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JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0000000000000286
Clinical Science

Factors Associated With CD8+ T-Cell Activation in HIV-1–Infected Patients on Long-term Antiretroviral Therapy

Zheng, Lu PhD*; Taiwo, Babafemi MBBS; Gandhi, Rajesh T. MD‡,§; Hunt, Peter W. MD; Collier, Ann C. MD; Flexner, Charles MD#; Bosch, Ronald J. PhD**

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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/mm3: 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.

© 2014 by Lippincott Williams & Wilkins

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