Metabolic Abnormalities in HIV

描述（由申请人提供）：本K23申请提出了一项综合研究和培训计划，以开发评估HIV感染患者全身糖脂代谢和身体成分的专业知识，这些患者被分配三种高效抗逆转录病毒治疗（HAART）方案之一。这些方案将包括：1)洛匹那韦/利托那韦+拉米夫定+他夫定或齐多夫定2)洛匹那韦/利托那韦+依非韦伦或3)依非韦伦+拉米夫定+他夫定或齐多夫定。HIV感染患者的HAART治疗与“HIV脂肪营养不良”综合征的发展有关，其特征是以下三个特征中的一个或多个的结合：1)胰岛素敏感性受损，可能导致糖尿病；2)躯干和腹腔内脂肪组织的积累，伴有或不伴有肢体和面部脂肪组织的损失；3)高甘油三酯血症，通常是严重的。这些特点导致心血管疾病的增加，因此心脏病可能超过艾滋病毒感染，成为死亡的主要原因。先前大多数检查抗逆转录病毒治疗代谢并发症的人类研究都是回顾性的，据我们所知，没有随机前瞻性研究评估三种不同的班级保留方案对初次接受抗逆转录病毒治疗的HIV感染患者的代谢影响。本项目旨在a)评估这三种HAART方案对胰岛素分泌和胰岛素对骨骼肌（葡萄糖处理）、肝脏（葡萄糖产生）和脂肪组织（全身脂肪分解）的作用以及葡萄糖耐量的影响，b)评估这些方案对极低密度脂蛋白-甘油三酯（VLDL-TG）和载脂蛋白- b100 （apoB）产生率的影响，c)评估方案对身体成分和肝脏脂肪含量的影响。d)评估体成分、肝脏脂肪含量与胰岛素作用、VLDL-TG和VLDL-apoB生成速率之间的关系。假设将通过测量来评估：1)使用稳定同位素示踪方法测量全身葡萄糖，脂质，VLDL-TG和vldl -载脂蛋白动力学，2)使用双能x射线吸收仪和磁共振成像测量身体成分，使用磁共振波谱测量肝脏脂肪含量，以及3)接受抗逆转录病毒治疗的受试者在接受HAART治疗前后6个月的葡萄糖耐量。

DESCRIPTION (provided by applicant): This K23 application proposes an integrated research and training plan to develop expertise in the assessment of whole-body glucose and lipid metabolism, and body composition in patients with HIV infection who are assigned one of three class-sparing Highly Active Anti-Retroviral Therapy (HAART) regimens. These regimens will consist of: 1) Lopinavir/Ritonavir + lamivudine + stavudine or zidovudine 2) Lopinavir/Ritonavir + efavirenz or 3) efavirenz + lamivudine + stavudine or zidovudine. HAART administration in subjects with HIV infection is associated with development of the "HIV lipodystrophy" syndrome which is characterized by a combination of one or more of three characteristics: 1) impaired insulin sensitivity, possibly leading to diabetes mellitus, 2) accumulation of truncal, intraabdominal adipose tissue with or without loss of adipose tissue in the limbs and face, and 3) hypertriglyceridemia which is frequently severe. These characteristics impart an increased of cardiovascular disease such that heart disease may surpass HIV infection as the primary cause of mortality. The majority of prior human studies examining metabolic complications of antiretroviral therapy have been retrospective and to our knowledge there are no randomized prospective studies evaluating the metabolic effects of three different class-sparing regimens in patients with HIV infection who are naive to antiretroviral therapy. This project aims to a) evaluate the effects of these three HAART regimens on insulin secretion and insulin actions on skeletal muscle (glucose disposal), liver (glucose production) and adipose tissue (whole-body lipolysis), and glucose tolerance, b) evaluate the effects of these regimens on very low density lipoprotein-triglyceride (VLDL-TG) and apolipoprotein-B100 (apoB) production rates, c) evaluate regimen effects on body composition, and hepatic fat content, and d) evaluate the relationship between body composition, and hepatic fat content with insulin action, and VLDL-TG and VLDL-apoB production rates. Hypotheses will be evaluated by measuring: 1) whole-body glucose, lipid, VLDL-TG and VLDL-apoB kinetics using stable isotope tracer methodology, 2) body composition using dual energy x-ray absorptiometry and magnetic resonance imaging, hepatic fat content using magnetic resonance spectroscopy, and 3) glucose tolerance, prior to and after receiving 6 months of HAART in subjects na'l've to antiretroviral therapy.