Body protein wasting is an important physical and clinical problem in patients with AIDS. However, the metabolic basis for this protein wasting is unknown and no acceptable anabolic intervention currently exists. This project has 3 objectives. First, the investigator will evaluate the alterations in whole body and skeletal muscle protein synthesis and breakdown rates that occur in three subject populations infected with HIV and referred to the ACTU at Washington University: a) HIV without weight loss or opportunistic infection and CD4>200; b) HIV with involuntary unexplained weight loss (>10 percent body weight within previous year) and CD4<200; and c) HIV with weight loss, non-life-threatening opportunistic infections and CD4 <200.Second, they will evaluate whether short-term (2 week) treatment with GH or resistance exercise training increase whole body and skeletal muscle protein anabolism in patients with HIV, weight loss, and CD4<200. Each subject will be studied during a two week control period that immediately precedes the two week treatment period. This short-term (within subject design) will minimize the potential confounding effects of different antiviral therapies in these subjects, and permit a rapid assessment of the potential muscle anabolic effects of the interventions. Third, they will evaluate whether long-term treatment (eight week) with either GH or resistance exercise training continues to enhance whole body and skeletal muscle protein anabolism, and results in increments in lean body mass, muscle cross-sectional area, and strength in these patients. Only the most anabolic short-term intervention will be studied in these long-term experiments. Whole body and skeletal muscle protein metabolism will be determined using an intravenous infusion of tracer quantities of stable isotopically labeled amino acids. The metabolic fate of these tracers is assessed by measuring the appearance rate of exhaled labeled CO2, their dilution with naturally occurring leucine and glutamine in the plasma, and their in vivo incorporation rate into vastus lateralis muscle protein during 12-13 hour tracer infusion. Alterations in body composition will be assessed with DXA, MRI of thigh muscle and fat cross-sectional area, and by measuring total body water. Knee extensor and flexor maximum voluntary muscle strength will be assessed on an isokinetic dynamometer.
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