Figure 4.

Hypothesized mechanisms and potential treatment targets of RAAS-mediated cardiovascular disease in HIV. Potential mediators of RAAS dysfunction may include direct viral effects, antiretroviral therapy effects, or the adipose depot. Increased RAAS activation activates the mineralocorticoid receptor, which may potentiate metabolic dysregulation, increased inflammation, and immune activation. Adverse cardiovascular sequalae of metabolic disease and inflammation may include coronary microvascular and myocardial dysfunction. US Food and Drug Administration–approved medications acting along the RAAS pathway, such as ACEi, ARB, and mineralocorticoid receptor blockers, are physiologically based treatment targets, which may be useful for CVD risk reduction based on strong data that RAAS blockade may reduce BP, decrease inflammation, and improve metabolic indices in PWH.