Antiviral inhibitory capacity of CD8+ T cells predicts the rate of CD4+ T-cell decline in HIV-1 infection
H Yang, H Wu, G Hancock, G Clutton… - The Journal of …, 2012 - academic.oup.com
H Yang, H Wu, G Hancock, G Clutton, N Sande, X Xu, H Yan, X Huang, B Angus…
The Journal of infectious diseases, 2012•academic.oup.comBackground. 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 …
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 …
Abstract
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.
Oxford University Press