EFFECT OF ATANZANAVIR IN HIV PATIENTS WITH DYSLIPIDEMIA

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。阿扎那韦是最近批准的蛋白酶抑制剂，与血脂异常有关。这种蛋白酶抑制剂（PI）可能导致改善血脂的机制尚不清楚。众所周知，许多接受含PI的高效抗逆转录病毒治疗（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，例如肝胰岛素抵抗、高肝葡萄糖输出以及最近的脂肪细胞因子。因此，我们想确定阿扎那韦对这些代谢标志物的影响。 主要研究目的是定量吸收后状态下肝脏葡萄糖生成和糖原分解产生的部分，并使用三步高胰岛素正葡萄糖钳夹法确定胰岛素对肝脏葡萄糖生成的影响。我们的次要目的是：1）确认将含PI的HAART治疗方案转换为含阿扎那韦的HAART治疗方案对血脂异常的HIV控制患者的血脂谱的影响; 2）确定转换治疗时脂蛋白谱的变化和对致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）确定阿扎那韦对作为脂肪代谢调节指标的脂肪细胞因子变化的影响; 5）确定全身DEXA扫描中体脂百分比、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.