Pathogenesis of antiretroviral induced sub-cutaneous fat wasting

强效抗逆转录病毒疗法的使用给艾滋病毒感染患者带来了巨大的临床和生存益处，在大多数情况下，超过了短期副作用的风险。然而，艾滋病患者的生存率并没有得到很大改善，长期慢性治疗的并发症已经成为一个关键问题。脂肪代谢障碍综合征是一组血脂、葡萄糖水平和体型变化的名称，通常发生在那些成功接受抗HIV治疗的患者中。面部和身体形态的变化是常见的，渐进的，经常毁容。除了这种变化的心理和社会影响外，许多患者无法保持他们作为艾滋病毒感染者的匿名性。此外，血脂的变化可能导致动脉粥样硬化。已经有几例年轻的艾滋病毒感染者过早患冠状动脉疾病的病例报告。由于所有这些问题，患者越来越难以严格遵守慢性治疗。迫切需要了解HIV感染患者脂肪代谢障碍综合征的确切生物学原因，以帮助确定我们目前可用的抗逆转录病毒疗法将提供强病毒抑制的长期临床和生存益处，而不会增加血管疾病的风险。基于我们以前对脂肪代谢障碍综合征的研究结果，我们提出脂肪代谢障碍可能是抗病毒药物耗尽脂肪细胞内线粒体DNA含量的结果。我们建议检查HIV感染志愿者的连续脂肪活检标本，以确定抗逆转录病毒治疗是否对线粒体DNA含量和功能产生不良影响。

The use of potent antiretroviral therapy has resulted in great clinical and survival benefit in patients with HIV infection and has in most cases, outweighed the risk of short term side effects. However, not that survival of patients with AIDS has considerably improved the long-term complications of chronic therapy have become a critical issue. Lipodystrophy syndrome(s) is the name given to a set of changes to blood lipids, glucose levels and body habitus and typically occurs in those successfully treated with anti-HIV therapy. The facial and body habitus changes are common, progressive and are frequently disfiguring. Aside from the psychological and social effects of such changes, many patiens are not able to retain their anonymity as HIV infected individuals. In addition, changes to blood lipids may lead to atherosclerosis. Already there have been several case reports of premature coronary disease in young HIV infected patients. It is increasingly difficult for patients to remain strictly adherent to chronic therapy because of all these concerns. There is an urgent need to understand the exact biological cause(s) of lipodystrophy syndrome(s) in HIV infected patients in order to help identify which of our currently available antiretroviral therapies will offer the long term clinical and survival benefit of strong viral suppression without increasing risk of vascular disease. Based on results of our previous studies on lipodystrophy syndrome, we have proposed that lipodystrophy may be the result of antiviral drugs depleting the DNA content of mitochondria within fat cells. We propose to examine sequential fat biopsy specimens from HIV infected volunteers to determine whether antiretroviral therapy has had adverse effects on mitochondrial DNA content and-or function.