smoking and HIV-1 infection in Haitian women. JAMA. 267(15):2062 6, 1992; and Biglan A, Metzler CW, Wirt R, et al. Social and behavioural factors associated with high-risk sexual behavior among adolescents. J Behavior Med 13(3):245 61, 1990. 2. VIIIth International Conference on AIDS, Abstract # PoC 4407, Amsterdam, July, 1992. 3. VIIIth International Conference on AIDS, Abstract # 2114, Amsterdam, July, 1992. 4. VIIIth International Conference on AIDS, Abstract # PoC 4407, Amsterdam, July, 1992. 5. VIIIth International Conference on AIDS, Abstract #PoC4383, Amsterdam, July, 1992 6. Burns, DN. Op. cit. 7. Coates RA, Farewell VT, Raboud I, et al. Cofactors of progression to acquired immunodeficiency syndrome in a chort of male sexual contacts of men with human immunodeficiency virus disease. Am J Epidiomiol. 132(4):717-22, 1990. 8. Royce RA, Winkelstein W. HIV infection, cigarette smoking, and CD4+ T lymphocyte counts: preliminary results from the San Francisco Men's Health Study. AIDS 4940:327-33, 1997. 9. VIIIth International Confference on AIDS, Abstract.#POB 3172, Amsterdam, July, 1992. 10. VIIIth international Conference on AIDS, Abstract# PoB 3362, Amsterdam, July, 1992. 11. VIIIth International Conkrence on AIDS, Abstract # WeC 1030, Amsterdam, July, 1992. 12. Handlin DS, and Baker T. The effects of smoking on postoperative recovery. Am J Med. 93(Supp 1A):1A-32S-37S. 13. Silverstein P. Smoking and wound healing. Am J Med. 93(Sup 1A):1A-22S-24S, 1992. 14. Brock KE, et al. Nutrients in diet and plasma and risk of in situ cervical cancer. J Nat'l Cancer Inst. 80(8):580-5, 1988 and Basu J et al. Plasma ascorbic acid and beta-carotene levels in women evaluated for HPV infection, smoking, and cervix dysplasia. Can Detec Preven. 15(3):165-70, 1991. 15. Licciardone JC, et al. Uterine cervical cancer risk in cigarette smokers: a meta-analytic study. Am J Prevent Med. 6(5):274-81, 1990. 16. Hellberg D et al. Smoking and cervical intraepithelial neoplasia: nicotine and cotinine in serum and cervical mucus in smokers and nonsmokers. Am J Obstet Gynecol. 158(4):910-3, 1988 and Barton SE, et al. Possible cofactors in the etiology of cervical intraepithelial neoplasia. An immunopathologic study. J Reproduct Med. 34(9):613-6, 1989. 17. Licciardone JC et al. Cigarette smoking and alcohol consumption in the aetiology of uterine cervical cancer. Int J Epidemiol. 18(3):5337, 1989. 18. VIIIth International Conference on AIDS, Abstract # PoC 4399, Amsterdam, July, 1992. 19. VIIIth International Conference on AIDS, Abstract # MoB 0058, Amsterdam, July, 1992 ***** PENTOXIFYLLINE UPDATE by Mike Barr Pentoxifylline is a prescription drug used to treat circulation disorders in the elderly, marked under the name "Trental" by Hoechst-Roussel since 1972. Ingested orally, pentoxifylline improves the flow of blood by reducing viscosity, which means altering the resistance of blood flow. Side effects are uncommon (reported in fewer than 3% of users), but can include nausea, bloating, and dizziness. The standard dose given to people with circulation disorders is 400-mg three times daily.[1] The drug is taken with meals in order to reduce adverse reactions. Pentoxifylline is available by prescription at a cost of $61.95 for a bottle of one hundred 400 mg tablets. This adds up to approximately $700 per year. Pentoxifylline and HIV Recently, two different research teams found that pentoxifylline exhibits anti-HIV activity in test tube experiments. Earlier work found that pentoxifylline reduces the level of tumor necrosis factor (TNF) in the blood.[2] TNF -- as its name suggests -- possesses antitumor activity, killing potential cancer cells in the body.[3] TNF has also been shown to increase the reproductive capacity of HIV itself and to interfere with the activity of antiretroviral therapies such as AZT and ddC. In persons with AIDS and cancer, levels of TNF are abnormally high, and it is believed that such high levels of TNF contribute to anemia and wasting.[4] A five-patient study conducted in 1989 at the Dana-Farber Cancer Institute in Boston found that pentoxifylline was successful in reducing abnormally high TNF levels to near normal in a group of cancer patients, thus resulting in a general improvement in well-being.