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）：这是一份Fogarty国际中心K 01国际研究科学家发展奖的申请书，申请人是查佩尔山的北卡罗来纳州大学的传染病医生Michael Vinikoor博士。Vinikoor博士作为撒哈拉以南非洲（SSA）艾滋病毒/B肝炎病毒（HBV）合并感染领域的年轻研究人员表现出了很大的希望;然而，正如许多人在他的职位上一样，他需要专门的支持，以确保他成功的职业发展。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）成为资源受限环境中临床研究实施的专家，（3）获得先进研究设计和生物统计方法的额外知识和技能，以及（4）发展多学科，远程合作的技能。为了实现这些目标，Vinikoor博士组建了一个由Michael Fried博士组成的经验丰富的导师团队。（美国主要导师），医学教授兼肝脏诊所主任，Benjamin Chi博士（赞比亚初级导师），赞比亚传染病研究中心首席科学官，赞比亚国立卫生研究院妇产科副教授，以及三位共同导师：Joseph Eron博士是临床和转化HIV研究以及多中心国际临床试验方面的专家，William Miler博士是分析方法方面的专家，他指导年轻研究人员实现研究独立性，Charles货车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疗法（ART）的艾滋病毒感染者死亡的主要原因。在撒哈拉以南非洲（SSA），估计有300万艾滋病毒感染者患有慢性乙型肝炎合并感染。与高收入环境相比，艾滋病毒/乙肝病毒的结果可能是不同的，由于不同的模式，在乙肝病毒传播，环境暴露，肝毒性合并感染的SSA。利用赞比亚现有的NIH资助的队列，Vinikoor博士的支持研究将包括两个主要组成部分。首先，他将使用非侵入性方法（包括瞬时弹性成像）评估HIV/HBV患者中显著肝纤维化的患病率。纤维化的预测因素包括酒精和草药以及合并感染，如血吸虫病和丁型肝炎感染。然后Vinikoor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 纤维化改善，包括HIV和HBV病毒抑制、酒精使用模式和CD 4+免疫恢复。还将确定其他HBV终点，如肝细胞癌和肝功能失代偿。本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局的数据，并将为资源有限的环境提供信息和优化HIV/HBV治疗指南。他们还为寻求在HIV/HBV感染领域建立职业生涯的年轻研究人员提供了理想的培训平台，并将为这一关键领域的未来干预性试验提供所需的关键流行病学数据。