Association of T-Cell Phenotypes With Peri-Coronary Inflammation in People With and Without HIV and Without Cardiovascular Disease

Abstract

Background: Persistent immune activation is linked to elevated cardiovascular diseases in people with HIV on antiretroviral therapy. The fat attenuation index (FAI) is a measure of peri-coronary inflammation that independently predicts cardiovascular disease risk in people without HIV. Whether FAI is associated with immune activation is unknown.

Methods: Peripheral blood T-cell activation and homing phenotypes were measured in people with HIV (n=58) and people without HIV (n=16) without known cardiovascular disease who underwent coronary computed tomography angiography and had FAI measurements. A cross-sectional analysis of an observational cohort was performed. The primary aim was to evaluate associations of T-cell activation and phenotypes with the outcome variables, FAI values of the right coronary artery and left anterior descending artery, which were assessed using multivariable regression models adjusted for age, natal sex, race, low-density lipoprotein cholesterol, body mass index, and use of lipid-lowering medication.

Results: T cells from people with HIV showed greater activation, as measured by cluster of differentiation (CD) 38/human leukocyte antigen - DR isotype coexpression on CD4 central memory and terminally-differentiated effector memory subsets and on CD8 effector memory (TEM), than did cells from people without HIV. Expression of the chemokine receptor C-C Chemokine Receptor 2 was reduced on CD4 central memory and TEM and CD8 TEM and terminally-differentiated effector memory subsets in people with HIV. Among all participants, PD-1 (programmed cell death 1) in CD8 central memory was associated with worsened peri-coronary inflammation of the right coronary artery, whereas perforin/granzyme B on CD8 TEM was associated with improved peri-coronary inflammation of the right coronary artery and left anterior descending artery in adjusted analyses. When accounting for HIV serostatus, CD38/human leukocyte antigen - DR isotype coexpression on CD8 central memory, TEM, and terminally-differentiated effector memory cells was associated with more peri-coronary inflammation of the left anterior descending artery.

Conclusions: The associations between T-cell activation with FAI are novel and suggest that T-cell activation may be an important driver of peri-coronary inflammation, occurring at an early stage of atherosclerosis, even before the development of clinical disease.

Keywords: HIV; T-lymphocytes; atherosclerosis; cardiovascular diseases; computed tomography angiography; inflammation; pericoronary adipose tissue.