School of Science and Technology, Nottingham Trent University, Nottingham, UK.
AIDS Rev. 2013 Jul-Sep;15(3):171-80.
The treatment of HIV-1 infected patients with HAART has resulted in long-term suppression of viral replication and reduced progression to AIDS. However, the use of HAART has been associated with adverse effects, including metabolic dysregulation and changes in body fat deposition. This syndrome, known as HIV/HAART-associated lipodystrophy syndrome, is characterized by insulin resistance, dyslipidemia, lipodystrophy, and increased visceral adiposity, which contribute to an increased risk of cardiovascular disease amongst these patients. The thiazolidinediones are a class of agonists for the nuclear receptors, the peroxisome proliferator-activated receptor. Since peroxisome proliferator-activated receptor is critically involved in the regulation of insulin sensitivity and lipid metabolism, a number of clinical trials have analyzed whether thiazolidinediones could ameliorate the signs of HIV/HAART-associated lipodystrophy syndrome. Based on these trials, thiazolidinediones appear to up-regulate peroxisome proliferator-activated receptor-dependent genes such as adiponectin, an effect that could have important physiological benefits in the long-term for HIV/HAART-associated lipodystrophy syndrome patients. Critically, many of the studies were of short duration and thus the beneficial effects of thiazolidinediones might have been missed. In addition, the few studies on the thiazolidinedione pioglitazone showed a beneficial effect on limb fat mass that was not associated with a pro-atherogenic lipid profile. Based on these studies, a large-scale clinical trial of pioglitazone use in HIV/HAART-associated lipodystrophy syndrome patients is warranted.
高效抗逆转录病毒治疗（HAART）已成功用于治疗 HIV-1 感染患者，可长期抑制病毒复制并降低 AIDS 的进展风险。然而，HAART 的使用与多种不良反应相关，包括代谢失调和体脂沉积改变。这种综合征被称为 HIV/HAART 相关脂肪营养不良综合征，其特征为胰岛素抵抗、血脂异常、脂肪营养不良和内脏脂肪增加，这些因素导致此类患者心血管疾病风险增加。噻唑烷二酮类药物是核受体（过氧化物酶体增殖物激活受体）的激动剂。过氧化物酶体增殖物激活受体在胰岛素敏感性和脂质代谢调节中起着关键作用，因此多项临床试验分析了噻唑烷二酮类药物是否能改善 HIV/HAART 相关脂肪营养不良综合征的症状。基于这些试验，噻唑烷二酮类药物似乎能上调过氧化物酶体增殖物激活受体依赖性基因，如脂联素，这种作用对 HIV/HAART 相关脂肪营养不良综合征患者的长期生理可能具有重要意义。重要的是，许多研究的持续时间都较短，因此噻唑烷二酮类药物的有益作用可能被忽略了。此外，关于噻唑烷二酮类药物吡格列酮的少数研究显示其对肢体脂肪量具有有益作用，而与致动脉粥样硬化的血脂谱无关。基于这些研究，有必要对吡格列酮在 HIV/HAART 相关脂肪营养不良综合征患者中的应用进行大规模临床试验。
