title: CD28-negative CD4+ and CD8+ T cells in antiretroviral therapy-naive HIV-infected adults enrolled in adult clinical trials group studies.
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.
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. ktassiop@hsph.harvard.edu
authors.forename: Katherine
authors.initials: K
authors.lastname: Tassiopoulos
authors.forename: Alan
authors.initials: A
authors.lastname: Landay
authors.forename: Ann C
authors.initials: AC
authors.lastname: Collier
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Connick
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.forename: Peter
authors.initials: P
authors.lastname: Hunt
authors.forename: Dorothy E
authors.initials: DE
authors.lastname: Lewis
authors.forename: Cara
authors.initials: C
authors.lastname: Wilson
authors.forename: Ronald
authors.initials: R
authors.lastname: Bosch
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018106:CD28 Antigens / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D016827:CD8 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D016131:Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D018106:CD28 Antigens; D015704:CD4 Antigens; D016827:CD8 Antigens