HIV infection is associated with increased cardiovascular disease (CVD), and increased rates of myocardial infarction and stroke have been observed in HIV-infected individuals. After traditional risk factors that are more common among people living with HIV infection (such as smoking and diabetes) are accounted for, the excess risk for CVD persists. Recent studies suggest that increased immune activation and inflammation may contribute to excess risk for CVD in the context of HIV infection. Imaging studies in the HIV-infected population have found inflamed, noncalcified plaque that is vulnerable to rupture. Statin therapy may represent a potentially useful primary prevention strategy for CVD in HIV-infected individuals, as this class of drugs lowers lipid levels and may simultaneously reduce immune activation and inflammation. REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) is a large, multicenter study funded by the National Institutes of Health. REPRIEVE will test whether pitavastatin, a newer statin that does not have substantial interactions with antiretroviral drugs, can prevent vascular events over time among HIV-infected individuals who do not have known CVD. This study is now open to enrollment at sites throughout the United States and abroad and will hopefully provide definitive data on this important question.