Antiviral Inhibitory Capacity of CD8+ T cells Predicts the Rate of CD4+ T-Cell Decline in HIV-1 Infection.

Background. Rare human immunodeficiency virus type 1 (HIV-1)–infected individuals who maintain control of viremia without therapy show potent CD8+ T-cell–mediated suppression of viral replication in vitro. Whether this is a determinant of the rate of disease progression in viremic individuals is unknown.Methods. We measured CD8+ T-cell–mediated inhibition of a heterologous HIV-1 isolate in 50 HIV-1–seropositive adults with diverse progression rates. Linear mixed models were used to determine whether CD8+ T-cell function could explain variation in the rate of CD4+ T-cell decline.Results. There was a significant interaction between CD8+ T-cell antiviral activity in vitro and the rate of CD4+ T-cell decline in chronically infected individuals (P < .0001). In a second prospective analysis of recently infected subjects followed for up to 3 years, CD8+ T-cell antiviral activity strongly predicted subsequent CD4+ T-cell decline (P < .0001) and explained up to 73% of the interindividual variation in the CD4+ T-cell slope. In addition, it was inversely associated with viral load set point (r = −0.68 and P = .002).Conclusions. The antiviral inhibitory capacity of CD8+ T cells is highly predictive of CD4+ T-cell loss in early HIV-1 infection. It has potential as a benchmark of effective immunity in vaccine evaluation. [ABSTRACT FROM AUTHOR]

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