A Multi-model Approach for Evaluating Caspase-1 Activation in Human Immunodeficiency Virus associated Atherosclerosis and Vascular Neurocognitive Disorders

Abstract

Combination antiretroviral therapy (cART)-treated people living with human immunodeficiency virus (HIV) (PLWH) face an increased risk of atherosclerosis associated cardiovascular disease (ASCVD) even after controlling for traditional and non-traditional risk factors (Freiberg et al. 2013). Persistent HIV-associated immune activation (monocyte and T-cell activation) is believed to contribute to heightened complications of ASCVD including, myocardial infarction (MI), and stroke in PLWH (Hsue et al. 2009; Kearns et al. 2017). Specifically, systemic immune activation predisposes PLWH to arterial inflammation (characterized by increased arterial macrophage infiltration), and accelerated atherogenesis (Lo et al. 2010; Burdo, Lo, et al. 2011; Fitch et al. 2013; Subramanian et al. 2012; Tawakol et al. 2016). Accelerated atherogenesis has even been noted among elite controllers, or PLWH who maintain undetectable virus levels in the absence of cART (Pereyra et al. 2012), suggesting that the proc