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

HIV 和乙型肝炎混合感染：乙型肝炎基因型、耐药性和结果

• 批准号: 7864184
• 负责人: DEBIKA BHATTACHARYA
• 金额: $ 12.34万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-15 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7864184
• 关键词: Accounting; Acquired Immunodeficiency Syndrome; Affect; Africa; Africa South of the Sahara; African; Anti-Retroviral Agents; Antiviral Agents; Antiviral Therapy; Area; Asia; CD4 Lymphocyte Count; Cessation of life; Characteristics; Cohort Studies; Data; Development; Diagnostic; Fostering; Funding; Future; Genotype; Goals; HBV Genotype; HIV; HIV Infections; Hepatitis; Hepatitis B; Hepatitis B Virus; Hepatitis C; Hepatotoxicity; Individual; Infection; International; Lamivudine; Liver diseases; Master' s Degree; Mentors; Molecular Epidemiology; Mono-S; Outcome; Patients; Pharmaceutical Preparations; Population; Population Study; Populations at Risk; Predictive Factor; Prevalence; Public Health; Publishing; Regimen; Research; Research Personnel; Resistance; Resources; Role; Simian B disease; South Africa; Statistical Models; Therapeutic; Training; Treatment outcome; United States National Institutes of Health; Viral Load result; antiretroviral therapy; career development; cohort; improved; pandemic disease; patient oriented research; programs; prospective; resistance mutation; response; viral resistance

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.

描述（由申请人提供）：HIV和B型肝炎（HBV）合并感染很常见，并显著增加肝脏疾病和死亡的进展。HIV/HBV合并感染的风险人群包括非洲和亚洲的人群，这些地区的HIV在HBV高流行的情况下继续传播。拉米夫定（3 TC）是一种有效抗HBV的抗逆转录病毒（ARV）药物，被列入4种WHO一线ARV治疗方案，但有关这些地区HIV/HBV治疗结果的数据很少。有证据表明，HBV基因型是对治疗反应的预测。同样，乙型肝炎病毒以及乙型肝炎病毒载量、基因型和耐药性等因素可能会导致非洲ARV治疗期间的肝毒性，但人们对乙型肝炎病毒在艾滋病毒治疗结果中的作用知之甚少。根据NIAID促进在资源有限的情况下对艾滋病毒、其合并感染和治疗战略进行国际合作研究的目标，本研究的目的是：1）描述HBV感染的患病率和HIV感染的基因型; 2）研究HBV基因型在HBV抑制和耐药形成中的作用; 3）在南非研究HBV感染与接受抗逆转录病毒治疗的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来支持申请人以患者为导向的研究职业发展。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NIH资助的南非艾滋病治疗研究。将对该人群的HIV/HBV合并感染和HBV基因型进行表征。然后在接受含3 TC的ARV治疗的135名HIV/HBV合并感染者中确定1年时的HBV抑制和耐药性。在估计的135例肝毒性患者中，将HBV感染和病毒学因素的存在与1215例对照进行比较。HBV对治疗结局影响的统计模型中将纳入潜在混杂因素，如丙型肝炎、肝病、ARV方案和其他肝毒性原因。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。这项研究是第一次在资源有限的情况下研究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，那么识别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。