Hepatoxicity in an African HIV Treatment Cohort

描述(申请人提供)：使用抗逆转录病毒(ARV)疗法抑制艾滋病毒并允许免疫重建，已将死亡率从机会性感染转移到慢性感染和ARV治疗的并发症。一个重要的和潜在的致命的不良反应是肝毒性。最近在发展中国家迅速扩大的抗逆转录病毒疗法有可能扭转目前对这些地区造成严重破坏的艾滋病死亡率，但药物毒性可能成为项目成功的障碍。已知的肝毒性风险因素之一是乙肝(乙肝)，在非洲部分地区高度流行。除了乙肝病毒，还可能存在多种其他已知的和潜在的肝毒性风险，包括酒精、传统药物和热带疾病。我们建议检验这一假设，即与ARV相关的肝毒性在非洲的发病率高于在北美，并且风险因素不同。这项研究将测量非洲ARV治疗队列中肝毒性的发生率，并通过将病例与对照相匹配、测试库中的血清和进行结构化访谈来确定肝毒性的风险。它将在一个正在进行的大型ARV队列中进行，该队列是南非一家工业集团和约翰·霍普金斯大学之间的合作项目。

DESCRIPTION (provided by applicant): Use of antiretroviral (ARV) therapy to suppress HIV and allow immune reconstitution has shifted mortality from opportunistic infections to complications of chronic infections and ARV therapy. A significant and potentially fatal adverse effect is hepatotoxicity. Recent rapid expansion of ARV therapy in developing countries has the potential to reverse the AIDS mortality currently devastating these areas but drug toxicity may present a barrier to program success. One known risk factor for hepatotoxicity, hepatitis B (HBV), is hyper-endemic in parts of Africa. In addition to HBV, multiple other known and potential risks for hepatotoxicity may exist including alcohol, traditional medicines, and tropical diseases. We propose to test the hypothesis that the incidence of ARV-related hepatotoxicity is greater in Africa than in North America and that risk factors differ. This study will measure incidence of hepatotoxicity in an African ARV therapy cohort and identify risks for hepatotoxicity by matching cases with controls and testing banked serum and a administering a structured interview. It will be conducted within a large and on-going ARV cohort established as a collaborative project between a South African industrial conglomerate and Johns Hopkins University.