NOVEL MECHANISMS AND ANTI-INFLAMMATORY STRATEGIES TO REDUCE CARDIOVASCULAR RISK IN HUMAN IMMUNODEFICIENCY VIRUS.

Cardiovascular disease (CVD) rates are 50% to 100% higher in human immunodeficiency virus (HIV) patients. Traditional risks account for only 25% of this excess risk. Excess CVD risk in HIV may relate in part to increases in ectopic adipose depots. CVD in HIV-infection is characterized by atypical highly vulnerable plaque lesions, which are inflamed, in tight relationship to immune, and monocyte activation pathways. Using 18fluorine-2-deoxy-D-glucose positron-emission tomography imaging techniques, we have shown increased arterial inflammation which persists even after effective antiretroviral therapy. More recent studies, using a novel macrophage specific imaging agent in humans, have shown highly increased inflammatory patterns in large vessels in HIV. In addition, statins may be uniquely valuable among HIV patients, not only lowering low-density lipoprotein, but also reducing monocyte chemo-attraction, and immune activation pathways. These data have led the National Institutes of Health to fund the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), the first large multicenter primary CVD prevention trial in HIV, aimed at assessing inflammatory mechanisms of CVD in HIV.