Background Individuals infected with human immunodeficiency virus (HIV) have higher risk than HIV-negative individuals for diseases associated with aging. T-cell senescence, characterized by expansion of cells lacking the costimulatory molecule CD28, has been hypothesized to mediate these risks.MethodsWe measured the percentage of CD28 -CD4 + and CD8 + T cells from HIV-infected treatment-naive adults from 5 Adult Clinical Trials Group (ACTG) antiretroviral therapy (ART) studies and the ALLRT (ACTG Longitudinal Linked Randomized Trials) cohort, and from 48 HIV-negative adults. Pretreatment and 96-week posttreatment CD28 - cells were assessed using linear regression for associations with age, sex, race/ethnicity, CD4 count, HIV RNA, ART regimen, and hepatitis C virus (HCV) infection.ResultsIn total, 1291 chronically HIV-infected adults were studied. Pretreatment, lower CD4 count was associated with higher CD28 -CD4 + and CD28 -CD8 + cells. For CD8 + cells, younger age and HCV infection were associated with a lower CD28 -. ART reduced CD28 - levels at week 96 among virally suppressed individuals. Older age was strongly predictive of higher CD28 -CD8 +. Compared to HIV-uninfected individuals, HIV-infected individuals maintained significantly higher CD28 -. Conclusions Effective ART reduced the proportion of CD28 - T cells. However, levels remained abnormally high and closer to levels in older HIV-uninfected individuals. This finding may inform future research of increased rates of age-associated disease in HIV-infected adults.
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