Impact of antiretroviral therapy on liver fibrosis in Zambian HIV/HBV patients

抗逆转录病毒治疗对赞比亚 HIV/HBV 患者肝纤维化的影响

• 批准号: 8817006
• 负责人: Michael Jeffrey Vinikoor
• 金额: $ 11.58万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8817006
• 关键词: Adult; Aflatoxins; Africa South of the Sahara; African; Age; Alcohol consumption; Alcohols; Anti-Retroviral Agents; Area; Award; Biological Markers; Biostatistical Methods; CD4 Positive T Lymphocytes; Caring; Cause of Death; Characteristics; Chronic Hepatitis B; Chronic viral hepatitis; Clinic; Clinical; Clinical Data; Clinical Research; Clinical Trials; Collaborations; Communicable Diseases; Country; Data; Development; Diet; Discipline of obstetrics; Ensure; Environmental Exposure; Factor Analysis; Failure; Fibrosis; Funding; Future; Goals; Guidelines; Gynecology; HBV Cirrhosis; HIV; Hepatitis B; Hepatitis B Transmission; Hepatitis B Virus; Hepatitis C; Hepatitis C virus; Hepatitis D; High Prevalence; Immune; Income; Individual; Infection; Infectious Diseases Research; Ingestion; Interdisciplinary Study; International; Investigation; Knowledge; Liver; Liver Fibrosis; Liver diseases; Measures; Medicine; Mentored Research Scientist Development Award; Mentors; Mentorship; Methods; Mono-S; North Carolina; Outcome; Patients; Pattern; Pharmaceutical Preparations; Physicians; Positioning Attribute; Prevalence; Prevention; Primary carcinoma of the liver cells; Recovery; Research; Research Design; Research Personnel; Research Support; Resources; Risk; Risk Factors; Schistosomiasis; Sexual Transmission; Time; Training; Translating; Tuberculosis; United States National Institutes of Health; Universities; Viral; Viral hepatitis; Virus Diseases; Zambia; antiretroviral therapy; career; career development; chronic liver disease; cohort; early childhood; elastography; epidemiologic data; experience; follow-up; global health; high risk; innovation; international center; liver injury; mortality; prevent; professor; public health relevance; skills; therapy outcome

DESCRIPTION (provided by applicant): This is an application for a Fogarty International Center K01 International Research Scientist Development Award for Dr. Michael Vinikoor, an infectious diseases physician at the University of North Carolina at Chapel Hill (UNC). Dr. Vinikoor has shown great promise as a young investigator in the area of HIV/hepatitis B virus (HBV) co-infection in sub-Saharan Africa (SSA); however, as many in his position, he requires dedicated support to ensure his successful career development. This award will provide Dr. Vinikoor with the necessary support to accomplish the following goals: (1) to become an expert in viral hepatitis, (2) to become an expert in clinical research implementation in resource-constrained settings, (3) to gain additional knowledge and skills in advanced study design and biostatistical methods, and (4) to develop skills in multi- disciplinary, long-distance collaboratin. To achieve these goals, Dr. Vinikoor has assembled a highly experienced mentorship team comprised of Dr. Michael Fried (U.S. Primary Mentor), Professor of Medicine and Director of the Liver Clinic at UNC, Dr. Benjamin Chi (Zambia Primary Mentor), Chief Scientific Officer of Centre for Infectious Disease Research in Zambia and Associate Professor of Obstetrics and Gynecology at UNC, as well as three Co-Mentors: Dr. Joseph Eron, expert in clinical and translational HIV research as well as in multi-center international clinical trials, Dr. William Miler, an expert in analytic methods and mentoring young investigators toward research independence, and Dr. Charles van der Horst, an expert in global health and in interdisciplinary research collaborations. Liver disease due to viral hepatitis has become a leading cause of death of HIV-infected individuals receiving antiretroviral therapy (ART) in upper-income settings. In sub-Saharan Africa (SSA), an estimated 3 million HIV-infected patients have chronic HBV co-infection. Compared with upper-income settings, the outcomes of HIV/HBV may be different in SSA due to diverse patterns in HBV transmission, environmental exposures, and hepatotoxic co-infections. Leveraging an existing NIH-funded cohort in Zambia, Dr. Vinikoor's supported research will comprise two main components. First, he will assess the prevalence of significant liver fibrosis in patients with HIV/HBV using non-invasive methods including transient elastography. Predictors of fibrosis will assessed including alcohol and herbal medication and co-infections such as schistosomiasis and hepatitis D infection. Then Dr. Vinikoor will measure changes in liver fibrosis during 3 years of longitudinal follow-up and analyze factors that predict improvement in fibrosis, include HIV and HBV viral suppression, patterns of alcohol use, and CD4+ immune recovery. Additional HBV end-points such as hepatocellular carcinoma and liver decompensation will also be ascertained. The studies outlined in this proposal will generate currently unavailable data on the outcomes of these at-risk patients, and will inform and optimize HIV/HBV treatment guidelines for resource-constrained settings. They also provide an ideal training platform for a young investigator seeking to establish a career in HIV/HBV infection and will provide key epidemiologic data needed for future interventional trials in this critical field.