[5] Additionally, pentoxifylline has been reported to prevent over-activation of immune system proteins such as Interleukin-1 and -2 (IL-1 and IL-2)[6] and to reduce the incidence of graft- versus-host disease among bone marrow transplant patients. It is also thought to ameliorate some of the toxic side effects of amphotericin-B, a drug used to treat cryptococcal meningitis and other fungal infections. Phase I-II Study Results At the VIIIth International Conference on AIDS in Amsterdam this past July, Dr. Bruce Dezube of Beth Israel Hospital presented encouraging results from an eight-to-sixteen-week study of pentoxifylline.[7] The drug was given to 17 people with AIDS and T4 cell counts below 100; all participants were taking anti- HIV medication (AZT, ddI, ddC). Perhaps the most dramatic finding is the observation that the quantity of HIV in the body is reduced on average by 97% in people taking pentoxifylline. Of the 13 patients able to be analyzed so far, levels of TNF were reduced to normal levels. Triglycerides, believed to reflect excessive activity of TNF, were also dramatically reduced, as were alpha interferon levels. Alpha interferon is a naturally occurring substance in the body that, when present in high levels, has been associated with disease progression in people with AIDS. The only side effect reported was recurrent fevers, which Dr. Dezube feels is "probably attributable to the drug."[8] All but three participants have chosen to continue taking the drug. Dezube said that his research team is encouraged by the results of the study so far. However, in an interview, he emphasized that pentoxifylline's mode of activity remains unclear. "It may not be the anti-TNF effect at all, but rather pentoxifylline's direct activity against HIV that accounts for the reduction in the quantity of virus," he explained. "Or it may be that pentoxifylline simply helps AZT [and ddI[9]] work better.[10] Although the drug appears safe and well-tolerated, Dezube feels there is not enough clinical evidence to warrant people with HIV/AIDS taking pentoxifylline outside a research setting. He also warned against the searching out of laboratories equipped to measure TNF levels. "There is no assay that is readily available and accurate," he cautioned. "Circulating TNF receptors block the TNF proteins, and TNF disappears from the blood within about six minutes.[11] Current Trials Dezube's team at Beth Israel Hospital has recently begun the second part of its pentoxifylline study, in which trial volunteers will receive twice the standard dose (800 mg three times daily). For more information about this trial, call (617) 735-4103. A 16-week placebo-controlled study of pentoxifylline is under way at Community Research Initiative on AIDS (CRIA) in New York. The trial still needs participants. Volunteers will be randomly assigned to receive either pentoxifylline or placebo. Eligible participants for the study must have a T4 cell counts below 300. Blood levels of TNF and alpha interferon will be monitored. For more information, call CRIA at (212) 924-3934. Other centers studying the use of pentoxifylline in HIV/AIDS are Case Western Reserve Medical School in Cleveland at (216) 844-8175 and Community Research Initiative of New England at (617) 424-1524. Participants at CRI New England will receive the drug for four months and placebo for one month. The study seeks to enroll 60 patients. References 1. Physician's Desk Reference, 1992. 2. Zabel P et al. Pentoxifylline -- an inhibitor of the synthesis of the TNF alpha. Immunitat Und Infektion 20 (3):80-3, 1992. 3. Fingert HJ et al. In vivo and in vitro enhanced antitumor effects of pentoxifylline in human cancer cells treated with triotepa. Cancer Research 48:4375 4381, 1988. 4. Bleckmann P et al. Activated B-lymphocytes from HIV-infected individuals induce virus expression in infected T cells and a promonocytic cell lines. J Exp Med 173:1, 1991. 5. Personal Communication, B. Dezube, November, 1992. 6. Sullivan GW Inhibition of the inflammatory action of n-2 and TNF (alpha) on neutrophil function by pentoxifylline. Infection and Immunity 56(7):1722-9,1988 and Edwards MJ et al. Pentoxifylline inhibits IL-2 induced toxicity in mice, but preserves anti-tumor efficacy. Clin Invest 90 (2):637 41, 1992. 7. VIII Int'l Conf on AIDS, Abstract # MoB. 0019, July, 1992. 8. Personal Communication, B. Dezube, November, 1992. 9. VIII Int'l Conf on AIDS, Abstract #PoA 2326, Amsterdam, July, 1992. 10. Personal Communication, B. Dezube, November, 1992. 