EFFECT OF ATANZANAVIR IN HIV PATIENTS WITH DYSLIPIDEMIA

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。阿扎那韦是最近批准的一种蛋白水解酶抑制剂，与血脂异常有关。这种蛋白水解酶抑制剂(PI)改善血脂的机制尚不清楚。已知，许多接受PI-高效抗逆转录病毒疗法(HAART)的HIV患者可发展为糖尿病和/或血脂异常。有几个因素可以影响这些合并症的发展，如肝脏胰岛素抵抗，肝脏高血糖输出，以及最近的脂肪细胞因子。因此，我们想要确定阿特拉那韦对这些代谢标志物的影响。主要研究目的是量化吸收后状态下糖异生和糖原分解所产生的肝脏葡萄糖产量(HGP)的比例，并使用三步高胰岛素正常血糖钳来确定胰岛素对糖异生的影响。我们的次要目标是：1)确认当接受PI-HAART治疗的受控HIV患者将含PI的HAART方案改为含他扎那韦的HAART方案时，对血脂谱的影响；2)确定转换治疗时脂蛋白谱的变化及其对动脉粥样硬化性血脂异常的影响；3)量化与静息能量消耗相关的从头脂肪生成；4)确定作为脂肪代谢调节指标的阿扎那韦对脂肪细胞因子变化的影响；5)在DEXA全身扫描中确定体脂百分比、瘦体重和骨密度的任何变化；6)确定全身蛋白质周转的任何变化。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Atazanavir, a recently approved protease inhibitor, has been associated with dyslipidemia. The mechanisms by which this protease inhibitor (PI) may result in improved lipid profiles is unknown. It is known that many HIV patients on PI-containing highly active antiretroviral therapy (HAART) can develop diabetes and/or dyslipidemia. there are several factors that can influence the development of these comorbidities, such as hepatic insulin resistance, high hepatic glucose output, and more recently, adipocytokines. Therefore, we want to determine the influence of atazanavir on these metabolic markers. The primary study objective is to quantify the portion of hepatic glucose production (HGP) derived from gluconeogenesis and glycogenolysis in the post-absorptive state and to determine insulin effects on gluconeogenesis using a three step hyperinsulinemic euglycemic clamp. Our secondary objectives are to 1) confirm the effect on the lipid profile when switching controlled HIV patient withs dyslipidemia on PI-containing HAART containing regimens to atazanavir containing HAART regimens; 2) determine changes in lipoprotein profile and effect on atherogenic dyslipidemia when switching therapy; 3) to quantify de novo lipogenesis in relationship to resting energy expenditure; 4) determine the effect of atazanavir on changes in adipocytokines as an indicator of fat metabolism regulation; 5) determine any changes in percent of body fat, lean body mass, and bone density on whole body DEXA scans; 6) determine any changes in whole body protein turnover.