AIDS INFORMATION NEWSLETTER Michael Howe, MSLS, Editor AIDS Information Center VA Medical Center, San Francisco (415) 221-4810 ext 3305 August 11, 1995 Opportunistic Infections (Part VI) Diarrhea, Malabsorption, Wasting DIARRHEA and MALABSORPTION [Oportunistic Infections and Related Disorders; From AmFAR's AIDS/HIV Treatment Directory, Vol. 7, No. 4 (January 1995)] Malabsorption is impaired uptake of nutrients from the intestines. Nutrients are normally absorbed from food in the intestines by cells that make up the finger-like villi lining the intestinal wall. Certain disease processescan cause the villi to become atrophied and shortened. This cell malfunction results in impaired absorption of nutrients. Diarrhea occurs at some point in the clinical course of most people with AIDS or HIV infection. It may occur early on or in end-stage infection, and may be sporadic or continuous. Diarrhea is a major source of mortality in HIV-infected children in Africa (Thea et al.); HIV-infected Zairian infants have an 11-fold increased risk of dying from diarrhea compared with uninfected infants. The GI symptoms of AIDS were originally attributed to opportunistic enteric pathogens or to malignancy. Smith et al. report that specific pathogens can be isolated in the majority of patients. Grohmann et al. detected viruses in 35% of fecal specimens from 65 HIV-positive patient with diarrhea compared to only 12% of specimens taken at the same time from 65 HIV-positive patients without diarrhea. Patients with diarrhea were more likely to have astrovirus, picobirnavirus, caliciviruses and adenoviruses. However, Ullrich et al. suggest that abnormalities of the intestinal lining can also result from HIV infection itself. The gastrointestinal tract can be affected by many types of infectious agents: Parasitic diseases: Cryptosporidiosis Isosporiasis Microsporidiosis Entameba histolytica and Giardia lamblia (both respond to conventional treatment). Viral infections: Cytomegalovirus. Colitis is the most commonly recognized GI manifestation of CMV disease in AIDS. Bacterial infections: Mycobacterium avium complex (MAC) Salmonellosis Campylobacter and chronic Shigella dysentery present with symptoms similar to those of salmonellosis. Standard treatments are effective. High rates of Clostridium difficile-associated diarrhea resulting from antibiotic therapy have been reported as well. TREATMENT RESULTS: Tierney et al. treated 9 HIV+ patients with chronic diarrhea and no enteric pathogens with 5-ASA (Mesalamine) 6 g/day PO. Diarrheal symptoms improved in 7/9 patients, and rectal p24 content was significantly reduced over 2 months. No side effects were reported. Cello et al. enrolled 51 patients with HIV-related wasting in an open-label dose-escalating study of octreotide acetate (Sandostatin) (50, 100, 250, 500 mcg SC three times daily). 21/51 patients (41.2%) had a complete response (reduction in daily stool volume by 50% or reduction to <250mL/d). 14/21 responders (67%) had no identifiable pathogens at initial screening compared to 9/30 (30%) nonresponders (P < 0.01). Reduction in stool volume from baseline was associated with doses higher than 50 mcg. Side effects included burning at injection site, nausea and vomiting. Octreotide acetate may inhibit pancreatic secretion, but this side effect is manageable with pancreatic enzyme replacement therapy. A phase I trial of the non-pathogenic yeast Saccharomyces boulardii is under way for the treatment of chronic diarrhea in HIV-infected people. REFERENCES: Cello et al. Effect of octreotide on refractory AIDS-associated diarrhea. Ann Int Med 115: 705-10, 1991. Grohmann G et al. Enteric viruses and diarrhea in HIV-infected patients. NEJM 329(1): 14-20, 1993. Smith PD, moderator. Gastrointestinal infections in AIDS. Ann Int Med 116: 63-77, 1992. Thea DM et al. A prospective study of diarrhea and HIV-1 infection among 429 Zairian infants. NEJM 329:1696-702, 1993. Tierney AR et al. Treatment of HIV-associated inflammatory bowel disease with oral 5-ASA. Abstract PoB 3725, VIII Intl Conf AIDS, Amsterdam, 1992. Ullrich R et al. Small intestinal structure and function in patients infected with human immunodeficiency virus (HIV): evidence of HIV-induced enteropathy. Ann Int Med 111: 15-21, 1989. OTHER REPORTS: Chlebowski R et al. Nutritional status, gastrointestinal dysfunction, and survival in patients with AIDS. J Gastro 84: 1288-93, 1989. Connolly G et al. Non-cryptosporidial diarrhoea in human immunodeficiency virus (HIV) infected patients. Gut 2: 195-200, 1989. Copyright (c) 1993 - American Foundation for AIDS Research (AmFAR) - All Rights Reserved. Permission to reproduce for non-profit use granted with the condition that the source and date of the information be given, and that AmFAR be notified. Eric Fretz, Treatment Information Services, AmFAR. DISTRIBUTED BY GENA/aegis (714.248.2836 * 8N1/Full Duplex * v.34); taking you to the edge of the electronic AIDS-information frontier and beyond. WASTING SYNDROME [Oportunistic Infections and Related Disorders; From AmFAR's AIDS/HIV Treatment Directory, Vol. 7, No. 4 (January 1995] Involuntary weight loss, or wasting, is one of the most common manifestations of HIV infection. It can occur at any stage of infection and is indicative of disease progression. It may be significant and progressive. In addition, chronic unintended weight loss is associated with malnutrition, which may contribute to increased immune suppression including reduction of T-lymphocyte helper and suppressor cells, altered phagocytic functions, and decreased killer-cell activity. Weight loss can result from reduced food intake, altered metabolism, or malabsorption and associated diarrhea. Neuropsychological disorders associated with HIV infection can result in loss of appetite (anorexia). Oral ulcerations and lesions, and the side effects of some drugs may also result in reduced food intake and subsequent weight loss. TREATMENT RESULTS: Dronabinol has been approved as an appetite stimulant in AIDS patients with wasting. Side effects associated with dronabinol include dizziness, thinking abnormalities, asthenia and euphoria. Olson et al. enrolled 139 AIDS patients in a double-blind placebo-controlled trial. All patients were at least 2.3 kg below their ideal body weights and were free from intercurrent illness. Patients were randomized to receive dronabinol 2.5 mg bid or placebo for six weeks, at which time all patients received dronabinol in an open-label extension of the study. After the randomized study, 50/72 dronabinol recipients and 38/67 placebo recipients were evaluable. Appetite (measured on a visual analog scale) was significantly improved in the dronabinol group (P = 0.02). Mean weight change was 0.1 kg in the dronabinol group and -0.4 kg in the placebo group (P = NS). At the end of the first month of the open-label extension study, 7/18 patients who had originally received dronabinol had gained 2 kg, compared to 2/17 patients who had originally received placebo (P = 0.07). Although CNS side effects were common in the dronabinol group, adverse reactions requiring discontinuation of therapy were equally frequent in the two groups (5 on dronabinol and 4 on placebo). Megestrol acetate (Megace) oral suspension has been approved by the FDA for the treatment of anorexia, cachexia, or unexplained significant weight loss in patients with AIDS. The recommended dose is 800 mg/day. This approval was based on data from two twelve-week placebo-controlled studies conducted in patients with AIDS-related wasting. Two-hundred and eighty three patients received megestrol acetate 400 to 800 mg/day, and 86 patients received placebo. A five- to seven-pound weight gain was observed in the megestrol acetate group, and a two-pound weight loss was observed in the placebo group. While there was a trend towards increased mortality in the megestrol acetate group (20/283 (7%) patients on megestrol acetate and 2/86 (2%) on placebo died), this difference was not statistically significant. Megestrol acetate is currently being investigated in liquid formulation (800 mg/d). Results from a twelve week, randomized, placebo-controlled study of 100 patients with AIDS-related weight loss of 10% or more of ideal body weight were reported by Oster et al. 52 patients received megestrol acetate and 48 received placebo. Body weight in the megestrol acetate group increased by 3.86 kg from baseline to week 8 (P=<.001), while body weight decreased in the placebo group 0.46 kg. Body water, lean mass, and patient survival were not statistically