11. Ibid. ***** PROPOSED DEFINITION OF AIDS: A BETTER FIT FOR WOMEN, POOR PEOPLE, AND INJECTION DRUG USERS by Catherine Lynch After three years of relentless pressure from HIV-positive women, AIDS activists and advocates, and health care providers, the Centers for Disease Control is on the verge of releasing a new, expanded AIDS case definition. The new definition will include recurrent pneumonia, tuberculosis in the lungs, invasive cervical cancer, and a T-cell count of fewer than 200, when they occur in conjunction with HIV infection. Background The CDC AIDS case definition has always been based on the opportunistic infections found primarily in gay men. Consequently, women, injection drug users, and other disenfranchised populations have been systematically excluded, and unable to be officially diagnosed as having AIDS. By the CDC's own admission the definition has under-counted AIDS cases by 40%-50%. The nationwide effort to force this expansion employed a full range of tactics to achieve a response from the CDC, including street demonstrations, meetings with CDC officials, testimony from HIV-positive women, and grassroots pressure campaigns from nationwide coalitions. The Power of Activism "The government is going to say, 'Look what we've done!' But HIV- positive women and activists compelled them to add us to the definition," commented Katrina Haslip, an HIV-positive woman, who has been active in the fight to change the definition. Ms. Haslip, presently hospitalized for renal failure, has suffered chronic, debilitating opportunistic infections for years, but has failed to meet the official diagnosis criteria for AIDS. She will qualify for a diagnosis under the new definition. About the Coalition The opportunistic infections incorporated in the new definition represent those chosen by the CDC Consensus Coalition, a coalition of AIDS activists and advocates initiated by Terry McGovern at the ASC HIV Law Project and members of ACT UP/NY. The effort incorporated intensive organizing by groups as diverse as the New Jersey Women and AIDS Network, Gay Men's Health Crisis, the People with AIDS Coalition, Housing Works, and the ACLU AIDS Project. Over 350 community-based organizations nationwide, as well as scores of individuals and clinicians, signed the Consensus Statement calling for this revision. Treatment Issues staff wishes to thank the many doctors and Treatment Issues readers who responded to a personal letter from the editor and signed the Consensus Statement. Concerns About Confidentiality Coalition members do have some critical concerns about the failure of the CDC's proposed policy to protect confidentiality adequately. In the guidelines issued in late October, the CDC left state and local health departments to determine how T4 cell test results will be reported to government officials and how information will be shared between HIV and TB surveillance offices. The CDC proposal would allow for laboratories to report T4 cell test results by name to state surveillance offices, without even the involvement of the patient's health care provider. Treatment Issues will continue reporting on this matter as details are revealed. More is Needed The coalition has sent comments to the CDC urging the following points: * Pelvic Inflammatory Disease (PID) must be returned to the classification system (it was once considered a category B condition), and the CDC must develop appropriate mechanisms to gather data on PID. * Appropriate mechanisms to gather data on other HIV- related gynecological diseases, like vaginal thrush and cervical dysplasia, must also be developed and implemented. * The CDC must initiate additional research into the reliability and clinical meaning of T4 cell testing. * The CDC must adopt confidentiality protections regarding T4 cell testing. Strict, enforceable and uniform confidentiality protections for HIV-related information, including T4 tests, must be established. * T4 cell tests, on which the definition now rests, must be made widely available at low or no cost to avoid the limited access of people who have traditionally been excluded from receiving an AIDS diagnosis. ***** DRUG COMPANY WATCH by Theo Smart and David Gold (Editors' note: This is the first of a monthly column which will focus on AIDS drug development at pharmaceutical companies. Information for this column has been provided by a number of individuals, some of whom cannot be mentioned by name.) GLAXO -3TC In September, Glaxo Pharmaceuticals held meetings with