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The impact of age on the prognostic capacity of CD8+ T-cell activation during suppressive antiretroviral therapy

Lok, Judith J.a,b; Hunt, Peter W.c; Collier, Ann C.d; Benson, Constance A.e; Witt, Mallory D.f; Luque, Amneris E.g; Deeks, Steven G.h; Bosch, Ronald J.b

doi: 10.1097/QAD.0b013e32836191b1
Clinical Science

Objective: To assess whether CD8+ T-cell activation predicts risk of AIDS and non-AIDS morbidity during suppressive antiretroviral treatment (ART).

Design: Posthoc 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 (%CD38+HLA-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.

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.

Correspondence to Dr Judith J. Lok, PhD, Department of Biostatistics, Harvard School of Public Health, 655 Huntington Avenue, Building 2, Room #409, Boston, MA 02115, USA. Tel: +1 617 432 4910; fax: +1 617 432 5619; e-mail: jlok@hsph.harvard.edu

Received 25 December, 2012

Revised 21 March, 2013

Accepted 22 March, 2013

© 2013 Lippincott Williams & Wilkins, Inc.