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).

Design: 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).

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT00000903 NCT00000919 NCT00001137 NCT00004855 NCT00013520.

Conflict of interest statement

Conflicts of interest: AC is a former member of a Data and Safety Monitoring Board for a study sponsored by Merck & Co., has received research support from Schering-Plough (past) and Merck & Co., and is a past stockholder of Abbott, Bristol-Myers-Squibb, Johnson & Johnson, and Pfizer. MW has received honoraria from Gilead Sciences, is on the Speaker’s Bureau for Viiv Healthcare, and received a grant from Pfizer. JL, CB, SD, and RB reported no conflicts of interest.