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

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PMID22711904 supplement.pdf
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Date
2012-08-15
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
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(15 total)
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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 article
Subject
Adult
Biomarkers
CD4 Lymphocyte Count
CD8-Positive T-Lymphocytes
Female
HIV Infections
HIV-1
Humans
Male
Middle Aged
Prognosis
Permalink
https://hdl.handle.net/10161/14731
Published Version (Please cite this version)
10.1093/infdis/jis379
Publication 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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Scholars@Duke

Denny

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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