INCREASED PLASMA GLN AND LEU R-A AND INAPPROPRIATELY LOW MUSCLE PROTEIN-SYNTHESIS RATE IN AIDS WASTING

Muscle protein wasting occurs in human immunodeficiency virus (HIV)-in fected individuals and is often the initial indication of acquired imm unodeficiency syndrome (AIDS). Little is known about the alterations i n muscle protein metabolism that occur with HIV infection. Nine subjec ts with AIDS wasting (CD4 < 200/mm(3)), chronic stable opportunistic i nfections (OI), and greater than or equal to 10% weight loss, fourteen HIV-infected men and one woman (CD4 > 200/mm(3)) without wasting or O I (asymptomatic), and six HIV-seronegative lean men (control) received a constant intravenous infusion of [1-C-13]leucine (Leu) and [2-N-15] glutamine (Gln). Plasma Leu and Gln rate of appearance (R-a), whole bo dy Leu turnover, disposal and oxidation rates, and [C-13]Leu incorpora tion rate into mixed muscle protein were assessed. Total body muscle m ass/fat-free mass was greater in controls (53%) than in AIDS wasting ( 43%; P = 0.04). Fasting whole body proteolysis and synthesis rates wer e increased above control in the HIV+ asymptomatic group and in the AI DS-wasting group (P = 0.009). Whole body Leu oxidation rate was greate r in the HIV+ asymptomatic group than in the control and AIDS-wasting groups (P < 0.05). Fasting mixed muscle protein synthesis rate was inc reased in the asymptomatic subjects (0.048%/h; P = 0.01) but was simil ar in AIDS-wasting and control subjects (0.035 vs. 0.037%/h). Plasma G in R-a, was increased in AIDS-wasting subjects but was similar in cont rol and HIV+ asymptomatic subjects (P < 0.001). These findings suggest that AIDS wasting results from 1) a preferential reduction in muscle protein, 2) a failure to sustain an elevated rate of mixed muscle prot ein synthesis while whole body protein synthesis is increased, and 3) a significant increase in Gin release into the circulation, probably f rom muscle. Several interesting explanations for the increased Gin R-a , in AIDS wasting exist.