activists from both coasts to discuss development plans for their new drug, 3TC (lamivudine). The drug is a nucleoside analogue like AZT, ddI, and ddC, but may be less toxic and possibly more active. Company officials reviewed data from the phase I/II dose-ranging trial, which was released in Amsterdam. At the two highest doses analyzed thus far (8 and 12 mg/kg-bodyweight), T4 cell counts either increased or stayed stable for as long as these patients have been on the drug (at that point, up to 12 weeks). Study results also include significant reductions in Beta-2 microglobulin and serum neopterin. At high doses, p24 antigen levels also appear to be reduced (although p24 reductions appear to be less than is usually experienced in patients taking other nucleosides). Studies are now using up to 20 mg/kg doses, and Glaxo projects that data from this dosage will be available by March 1993. So far, few significant toxicities have been experienced. A concurrent dose-ranging phase I/II trial in pediatrics has begun at the National Cancer Institute (NCI) in Washington with an additional site opening in Los Angeles. Seeking activist input, Glaxo presented drafts of four trials for 3TC. Two of these trial are planned to begin in early 1993. The company has taken activists' suggestions under consideration and is now engaged in negotiations over the proposed protocols with the FDA. 3TC has also shown promising activity in the test tube and in clinical trials against the hepatitis B virus (HBV). In fact, the drug has inhibited the replication of HBV in chronically- infected chimpanzees. Given the large number of HIV-positive individuals with chronic HBV infection, trials for HBV must be initiated without delay. (UN)WELLCOME PROFITS Burroughs Wellcome reported annual worldwide sales of AZT jumped 22% to $337.7 million in 1992. Annual sales of the very high-priced antiherpes medication, Zovirax (acyclovir) ballooned to $929.1 million. Since many PWAs are now taking Zovirax, activists have demanded that the company reduce the price of Zovirax by at least 50% for those who must use the drug on a continual basis. So far, the company has refused to do so, and rumblings of some sort of action against Burroughs are beginning to be heard. HOFFMANN-LA ROCHE COMMUNITY ADVISORY BOARD Relations between activists and Hoffmann-La Roche have been strained since a recent meeting of the company's Community Advisory Board (CAB) in New York. Other than announcing the opening of ACTG 213, an activity trial for the TAT inhibitor called RO 24-7429, and a promise to perform a trial of this drug in KS patients (based on Robert Gallo's report that the TAT gene stimulates the growth of lesions), the company has offered little in the way of news. There were no plans for post-marketing studies of ddC (which must be performed to satisfy the FDA's conditional approval requirements), nor did the company release designs for other TAT inhibitor studies which were to start concurrently with ACTG 213. Many CAB members feel that activist concerns are being ignored, and that Roche has rescinded on promises made to the community. Organizations such as TAG and ACT UP are also considering an appropriate response to Roche's perceived duplicity. In fact, ACT UP/NY has issued a statement demanding the following: 1) a detailed plan for ddC post marketing studies; 2) no more delays on ACTG 213; 3) the release of TAT for quick small efficacy trials for TAT in the NIH intramural trials program and in the pediatric program; and 4) immediate plans for a large scale efficacy trial of TAT if ACTG 213 shows no major toxicities. ACT UP also warned that it intends to make the development of TAT a priority of the new administration. MICROGENESYS -- GP160 VACCINE On November 5, 1992, a panel convened by the NIH met to evaluate the merits of initiating a large-scale efficacy trial for gp160, a vaccine manufactured from the outer envelope of HIV which some believe may be useful as a therapy. A congressional appropriation earmarking $20 million to the Department of Defense for large-scale tests of this compound was the impetus for this meeting. The congressional appropriation is the result of lobbying efforts by one of the manufacturers of gp160, MicroGeneSys. The Director of the NIH, the Commissioner of the FDA, and the Secretary of Defense must approve the initiation of such a trial. Treatment activists from around the country are working