different between the two groups. Krentz et al. randomized ten patients with symptomatic HIV infection and weight loss to receive recombinant human growth hormone (rHGH) 2.5 or 5.0 mg SC tiw for three months. Three patients were discontinued from the study after developing opportunistic infections. In four patients who completed the high-dose treatment, significant increases in lean body mass (3.8 +1.9 kg, P <0.05) and body weight (3.2 +2.4 kg, P <0.05) and a significant decrease in fat mass (1.3 +0.8 kg, P <0.05) were observed. Muscle strength and endurance were also enhanced. These improvements were not sustained after stopping treatment. Significant improvements were not observed in the low-dose group. Preliminary data from a twelve-week, phase III, multicenter; placebo-controlled trial of rHGH (average dose of 6 mg daily) in 178 patients with AIDS-associated weight loss was recently presented by Schambelan et al. Patients enrolled in the trial had lost an verage of 14% of their normal body weight. There were five deaths among the participants; three were receiving the hormone and two were on placebo. Without unblinding, preliminary data from 78 subjects were reported. Weight change ranged from -12.3 to +9.1 kg; in the 41 subjects who gained 1 kg or more (mean +3.7 0.3 kg), increased body mass was 90% fat-free mass. Weight change in the remaining 37 subjects averged -2.5 0.4 kg. Therapy with rHGH/placebo was well tolerated with common side effects. Mulligan et al. treated six men with HIV-related weight loss (mean loss of 19%) with a constant metabolic diet and rHGH 0.1 mg/kg/day for seven days. The men were hospitalized, as were six HIV-negative volunteers who served as controls. A mean body weight increase of 2.0 +0.3 kg was observed in the HIV-positive men (compared with 1.6 +0.2 kg increase in the control group). Increases in protein anabolism and lipid oxidation were observed. Landman et al. treated five patients with AIDS-related wasting with pentoxifylline 400 mg three times daily. The rationale for the treatment was based on pentoxifylline's anti-TNF-à activity; TNF-à may a role in the pathogenesis of AIDS wasting. 3/5 patients had elevated serum TNF-à levels. No significant weight gain was observed in any of the patients. In the two patients without elevetaed TNF-à, continued to lose weight and also developed bacterial pneumonia within 3 weeks of starting therapy. Thalidomide is being investigated as a possible treatment for AIDS-related wasting, due to its anti-TNF-activity. In a study presented by Reyes-Teran et al., 23 patients receiving antiretroviral therapy, without active opportunistic infection, andwith 10% or greater weight loss in the previous six months were included into a randomized, double-blind, placebo-controlled efficacy trial. 18 patients have finished the treatment protocol. Stabilization or weight gain occured in 8/9 patients from thalidomide group and in 2/9 from the placebo group (P=0.008). Mild and transient somnolence and erythematous macular lesions were only observed in the thalidomide group. Couderc et al. reported their experience treating three AIDS patients with wasting with open-label thalidomide 100 mg daily. The three patients all gained weight (mean gain of 5 kg within three weeks) and had reduced constitutional symptoms. No changes in CD4 counts or serum TNF-à levels were observed. No adverse reactions were noted. Some anecdotal reports have suggested that anabolic steroids may have a role in the treatment of AIDS-related weight loss (Jekot and Purdy). However, no data from controlled clinical trials in AIDS patients have been reported. ONGOING TRIALS: A phase I/II study comparing the combination of dronabinol and megestrol acetate with either drug alone in patients with HIV-wasting syndrome is under way through the Division of AIDS Treatment Research Initiative (DATRI 004). Several trials are ongoing to investigate the anabolic steroid oxandrolone as a treatment for muscle wasting and weight loss in AIDS patients. No data are yet available. REFERENCES Couderc LJ et al. Thalidomide in wasting syndrome in AIDS. Abstract P321, Fourth European Conference on Clinical Aspects and Treatment of HIV Infection. Milan, 1994. Jekot WF and Purdy DW. Treating HIV/AIDS patients with anabolic