Plasma glutathione concentrations in children infected with human immunodeficiency virus.
BACKGROUND: Glutathione (GSH) is the principal intracellular defense against oxidants, and HIV-infected individuals tend to have subnormal concentrations in plasma. This GSH deficiency may contribute to the pathogenesis of disease progression. In the pediatric population correlations between GSH concentrations with clinical, immunologic and virologic disease profiles are scarce. OBJECTIVES: The main objectives of this study were (1) to compare plasma GSH concentrations of HIV-infected children and healthy controls and (2) to correlate GSH values with clinical, immunologic and virologic disease indices. METHODS: Twenty-four HIV-infected and 24 healthy control children entered the study. Plasma concentrations of total glutathione and related thiols were determined. RESULTS: The difference in mean plasma GSH concentrations between HIV-infected (2.96 +/- 0.31 microM) and control (6.62 +/- 0.58 microM) groups was highly significant (P < 0.0001). Linear regression analyses in HIV-infected patients revealed significant correlations between GSH and both absolute CD4+ cell counts (r = 0.56, P = 0.004) and viral load measured as log HIV-RNA PCR (r = -0.49, P = 0.018). GSH concentrations did not significantly correlate with CDC clinical stage but were lower in HIV-infected patients with growth failure (1.60 +/- 0.54 microM) vs. non-growth failure (3.23 +/- 0.33 microM); P = 0.05. CONCLUSIONS: This study confirmed that HIV-infected children are deficient in plasma GSH concentrations compared with healthy controls. We documented that low GSH concentrations in HIV-infected children are directly correlated with CD4+ cell counts and inversely correlated with viral loads. These findings support a possible role of GSH in the pathogenesis of HIV disease progression.