Longitudinal analysis during acute infection and the impact of therapy on IL-10 suggest an indirect link with plasma viremia. Plasma IL-10 protein concentration was measured in 3 individuals identified during acute/early HIV infection. Longitudinal samples indicated that IL-10 protein levels (solid line) were initially high, and decreased over time in 2 untreated (A-B) as well as 1 treated subject (C), corresponding with a decline in HIV viral load (dashed line). A statistically significant decline in IL-10 protein (P = .004; Wilcoxon matched pairs test) in panel D was observed in a cross-sectional analysis of 10 HIV⁺ individuals captured at acute/early (within the first 30 days after infection) and chronic (6-12 months after infection) time points. IL-10 protein and mRNA expression were analyzed in 2 chronically infected individuals who interrupted antiretroviral therapy. Initially, both subjects displayed undetectable plasma viral loads while on ARV, which increased substantially in the absence of treatment (E-F). Plasma IL-10 protein concentration (●) as well as IL-10 mRNA expression (□) increased slowly over time in both individuals while off of therapy, but declined after reinitiation of suppressive antiretroviral treatment. Time points on ARV therapy are indicated by shaded regions in panels B-C and E-F.