steroids. A retrospective study. AIDS Pat Care, 68-74, April, 1993. Krentz AJ et al. Anthropometric, metabolic, and immunological effects of recombinant human growth hormone in AIDS and AIDS-related complex. J AIDS 6:245-51, 1993. Landman D et al. Use of pentoxifylline therapy for patients with AIDS-related wasting: pilot study. Clin Inf Disease 18:97-9, 1994. Mulligan CK et al. Anabolic effects of recombinant human growth hormone in patients with wasting associated with human immunodeficiency virus infection. J Clin Endocrin Metab 77:956-62, 1993. Olson R et al. Dronabinol for treatment of anorexia and weight loss in AIDS patients. Oral presentation, VIII Intl Conf AIDS, Amsterdam, 1992. Oster et al. Megestrol acetate in patients with AIDS and cachexia. Ann Int Med 121:400-408, 1994. Reyes-Teran G et al. Effects of thalidomide on wasting syndrome in patients with AIDS, A randomized double-blind, placebo- controlled clinical trial. Abstract #536B, X Intl Conf AIDS, Yokohama, 1994. Schambelan M et al. Growth Hormone therapy of AIDS wasting. Abstract #432B, X Int Conf AIDS, Yokohama, 1994. Von Roenn JH et al. Megastrol acetate in patients with AIDS- related cachexia. Ann Intern Med 121:393,300, 1994. OTHER REPORTS: Flynn N et al. Megestrol acetate 800 mg/day vs placebo for treatment of weight loss and anorexia in AIDS patients. Abstract PoB 3687, VIII Intl Conf AIDS, Amsterdam, 1992. Graham KK et al. Steady-state pharmacokinetic and pharmacodynamic evaluation of megestrol acetate oral suspension in cachectic AIDS patients. 31st ICAAC, abstract 550, 1991. Grunfeld C et al. Metabolic disturbances and wasting in the acquired immunodeficiency syndrome. NEJM 327: 329-37, 1992. Hickey M et al. Nutritional management of patients with ARC or AIDS. Gastro Cl N Amer 17: 546-61, 1988. Kotler D et al. Malnutrition in HIV infection and AIDS. AIDS 3(supp.1): 175-80, 1989. Koster F et al. A randomized, double blind, place-contrlled Phase II trial of growth hormone and insulin-like growth factor- I for AIDS wasting. Abstract #110, ICAAC, Orlando, 1994. Krentz A et al. Treatment of AIDS patients with growth hormone. American College of Physicians meeting, Albuquerque, 1990. Plasse T et al. Dronabinol stimulates appetite and causes weight gain in HIV patients. Abstract PuB 7442, VIII Intl Conf AIDS, Amsterdam, 1992. Von Roenn et al. Controlled trial of megestrol acetate for the treatment of AIDS related anorexia and cachexia. VII Intl Conf AIDS, Florence. Vol 2: 280(W.B.2392), 1991. Winick M et al. Guidelines for nutrition support in AIDS. Nutrition 5(1): 39-46, 1989. Copyright (c) 1995. American Foundation for AIDS Research (AmFAR). All rights reserved. Permission to reproduce for non-profit use granted with the condition that the source and date of the information be given, and that AmFAR be notified. Eric Fretz, Treatment Information Services, AmFAR. DISTRIBUTED BY GENA/aegis (714.248.2836 * 8N1/Full Duplex * v.34); taking you to the edge of the electronic AIDS-information frontier and beyond. DRONABINOL FOR ANOREXIA IN AIDS [For more information about the study described below, see: Beal JE et al. Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. J Pain Symptom Manage 1995 Feb;10:89-97.] Dronabinol (Marinol), a medicinal form of tetrahydro- cannabinol, has been used to treat nausea and vomiting in chemothrapy patients. This six-week randomized, placebo- controlled trial tested dronabinol (2.5 mg twice daily) as a treatment for anorexia and poor appetite in 139 AIDS patients at 18 U.S. centers. All patients had lost at least 2.3 kg from normal body weight but were physically able to eat a normal diet. The efficacy analysis focused on 88 patients who took at least 75% of planned doses and did not violate protocol by using marijuana, megestrol acetate, or corticosteroids. At last follow-up, the dronabinol group had significantly greater improvements than the placebo group in self-reported appetite (38% vs 8%) and nausea (a 20% vs 7% decline). They also showed a trend toward greater weight stabilization. Side effects were common (43%), consisting mainly of mild-to-moderate euphoria, dizziness, thinking abnormalities, and sleepiness. Other evidence, though sparse, suggests a benefit from dronabinol in AIDS patients, and the drug