Metabolic Abnormalities in HIV

描述（由申请人提供）：该K23申请提出了一项综合研究和培训计划，旨在开发评估全身葡萄糖和脂质代谢以及HIV感染患者身体组成的专业知识，这些患者被分配了三种保留类的高活性抗逆转录病毒治疗（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+司他夫定或齐多夫定2）洛匹那韦/利托那韦+依法韦仑或3）依法韦仑+拉米夫定+司他夫定或齐多夫定。在HIV感染的受试者中施用HAART与“HIV脂肪营养不良”综合征的发展相关，所述综合征的特征在于以下三个特征中的一个或多个的组合：1）受损的胰岛素敏感性，可能导致糖尿病，2）躯干、腹内脂肪组织积聚，伴有或不伴有四肢和面部脂肪组织损失，和3）高甘油三酯血症，其通常是严重的。这些特征导致心血管疾病的增加，使得心脏病可能超过HIV感染，成为死亡的主要原因。大多数先前的人体研究检查抗逆转录病毒治疗的代谢并发症是回顾性的，据我们所知，没有随机前瞻性研究评估三种不同的类保留方案对未经抗逆转录病毒治疗的HIV感染患者的代谢影响。本研究的目的是：a）评价这三种HAART方案对胰岛素分泌和胰岛素对骨骼肌作用的影响（葡萄糖处置），肝脏（葡萄糖生成）和脂肪组织（全身脂解）和葡萄糖耐量，B）评价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）产生速率的影响，d）评估身体组成和肝脂肪含量与胰岛素作用以及VLDL-TG和VLDL-apoB产生速率之间的关系。将通过测量以下各项来评价假设：1）使用稳定同位素示踪剂方法的全身葡萄糖、脂质、VLDL-TG和VLDL-apoB动力学，2）使用双能X射线吸收测定法和磁共振成像的身体组成，使用磁共振光谱法的肝脂肪含量，以及3）在未接受过抗逆转录病毒治疗的受试者中接受6个月HAART之前和之后的葡萄糖耐量。

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.