Lopinavir-ritonavir is one of the most commonly used antiretroviral therapy. It also produces lipid abnormalities. Thus, an important part of investigating factors contributing to atherosclerosis would be to determine if this drug can adversely influence endothelial cells in the absence of HIV infection or low CD4 counts. This would suggest that this drug directly or indirectly could predispose to atherosclerosis. Endothelial function is an important contributor to atherosclerosis. Invasive and non-invasive methods to evaluate endothelial cell function have been validated as predictors of coronary artery disease. These techniques have been used at NIH for clinical investigation for many years. This protocol is designed to determine whether there is a pathologic effect on endothelial function from the lopinavir-ritonavir. By measuring endothelial function in HIV non-infected subjects both before and after four weeks of therapy, we will be able to investigate whether the medications have a direct toxic effect on the endothelium. Collection of metabolic data will allow us to evaluate whether endothelial function occurs in conjunction or separate from lipoprotein and glucose metabolic changes. As ARV options increase, it may be possible to choose specific regimens that may minimize acceleration of cardiovascular risk factors associated with endothelial dysfunction, especially in patients with other cardiovascular risk factors. These findings may help elucidate the pathophysiology of premature cardiovascular disease in HIV positive patients and also plan interventions to minimize endothelial dysfunction and subsequent cardiovascular disease. The study has been completed and a manuscript is under review. Surprisingly, lopinavir-ritonavir has no adverse effects on endothelial function in this study. This has important implications regarding the pathogenesis of HIV associated coronary artery disease.
