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

TitleThe impact of age on the prognostic capacity of CD8+ T-cell activation during suppressive antiretroviral therapy.
Publication TypeJournal Article
Year of Publication2013
AuthorsLok JJ, Hunt PW, Collier AC, Benson CA, Witt MD, Luque AE, Deeks SG, Bosch RJ
JournalAIDS
Volume27
Issue13
Pagination2101-10
Date Published2013 Aug 24
ISSN1473-5571
KeywordsAdult, Age Factors, Antiretroviral Therapy, Highly Active, CD8-Positive T-Lymphocytes, Female, HIV, HIV Infections, Humans, Lymphocyte Activation, Male, Prognosis, Prospective Studies, RNA, Viral, Treatment Outcome, Viral Load
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.

DOI10.1097/QAD.0b013e32836191b1
Alternate JournalAIDS
PubMed ID24326304
PubMed Central IDPMC3933027
Grant List5U01 AI-069426 / AI / NIAID NIH HHS / United States
AI-069432 / AI / NIAID NIH HHS / United States
AI-069434 / AI / NIAID NIH HHS / United States
AI-069511 / AI / NIAID NIH HHS / United States
AI-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 AI-069994 / AI / NIAID NIH HHS / United States
P30 AI027763 / AI / NIAID NIH HHS / United States
R01 AI-100762 / AI / NIAID NIH HHS / United States
R01 AI100762 / AI / NIAID NIH HHS / United States
R21 AI-087035 / AI / NIAID NIH HHS / United States
R56 AI-100765 / AI / NIAID NIH HHS / United States
UM1 AI069424 / AI / NIAID NIH HHS / United States
UM1 AI069432 / AI / NIAID NIH HHS / United States
UM1 AI069496 / AI / NIAID NIH HHS / United States