In a recent study of short-term treatment with recombinant human growth hormone (rhGH) of HIV-infected men who had lost an average of 19% of their pre-illness weight, we observed marked weight gain, positive nitrogen balance, and a significant increase in protein-sparing fatty acid oxidation. In the studies proposed herein, we will measure body composition (nitrogen and electrolyte balance, bioelectrical impedance, dual energy X-ray absorptiometry, D(2)O dilution), energy expenditure and substrate oxidation (indirect calorimetry), and integrated carbohydrate and lipid metabolism (glucose and lipid tolerance, stable isotope tracer studies) in order to further define the mechanisms by which anabolic agents affect body composition and their potential therapeutic role in AIDS-associated catabolism. Specifically we plan to: 1). determine whether the salutary effects of rhGH that we observed in HIV-infected men can also be achieved in women. Since there are fundamental differences in body composition and lipid metabolism between healthy men and women which may affect the response to catabolic stress, these studies should also elucidate the metabolic consequences of these differences and determine their potential impact on the response to anabolic therapy. 2). determine the effects of chronic treatment with rhGH in patients with AIDS, by performing these metabolic assessments prior to and at the end of three months of treatment. These studies will make it possible to establish the extent to which the strikingly positive nitrogen balance observed with short-term therapy can be sustained during chronic outpatient treatment. 3). determine the potential value of anabolic steroids in the treatment of AIDS-associated catabolism, by characterizing the effects of treatment with nandrolone decanoate (ND), a synthetic derivative of testosterone with a favorable ratio of anabolic to androgenic activity, in normal and HIV-infected men. Since anabolic steroids may cause nitrogen retention without directly affecting whole body lipid and carbohydrate metabolism, a direct comparison of the results of rhGH treatment, which has effects on both protein anabolism and intermediary energy metabolism, with those of ND, which has specific protein anabolic effects, may make it possible to distinguish the role of each process in GH-induced lean tissue accrual. 4). determine whether there are gender differences in the response to anabolic steroids in both healthy and HIV-infected individuals. In view of the pre-treatment differences in endogenous levels of testosterone, we hypothesize that the magnitude of the anabolic response might be even greater in women.
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