Patient Oriented Research in Hepatitis C-infected Injection Drug Users

描述(由申请人提供)：这是为约翰霍普金斯大学医学院医学博士Mark S.Sulkowski颁发的K24以患者为中心的研究(POR)职业中期调查员奖的建议。Sulkowski博士是传染病学部的医学副教授和传染病学部病毒性肝炎中心的医学主任。他领导着两个互补的丙型肝炎病毒(丙型肝炎病毒)POR项目：丙型肝炎病毒/艾滋病毒肝脏结局研究。这项研究的目的是评估美国国立卫生研究院支持的HIV和丙型肝炎共同感染的成年人纵向队列中丙型肝炎病毒疾病的长期结果。目前的工作重点是使用工具来确定抗逆转录病毒治疗和丙型肝炎病毒治疗对肝病的影响，包括组织学和非侵入性瞬时弹性成像，以及改善丙型肝炎病毒结局的干预措施，如丙型肝炎病毒治疗的行为强化。丙型肝炎治疗公司。这项研究的目的是进行治疗丙型肝炎病毒的新型直接作用抗病毒药物(DAA)的临床试验，其广泛目标是验证新的治疗靶点，提高根治率，改善安全性和耐受性，并将这些结果转化为社区。这项K24奖计划的主要目的是：1)创建一个综合培训计划，将结果研究和临床试验方面的专业知识结合在一起，为丙型肝炎病毒相关POR的学术生涯培养早期临床研究员；2)致力于研究工作，推进艾滋病临床试验小组(ACTG)的丙型肝炎病毒研究议程。该网络引领了艾滋病毒/丙型肝炎病毒混合感染的研究，并在病毒学、免疫学、药理学、新陈代谢、生物静力学、生物伦理学和研究实施方面拥有对丙型肝炎病毒领域至关重要的专业知识；3)通过开发一项专注于有害酒精摄入的研究计划，扩大混合感染成年人的丙型肝炎病毒疾病管理范围；有害酒精摄入在这一人群中普遍存在，会加速丙型肝炎病毒疾病，并且是丙型肝炎治疗的禁忌症。这些目标将在为新的和现有的初级教员、传染病研究员和研究生提供指导的背景下实现。K24将使苏尔科夫斯基博士能够更有效地实现他的长期职业目标，即改善丙型肝炎的治疗，并将这些治疗转化为丙型肝炎病毒疾病负担最高的人群。 公共卫生相关性：这是一项授予Mark S.Sulkowski医学博士的以患者为中心的研究(K24)职业生涯中期奖的建议。该奖项将支持Sulkowski博士在丙型肝炎方面的临床研究计划；这项研究的首要目标是通过对治疗丙型肝炎的新型直接作用抗病毒药物(DAA)进行临床试验，并将改进的治疗方法转化为疾病负担最重的人群，来改善丙型肝炎患者的临床结果。这些目标是在为新的和现有的初级教员、传染病研究员和研究生提供指导的背景下提出的。

DESCRIPTION (provided by applicant): This is a proposal for a K24 Midcareer Investigator Award in Patient-oriented research (POR) for Mark S. Sulkowski, MD of the Johns Hopkins University School of Medicine. Dr. Sulkowski is an Associate Professor of Medicine in the Division of Infectious Diseases (ID) and Medical Director of the ID Viral Hepatitis Center. He leads two complementary POR programs for hepatitis C virus (HCV): HCV/HIV Liver Outcomes Research. The aims of this research are to evaluate long-term outcomes of HCV disease in an NIH-supported longitudinal cohort of adults coinfected with HIV and HCV. Current efforts emphasize the use of tools to determine the impact of antiretroviral therapy and HCV treatment on liver disease including histology and noninvasive transient elastography as well as interventions to improve HCV outcomes such as behavioral reinforcement for HCV treatment. HCV Therapeutics. The aim of this research is to conduct clinical trials of novel direct acting antivirals (DAAs) for the treatment of HCV with the broad goals of validating new therapeutic targets, increasing eradication rates, improving safety and tolerability and translating these findings to the community. The principal aims of this K24 Award proposal are: 1) To create a comprehensive training program that brings together expertise in outcomes research and clinical trials to prepare early clinical investigator for academic careers in POR related to HCV; 2) To dedicate research effort to the advancement of the HCV research agenda in the AIDS Clinical Trials Group (ACTG). This network has led research in HIV/HCV coinfection and has expertise in virology, immunology, pharmacology, metabolic, biostatics, bioethics, and research implementation that are critical to the HCV field; 3) To expand the scope HCV disease management in coinfected adults through the development of a research program focused on harmful alcohol intake which is prevalent in this population, accelerates HCV disease and is a contraindication to HCV treatment. These aims will be addressed in the context of providing mentorship to new and existing junior faculty, infectious diseases fellows and graduate students. The K24 will allow Dr. Sulkowski to more effectively pursue his long-term career goals of improving HCV treatment and translating these treatments to populations of individuals with the highest HCV disease burden. Public Health Relevance: This is a proposal for a Midcareer Investigator Award in Patient-Oriented Research (K24) for Mark S. Sulkowski, M.D. This award will support Dr. Sulkowski's clinical research programs in Hepatitis C; the overarching aim of this research is to improve clinical outcomes in persons with HCV through the conduct clinical trials of novel direct acting antivirals (DAAs) for the treatment of HCV and the translation of improved therapies to populations with the greatest disease burden. These aims are addressed in the context of providing mentorship to new and existing junior faculty, infectious diseases fellows and graduate students.