Cardiovascular disease and inflammation in Ugandan children with HIV

项目概要/摘要： 成年艾滋病毒感染者患心血管和代谢疾病的风险增加 与未感染艾滋病毒的对照人群相比。相比之下 在成人中已知，对儿科人群中的这些风险知之甚少，甚至 在撒哈拉以南的非洲地区，尽管炎症与 心血管疾病的成年人与艾滋病毒，炎症的作用， 心血管疾病的风险几乎没有调查艾滋病毒感染的儿童， 青少年。此外，非艾滋病合并症的影响可能更大， 撒哈拉以南非洲，尽管尚未在接受抗逆转录病毒治疗的儿童中进行心血管疾病研究 在这种情况下。 K23研究计划的总体目标是使用替代品 心血管疾病的标志物，以确定艾滋病毒感染的儿童和青少年的风险， 早期心脏病，并了解这些变化的机制，使风险- 减少治疗可以适当的针对性和新的预防策略， 在未来发展。在一项对100名艾滋病毒感染青年和100名 健康对照，本项目旨在使用颈动脉内膜中层厚度（cIMT），脉搏 波速度（PWV）和胰岛素抵抗，以确定艾滋病毒感染者的早期心脏代谢风险， 受感染的青年与坎帕拉未感染艾滋病毒的对照组相比， 乌干达此外，我们将研究这些心脏代谢的制造商是否 疾病与炎症和肠道完整性的生物标志物相关。本研究将 提供了一个全面的观点，如何炎症，免疫激活和细菌 HIV感染儿童心脏代谢疾病相关易位 青少年。 PI，Dirajlal-Fargo博士，是一个特殊的候选人，他正在寻求成为 国际公认的心脏代谢领域的临床研究者 儿科艾滋病并发症。她也有经验进行临床研究， 乌干达 Dirajlal-Fargo博士拥有凯斯西储的强大机构支持 大学和彩虹婴儿和儿童医院儿科。 她将保证75%的研究时间受到保护，并获得丰富的 确保成功过渡到独立供资的调查员的资源。 她稳健的培训计划包括：1）她的主要导师Dr Grace McComsey，以及免疫学、传染病 艾滋病毒和艾滋病儿童的心血管并发症， 和一组合作者; 2）基础免疫学课程，重点是 慢性HIV感染; 3）心血管成像和生理学培训; 4） 临床研究设计和统计; 5）国际跨学科经验 团队科学; 6）整合临床护理和研究计划的现场经验。

Project Summary/Abstract: Adults with HIV are at increased risk of cardiovascular and metabolic complications compared to HIV-uninfected control populations. Compared to what is known in adults, little is known about these risks in the pediatric population and even less in the setting of sub-Saharan Africa. Although inflammation has been linked to cardiovascular disease in adults with HIV, the role of inflammation on markers of cardiovascular disease risk has been scarcely investigated in HIV-infected children and adolescents. Furthermore, the impact of non-AIDS co morbidities may be greater in sub-Saharan Africa, though no studies of CVD have been conducted in children on ART in this setting. The overall objective of this proposed K23 research plan is to use surrogate markers of cardiovascular disease to identify HIV-infected children and youth at risk of early heart disease and to understand the mechanisms of these changes, so that risk- reduction therapies can be appropriately targeted and novel preventive strategies may be developed in the future. In a longitudinal study of 100 HIV-infected youth and 100 healthy controls, this project aims to use carotid intima media thickness (cIMT), pulse wave velocity (PWV) and insulin resistance to identify early cardiometabolic risks in HIV- infected youth compared to age and gender match HIV uninfected controls in Kampala, Uganda. Additionally, we will investigate whether these makers of cardiometabolic disease correlate with biomarkers of inflammation and gut integrity. This study will provide a comprehensive view of how inflammation, immune activation and bacterial translocation relate to cardiometabolic disease among HIV-infected children and adolescents. The PI, Dr Dirajlal-Fargo, is an exceptional candidate who is seeking to become an internationally recognized clinician-investigator in the field of cardiometabolic complications in pediatric HIV. She also has experience conducting clinical research in Uganda. Dr Dirajlal-Fargo has strong institutional support from Case Western Reserve University and the Department of Pediatrics at Rainbow Babies and Children's Hospital. She will have guaranteed 75% protected research time and access to a wealth of resources that will ensure a successful transition to independently funded investigator. Her robust training plan includes: 1)high quality mentorship from her primary mentor, Dr Grace McComsey, as well as co-mentors in the field of immunology, infectious disease and cardiovascular complications of HIV and pediatric HIV in Uganda, a biostatistician and a group of collaborators; 2) coursework in fundamental immunology with a focus on chronic HIV infection; 3) training in cardiovascular imaging and physiology; 4) training in clinical research design and statistics; 5) experience in international interdisciplinary team science; and 6) field experience in integrating clinical care and research programs.