Anticytomegalovirus CD4+T Cells Are Associated With Subclinical Atherosclerosis in Persons With HIV

Abstract

Objective: Persons with HIV have double the risk of developing cardiovascular disease compared with the general population. A persistent and heightened immune response to cytomegalovirus coinfection may be one contributing factor, but the relationship between cytomegalovirus replication, virus-specific immune cells, and plaque burden is unclear. Approach and Results: We assessed the relationship between CD4+T-cell subsets and carotid plaque burden in a cohort of 70 HIV-positive participants with sustained viral suppression on a single antiretroviral regimen and without known cardiovascular disease. We evaluated relationships between immune parameters, carotid plaque burden, and brachial artery flow-mediated vasodilation using multivariable linear and logistic regression models. We found that participants with carotid plaque had increased circulating CX3CR1+∼GPR56+∼CD57+(ie, C∼G∼C)+CD4+T cells (P=0.03), which is a marker combination associated with antiviral and cytotoxic responses. In addition, a median of 14.4% (IQR, 4.7%-32.7%) of the C∼G∼C+CD4+T-cells expressed antigen receptors that recognized a single cytomegalovirus glycoprotein-B epitope. Using immunofluorescence staining, we found that CX3CR1+CD4+T cells were present in coronary plaque from deceased HIV-positive persons. C∼G∼C+CD4+T cells were also present in cells isolated from the aorta of HIV-negative donors. Conclusions: HIV-positive persons with carotid atheroma have a higher proportion of circulating CD4+T-cells expressing the C∼G∼C surface marker combination associated with antiviral and cytotoxic responses. These cells can be cytomegalovirus-specific and are also present in the aorta.