Factors associated with CD8+ T-cell activation in HIV-1-infected patients on long-term antiretroviral therapy.

TitleFactors associated with CD8+ T-cell activation in HIV-1-infected patients on long-term antiretroviral therapy.
Publication TypeJournal Article
Year of Publication2014
AuthorsZheng L, Taiwo B, Gandhi RT, Hunt PW, Collier AC, Flexner C, Bosch RJ
JournalJ Acquir Immune Defic Syndr
Volume67
Issue2
Pagination153-60
Date Published2014 Oct 1
ISSN1944-7884
KeywordsAdult, Anti-Retroviral Agents, Antigens, CD38, Antiretroviral Therapy, Highly Active, CD8-Positive T-Lymphocytes, Cohort Studies, Female, HIV Infections, HIV-1, HLA-DR Antigens, Humans, Lymphocyte Activation, Male, Membrane Glycoproteins, Middle Aged, RNA, Viral, Viral Load
Abstract

BACKGROUND: Abnormal levels of CD8 T-cell activation persist in HIV-1-infected patients on suppressive antiretroviral therapy (ART) and may be deleterious.

METHODS: CD8 T-cell activation (% coexpressing CD38/HLA-DR) was analyzed on blood specimens from 833 HIV-1-infected patients on ART for ≥96 weeks with concurrent plasma HIV RNA (vRNA) ≤200 copies per milliliter. Factors associated with CD8 T-cell activation were assessed using generalized estimating equations to incorporate longitudinal measurements (median 4/participant).

RESULTS: Participants were 84% men, 47% white, 28% black, and 22% Hispanic, with median pre-ART age 38 years and median ART exposure 144 weeks. CD8 T-cell activation was higher at timepoints when vRNA was 51-200 versus ≤50 copies per milliliter [mean CD8 T-cell activation 23.4% vs. 19.7%; adjusted difference: 1.7% (95% confidence interval: 0.1 to 3.4), P = 0.042]. Restricting to vRNA ≤50 copies per milliliter, multivariable models showed the following factors associated with higher CD8 T-cell activation: older age [≥45 vs. ≤30 years: 3.6% (1.4 to 5.7), P = 0.004], hepatitis C virus antibody positivity [3.6% (0.9 to 6.2), P = 0.032], Hispanic vs. white [7.2% (5.3 to 9.0), P < 0.001], lower concurrent CD4 count [≤200 vs. >500 cells/mm: 2.2% (0.7 to 3.7), P < 0.001], lower concurrent CD4/CD8 ratio [-2.6% (-3.7 to -1.5) per 0.5 unit increase, P < 0.001], and higher pre-ART CD8 T-cell activation [2.0% (1.6 to 2.5) per 10% higher, P < 0.001].

CONCLUSIONS: In participants included in our analysis, residual low-level viremia between 51 and 200 copies per milliliter during ART was shown to be associated with greater CD8 T-cell activation than full suppression to <50 copies per milliliter. Older age, hepatitis C virus antibody positivity, race/ethnicity, higher pre-ART CD8 T-cell activation, and lower concurrent CD4/CD8 ratio and CD4 T-cell count also contribute to greater CD8 T-cell activation during suppressive ART.

DOI10.1097/QAI.0000000000000286
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID25072610
PubMed Central IDPMC4167746
Grant ListAI-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
AI-69434 / AI / NIAID NIH HHS / United States
P30 MH062246 / MH / NIMH NIH HHS / United States
U01 AI038855 / AI / NIAID NIH HHS / United States
U01 AI038858 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
U01 AI069434 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069412 / AI / NIAID NIH HHS / United States
UM1 AI069465 / AI / NIAID NIH HHS / United States
UM1 AI069496 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States