HIV, Combination Antiretroviral Therapy, and Vascular Diseases in Men and Women

Abstract

Thanks to the advent of combination antiretroviral therapy (cART), people living with human immunodeficiency virus (HIV) (PLWH) experienced a marked increase in life expectancy but are now at higher risk for cardiovascular disease (CVD), the current leading cause of death in PLWH on cART. Although HIV preponderantly affects men over women, manifestations of HIV-related CVD differ by sex with women experiencing greater risks than men. Despite extensive investigation, the etiopathology of CVD, notably the respective contribution of viral infection and cART, remain ill-defined. However, both viral infection and cART have been reported to contribute to endothelial dysfunction, the precursor and major cause of atherosclerosis-associated CVD, through mechanisms involving endothelial cell activation, inflammation, and oxidative stress, all leading to reduced nitric oxide bioavailability. Therefore, preserving endothelial function in PLWH on cART should be a main target to reduce CVD morbidity and mortality, notably in females.

Keywords: CVD, cardiovascular disease; FMD, flow-mediated dilatation; HF, heart failure; HIV; HIV, human immunodeficiency virus; MI, myocardial infarction; NO, nitric oxide; PAD, peripheral artery disease; PH, pulmonary hypertension; PLWH, people living with HIV; cART, combination antiretroviral therapy; cIMT, carotid intima-media thickness; combination antiretroviral therapy; endothelial dysfunction; sex differences.

Graphical abstract

Central Illustration

Contribution of HIV Infection and cART to HIV-Associated CVD Schematic illustrating the potential mechanisms whereby viral infection and combination antiretroviral therapy contribute to vascular disease in patients living with HIV. AMI = acute myocardial infarction; cART = combination antiretroviral therapy; CVD = cardiovascular disease; HF = heart failure; HIV = human immunodeficiency virus; NO = nitric oxide; PAD = peripheral artery disease; PH = pulmonary hypertension