THERAPEUTIC APPROACHES TO HAART-INDUCED LIPODYSTROPHY IN HIV PTS

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。 5月份，感染人类免疫缺陷病毒(HIV)的患者正在接受高效抗逆转录病毒疗法(HAART)治疗，其中包括HIV-1蛋白酶抑制剂。这种HAART疗法可以延长寿命，但与脂肪营养不良有关。HAART诱导的脂肪营养不良症患者报告四肢和面部皮下脂肪丢失，颈部和躯干区域多余脂肪堆积。他们也容易发生胰岛素抵抗的代谢并发症，如血脂异常和糖尿病。HAART诱导的脂肪营养不良的发病机制尚不完全清楚，尽管HIV-1蛋白水解酶抑制剂被认为是其原因。代谢并发症会增加动脉粥样硬化和急性胰腺炎的风险，而身体脂肪分布的变化会导致身体不适和心理痛苦。这些问题的处理带来了治疗方面的挑战。我们提出了潜在安全的治疗生活方式的改变，以及管理HAART诱导的脂肪营养不良及其代谢并发症的新疗法。 这些研究的结果可能有助于设计治疗HAART引起的脂肪营养不良及其代谢并发症的治疗方法，并有助于预防接受HAART治疗的HIV感染患者出现这些问题。

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. May human immunodeficiency virus (HIV) infected patients are being treated with highly active antiretroviral therapy (HAART) including HIV-1 protease inhibitors. This HAART therapy increases longevity, however is associated with lipodystrophy. Patients with HAART-induced lipodystrophy report loss of subcutaneous fat from the extremities and face and excess fat accumulation in the neck and truncal region. they are also predisposed to metabolic complications of insulin resistance, such as, dyslipidemia and diabetes mellitus. The pathogenesis of HAART-induced lipodystrophy is not fully understood although HIV-1 protease inhibitors have been strongly implicated as the cause. The metabolic complications pose an increased risk of atherosclerosis and acute pancreatitis whereas changes in body fat distribution cause physical discomfort and psychological distress. Management of these problems poses a therapeutic challenge. We propose potentially safe therapeutic lifestyle changes as well as novel therapies for management of HAART-induced lipodystrophy and its metabolic complications. Results from these studies may help in designing therapeutic approaches to HAART-induced lipodystrophy and its metabolic complications as well as for prevention of these problems in HIV-infected patients being placed on HAART.