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J Infect Dis. 2014 Aug 1;210(3):374-82. doi: 10.1093/infdis/jiu109. Epub 2014 Feb 28.

Low proportions of CD28- CD8+ T cells expressing CD57 can be reversed by early ART initiation and predict mortality in treated HIV infection.

Author information

1
University of California San Francisco, San Francisco, California.
2
Johns Hopkins University, Baltimore, Maryland.
3
Case Western Reserve University, Cleveland, Ohio.

Abstract

BACKGROUND:

Unlike cytomegalovirus (CMV) infection and aging, human immunodeficiency virus (HIV) decreases the proportion of CD28(-)CD8(+) T cells expressing CD57. Whether this abnormality predicts mortality in treated HIV infection and can be reversed by early antiretroviral therapy (ART) remains unknown.

METHODS:

We sampled recently HIV-infected individuals (<6 months) and HIV-uninfected controls and compared longitudinal changes in the proportion of CD28(-)CD8(+) T cells expressing CD57 between those who initiated ART early (<6 months) vs later (≥2 years). We also assessed the relationship between this phenotype and mortality in a nested case-control study of ART-suppressed chronically infected individuals.

RESULTS:

Compared to HIV-uninfected controls (n = 15), individuals who were recently infected with HIV had lower proportions of CD28(-)CD8(+) T cells expressing CD57 (P < .001), and these proportions increased during ART. The early ART group (n = 33) achieved normal levels, whereas the later ART group (n = 30) continued to have lower levels than HIV-uninfected controls (P = .02). Among 141 ART-suppressed participants in the SOCA study, those in the lowest quartile of CD28(-)CD8(+) T cells expressing CD57 had 5-fold higher odds of mortality than those in the highest quartile (95% CI, 1.6-15.9, P = .007).

CONCLUSIONS:

Abnormally low proportions of CD28(-)CD8(+) T cells expressing CD57 predict increased mortality during treated HIV infection and may be reversed with early ART initiation.

KEYWORDS:

CD28; CD57; HIV; Immunosenescence; aging; antiretroviral therapy; immune activation; mortality

PMID:
24585893
PMCID:
PMC4110459
DOI:
10.1093/infdis/jiu109
[Indexed for MEDLINE]
Free PMC Article

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