Antiviral inhibitory capacity of CD8+ T cells predicts the rate of CD4+ T-cell decline in HIV-1 infection.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Yang, H; Wu, H; Hancock, G; Clutton, G; Sande, N; Xu, X; Yan, H; Huang, X; Angus, B; Kuldanek, K; Fidler, S; Denny, TN; Birks, J; McMichael, A; Dorrell, L

Published Date

  • August 15, 2012

Published In

Volume / Issue

  • 206 / 4

Start / End Page

  • 552 - 561

PubMed ID

  • 22711904

Pubmed Central ID

  • 22711904

Electronic International Standard Serial Number (EISSN)

  • 1537-6613

Digital Object Identifier (DOI)

  • 10.1093/infdis/jis379

Language

  • eng

Conference Location

  • United States