Abstract
Given advances in antiretroviral therapy, the mortality rate for HIV infection has dropped considerably over recent decades. However, people living with HIV (PLWH) experience longer life spans coupled with persistent immune activation despite viral suppression and potential toxicity from long-term antiretroviral therapy use. Consequently, PLWH face a cardiovascular disease (CVD) risk more than twice that of the general population, making it the leading cause of death among this group. Here, we briefly review the epidemiology of CVD in PLWH highlighting disparities at the intersections of sex and gender, age, race/ethnicity, and the contributions of social determinants of health and psychosocial stress to increased CVD risk among individuals with marginalized identities. We then overview the pathophysiology of HIV and discuss the primary factors implicated as contributors to CVD risk among PLWH on antiretroviral therapy. Subsequently, we highlight the functional evidence of premature vascular dysfunction as an early pathophysiological determinant of CVD risk among PLWH, discuss several mechanisms underlying premature vascular dysfunction in PLWH, and synthesize current research on the pathophysiological mechanisms underlying accelerated vascular aging in PLWH, focusing on immune activation, chronic inflammation, and oxidative stress. We consider understudied aspects such as HIV-related changes to the gut microbiome and psychosocial stress, which may serve as mechanisms through which exercise can abrogate accelerated vascular aging. Emphasizing the significance of exercise, we review various modalities and their impacts on vascular health, proposing a holistic approach to managing CVD risks in PLWH. The discussion extends to critical future study areas related to vascular aging, CVD, and the efficacy of exercise interventions, with a call for more inclusive research that considers the diversity of the PLWH population.