Impact of antiretrovial 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: 9128155
• 负责人: Michael Jeffrey Vinikoor
• 金额: $ 13.76万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9128155
• 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; Intervention Trial; Investigation; Knowledge; Liver; Liver Fibrosis; Liver diseases; Measures; Medicine; Mentored Research Scientist Development Award; Mentors; Mentorship; Methods; Mono-S; North Carolina; Outcome; Patient risk; 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; co-infection; 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)：这是为北卡罗来纳大学教堂山分校(UNC)传染病内科医生Michael Vinikoor博士申请Fogarty国际中心K01国际研究科学家发展奖。作为撒哈拉以南非洲(SSA)地区艾滋病毒/乙肝病毒(乙肝)混合感染领域的一名年轻研究员，Vinikoor博士表现出了巨大的潜力；然而，与他职位上的许多人一样，他需要专门的支持来确保他的职业发展成功。这一奖项将为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)成为在资源有限的情况下实施临床研究的专家，(3)获得先进研究设计和生物统计学方法方面的更多知识和技能，以及(4)发展多学科、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，成员包括北卡罗来纳大学医学教授兼肝脏诊所主任Michael Fry博士(美国首席导师)，赞比亚传染病研究中心首席科学官、北卡罗来纳大学妇产科副教授Benjamin chi博士，以及三位共同导师：临床和转化性艾滋病毒研究以及多中心国际临床试验专家Joseph Eron博士，分析方法专家威廉·米勒博士，指导年轻研究人员实现研究独立，全球卫生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在高收入环境中接受抗逆转录病毒治疗(ART)的艾滋病毒感染者的主要死亡原因。在撒哈拉以南非洲(SSA)，估计有300万艾滋病毒感染患者患有慢性乙肝病毒混合感染。与高收入人群相比，由于乙肝病毒传播、环境暴露和肝毒性混合感染的不同模式，SSA地区艾滋病毒/乙肝病毒的结果可能不同。利用国家卫生研究院在赞比亚现有的资助队列，Vinikoor博士支持的研究将包括两个主要部分。首先，他将使用包括瞬时弹性成像在内的非侵入性方法评估艾滋病毒/乙肝患者中显著肝纤维化的患病率。将评估纤维化的预测因素，包括酒精和草药药物以及血吸虫病和丁型肝炎感染等混合感染。然后，维尼科博士将在3年的纵向随访中测量肝纤维化的变化，并分析预测 改善纤维化，包括抑制艾滋病毒和乙肝病毒，酒精使用模式，以及CD4+免疫恢复。其他的乙肝终点，如肝细胞癌和肝脏失代偿，也将被确定。这项提案中概述的研究将产生目前无法获得的关于这些高危患者结果的数据，并将为资源有限的环境提供信息和优化艾滋病毒/乙肝治疗指南。它们还为寻求在艾滋病毒/乙肝病毒感染领域建立职业生涯的年轻研究人员提供了一个理想的培训平台，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。