to insure that $20 million is used for a large (possibly simple) trial of a number of promising vaccine therapies. GENETECH INSULIN GROWTH FACTOR (IGF- 1) Positive rumors have been heard from the phase II trials of Genetech's IGF-1 in HIV wasting syndrome. In small trials involving one diabetic patient and HIV-negative volunteers placed on calorie-restricted diets, IGF-1 preserved lean body mass and nitrogen balance. In laboratory animals receiving IGF-1 infusions, increased thymocytes, CD4 cells, splenocytes, and B- cells were seen. The current clinical trial of HIV-positive individuals with wasting syndrome is ongoing and the company has stated in public meetings that early data from this trial has been very exciting and that it is going to push forward aggressively. PFIZER NOTES A recent study in the Annals of Internal Medicine (10/15/92, p. 655) concluded that Pfizer's fluconazole (Diflucan) is more effective than Janssen's ketoconazole (Nizoral) in the treatment of AIDS-associated esophageal candidiasis. In the 169 patient study, participants were randomized to receive 100 mg/day of fluconazole or 200 mg/day of ketazonazole. Of the fluconazole-treated patients, symptoms resolved in 85% of patients and 91% were cured. Comparatively, symptoms were resolved in 65% of patients on ketoconazole, and 52% were considered cured. In related matters, Pfizer has also announced that it has increased its production of streptomycin due to the outbreaks of multi-drug-resistant TB. Activists will be meeting with Pfizer officials in December to discuss the company's HIV research program and the pricing of fluconazole and azithromycin. ***** MORE ON NUTRITION by Lark Lands, Ph.D. [Editors' Note: We have received a lot of feedback regarding the article, Nutrition and HIV, published in October, and we encourage others to express their views in writing. The article was comprised of the professional opinions of Dr. Lark Lands, a compilation of other commonly-regarded nutritional practices, and some additional edits. Dr. Lands requested the opportunity to clarify her position and to add a few more points. An additiorlal editorial error needs correcting; vitamin A is not water- soluble.] New Research Very important research recently reported by Dr. Marianna Baum and her colleagues at the University of Miami School of Medicine has shown that nutrient deficiencies in HIV disease begin far earlier and require higher levels of supplementation than had previously been accepted by most physicians. The authors state that "multiple nutritional abnormalities occur relatively early in the course of HIV-1 infection and appear to facilitate disease progression."[1] These researchers report that to reach adequate blood levels of nutrients requires consumption of 6-25 times the RDA of the nutrients most often lost (i.e., B2, B6, A,C,E, and Zinc). Even at such high doses, some people did not maintain adequate blood levels. This obviously suggests the recommendations made by some dieticians and physicians for consuming only RDA levels are inadequate. Dr. Baum and her colleagues also clearly show that at those dose levels there was no toxicity, which contradicts the warnings so often issued. Importance of Nutrient Replacement Referring to the need for high-dose supplementation, Richard Beach, M. D., another member of the University of Miami research team, said that "there is a significant relationship between these specific nutrient levels and disease progression," and that people with deficiencies "tend to have more rapid disease progression."[2] Overall, more than four dozen studies presented at the VII (Florence, June 1991) and VIII (Amsterdam, July, 1992) International Conferences on AIDS emphasized the importance of nutrient replenishment for people living with HIV. A number of those studies showed that supplementation with certain nutrients could actually yield T4 increases. Of particular interest is research carried out at Yale University School of Medicine showing that a dose of 200,000 IU per day of beta carotene (60 mg taken twice a day) yielded significant increases in T4 counts in those with very low counts, and that such doses were nontoxic.