CD28-negative CD4 ⁺ and CD8 ⁺ T cells in antiretroviral therapy-naive HIV-infected adults enrolled in adult clinical trials group studies

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.