MECHANISMS OF LIPODYSTROPHY IN HIV-INFECTED PATIENTS

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。人类免疫缺陷病毒（HIV）感染是一个重大的全球性健康问题。最近，包括HIV-1蛋白酶抑制剂（PI）在内的联合治疗显著提高了HIV（+）患者的长期生存率。然而，这种治疗与脂肪营养不良综合征有关，其特征是面部和四肢的皮下（SC）脂肪明显减少，但颈部、颈背部和躯干周围的SC脂肪过多。这样的患者具有增加的胰岛素抵抗、糖尿病和血脂异常的倾向。HIV感染患者脂肪代谢障碍综合征的代谢和分子基础尚不清楚。除了PI之外，其他抗逆转录病毒药物、HIV感染和病毒载量的减少是否会导致脂肪代谢障碍综合征的发生尚不清楚。 因此，该项目有以下目标：1）确定代谢异常和体脂分布变化的特征，2）制定定义综合征的客观标准并确定预后指标，3）阐明艾滋病毒感染患者脂肪代谢障碍综合征的分子基础。 为了实现这些目标，将在200名无症状HIV（+）患者中进行一项为期2年的前瞻性、随机、双盲安慰剂对照研究，以比较两种同等有效的抗逆转录病毒治疗方案，一种使用蛋白酶抑制剂，另一种不使用蛋白酶抑制剂。

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. Human immunodeficiency virus (HIV) infection is a major global health problem. Recently, combination therapy including HIV-1 protease inhibitors (PIs) has dramatically improved the long-term survival of HIV (+) patients. However, such therapy is associated with a lipodystrophy syndrome characterized by marked loss of subcutaneous (sc) fat from the face and extremities but excess of sc fat around the neck, dorsocervial region and trunk. such patients have increased propensity to insulin resistance, diabetes mellitus and dyslipidemia. The metabolic and molecular basis of lipodystrophy syndrome in HIV-infected patients is not known. Whether besides PIs, other antiretroviral drugs, HIV infection and reduction in viral load contribute to the development of lipodystrophy syndrome is not clear. The project therefore has the following aims: 1) to characterize metabolic abnormalities and changes in body fat distribution, 2) to develop objective criteria for defining the syndrome and to ascertain prognostic indicators and 3) to elucidate the molecular basis of the lipodystrophy syndrome in HIV-infected patients. To accomplish these aims, a 2-year prospective, randomized, double blind placebo-controlled study will be conducted in 200 asymptomatic HIV (+) patients to compare two equally effective antiretroviral regimens, one with and the other without a protease inhibitor.