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

描述（由申请人提供）：HIV和乙型肝炎（HBV）合并感染是常见的，并显著增加肝脏疾病的进展和死亡。艾滋病毒/乙型肝炎病毒合并感染的危险人群包括非洲和亚洲的人群，这些地区的艾滋病毒在乙型肝炎病毒高流行的情况下继续传播。拉米夫定（3TC）是一种对HBV有效的抗逆转录病毒（ARV），被列入世卫组织的4种一线抗逆转录病毒治疗方案中，但这些领域关于艾滋病毒/HBV治疗结果的数据很少。有证据表明HBV基因型可预测对治疗的反应。同样，在非洲，乙肝病毒和诸如乙肝病毒载量、基因型和耐药性等因素可能导致抗逆转录病毒治疗期间的肝毒性，但对乙肝病毒在艾滋病毒治疗结果中的作用知之甚少。NIAID的目标是在资源有限的情况下促进艾滋病毒、其合并感染和治疗策略的国际合作研究，与此目标一致，本研究的目的是：1)表征HIV感染中HBV感染的流行程度和基因型；2)检验HBV基因型在HBV抑制和耐药性形成中的作用；3)检验HBV感染与南非抗逆转录病毒药物治疗的HIV患者严重肝毒性的关系。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，支持申请人以患者为导向的研究事业发展。拟议的研究是一项前瞻性队列研究，嵌套在开普敦艾滋病队列中，这是一项由美国国立卫生研究院资助的南非艾滋病治疗研究。该人群将以HIV/HBV合并感染和HBV基因型为特征。然后在135名接受3TC含ARV治疗的HIV/HBV合并感染者1年后确定HBV抑制和耐药性。在估计的135例肝毒性患者中，HBV感染和病毒学因素的存在将与1215例对照进行比较。潜在的混杂因素，如丙型肝炎、肝病、抗逆转录病毒治疗方案和其他肝毒性原因将被纳入HBV对治疗结果影响的统计模型中。本研究的长期目标是确定HIV/HBV合并感染治疗结果的预测因素。这项研究首次在资源有限的情况下研究了HBV基因型在HIV/HBV治疗结果中的作用。如果HBV病毒学因素与HIV/HBV合并感染的治疗结果相关，那么确定这些因素可能会改善HIV/HBV合并感染的未来诊断和治疗策略。

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.