[3] In fact, increases were achieved in all those participants with T4 counts over ten at entry and in one participant with a T4 cell count less than ten. Transient yellow skin discoloration in two patients and an asymptomatic increase in liver enzymes in one person were the noted side effects. The study was very small (seven participants), but indicates that high doses of beta carotene are safe and may improve immune function. Dr. Beach summarizes that the most important finding of recent research "is to start nutritional intervention as soon as possible. Unfortunately, our entire orientation is treating the nutritional aspect of HIV infection is directed toward end-stage disease. It is often a little late at that point because these patients frequently arrive very depleted in overall nutritional status. The studies of AIDS patients we have done both in the pediatric population and in the adult population show that these patients frequently have deficiencies of zinc, selenium, copper, pyridoxine, and B-12 even while remaining asymptomatic. In patients with AIDS, nearly every specific nutrient is deficient."[4] A Complete Nutritional Approach In addition to the potential impact on improving immune function and slowing disease progression, both published research and much anecdotal evidence have shown that at all T4 levels, nutrient supplementation and appropriate dietary changes can significantly affect symptomatology. Suggestions were made in the October Treatment Issues for nutrition that might eliminate or improve certain symptoms such as fatigue, depression, memory problems and neuropathy, etc. However, it is important to remember than any supplementation aimed at specific symptoms must be in the context of a complete nutritional approach that provides resupply to all missing nutrients for best effect. Nutrients seldom work singly in the body. Rather they work as a package that only affect total body changes such as immunological improvement and symptom elimination. For this reason, a good, bioavailable multiple vitamin should be the base upon which all additional supplementation are added. In addition, no single nutrient should ever be thought of as a magical solution in and of itself. Instead, look to a total resupply for all missing nutrients as a solution for nutrient deficiency problems. During an oral session at the VIII International Conference on AIDS entitled "HIV and Nutrition," Dr. Beach stated emphatically that "one would never begin to manage a diabetic without a nutritional plan. I think it's absurd to try to manage an HIV-infected patient without a comprehensive nutritional plan that incorporates all stages of disease progression."[5] Based on the finding of the University of Miami researchers and others that maintaining normal nutrient status requires levels far above the RDA, suggestions follow for the basic elements of a program airned at resupply of the nutrients most often found to be deficient. Some Practical Suggestions A supplement program should have as its base a hypoallergenic, very bioavailable multiple vitamin and mineral that will supply a good, basic level of all the nutrients most important to human function in a form likely to be taken up by those suffering from the absorption problems common to the infection (wasting, diarrhea, etc.) The multiple vitamin and mineral should generally contain levels higher than the RDA, a level designed to prevent obvious deficiency diseases (like beriberi and pellagra) in the population as a whole, but according to many research scientists, far from the level needed for optimal function, even in healthy people. This type of supplement will provide a balanced supply of nutrients in appropriate ratios for normal function. With all the added deficiencies of advanced HI~ disease, it is almost always necessary to add to the multiple vitamin and mineral with additional supplements. This will increase dose levels and include what is often lacking in even the best multiple. Higher levels of the following are needed: 1. Antioxidants (Vitamin E, beta carotene, ascorbic acid, glutathione, etc.). 2. Coenzyme Q in a dose high enough for cellular replenishment 3. Essential fatty acids 4. Zinc 5. B-12 (nasal gel or injection). Reference 1. VIII Int'l Conf on AIDS. Abstract # PoB 3675, Amsterdam, July 1992. 2. Williams S. Vitamins and minerals are important HIV therapies. Positively Aware:7, September, 1992. 3. VIII Int'l Conf on AIDS, Asgtracrt #PoB. 3458, Amsterdam, July, 1992. 4. Beach, RS & Lefkowitz M. Nutritional aspects of HIV infection. PAACNOTES 1(6):221-223, 19849. 