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

描述（由申请人提供）：这是一份申请福格蒂国际中心K01国际研究科学家发展奖的申请，申请对象是北卡罗来纳大学教堂山分校（UNC）的传染病医生Michael Vinikoor博士。作为撒哈拉以南非洲（SSA）艾滋病毒/乙型肝炎病毒（HBV）合并感染领域的一名年轻研究者，Vinikoor博士显示出了巨大的希望；然而，和许多处于他这个位置的人一样，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)成为病毒性肝炎方面的专家；(2)在资源有限的情况下成为临床研究实施方面的专家；(3)在高级研究设计和生物统计方法方面获得额外的知识和技能；(4)培养多学科、远程合作的技能。为了实现这些目标，Vinikoor博士组建了一个经验丰富的指导团队，包括Michael Fried博士（美国主要导师），UNC医学教授兼肝脏诊所主任，Benjamin Chi博士（赞比亚主要导师），赞比亚传染病研究中心首席科学官，UNC妇产科学副教授，以及三位共同导师：Joseph Eron博士是艾滋病毒临床和转化研究以及多中心国际临床试验方面的专家，William miller博士是分析方法和指导年轻研究人员独立研究方面的专家，Charles van der Horst博士是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高收入环境中接受抗逆转录病毒治疗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同时患有慢性乙型肝炎病毒感染。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不同模式，SSA中HIV/HBV的结局可能不同。利用现有的美国国立卫生研究院资助的赞比亚队列，Vinikoor博士支持的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，包括酒精和草药以及血吸虫病和丁型肝炎感染等合并感染。然后，Vinikoor博士将在3年的纵向随访中测量肝纤维化的变化，并分析预测因素

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.