Cardiovascular disease and inflammation in Ugandan children with HIV

乌干达艾滋病毒感染者的心血管疾病和炎症

• 批准号: 9270212
• 负责人: Sahera Dirajlal-Fargo
• 金额: $ 13.02万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-25 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9270212
• 关键词: Adolescent; Adult; Africa South of the Sahara; Age; Bacterial Translocation; Biological Markers; Birth; Cardiac; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Child; Childhood; Chronic; Clinical Research; Comorbidity; Data; Disease; Disease Marker; Disease Resistance; Ensure; Exposure to; Face; FarGo; Funding; Future; Gastrointestinal tract structure; Gender; HIV; HIV Infections; HIV antiretroviral; Health; Heart Diseases; High Prevalence; Homeostasis; Immunology; Individual; Infectious Disease Immunology; Inflammation; Inflammatory; Inflammatory disease of the intestine; Insulin Resistance; International; Intervention; Knowledge; Life; Link; Longitudinal Studies; Measures; Mentors; Mentorship; Metabolic; Modeling; Nutritional; Outcome; Participant; Patients; Pediatric Hospitals; Pharmaceutical Preparations; Physiologic pulse; Play; Population; Population Control; Prevention strategy; Research; Research Design; Research Personnel; Resources; Risk; Risk Factors; Risk Reduction; Role; Science; Surrogate Markers; Testing; Time; Training; Uganda; Universities; Vascular Diseases; Youth; abstracting; antiretroviral therapy; cardiometabolic risk; cardiovascular disorder risk; cardiovascular imaging; cardiovascular risk factor; clinical care; clinically significant; co-infection; cohort; experience; high risk; immune activation; immune function; improved; indexing; inflammatory marker; intimal medial thickening; microbial; monocyte; novel; pediatric department; pediatric human immunodeficiency virus; pediatric patients; programs; restoration; sex; statistics

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.

项目摘要/摘要： 感染艾滋病毒的成年人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，出现了并发症。与什么相比 对于成人中的这些风险知之甚少，甚至对儿科人群中的这些风险知之甚少 撒哈拉以南非洲地区的情况较少。尽管炎症与 成人艾滋病毒感染者的心血管疾病，炎症对标志物的作用 几乎没有对感染艾滋病毒的儿童进行心血管疾病风险的研究 青少年。此外，非艾滋病合并症的影响可能更大 撒哈拉以南非洲地区，尽管尚未对接受抗逆转录病毒疗法的儿童进行心血管疾病研究 在这个设置下。 拟议的 K23 研究计划的总体目标是使用替代品 心血管疾病标志物可识别感染艾滋病毒的儿童和青少年 早期心脏病并了解这些变化的机制，以便 减少治疗可以有适当的针对性，新的预防策略可能会 未来会得到发展。在一项针对 100 名 HIV 感染青少年和 100 名 HIV 感染者的纵向研究中 健康对照，该项目旨在使用颈动脉内膜中层厚度（cIMT）、脉搏 波速 (PWV) 和胰岛素抵抗可识别 HIV 患者的早期心脏代谢风险 坎帕拉感染艾滋病毒的青少年与年龄和性别匹配的未感染艾滋病毒的对照者进行比较， 乌干达。此外，我们将调查这些心脏代谢的制造者是否 疾病与炎症和肠道完整性的生物标志物相关。这项研究将 全面了解炎症、免疫激活和细菌如何 易位与艾滋病毒感染儿童的心脏代谢疾病有关 青少年。 PI Dirajlal-Fargo 博士是一位杰出的候选人，他正在寻求成为 心脏代谢领域国际公认的临床医生研究员 儿童艾滋病毒的并发症。她还拥有进行临床研究的经验 乌干达。 Dirajlal-Fargo 博士得到凯斯西储大学强有力的机构支持 大学和彩虹婴儿儿童医院儿科。 她将保证 75% 的受保护研究时间并获得丰富的研究成果 确保成功过渡到独立资助的研究者的资源。 她稳健的培训计划包括：1）来自她的主要导师 Dr. 的高质量指导 Grace McComsey，以及免疫学、传染病领域的共同导师 乌干达的艾滋病毒和儿童艾滋病毒的心血管并发症，生物统计学家 以及一群合作者； 2）基础免疫学课程，重点是 慢性艾滋病毒感染； 3）心血管影像和生理学培训； 4）培训 临床研究设计和统计； 5）国际跨学科经验 团队科学； 6) 整合临床护理和研究项目的现场经验。