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）：这是为Fogarty International Center K01国际研究科学家发展奖Michael Vinikoor博士的申请，他是北卡罗来纳大学教堂山（UNC）的传染病医师。 Vinikoor博士在撒哈拉以南非洲（SSA）的HIV/HIV/肝炎病毒（HBV）共同感染方面表现出了巨大的希望。但是，正如他的职位上一样，他需要专门的支持来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）成为病毒性肝炎的专家，（2）成为资源受限设置的临床研究实施专家，（3）以获得高级研究设计和生物稳定方法的其他知识和技能，以及（4）在多学科阶段合作，远程合作中发展技能。为了实现这些目标，维尼科尔博士组建了一个经验丰富的指导团队，由迈克尔·弗里德（Michael Fried）博士（美国主要导师），医学教授和UNC肝诊所主任本杰明·奇（Benjamin Chi），Zambia Chi博士（Zambia Primary Mentor）（Zambia Primary Mentor），首席科学官员，首席科学官员，埃默特（Ernecology）的感染性疾病研究中心，以及埃默特（Ertoric）以及埃默特（INV），以及杰兰科（INC），以及杰兰（Ertor）的研究：临床和转化艾滋病毒研究以及多中心国际临床试验的专家威廉·米勒（William Miler）博士是分析方法的专家，并指导了年轻的研究人员迈向研究独立性，以及全球卫生和跨学科研究专家Charles van der Horst博士。 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）中，估计有300万HIV感染的患者患有慢性HBV共同感染。与高收入的设置相比，由于HBV传播，环境暴露和肝毒性共感染的不同模式，SSA的HIV/HBV结果可能有所不同。维尼科尔博士的支持研究利用了赞比亚现有的现有资助的同胞，将构成两个主要组成部分。首先，他将使用包括瞬态弹性图（瞬时弹性摄影）的非侵入性方法评估HIV/HBV患者的明显肝纤维化患病率。将评估纤维化的预测因子，包括酒精和草药药物以及联合感染，例如血吸虫病和乙型肝炎感染。然后，Vinikoor博士将在纵向随访3年期间衡量肝纤维化的变化，并分析预测的因素 纤维化的改善包括HIV和HBV病毒抑制，酒精使用模式以及CD4+免疫恢复。还将确定其他HBV终点，例如肝细胞癌和肝脏代理。该提案中概述的研究将产生有关这些高危患者结果的目前无法获得的数据，并将为资源受限的环境提供信息和优化HIV/HBV治疗指南。他们还为寻求建立艾滋病毒/HBV感染职业的年轻调查员提供了理想的培训平台，并将在这个关键领域提供未来介入的试验所需的关键流行病学数据。