描述（由申请人提供）：这是北卡罗来纳大学教堂山分校 (UNC) 传染病医生 Michael Vinikoor 博士申请福格蒂国际中心 K01 国际研究科学家发展奖的申请。 Vinikoor 博士作为一名年轻研究者，在撒哈拉以南非洲 (SSA) 的 HIV/乙型肝炎病毒 (HBV) 混合感染领域表现出了巨大的潜力；然而，与许多处于其职位的人一样，他需要专门的支持以确保他的职业发展取得成功。该奖项将为 Vinikoor 博士提供必要的支持，以实现以下目标：(1) 成为病毒性肝炎专家，(2) 成为资源有限环境下实施临床研究的专家，(3) 获得高级研究设计和生物统计方法方面的额外知识和技能，以及 (4) 培养多学科、远程合作的技能。为了实现这些目标，Vinikoor 博士组建了一支经验丰富的导师团队，由北卡罗来纳大学医学教授兼肝脏诊所主任 Michael Fried 博士（美国首席导师）、赞比亚传染病研究中心首席科学官兼北卡罗来纳大学妇产科副教授 Benjamin Chi 博士（赞比亚首席导师）以及三位共同导师：Joseph Eron 博士、 临床和转化艾滋病毒研究以及多中心国际临床试验专家 William Miler 博士是分析方法和指导年轻研究人员独立研究的专家，Charles van der Horst 博士是全球健康和跨学科研究合作方面的专家。 病毒性肝炎引起的肝病已成为高收入环境中接受抗逆转录病毒治疗 (ART) 的 HIV 感染者死亡的主要原因。在撒哈拉以南非洲 (SSA)，估计有 300 万 HIV 感染者患有慢性 HBV 合并感染。与高收入环境相比，由于 HBV 传播、环境暴露和肝毒性合并感染的模式不同，SSA 中 HIV/HBV 的结果可能有所不同。 Vinikoor 博士支持的研究将利用赞比亚现有的 NIH 资助的队列，包括两个主要部分。首先，他将使用瞬时弹性成像等非侵入性方法评估 HIV/HBV 患者显着肝纤维化的患病率。将评估纤维化的预测因素，包括酒精和草药以及血吸虫病和丁型肝炎感染等合并感染。然后 Vinikoor 博士将测量 3 年纵向随访期间肝纤维化的变化，并分析预测因素 纤维化的改善，包括 HIV 和 HBV 病毒抑制、饮酒模式和 CD4+ 免疫恢复。其他乙型肝炎终点，如肝细胞癌和肝脏失代偿也将得到确定。该提案中概述的研究将产生目前无法获得的有关这些高危患者的结果的数据，并将为资源有限的环境提供信息和优化 HIV/HBV 治疗指南。它们还为寻求在 HIV/HBV 感染领域建立职业生涯的年轻研究者提供了理想的培训平台，并将为这一关键领域的未来干预试验提供所需的关键流行病学数据。