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 ratiolesions associated with activated CD4+ T cells, 1.6 per SD [95% confidence interval {CI}, 1.1–2.2]; P = .02; prevalence ratiolesions associated with activated CD8+ T cells, 2.0 per SD [95% CI, 1.2–3.3]; P < .01; prevalence ratiolesions 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.

Polyclonal Antithymocyte Globulin and Cardiovascular Disease in Kidney Transplant Recipients

“…Recent data showed that a higher frequency of activated CD8 + T cells among HIV-infected patients was associated with subclinical carotid disease. [10][11][12][13] An expansion of CD28 -CD57 + CD8 + T cells has also been described in patients with coronary artery disease compared with healthy individuals. 14,15 Finally, CD8 + T-lymphocyte depletion by anti-CD8 mAb in apoE-deficient mice fed a high-fat diet ameliorates atherosclerosis and infusion of CD8 + T lymphocytes promotes the development of vulnerable atherosclerotic plaques in lymphocyte-deficient apoE 2/2 mice.…”

The Association of Human Cytomegalovirus with Biomarkers of Inflammation and Immune Activation in HIV-1-Infected Women

“…All of these biomarkers have been associated with a greater risk of cardiovascular disease and all-cause mortality as reported in several studies. 5,[12][13][14][15][16][17][18][19][20][21] Thus, it appears that the inflammatory response to CMV reactivation and replication could be linked to endothelial cell damage that in turn could lead to subclinical vascular changes and atherosclerosis. 6,8,[22][23][24] Although there have been multiple studies of CMV coinfection in HIV-infected patients, the results have not always been consistent, which may be attributed in part to differences in study populations and types of specimens analyzed.…”

Association of T Cell and Macrophage Activation with Arterial Vascular Health in HIV

“…Prior studies have found that increased T cell activation is associated with carotid plaque formation and intima thickness and reduced carotid distensibility in HIV-infected patients. [11][12][13][14] While the initiation of ART can improve arterial responsiveness, 15 markers of endothelial cell activation often remain persistently elevated despite the suppression of plasma viremia. 6,16,17 However, few studies have investigated how persistent innate and cellular immune activation simultaneously affect functional arterial response and endothelial activation in the context of long-term treated HIV infection.…”