HIV-associated Myocardial Diastolic Dysfunction: A Prospective Cohort Study

项目总结/摘要 候选人：Dr. Justin Kingery拥有内科认证，并拥有心血管博士学位 生理学和免疫学。过去四年，他作为全球卫生研究员在坦桑尼亚接受培训， 与坦桑尼亚科学家开展合作，培训了当地研究团队，并撰写了六份出版物。 博士Kingery的工作主要集中在单核细胞在心肌功能障碍中的作用以及 艾滋病毒相关的心脏病在坦桑尼亚，这两者构成了拟议的研究培训的基础。 职业发展计划：金瑞博士的长期目标是成为一名独立的内科医生和科学家 致力于艾滋病病毒感染者心血管疾病防治的临床研究 患者K23奖项的目标包括：1）通过以下方式获得临床流行病学方面的专业知识： 在菲茨杰拉德、卡皮加和德弗罗博士的指导下，完成了一个临床队列的课程和注册。 2)通过课程和马丁威尔斯博士指导的自己的数据分析来提高生物统计学技能。 3)通过课程增加对HIV病毒学，免疫学和HIV诱导的炎症的理解， 会议，并指导下菲茨杰拉德博士，Kapiga和Koretzky的研究。4)转换到 独立的以患者为导向的调查员，并通过威尔康奈尔大学的课程加强领导技能 关于补助金写作的医学，关于指导的研讨会和在补助金第4年提交R 01申请。 环境：拟议的研究和培训将在威尔布甘多医学院进行。 诊所（坦桑尼亚），姆万扎干预试验单位（坦桑尼亚）和威尔康奈尔医学（美国）。的 这些机构之间的伙伴关系提供了一个独特的合作环境， 包括大型临床研究和转化研究。这些机构致力于金瑞博士的事业。 研究：拟议的研究建立在金瑞博士先前在坦桑尼亚的工作基础上。在目标1中，他将进行 一项前瞻性队列研究，旨在确定500名受试者中舒张功能障碍的发生率和预测因素， 坦桑尼亚的艾滋病毒感染者和500名未感染的成年人。他推测，新的发病率 HIV感染成人的舒张功能障碍比未感染HIV的对照组高≥ 2倍， 先天免疫因子sST 2升高他还将确定传统风险的贡献 因素（年龄、高血压、肥胖和糖尿病）和HIV特异性因素（抗逆转录病毒药物、最低CD 4 计数和病毒载量）。在目标2中，他将在目标1队列中进行巢式病例对照研究， 确定外周血单核细胞表型和事件之间的时间关系 舒张功能障碍在四组各25名HIV感染和未感染的成年人中， 没有舒张功能障碍。他推测，外周血中交替激活的 在HIV感染的成人中，单核细胞（AAM）/经典活化单核细胞（CAM）将高出≥ 2.5倍， AAM/CAM比值增加将先于并预测舒张功能障碍的发生。

PROJECT SUMMARY / ABSTRACT Candidate: Dr. Justin Kingery is board certified in Internal Medicine and holds a PhD in cardiovascular physiology and immunology. Training in Tanzania as a global health fellow for the past four years, he has developed collaborations with Tanzanian scientists, trained a local study team, and authored six publications. Dr. Kingery’s work has focused on the role of monocytes in myocardial dysfunction and the epidemiology of HIV-associated heart disease in Tanzania, both of which form the basis for the proposed research training. Career Development Plan: Dr. Kingery’s long-term goal is to become an independent physician scientist dedicated to clinical research in the prevention and treatment of cardiovascular disease in HIV-infected patients. Objectives during this K23 award include: 1) to gain expertise in clinical epidemiology through coursework and enrollment of a clinical cohort under the mentorship of Drs. Fitzgerald, Kapiga and Devereux. 2) To increase biostatistics skills through courses and analysis of his own data mentored by Dr. Martin Wells. 3) To increase understanding of HIV virology, immunology, and HIV-induced inflammation through courses, conferences, and mentored research under Drs. Fitzgerald, Kapiga and Koretzky. 4) To transition to an independent patient-oriented investigator and strengthen leadership skills through coursework at Weill Cornell Medicine on grant writing, workshops on mentorship and submission of a R01 application in grant Year 4. Environment: The proposed research and training will take place at the Weill Bugando School of Medicine HIV Clinic (Tanzania), the Mwanza Intervention Trials Unit (Tanzania) and Weill Cornell Medicine (USA). The partnership between these institutions provides a unique collaborative environment with the infrastructure for both large clinical studies and translational research. These institutions are committed Dr. Kingery’s career. Research: The proposed research builds upon Dr. Kingery’s prior work in Tanzania. In Aim 1, he will conduct a prospective cohort study to determine the incidence and predictors of diastolic dysfunction in 500 HIV-infected and 500 uninfected adults in Tanzania. He hypothesize that the incidence of new-onset diastolic dysfunction will be ≥ 2-times higher in HIV-infected adults than in HIV-uninfected controls and preceded by elevated innate immune factor sST2. He will also determine the contributions of traditional risk factors (age, hypertension, obesity, and diabetes) and HIV-specific factors (antiretroviral drugs, nadir CD4 count, and viral loads). In Aim 2, he will conduct a nested case control study within the Aim 1 cohort to determine the temporal relationship between peripheral blood monocyte phenotype and incident diastolic dysfunction in four groups of 25 each of HIV-infected and uninfected adults with and without diastolic dysfunction. He hypothesize that the ratio of peripheral blood alternatively activated monocytes (AAM)/classically activated monocytes (CAM) will be ≥ 2.5 times higher in HIV-infected adults and that an increased AAM/CAM ratio will precede and predict incident diastolic dysfunction.