5. Williams S. Vitamins and minerals are important HIV therapies. Positively Aware:7, September, 1992. ***** TREATMENT BRIEFS by David Gold Passive Hyperimmune Therapy Results Reported HemaCare Corp announced the 1 2-month results from its placebo- controlled trial of passive hyperimmune therapy (PHT). This therapy involves the removal of blood platelets of an HIV- positive person with early disease and infusing them into the blood of a person with more advanced HIV disease. In the trial individuals were randomized to three anms: full-strength PHT; half-strength PHT; and placebo. According to the company, PHT improves survival, preserves T4 levels, and maintains immune competence in recipients with at least 50 T4 cells. No clinical benefits were seen in individuals with less than 50 T4 cells. A more detailed report on PHT will appear in a future Treatment Issues. A Softer, Smaller, and More Tasty ddI Activists met with representatives and researchers from Bristol-Myers Squibb in October. In the meeting, Bristol disclosed that it is working on a new oral formulation for ddI that should be 20% softer and 40% smaller than current ddI tablets. In addition, the new formulation is likely to reappear in mandarin orange flavor. Company researchers also said that coffee, tea, and sugar may be taken during the two hours before and after ddI. Fats, grains, and proteins should be avoided within this period. The company also suggest that physicians use a test called "fractional amylase" instead of the serum amylase now used to monitor for pancreatitis. The test, manufactured by Smith-Kline, is believed to detect increases in enzymes earlier than the serum amylase test. Controversy About Funding of Pediatric Sites The Washington Post reported that the National Institute of Health (NIH) is spending $44 million -- that is, 40% of the entire NIH AIDS drug testing budget -- on pediatric research. Pediatric AIDS cases comprise 2% of all U. S. AIDS cases. This is the result of congressional action which mandated funding for pediatric AIDS, while failing to provide new funding for such research. Hopefully, AIDS activists will learn from the effective lobbying efforts of the Pediatric AIDS Foundation and work closely with other AIDS organizations as well in lobbying for an AIDS research budget which sufficiently meets the needs of all people with HIV. Still More on Nutrition A study published in a recent Lancet reported that men and women over 65 who took a daily capsule of 18 vitamins, minerals, and other supplements had markedly fewer infections and statistically significant improvements in immune functions compared to individuals given a placebo. The capsule included vitamin A, thiamin, riboflavin, niacin, vitamin B6, B-12, C, D, calcium, copper, iodine, iron, magnesium, folate, selenium, and zinc in approximately the same daily amounts recommended by government officials and three to four times the amount of vitamin E and beta carotene. Improvements in immune functions included increases in T4 cells, natural killer cells, production of Interleukin-2, and antibody response to influenza vaccines. The author reports that nutritional supplements may, in healthy adults, help restore immune functions in six and possibly three months. CDC Changes Its Name (And Hopefully Its Leaders) The Centers for Disease Control has announced that, as of October 29, 1992, it will change its name to the Centers for Disease Control and Prevention. No word on whether this means that the CDC will actually begin prevention programs in regard to HIV. However, soon-to-be-former CDC Director William Roper proudly proclaimed, "Prevention's time has come in America." Ampligen May Show Promise (Again) A recent report in the Journal of Infectious Diseases (October 1992) indicates that Ampligen may limit the declines in T4 counts among people with HIV. The phase I study of 39 patients with under 500 T4 cells found that those who had received lower doses of Ampligen experienced a typical decline in T4 levels, while those who received the higher doses had no significant decline. Ampligen was admistered intravenously, twice weekly. The authors suggest a significant positive correlation between dose of ampligen and increase in T4 count. While these results suggest some promise, the study was small one with between five and seven people in each arm. Studies presented at the 31st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICCAC) in 1991 suggested that Ampligen may also be effective in treating Chronic