Association of HIV-Infection and Antiretroviral Therapy With Levels of Endothelial Progenitor Cells and Subclinical Atherosclerosis

Background: Although in the general population circulating vascular progenitor cell levels have been implicated in the homeostasis of the vascular wall through differentiation into endothelium and/or smooth muscle cells, it has not yet been assessed in HIV-infected patients. We herein investigated the number of progenitor cell subpopulations in HIV-infected patients and its relationship to carotid intima-media thickness (c-IMT). Methods: Blood samples were collected from 200 HIV-infected patients and CD34(+)/KDR+, CD34(+)/VE-cadherin(+), and CD14(+)/Endoglin(+) progenitor cells were identified by flow cytometry. c-IMT was determined by ultrasonography. A group of 27 healthy subjects was used as control group. Results: In our population (20 ART-naive patients and 180 treated patients), traditional cardiovascular risk factors were not found predictive of vascular progenitor cell levels. However, antiretroviral therapy (ART)-treatment was identified as the main predictive value for low CD34(+)/KDR+ cells and high CD14(+)/Endoglin(+) cells after adjustment by cardiovascular risk factors (age, sex, hypertension, diabetes, and hyperlipidaemia) and HIV-related characteristics (HIV duration and ART treatment). Low levels of circulating CD34(+)/KDR+ or CD34(+)/VE-cadherin(+) endothelial progenitor cells tended to be associated with increased c-IMT. However, a positive association was found between CD14(+)/Endoglin(+) cells and c-IMT. Low number of CD34(+)/KDR+ cells was also associated with the longest exposure to nucleoside reverse transcriptase inhibitors and/or protease inhibitors. Conclusions: ART exposure is the main predictor of circulating vascular progenitor cell levels. However, their levels are only partially associated with high c-IMT in HIV-infected patients. ART has already been found to have proatherogenic effect, but our data first describe its relationship with vascular progenitor cells and c-IMT.