MECHANISMS OF LIPODYSTROPHY IN HIV-INFECTED PATIENTS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 人类免疫缺陷病毒(HIV)感染是一个重大的全球健康问题。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阳性患者的长期存活率。然而，这种疗法与脂肪营养不良综合征有关，其特征是面部和四肢的皮下脂肪显著减少，但颈部、背小脑区和躯干周围的皮下脂肪过剩。这些患者增加了胰岛素抵抗、糖尿病和血脂异常的倾向。HIV感染患者脂营养不良综合征的代谢和分子基础尚不清楚。除PI外，其他抗逆转录病毒药物、艾滋病毒感染和病毒载量的减少是否有助于脂肪营养不良综合征的发展尚不清楚。 因此，该项目有以下目标：1)表征代谢异常和体内脂肪分布的变化，2)制定客观标准来定义综合征和确定预后指标，以及3)阐明艾滋病毒感染患者中脂营养不良综合征的分子基础。 为了实现这些目标，一项为期两年的前瞻性、随机、双盲安慰剂对照研究将在200名无症状的HIV(+)患者中进行，以比较两种同样有效的抗逆转录病毒疗法，一种使用蛋白酶抑制剂，另一种不使用。

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.