CD28-Negative CD4+ and CD8+ T Cells in Antiretroviral Therapy–Naive HIV-Infected Adults Enrolled in Adult Clinical Trials Group Studies

Abstract

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. We 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. In 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(-). 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.