HIV and Hepatitis B Coinfection: Hepatitis B Genotype, Resistance and Outcomes

描述(由申请人提供)：艾滋病毒和乙肝(乙肝)混合感染很常见，并显著增加肝脏疾病和死亡的进展。艾滋病毒/乙肝病毒混合感染的风险人群包括非洲和亚洲的人群，这些地区的艾滋病毒在乙肝病毒高度流行的背景下继续传播。拉米夫定(3TC)是一种有效对抗乙肝病毒的抗逆转录病毒(ARV)药物，被列入世卫组织的4种一线ARV方案，但关于这些地区的艾滋病毒/乙肝病毒治疗结果的数据很少。有证据表明，HBV型可预测对治疗的反应。同样，在非洲，在抗逆转录病毒治疗期间，乙肝病毒和诸如乙肝病毒载量、基因和耐药性等因素可能会导致肝毒性，但人们对乙肝病毒在艾滋病毒治疗结果中的作用知之甚少。与NIAID的目标一致的是，在资源有限的情况下促进对艾滋病毒、其合并感染和治疗策略的国际合作研究，这项研究的目的是1)表征艾滋病毒感染的流行率和艾滋病毒感染中的基因类型，2)检查HBV型在乙肝抑制和耐药性形成中的作用，以及3)研究在南非使用抗逆转录病毒药物的艾滋病毒个体中，乙肝病毒感染与严重肝毒性的关系。主要目的是通过指导、分子流行病学培训和获得公共卫生硕士学位，支持申请者以患者为导向的研究职业发展。这项拟议的研究是一项嵌套在开普敦艾滋病队列中的前瞻性队列研究，这是一项由NIH资助的南非艾滋病毒治疗研究。这一人群将具有艾滋病毒/乙肝病毒混合感染和乙肝病毒基因分型的特征。然后，将在一年后确定135名接受含有ARV的3TC治疗的艾滋病毒/乙肝病毒混合感染者的乙肝病毒抑制和耐药性。在估计有肝毒性的135名患者中，存在乙肝病毒感染和病毒学因素的患者将与1215名对照进行比较。潜在的混杂因素，如丙型肝炎、肝病、ARV方案和其他引起肝毒性的原因将被包括在乙肝病毒对治疗结果影响的统计模型中。这项研究的长期目标是确定艾滋病毒/乙肝病毒混合感染的治疗结果的预测因素。这项研究首次在资源有限的情况下考察了乙肝病毒基因型在艾滋病毒/乙肝治疗结果中的作用。如果乙肝病毒病毒学因素与艾滋病毒/乙肝病毒混合感染的治疗结果相关，那么识别这些因素可能会改进未来艾滋病毒/乙肝病毒混合感染的诊断和治疗策略。

DESCRIPTION (provided by applicant): HIV and hepatitis B (HBV) co-infection is common and significantly increases the progression to liver disease and death. Populations at risk for HIV/HBV co-infection include those in Africa and Asia, regions where HIV continues to spread in the setting of HBV hyperendemicity. Lamivudine (3TC), an antiretroviral (ARV) effective against HBV, is included in 4 WHO first-line ARV regimens, yet there is little data on HIV/HBV treatment outcomes in these areas. Evidence suggests that HBV genotype is predictive of response to therapy. Likewise, HBV and factors such as HBV viral load, genotype, and resistance may contribute to hepatotoxicity during ARV therapy in Africa, and yet little is known about the role of HBV in HIV treatment outcomes. Consistent with the NIAID's goal to foster international collaborative research on HIV, its coinfections, and therapeutic strategies in resource limited settings, the aims of this study are 1) to characterize the prevalence of HBV infection and genotypes in HIV infection 2) to examine the role of HBV genotype in HBV suppression and resistance formation and 3) to examine the association of HBV infection to severe hepatotoxicity in HIV individuals on ARVs in South Africa. A primary aim is to support the applicant's patient-oriented research career development through mentoring, training in molecular epidemiology, and the receipt of a Master's Degree in Public Health. The proposed research is a prospective cohort study nested within the Cape Town AIDS Cohort, an NIH funded study of HIV treatment in South Africa. This population will be characterized for HIV/HBV coinfection and HBV genotype. HBV suppression and resistance will then be determined at 1 year in 135 HIV/HBV coinfected individuals receiving 3TC containing ARV therapy. In an estimated 135 with hepatotoxicity, the presence of HBV infection and virologic factors will be compared to 1215 controls. Potential confounders such as hepatitis C, liver disease, ARV regimen, and other causes of hepatotoxicity will be included in the statistical models of HBV effect on treatment outcomes. The long-term goals of this research are to identify predictors of therapeutic outcomes in HIV/HBV coinfection. This study is the first to examine the role of HBV genotype in HIV/HBV treatment outcomes in a resource limited setting. If HBV virologic factors are associated with treatment outcomes in HIV/HBV coinfection, then identifying such factors may improve future diagnostic and therapeutic strategies in HIV/HBV co-infection.