Anti-lipolytic Therapy for HIV Lipodystrophy

描述(由申请人提供)：接受高效抗逆转录病毒疗法(HAART)治疗的艾滋病毒感染患者患严重血脂异常、胰岛素抵抗和脂肪分布异常模式的风险增加。虽然导致这些变化的确切机制尚不清楚，但越来越多的证据表明，艾滋病毒感染和脂肪重新分布的患者基础脂解率增加，循环中游离脂肪酸(FFA)升高。HIV相关性脂肪营养不良患者的FFA水平升高，这与糖代谢受损和甘油三酯浓度直接相关。此外，在HIV脂营养不良和胰岛素抵抗患者中，急性抑制脂解导致胰岛素敏感性的改善。然而，在这一患者群体中，长期服用溶脂阻滞剂还没有得到评估。Acipimox是一种烟酸类似物，是一种有效的脂解抑制剂，是一种公认的治疗血脂异常的方法。此外，通过降低循环FFA的效果，急性服用阿昔莫司已被证明可以改善其他人群的胰岛素敏感性，包括瘦人和肥胖者以及II型糖尿病患者。我们假设，慢性服用阿昔莫司将改善经历HAART相关代谢障碍的HIV感染患者的高脂血症和胰岛素敏感性。我们提出了一项为期3个月的随机、双盲、安慰剂对照试验，以确定阿昔莫司对脂肪重分布的HIV感染患者的脂解、葡萄糖稳态和身体成分的影响。这项拟议的研究将提供有价值的初步数据，评估抗脂治疗策略治疗HAART代谢并发症的有效性，并可能深入了解这些紊乱的机制。总之，这些数据将被用来开发未来的长期研究，以评估抗脂治疗策略对患有HAART相关代谢异常和脂肪重新分布的HIV感染患者的有效性和安全性。

DESCRIPTION (provided by applicant): HIV-infected patients treated with highly active antiretroviral therapy (HAART) are at increased risk for developing significant dyslipidemia, insulin resistance and abnormal patterns of fat distribution. While the exact mechanism responsible for these changes is not known, there is increasing evidence that patients with HIV infection and fat redistribution have increased basal rates of lipolysis and elevated circulating free fatty acids (FFA). Patients with HIV-associated lipodystrophy have increased FFA levels that correlated directly with impaired glucose metabolism and triglyceride concentrations. Furthermore, acute inhibition of lipolysis in patients with HIV lipodystrophy and insulin resistance results in improvement in insulin sensitivity. However, long-term administration of lipolytic blocking agents has not been evaluated in this patient population. Acipimox, a nicotinic acid analogue and a potent inhibitor of lipolysis, is an established therapy for dyslipidemia. In addition, through effects on lowering circulating FFA, acute administration of acipimox has been shown to improve insulin sensitivity in other populations including lean and obese individuals and patients with type II diabetes. We hypothesize that chronic administration of acipimox will improve hyperlipidemia and insulin sensitivity among HIV infected patients experiencing HAART-associated metabolic disturbances. We propose a 3-month randomized, double-blind, placebo-controlled trial of acipimox in HIV infected patients with fat redistribution in order to determine the effects of acipimox on lipolysis, glucose homeostasis and body composition. The proposed study will provide valuable preliminary data assessing the utility of an anti-lipolytic strategy to treat the metabolic complications of HAART as well as potential insight into the mechanism of these disturbances. Together, these data will be used to develop future long-term studies to evaluate the efficacy and safety of anti-lipolytic strategies in HIV infected patients with HAART-associated metabolic abnormalities and fat redistribution.