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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.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.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).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.

Original publication

DOI

10.1093/infdis/jis379

Type

Journal article

Journal

The Journal of infectious diseases

Publication Date

08/2012

Volume

206

Pages

552 - 561

Addresses

Oxford NIHR Biomedical Research Centre, United Kingdom.

Keywords

CD8-Positive T-Lymphocytes, Humans, HIV-1, HIV Infections, CD4 Lymphocyte Count, Prognosis, Adult, Middle Aged, Female, Male, Biomarkers