Cardiovascular disease and inflammation in Ugandan children with HIV

项目摘要/摘要： 携带艾滋病毒的成年人患心血管疾病和代谢疾病的风险增加 并发症与未感染艾滋病毒的对照人群相比。与之相比， 在成人中已知，对儿科人群中的这些风险知之甚少，甚至 在撒哈拉以南非洲的背景下就更少了。尽管炎症已经被认为与 成人HIV感染者的心血管疾病，炎症对标记物的作用 在感染艾滋病毒的儿童中，心血管疾病的风险很少被调查， 青少年。此外，非艾滋病并存的影响可能在 撒哈拉以南非洲，尽管还没有对接受抗逆转录病毒治疗的儿童进行心血管疾病的研究 在这种情况下。 这项拟议的K23研究计划的总体目标是使用替代 心血管疾病标记物用于识别感染艾滋病毒的儿童和青年 早期心脏病并了解这些变化的机制，因此风险- 减少疗法可以有适当的针对性，新的预防策略可以 将在未来得到发展。在一项对100名感染艾滋病毒的青年和100名 健康对照组，本项目旨在用颈动脉内膜中层厚度(CIMT)、脉搏 波速(PWV)和胰岛素抵抗用于识别HIV患者早期心脏代谢风险 在坎帕拉，感染艾滋病毒的青年与年龄和性别匹配的未感染艾滋病毒的对照人员， 乌干达。此外，我们将调查这些心脏代谢的标记物 疾病与炎症和肠道完整性的生物标志物相关。这项研究将 提供炎症、免疫激活和细菌如何 易位与HIV感染儿童的心脏代谢性疾病有关 青少年。 PI，Dirajlal-Fargo博士，是一位特殊的候选人，他正在寻求成为 国际公认的心脏代谢领域的临床医生兼研究员 儿童艾滋病毒的并发症。她还拥有从事临床研究的经验。 乌干达。 Dirajlal-Fargo博士得到了凯斯西部储备银行的大力机构支持 和彩虹婴儿和儿童医院的儿科。 她将保证75%受保护的研究时间和访问丰富的 确保成功过渡到独立资助的调查员的资源。 她强有力的培训计划包括：1)她的主要导师Dr。 Grace McComsey，以及免疫学、传染病领域的共同导师 生物统计学家，乌干达艾滋病毒和儿童艾滋病毒的心血管并发症 和一群合作者；2)基础免疫学课程，重点是 慢性艾滋病毒感染；3)心血管成像和生理学培训；4)培训 临床研究设计和统计；5)国际跨学科经验 团队科学；以及6)整合临床护理和研究项目的现场经验。

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.