Antiviral inhibitory capacity of CD8+ T cells predicts the rate of CD4+ T-cell decline in HIV-1 infection.
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.
Type
Journal articleSubject
AdultBiomarkers
CD4 Lymphocyte Count
CD8-Positive T-Lymphocytes
Female
HIV Infections
HIV-1
Humans
Male
Middle Aged
Prognosis
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https://hdl.handle.net/10161/14731Published Version (Please cite this version)
10.1093/infdis/jis379Publication Info
Yang, H; Wu, H; Hancock, G; Clutton, G; Sande, N; Xu, X; ... Dorrell, L (2012). Antiviral inhibitory capacity of CD8+ T cells predicts the rate of CD4+ T-cell decline
in HIV-1 infection. J Infect Dis, 206(4). pp. 552-561. 10.1093/infdis/jis379. Retrieved from https://hdl.handle.net/10161/14731.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Thomas Norton Denny
Professor in Medicine
Thomas N. Denny, MSc, M.Phil, is the Chief Operating Officer of the Duke Human Vaccine
Institute (DHVI), Associate Dean for Duke Research and Discovery @RTP, and a Professor
of Medicine in the Department of Medicine at Duke University Medical Center. He is
also an Affiliate Member of the Duke Global Health Institute. Previously, he served
on the Health Sector Advisory Council of the Duke University Fuquay School of Business.
Prior to joining Duke, he was an Associate Professor of Pathology, Labo

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