deserves further evaluation. In this study, differneces in weight loss were not statistically significant, but follow-up averaged only 35 to 36 days, perhaps too short to allow gains in appetite to take effect. DRONABINOL (MARINOL) - DESCRIPTION - FROM AIDSDRUGS PHARMACOLOGY - Forms numerous metabolites, including 11-hydroxy- tetrahydrocannabinol, which is psychoactive and is the principal active metabolite. Maximum plasma concentration of dronabinol and several metabolites occurs approximately 2-3 hours after oral dosing. Biliary excretion is the major route of elimination. The elimination phase exhibits biphasic kinetics with an alpha half-life of about 4 hours and a terminal half-life of 25-36 hours. The terminal plasma half-life for the principal active metabolite is approximately 15-18 hours. [PDR 1993] DISEASES STUDIED - FDA approved 12/23/92 for appetite stimulation and the prevention of weight loss in HIV-infected patients [AmFAR Tx Dir 1993;6(4)] CLASSIFICATION CODE - Appetite stimulant [AmFAR Tx Dir 1993;6(4)]; Antiemetic [USAN 1993] OTHER MAJOR USES - Nausea and vomiting associated with cancer hemotherapy [PDR 1993] SUBSTANCE INTERACTIONS - May interact with barbiturates and hypnotics and sedatives. May delay absorption of alcohol. [Drug Interactions and Side Effects Index 1992] ADVERSE EFFECTS - The most frequently reported adverse reaction involved the central nervous system. In decreasing order of frequency these events were drowsiness, dizziness, muddled thinking and brief impairment of coordination, sensory and perceptual functions. Easy laughing, elation and heightened awareness, often termed a high, was observed in 24% of patients. [PDR 1993] CONTRAINDICATIONS - Contraindicated in pregnant and nursing women, in patients whose nausea and vomiting arise from any cause other than cancer chemotherapy, and in patients with known hypersensitivity to either dronabinol or sesame oil. Should be used with caution in patients with hypertension or heart disease; in manic, depressive, or schizophrenic patients; and in patients receiving other psychoactive drugs. [PDR 1993] CHEMICAL/PHYSICAL DATA - DRUG DESCRIPTION: Synthetically manufactured version of the active substance in marijuana, delta-9-tetrahydrocannabinol [AmFAR Tx Dir 1993;6(4)] SUBSTANCE DELIVERY DATA - DOSAGE FORM: 2.5, 5, and 10 mg soft gelatin capsules. [PDR 1993]. MODE OF DELIVERY: Oral. [PDR 1993]. STORAGE: Store between 8 and 15 C (46 and 59 F). Protect from freezing. [USP DI 1989] MANUFACTURER - Roxane Laboratories, Incorporated REFERENCES Cat LK, Coleman RL. Treatment for HIV wasting syndrom. Ann Pharmacother. 1994 May;28(5):595-597. Struwe M, Kaempfer SH, Geiger CJ, Pavia AT, Plasse TF, Shepard KV, Ries K, Evans TG. Effect of dronabinol on nutritional status in HIV infection. Ann Pharmacother. 1993 Jul-Aug;27(7-8):827-831. Beal J, Olson R, Shepard KV, Plasse T. Effect of dronabinol on appetite and weight in AIDS: long-term follow-up. Int Conf AIDS 1993 Jun 6-11;9(1):527 (abstract no. PO-B36-2354). Struwe M, Kaempfer SH, Pavia AT, Geiger CJ, Shepard KV, Plasse TF, Evans T. Randomized study of dronabinol in HIV related weight loss. Int Conf AIDS. 1992 Jul 19-24;8(3):137 (abstract no. PuB 7531). Plasse T, Conant M, Gorter R, Shepard KV. Dronabinol stimulates appetite and causes weight gain in HIV patients. Int Conf AIDS. 1992 Jul 19-24;8(3):122 (abstract nol PuB 7442). Plasse TF, Gorter RW, Krasnow SH, Lane M, Shepard KV, Wadleigh RG. Recent clinical experience with dronabinol. Pharmacol Biochem Behav. 1991 Nov;40(3):695-700. Conant M, Roy D, Shepard KV, Plasse TF. DRONABINOL ENHANCES APPETITE AND CONTROLS WEIGHT LOSS IN HIV PATIENTS (MEETING ABSTRACT) Proc Annu Meet Am Soc Clin Oncol;10:A9 1991. Beal JA. Appetite effect of dronabinol [letter;comment]. J Clin Oncol. 