Persistent Functional Immune Defects in Treated HIV Infection

项目摘要 Peter Hunt，医学博士，加州大学旧金山分校实验医学部医学副教授， 国际公认的以患者为中心的转化型研究(POR)的领导者，专注于原因和 免疫激活在接受治疗的艾滋病毒感染中的后果。他正在提交这份职业生涯中期的K24 开发应用程序，为他提供受保护的时间来指导初级调查人员，为他提供 专注于导师技能培训，并继续发展他的POR计划。候选人：这份提案 将建立在亨特博士富有成效的研究计划的基础上，200多名同行评议是例证 出版物，引文h指数为52，以及强大的研究资金基础，包括三项R01赠款和两项 DARE协作室和AMFAR艾滋病毒治疗研究所的大型项目。他已经这么做了 表现出良好的指导记录，特别是在多学科团队科学方面，包括4 成功申请K23/K01奖项的学员，以及两名继续获得 独立R系列奖助金。他也是2015年加州大学旧金山分校艾滋病研究所奖的获得者 辅导。环境：他有丰富的基础来支持他的学员，包括访问 旧金山加州大学旧金山分校2000名HIV感染者的范围队列及其与其他几个人的联系 多中心队列(LSOCA、UARTO、CNICs)和研究网络，包括他服务的ACTG 担任炎症和最终器官疾病委员会主席。导师培训：这个K24奖项将 通过密集的工作坊和培训模块进一步提高他的指导技能 加州大学旧金山分校的CTSI导师培训计划和UCSF-GIVI导师计划。他也将成为 在他职业生涯的下一阶段，他得到了一群强大的职业导师的指导。研究计划： 激励这项研究计划的首要假设是，尽管治疗了亚临床免疫缺陷，但 HIV感染减少了CD8+T细胞介导的CMV监测，这反过来又导致微生物易位 和心脏新陈代谢并发症。具体目标是：1)评估无症状巨细胞病毒的作用 复制到接受治疗的HIV感染中微生物易位和血管功能障碍的可溶性标记物，2) 评估接受治疗的HIV感染与炎性CMV特异性CD8+T细胞的相关性程度 脂肪组织的渗透和胰岛素抵抗，以及3)评估CMV特异性成熟缺陷 经治疗的HIV感染者体内存在CD8+T细胞。这些研究还将作为理想的POR培训平台 他的师徒。

Project Summary Peter Hunt, MD is an Associate Professor of Medicine in the UCSF Division of Experimental Medicine and an internationally recognized leader in translational Patient-Oriented Research (POR) focused on the causes and consequences of immune activation in treated HIV infection. He is submitting this K24 Mid-Career Development application to afford him protected time to mentor junior investigators, to provide him with dedicated mentorship skills training, and to continue to grow his POR program. The candidate: This proposal will build upon Dr. Hunt's highly productive research program, exemplified by over 200 peer-reviewed publications, a citation h-index of 52, and robust research funding base including three R01 grants and two large projects in the DARE collaboratory and amfAR Institute for HIV Cure Research. He has already demonstrated a strong track record for mentoring, particularly in multidisciplinary team science, including 4 mentees who have successfully applied for K23/K01 awards, and two who have gone on to secure independent R-series grants. He is also the recipient of the 2015 UCSF AIDS Research Institute Award for Mentoring. The environment: He has a rich foundation for supporting his mentees including access to the UCSF SCOPE cohort of >2000 HIV-infected individuals in San Francisco and connections to several other multicenter cohorts (LSOCA, UARTO, CNICS) and research networks including the ACTG, where he served as Chair of the Inflammation and End Organ Disease Committee. Mentorship training: This K24 award will further enhance his mentorship skills through intensive workshops and training modules supported by the UCSF CTSI Mentorship Training Program and the UCSF-GIVI Mentoring the Mentors program. He will also be coached by a robust group of career mentors as he navigates this next phase of his career. Research plan: The overarching hypothesis motivating the research plan is that subclinical immunodeficiency despite treated HIV infection decreases CD8+ T cell-mediated CMV surveillance, which in turn leads to microbial translocation and cardiometabolic complications. The specific aims will: 1) assess the contribution of asymptomatic CMV replication to soluble markers of microbial translocation and vascular dysfunction in treated HIV infection, 2) assess the degree to which treated HIV infection is associated with inflammatory CMV-specific CD8+ T cell infiltration of adipose tissue and insulin resistance, and 3) assess whether maturational defects in CMV-specific CD8+ T cells occur in treated HIV infection. These studies will also serve as ideal POR training platforms for his mentees.