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

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 [22.6% (23.7 to 21.5) 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 lowlevel 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.