Endothelial Function in Normal Volunteers

随着高活性抗逆转录病毒（ARV）治疗时代的到来，人类免疫缺陷病毒（HIV）患者的死亡率和发病率显著降低。随着越来越多的患者长期接受抗逆转录病毒治疗，导致动脉粥样硬化的脂蛋白谱（高胆固醇、高甘油三酯、低高密度脂蛋白）、胰岛素抵抗、脂肪再分配和冠状动脉疾病增加。HIV病毒复制、抗逆转录病毒治疗方案、血脂、葡萄糖耐受不良、宿主免疫反应或多种因素的组合都可能导致心血管危险因素的增加。不考虑对血脂的影响，HIV阳性患者似乎有心血管风险增加。研究结果并不完全一致，但迄今为止最具说服力的研究，即EURO-SIDA的D.A.D.研究显示，在接受ART治疗的前7年，每年接受ART治疗的心肌梗死发生率相对增加27%。

With the advent of the highly active antiretroviral (ARV) therapy era, patients with human immunodeficiency virus (HIV) have had significantly decreased mortality and morbidity. Concomitant with more patients chronically taking antiretroviral therapy, there has been an increase in atherogenic lipoprotein profiles (high cholesterol, high triglycerides, low HDL's), insulin resistance, fat redistribution and coronary artery disease. HIV viral replication, anti-retroviral treatment regimens, lipids, glucose intolerance, host immune response or a combination of factors may contribute to the increase in cardiovascular risk factors. HIV positive patients, independent of the effect on lipids, appear to have increased cardiovascular risk. Studies are not entirely consistent, but the most convincing study to date, the D.A.D. study from EURO-SIDA, shows a 27% relative increased rate of myocardial infarction per year of exposure over the first seven years of ART[1]. 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.