Targeting Inflammation to Reduce Atherosclerotic Cardiovascular Risk in People With HIV Infection

In almost 4 decades since the start of the HIV epidemic, the world has witnessed an unprecedented evolution of this disease from a debilitating and rapidly fatal syndrome to a chronic condition, effectively managed with combination antiretroviral therapy (cART). Today people living with HIV (PLWH) who receive treatment have nearly the same life expectancy as HIV?negative individuals.1 With the exception of 2 people cured by human stem?cell transplantation,2, 3 a widely applicable cure for HIV remains elusive and infection still requires lifelong therapy for PLWH. Although effective cART suppresses viral replication, inflammation and immune activation persist for PLWH and are driven by a combination of HIV?dependent and HIV?independent factors.4 These immune factors contribute to an excess of non?AIDS comorbidities in PLWH, including cardiovascular disease (CVD), frailty, malignancy, neurocognitive disease, osteoporosis, and renal and liver diseases.4 It is increasingly recognized that as the population of PLWH ages, targeting non?AIDS comorbidities is essential to effectively care for and treat this population.

CVD is the leading cause of death worldwide, accounting for 56.9 million deaths in 2016.5 The relative risk of CVD in PLWH is significantly higher than in HIV?negative controls, including: higher rates of acute myocardial infarction6 and increased risk for ischemic stroke,7 heart failure,8 and sudden cardiac death.9 In fact, it is estimated that the HIV?associated risk for CVD may be similar to that of traditional risk factors such as smoking, hyperlipidemia, diabetes mellitus, and hypertension.10 Despite several studies showing the higher risk of cardiovascular events in PLWH, the greatest challenge has been defining the overarching mechanisms by which HIV?mediated immune activation and chronic inflammation increase the risk for CVD.11 This has made it difficult to identify effective interventions to target and reduce cardiovascular risk in this population despite considerable efforts.

In this review, we examine the effects of HIV?associated inflammation and immune activation on the cardiovascular system with a focus on atherosclerotic CVD and discuss existing and proposed therapeutic strategies targeting inflammation to reduce CVD risk. The factors contributing to immune activation and CVD in PLWH are summarized in