HIV infection, antiretroviral therapy and vascular dysfunction: Effects, mechanisms and treatments

Abstract

With the extensive implementation of antiretroviral therapy (ART), the life expectancy of people living with HIV (PLWH) has markedly extended. However, this clinical success has been followed with a rising incidence of cardiovascular disease (CVD). HIV infection has the ability to induce endothelial dysfunction (ED) by means of several distinct mechanisms, including sustained viral replication, viral protein expression, chronic inflammation, and oxidative stress. These factors exert adverse effects on the structure and function of the vasculature. In addition, ART-treated patients often exhibit endothelial cell (EC) activation, increased vascular stiffness, impaired vasodilatory function, and disorganized elastic architecture of the endothelium-all of which collectively further promote the progression and exacerbation of CVD in PLWH. Therefore, we aim to review the recent advances in understanding the effects of HIV infection as well as various ART regimens on endothelial function (HIV-endotheliology), by focusing on clinical studies and animal models. We also overviwed the potential mechanisms suggested by in vitro studies, including dysregulated inflammatory pathways, oxidative stress, and EC senescence. Highlighting the importance of ART-induced vascular impairment, particularly on patients who are at high risk of CVD, this review provides a theoretical and research framework for guiding the development of individualized, long-term, and safer HIV treatment strategies.