Pathogenesis of antiretroviral induced sub-cutaneous fat wasting

抗逆转录病毒引起的皮下脂肪消耗的发病机制

• 批准号: nhmrc : 194808
• 负责人: A/Pr Mina John
• 金额: $ 22.11万
• 依托单位: Murdoch University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2002
• 资助国家: 澳大利亚
• 起止时间: 2002-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/pathogenesis-antiretroviral-induced-fat-wasting/96066
• 关键词: Pathogenesis; antiretroviral; induced; sub; cutaneous

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.

有效的抗逆转录病毒疗法的使用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，艾滋病患者的生存率并没有显着改善，长期治疗的长期并发症已成为一个关键问题。脂肪营养不良综合征是指血脂、血糖水平和身体形态发生一系列变化的名称，通常发生在那些成功接受抗 HIV 治疗的患者中。面部和身体习惯的改变是常见的、进行性的，并且经常会毁容。除了这些变化的心理和社会影响之外，许多患者无法保持艾滋病毒感染者的匿名性。此外，血脂的改变还可能导致动脉粥样硬化。已经有几例年轻艾滋病毒感染者出现早发冠心病的病例报告。由于所有这些问题，患者越来越难以严格遵守长期治疗。迫切需要了解 HIV 感染患者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中的哪种能够提供强大的病毒抑制的长期临床和生存益处，而不增加血管疾病的风险。根据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耗尽脂肪细胞内线粒体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。