title: The impact of age on the prognostic capacity of CD8+ T-cell activation during suppressive antiretroviral therapy.
abstract: OBJECTIVE
  To assess whether CD8 T-cell activation predicts risk of AIDS and non-AIDS morbidity during suppressive antiretroviral treatment (ART).
  
  
  METHODS
  Post-hoc analyses of ART-naive participants in prospective ART studies. Participants with HIV-RNA levels 200 copies/ml or less and CD8 T-cell activation data (%CD38HLA-DR) at year-1 of ART were selected to determine years 2-5 incidence of AIDS and non-AIDS events.
  
  
  METHODS
  We censored data at time of ART interruption or virologic failure. Inverse probability of censoring-weighted logistic regression was used to correct for informative censoring.
  
  
  RESULTS
  We included 1025 participants; 82% were men, median age 38 years, pre-ART CD4 cell count 255 cells/μl, and year-1-activated CD8 T cells 24%. Of these, 752 had 5 years of follow-up; 379 remained on ART and had no confirmed plasma HIV-RNA more than 200 copies/ml. The overall probability of an AIDS or non-AIDS event in years 2-5 was estimated at 13% [95% confidence interval (CI) 10-15%] had everyone remained on suppressive ART. Higher year-1-activated CD8 T-cell percentage increased the probability of subsequent events [odds ratio 1.22 per 10% higher (95% CI 1.04-1.44)]; this effect was not significant after adjusting for age. Among those age 50 years at least (n=108 at year 1), the probability of an event in years 2-5 was 37% and the effect of CD8 T-cell activation was more apparent (odds ratio=1.42, P=0.02 unadjusted and adjusted for age).
  
  
  CONCLUSIONS
  CD8 T-cell activation is prognostic of clinical events during suppressive ART, although this association is confounded by age. The consequences of HIV-associated immune activation may be more important in patients 50 years and older.
authors: aHarvard School of Public Health bCenter for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts cSFGH HIV/AIDS Division, University of California, San Francisco, California dUniversity of Washington School of Medicine, Seattle, Washington eUniversity of California, San Diego, California fDavid Geffen School of Medicine at UCLA and the Los Angeles Biomedical Institute of Research at Harbor-UCLA, Los Angeles, California gUniversity of Rochester Medical Center, Rochester, New York hUniversity of California, San Francisco, California, USA.
authors: Judith J
authors: JJ
authors: Lok
authors: Peter W
authors: PW
authors: Hunt
authors: Ann C
authors: AC
authors: Collier
authors: Constance A
authors: CA
authors: Benson
authors: Mallory D
authors: MD
authors: Witt
authors: Amneris E
authors: AE
authors: Luque
authors: Steven G
authors: SG
authors: Deeks
authors: Ronald J
authors: RJ
authors: Bosch
mesh_terms: D000328:Adult; D000367:Age Factors; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006678:HIV / Q000302:isolation & purification; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D012367:RNA, Viral