Pathogenesis of antiretroviral induced sub-cutaneous fat wasting

使用强效抗逆转录病毒疗法为艾滋病毒感染患者带来了巨大的临床和生存益处，并且在大多数情况下超过了短期副作用的风险。然而，并不是说艾滋病患者的生存率有了很大的提高，长期的并发症已成为慢性治疗的一个关键问题。脂质营养不良综合征是指一系列血脂、血糖水平和身体习惯的变化，通常发生在那些成功接受抗艾滋病毒治疗的患者身上。面部和身体习惯的改变是常见的，渐进的，经常毁容。除了这种变化的心理和社会影响外，许多患者无法保持其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。已经有几例报告说，年轻的艾滋病毒感染者过早患上冠状动脉疾病。由于所有这些问题，患者越来越难以严格坚持慢性治疗。迫切需要了解艾滋病毒感染患者中脂肪营养不良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在不增加血管疾病风险的情况下提供长期的临床和生存益处。基于我们之前对脂肪营养不良综合征的研究结果，我们提出脂肪营养不良可能是抗病毒药物消耗脂肪细胞内线粒体DNA含量的结果。我们建议对HIV感染志愿者的连续脂肪活检标本进行检查，以确定抗逆转录病毒治疗是否对线粒体DNA含量和/或功能产生不利影响。

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.