1994 Jul;12(7):1524-1525. MEGESTROL ACETATE (MEGACE) - DESCRIPTION - FROM AIDSDRUGS PHARMACOLOGY - While the precise mechanism by which megestrol acetate produces its antineoplastic effects against endometrial carcinoma is unknown at the present time, inhibition of pituitary gonadotropin production and resultant decrease in estrogen secretions may be factors. There is evidence to suggest a local effect as a result of the marked changes brought about by the direct instillation of progestational agents into the endometrial cavity. Metabolites account for only 5-8% of the administered dose and are considered negligible. The major route of drug elimination in humans is the urine. Peak drug levels for the first 40 mg dose ranged from 1.0 to 3.0 hours (mean 2.2 hours). Plasma elimination half-life ranged from 13.0 to 104.9 hours (mean 34.2 hours). The steady state plasma concentrations for a 40 mg qid regimen have not been established. [PDR 1993] DISEASES STUDIED - Indicated for the treatment of anorexia, cachexia or an unexplained significant weight loss in people with AIDS [Bristol-Myers Squibb News Release 09/15/93 Megace Approved] CLASSIFICATION CODE - Antineoplastic agent [Merck Index 1989]; Oral contraceptive [Merck Index 1989]; Appetite stimulant [USAN 1990] OTHER MAJOR USES - Palliative treatment of advanced carcinoma of the breast or endometrium; dysfunctional uterine bleeding [PDR 1993] [Drug Evaluations Annual 1992] ADVERSE EFFECTS - The most common adverse events observed at a dosage of 800 mg per day were diarrhea, rash, impotence, edema, flatulence and weakness. The weight gain has been associated with increased appetite and is not necessarily associated with fluid retention. Thromboembolic phenomena including thrombophlebitis and pulmonary embolism have been rarely reported. Also nausea and vomiting, edema, breakthrough bleeding, dyspnea, tumor flare (with or without hypercalcemia), hyperglycemia, alopecia, hypertension, and carpal tunnel syndrome have been reported as adverse effects. [Bristol-Myers Squibb News Release 09/15/93 Megace Approved] [PDR 1993] CONTRAINDICATIONS - Contraindicated as a diagnostic test for pregnancy. Should not be used during pregnancy. [PDR 1993] CHEMICAL/PHYSICAL DATA - DRUG DESCRIPTION: A synthetic derivative of the naturally occurring steroid hormone progesterone [Bristol-Myers Squibb News Release 09/15/93 Megace Approved]; MOLECULAR FORMULA: C24H32O4 [Merck Index 1989]; MOLECULAR WEIGHT: 384.5 [Merck Index 1989]; MELTING POINT: 214-215 C [Merck Index 1989]; SOLUBILITY: (37 C) water, 2 mcg/ml; plasma, 24 mcg/ml [Merck Index 1989]; PHYSICAL DESCRIPTION: White crystalline solid [PDR 1993]; ELEMENTAL COMPOSITION: C74.97%, H8.39%, O16.65% [Merck Index 1989]; DOSAGE FORM: Lemon-lime flavored suspension containing 40 mg megestrol acetate per ml. [Bristol-Myers Squibb News Release 09/15/93 Megace Approved] SUBSTANCE DELIVERY DATA - MODE OF DELIVERY: Oral. [PDR 1993]; STORAGE: Store at room temperature. Protect from temperatures above 40 C. [PDR 1993] MANUFACTURERS - Bristol-Myers; Mead Johnson; Schering Plough REFERENCES Aronson NE, Amegin GP. Posterior subscapular cataracts associated with megestrol acetate therapy. J Cataract Refract Surg. 1993 Jan;19(1):90-1. Von Roenn JH, Roth EL, Craig R. HIV-related cachexia: potential mechanisms and treatment. Oncology. 1992;49 Suppl 2:50-4. Orzechowski A, del Rio C, Tellez I. Weight gain with the use of megace in patients with AIDS in Mexico. Int Conf AIDS. 1992 Jul 19-24;8(3):115 (abstract no. PuB 7397). Flynn N, Enders S, Oster M, Cone L, Hooten T. Megestrol acetate 800 mg/day vs placebo for treatment of weight loss and anorexia in AIDS patients. Int Conf AIDS. 1992 Jul 19-24;8(2):B205 (abstract no. PoB 3687). Henry K, Rathgaber S, Sullivan C, McCabe K. Diabetes mellitus induced by megestrol acetate in a patient with AIDS and cachexia [see comments]. Ann Intern Med. 1992 Jan 1;116(1):53-4. Mahayni H, Minor JR. Megestrol acetate in AIDS-related cachexia. Am J Hosp Pharm. 1991 Nov;48(11):2479-80. Von Roenn J, Roth E, Murphy R, Weitzman S, Armstrong D. Controlled trial of megestrol acetate for the treatment of anorexia and cachexia. Int Conf AIDS. 1991 Jun 16-21;7(2):280 (abstract no. W.B.2392). Tierney A, Cuff P, Kotler DP. The effect of megestrol acetate (Megace) on appetite, nutritional repletion, and quality of life in AIDS cachexia. Int Conf AIDS. 1991 Jun 16-21;7(1):247 (abstract no. M.B.2263). Gold J, Oliver C. Evaluation of megestrol acetate treatment in AIDS. Int Conf AIDS. 1989 Jun 4-9;5:336 (abstract no. T.B.P.298). von Roenn JH, Murphy RL, Weber KM, Williams LM, Weitzman SA. Megestrol acetate for treatment of cachexia associated with human immunodeficiency virus (HIV) infection. Ann Intern Med. 1988 Nov 15;109(10):840-1.