Erythrocyte glutathione deficiency in symptom-free HIV infection is associated with decreased synthesis rate

Although several studies have documented intra- and extracellular glutathio ne (GSH) deficiency in asymptomatic human immunodeficiency virus (HIV) infe ction, the mechanisms responsible for the altered GSH homeostasis remain un known. To determine whether decreased synthesis contributes to this alterat ion of GSH homeostasis, a primed-constant infusion of[H-2(2)]glycine was us ed to measure the fractional and absolute rates of synthesis of GSH in five healthy and five symptom-free HIV-infected subjects before and after suppl ementation for 1 wk with N-acetylcysteine. The erythrocyte GSH concentratio n of the HIV-infected group was lower (P < 0.01) than that of the control g roup (1.4 +/- 0.16 vs. 2.4 +/- 0.08 mmol/l). The smaller erythrocyte GSH po ol of the HIV-infected group was associated with a significantly slower (P < 0.01) absolute synthesis rate of GSH (1.15 +/- 0.14 vs. 1.71 +/- 0.15 mmo l.l(-1).day(-1)) compared with controls. Cysteine supplementation elicited significant increases in both the absolute rate of synthesis and the concen tration of erythrocyte GSH. These results suggest that the GSH deficiency o f HIV infection is due in part to a reduced synthesis rate secondary to a s hortage in cysteine availability.