Non-classical monocytes predict progression of carotid artery bifurcation intima-media thickness in HIV-infected individuals on stable antiretroviral therapy

Abstract

Background: Inflammation may contribute to cardiovascular disease (CVD) among antiretrovirally suppressed HIV-infected individuals. We assessed relationships of monocyte, CD8 T-cell activation and plasma biomarkers to changes in carotid artery intima-media thickness (CIMT).

Methods: Longitudinal study of HIV-infected subjects ≥40 years and on stable antiretroviral therapy (ART) ≥3 months. Peripheral blood mononuclear cells were immunophenotyped by multiparameteric flow cytometry to quantify classical (CD14⁺⁺CD16^–), intermediate (CD14⁺⁺CD16⁺), non-classical (CD14^low/+CD16⁺⁺) and transitional (CD14⁺CD16^–) monocyte subsets and activated (CD38⁺HLA-DR⁺) CD8⁺ T-cells at baseline. Plasma biomarkers were assessed by multiplex Luminex assay. High-resolution B-mode ultrasounds of right carotid arteries were obtained. Changes in CIMT over two years at the right common carotid artery (CIMT_CCA) and right bifurcation (CIMT_BIF) were outcome variables.

Results: We studied 50 subjects: 84% male, median age 49 (Q1, Q3; 46, 56) years, median CD4 count 461 (317, 578) cells/mm³, and with HIV RNA ≤ 50 copies/mL in 84%. Change in CIMT_BIF correlated with log values of baseline absolute count of non-classical monocytes (r = 0.37, p = 0.020), and with MCP-1 (r = 0.42, p = 0.0024) and TNF-α (r = 0.30, p = 0.036) levels. In multivariable linear regression, only non-classical monocytes and MCP-1 predicted the change in CIMT_BIF, independent of Framingham Risk Score and baseline CIMT_BIF. No correlation was noted between CD8 T-cell activation and CIMT_BIF change. Monocyte subsets, CD8 T-cell activation, and biomarker concentrations were not correlated with changes in CIMT_CCA.

Conclusions: Our findings highlight the role of non-classical monocytes and MCP-1 in the progression of CIMT_BIF in HIV-infected individuals on stable ART independent of traditional cardio-metabolic risk factors.

Keywords:

• HIV
• CIMT
• Monocytes
• Biomarkers