Fatigue Syndrome. Bulk Subscriptions For Health Care Providers Many physicians and health care providers have already taken advantage of our new Treatrnent Issues Bulk Subscription Program. with this program, health care providers are able to receive between 25-200 copies of Treatment Issues per month, ot a fraction of the regular subscription price, to distribute either in their office or to mail out to patients. Call Paul Warren for more information at (212) 337-3569. New Staff Welcome Treatment Issues staff welcomes Tim McCarron on board as a part-time Medical Information Associate. ***** Counseling and Support Resources* A-Team -- GMHC (212) 807-6655 AIDS Center of Queens County (718) 896-2500 AIDS Resource Center (212) 633-2500 ARRIVE (212) 966-8700 ASC Lower Manhattan (212) 645-0875 Bronx AIDS Services (212) 295-5606 Body Positive (212) 721-1346 Bronx Lebanon Hospital Center (212) 901-8940 Community Health Project (212) 675 3559 Health Outreach to Teens (212) 255-1673 HELP/AYUDA (212) 410-5741 Lifeforce (718) 797-0937 Manhattan Center for Living (212) 533-3550 Minority Task Force on AIDS (212) 563-8340 Morris Heights Health Center (212) 716-4400 NENA Health Center for Positive Action (212) 268-4196 Sister-to-Sister Project (212) 532-0290 Staten Island AIDS Task Force (718) 981-3366 SUNY Health Science Center (718) 270-1056 Upper Manhattan Task Force (212) 491-2929 West Side AIDS Project (212) 877 6020 Women & AIDS Resource Network (718) 596-6007 All of the following drop-in groups are held at 129 West 20th Street, unless otherwise noted. A referral is not necessary to attend the dropin groups and you do not need to be a GMHC Client Services client to use these services unless otherwise noted. PWA Support Group Tuesday 5:45 PM PWA Chemical Dependence and Alcohol Recovery Support Group Tuesday 2:30 PM To attend you must be a registered client through Client Services Intake Women with HIV Drop-In Support Group Monday 1:30-3:00 PM (Baby/Child-Sitting Available) (212) 337-3524 Lesbians With HIV Drop-In Support Groups Wednesday 7:00-8:30 PM Stand Up/Harlem 145 W. 130th Street Between Lenox & 7th Avenue (212) 926-4072 Lesbians With HIV Drop-In Support Groups Thursday 11:OOAM -- 12:30PM (Baby/Child-Sitting Available) (212) 337-3579 Spanish-Speaking PWA Support Group Friday 4:15 PM Carepartner Support Groups Wednesday 8:00 PM Every other Friday 5:30 PM Call the GMHC hotline for the next available Friday at (212) 807-6655 Bereavement Support Group Wednesday 8:00PM ***** Glossary Anogenital: Relating to the area around or on the anus and genitalia. Beta-2-microglobulin: A naturallyoccurring protein in the body that is linked with immune response. Increased levels of this protein are thought to indicate sustained activity of certain white blood cells called Iymphocytes, which help the immune system fight infections of all kinds. Cryptococcal infection: A fungal infection that usually causes severe disease in the brain, called meningitis. Leukocytosis: An abnormally large number of leukocytes, which are white blood cells, a condition that can occur in acute infection. PAP Smear: A microscopic exmaination of the surface cells of the cervix. Phase I: The category of a federallyfunded trial which tests experimental drugs in humans to determine the drug's safety and finds the most effective dose to use. Phase I trials also try to ascertain how the drug works, where it goes, how much is absorbed, and how it leaves the body. Everybody in a phase I trial receives some amount of drug. Phase II: The category of a federallyfunded trial which tests an experimental drug to see how well it works, and to study the drug's side effectsn Phase II trials often involve severa)hundred people who are randomly assigned to take either the experimental drug or a "control" (the standard treatment for the disease or no treatment at all). Usually the trial is double-blinded, which means no one knows who is getting the drug until the trial is done. Phase II trials usually last a long time, possibly up to two years. ***** A very talented activist from Chicago is hoping to work os an intern for the Medical Information Program during February and March of 1993. She needs an apartment or room in Manhattan or Brooklyn and is willing to house or pet sit. Any reader who may be able to help us out can contact David Gold at (212) 337-3505. &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& End of display