T Cell Activation and Senescence Predict Subclinical Carotid Artery Disease in HIV-Infected Women

Abstract

Background. Individuals infected with human immunodeficiency virus (HIV) have increased risk of cardiovascular events. It is unknown whether T cell activation and senescence, 2 immunologic sequelae of HIV infection, are associated with vascular disease among HIV-infected adults. Methods. T cell phenotyping and carotid ultrasound were assessed among 115 HIV-infected women and 43 age- and race/ethnicity-matched HIV-uninfected controls participating in the Women's Interagency HIV Study. Multivariate analyses were used to assess the association of T cell activation (CD38⁺HLA-DR⁺) and senescence (CD28⁻CD57⁺) with subclinical carotid artery disease. Results. Compared with HIV-uninfected women, frequencies of CD4⁺CD38⁺HLA-DR⁺, CD8⁺CD38⁺HLA-DR⁺, and CD8⁺CD28⁻CD57⁺ T cells were higher among HIV-infected women, including those who achieved viral suppression while receiving antiretroviral treatment. Among HIV-infected women, adjusted for age, antiretroviral medications, and viral load, higher frequencies of activated CD4⁺ and CD8⁺ T cells and immunosenescent CD8⁺ T cells were associated with increased prevalence of carotid artery lesions (prevalence ratio_lesions associated with activated CD4⁺ T cells, 1.6 per SD [95% confidence interval {CI}, 1.1–2.2]; P = .02; prevalence ratio_lesions associated with activated CD8⁺ T cells, 2.0 per SD [95% CI, 1.2–3.3]; P < .01; prevalence ratio_lesions associated with senescent CD8⁺ T cells, 1.9 per SD [95% CI, 1.1–3.1]; P = .01). Conclusions. HIV-associated T cell changes are associated with subclinical carotid artery abnormalities, which may be observed even among those patients achieving viral suppression with effective antiretroviral therapy.