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

TitleCD28-negative CD4+ and CD8+ T cells in antiretroviral therapy-naive HIV-infected adults enrolled in adult clinical trials group studies.
Publication TypeJournal Article
Year of Publication2012
AuthorsTassiopoulos K, Landay A, Collier AC, Connick E, Deeks SG, Hunt P, Lewis DE, Wilson C, Bosch R
JournalJ Infect Dis
Volume205
Issue11
Pagination1730-8
Date Published2012 Jun
ISSN1537-6613
KeywordsAdolescent, Adult, Aged, Anti-HIV Agents, Antigens, CD28, Antigens, CD4, Antigens, CD8, Antiretroviral Therapy, Highly Active, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Female, HIV Infections, Humans, Lymphocyte Subsets, Male, Middle Aged, Young Adult
Abstract

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.

METHODS: 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.

RESULTS: 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(-).

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.

DOI10.1093/infdis/jis260
Alternate JournalJ. Infect. Dis.
PubMed ID22448010
PubMed Central IDPMC3415854
Grant ListAI 38855 / AI / NIAID NIH HHS / United States
AI 38858 / AI / NIAID NIH HHS / United States
AI 68634 / AI / NIAID NIH HHS / United States
AI 68636 / AI / NIAID NIH HHS / United States
K24 AI069994 / AI / NIAID NIH HHS / United States
K24 AI069994 / AI / NIAID NIH HHS / United States
P30 AI027763 / AI / NIAID NIH HHS / United States
P30 AI036211 / AI / NIAID NIH HHS / United States