RESPONSIVENESS OF MUSCLE PROTEIN-SYNTHESIS TO GROWTH-HORMONE ADMINISTRATION IN HIV-INFECTED INDIVIDUALS DECLINES WITH SEVERITY OF DISEASE

This study was undertaken to determine if human recombinant growth hor mone (hrGH, 6 mg/d for 2 wk) would stimulate muscle protein synthesis in AIDS wasting, Healthy controls were compared with patients who were HIV+, had AIDS without weight loss, and had AIDS with > 10% weight lo ss, Before hrGH, rates of skeletal muscle protein synthesis, measured with L-[H-2(5)]phenylalanine, were the same in controls and in all sta ges of disease. Rates of myofibrillar protein degradation, however, as sessed from urinary excretion of 3-methyl histidine, were higher in AI DS and AIDS wasting than in HIV+ or healthy individuals, The group wit h weight loss had significantly higher TNF alpha levels but not higher HIV viral loads. Muscle function, as determined by isokinetic knee ex tension and shoulder flexion, was significantly higher in controls tha n all infected individuals. After GH, rates of protein synthesis were stimulated 27% in controls, with a smaller increase (11%) in HIV+, and a significant depression (42%) in AIDS with weight loss, despite four fold elevation in insulin-like growth factor-I in all groups, There wa s a significant correlation of hrGH-induced changes in muscle protein synthesis with severity-of disease (P = 0.002). The results indicate i ncreased basal muscle protein degradation and decreased responsiveness of muscle protein synthesis to GH in the later stages of disease.