Gut Integrity and Metabolic Complications in Youth Living with HIV in Uganda

乌干达青年艾滋病毒感染者的肠道完整性和代谢并发症

基本信息

批准号：
10183245
负责人：
Sahera Dirajlal-Fargo
金额：
$ 20.58万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10183245
关键词：
Adipose tissue Adolescent and Young Adult Adult Affect Africa South of the Sahara Age Air Pollution Bacterial Translocation Biological Markers Blood Circulation Cardiovascular Diseases Clinical Clinical Research Complex Complication Cosmetics Country Cross-Sectional Studies Diabetes Mellitus Diet Dual-Energy X-Ray Absorptiometry Eastern Africa Elderly Ensure Environmental Risk Factor FarGo Fatty acid glycerol esters Funding Future Gender Geographic Locations HIV Health Heart Diseases Human Income Inflammation Inflammatory Insulin Resistance International Intestines Knowledge Lead Leaky Gut Link Longitudinal Studies Measures Metabolic Metabolic Diseases Nutritional Obesity Outcome Participant Pathogenicity Pediatric Hospitals Perinatal Physical activity Play Population Population Control Prevention strategy Process Research Research Personnel Residual state Resources Risk Risk Reduction Role Rural Scanning Serum Socioeconomic Factors Socioeconomic Status Southern Africa Surrogate Markers Testing Uganda Universities Viral Visceral Youth antiretroviral therapy burden of illness cardiometabolism cardiovascular disorder risk cardiovascular risk factor co-infection cohort comorbidity design experience immune activation inflammatory marker insight lifestyle factors low and middle-income countries metabolic abnormality assessment microbial mycobiome novel pediatric department pediatric human immunodeficiency virus rural setting social systemic inflammatory response urban setting young adult

项目摘要

Project Summary/Abstract: People living with HIV are at increased risk of cardiovascular and metabolic complications compared to HIV-uninfected control populations. Compared to what is known in older adults, little is known about these risks in adolescents and young adults 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 alteration in gut integrity and environmental factors on metabolic complication has been scarcely investigated in youth living with HIV. Furthermore, the impact of non-AIDS co morbidities may be greater in sub-Saharan Africa, though no studies of metabolic complications have been conducted in youth on ART in this setting. The overall objective of this proposed R21 research plan is to use surrogate markers of gut integrity, microbial translocation and inflammation to understand the mechanisms underlying adiposity and insulin resistance in youth living with HIV, so that risk-reduction therapies can be appropriately targeted and novel preventive strategies may be developed in the future. In a cross-sectional study of 100 adolescents and young adults living with HIV and 100 uninfected controls, this project aims to measure biomarkers of gut integrity and bacterial translocation to identify ongoing evidence of a “leaky gut” in youth living with HIV compared to age and gender match HIV uninfected controls in Kampala, an urban setting, and Gulu, a rural setting Uganda. We will investigate whether these measures of gut integrity and bacterial translocation correlate with metabolic disease using DXA scan to measure adiposity and insulin resistance. Additionally, we will examine the role of environmental, nutritional and socioeconomic factors that may differ between urban and rural settings and their associations with markers of gut integrity and microbial translocation. This study will provide a comprehensive view of how gut integrity, bacterial translocation and inflammation relate to metabolic disease among adolescents and young adults living with HIV and the role that important environmental and social differences play in urban versus rural settings in Uganda. 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 extensive 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 access to a wealth of resources that will ensure a successful transition to independently funded investigator.

项目摘要/摘要：感染艾滋病毒的人的心血管和代谢并发症的风险增加与艾滋病毒未感染的对照群体相比。与老年人已知的相比对于青少年和年轻人的这些风险知之甚少，在撒哈拉以南非洲。尽管炎症已与成人的心血管疾病有关使用艾滋病毒，改变肠道完整性和环境因素对代谢的作用在艾滋病毒的青年中，几乎没有对并发症进行调查。此外，撒哈拉以南非洲的非辅助率可能更大，尽管没有代谢的研究在这种情况下，青年对艺术的并发症发生了。该提出的R21研究计划的总体目标是使用肠道的替代标记完整性，微生物易位和注入以了解基本机制艾滋病毒青年的肥胖性和胰岛素抵抗，因此降低风险疗法可以是将来可能会制定适当的针对性和新颖的预防策略。在对100名青少年和艾滋病毒和100个未感染的年轻人的横断面研究控件，该项目旨在测量肠道完整性和细菌易位的生物标志物与年龄和性别相比，确定艾滋病毒青年的持续证据在坎帕拉（Kampala）和乌干达（Gulu）的古卢（Gulu）中，艾滋病毒未感染的对照组合。我们将研究这些肠道完整性和细菌易位的度量是否相关使用DXA扫描的代谢疾病来测量肥胖和胰岛素抵抗。此外，我们将研究环境，营养和社会经济因素的作用这在城市和粗糙环境之间可能有所不同，及其与肠道标记的关联完整性和微生物易位。这项研究将提供有关肠道如何肠道的全面看法与代谢疾病有关的完整性，细菌易位和炎症青少年和艾滋病毒的年轻人以及重要的环境和重要的作用在乌干达的城市与农村环境中，社会差异发挥了作用。 PI，Dirajlal-Fargo博士是一位杰出的候选人，正在寻求成为一个在心脏代谢并发症领域的国际公认的临床评估剂小儿艾滋病毒。她还拥有在乌干达进行临床研究的丰富经验。 Dirajlal-Fargo博士在Case Western Reserve University和The 彩虹婴儿和儿童医院的儿科系。她将可以访问大量资源将确保成功过渡到独立资助的调查员。