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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.

项目概要/摘要：艾滋病毒感染者患心血管和代谢并发症的风险增加与未感染艾滋病毒的对照人群相比。与已知的老年人相比，对青少年和年轻人的这些风险知之甚少，撒哈拉以南非洲尽管炎症与成人心血管疾病有关在HIV感染者中，肠道完整性的改变和环境因素对代谢的影响，在感染艾滋病毒的青年中，几乎没有对并发症进行调查。此外，在撒哈拉以南非洲，非艾滋病合并症可能更高，尽管没有关于代谢的研究，在这种情况下，对年轻人进行了抗逆转录病毒治疗。这项拟议的R21研究计划的总体目标是使用肠道的替代标志物，完整性，微生物易位和炎症，以了解潜在的机制肥胖症和胰岛素抵抗的艾滋病毒感染者的青年，使降低风险的治疗，今后可能会制定有适当针对性的新的预防战略。中对100名感染艾滋病毒的青少年和年轻人以及100名未感染者进行的横断面研究对照，该项目旨在测量肠道完整性和细菌移位的生物标志物，确定与年龄和性别相比，青年艾滋病毒感染者“肠漏”的持续证据与乌干达城市地区坎帕拉和农村地区古卢的艾滋病毒未感染对照组相匹配。我们将研究这些肠道完整性和细菌移位的指标是否相关用DXA扫描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城市和农村环境之间可能存在差异，完整性和微生物移位。这项研究将提供一个全面的观点，如何肠道完整性、细菌移位和炎症与代谢性疾病相关感染艾滋病毒的青少年和青年以及环境和社会差异在乌干达城乡环境中发挥作用。 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并发症领域的临床研究者，儿科艾滋病她在乌干达进行临床研究也有丰富的经验。 Dirajlal-Fargo博士得到了凯斯西储大学和彩虹婴儿和儿童医院儿科。她将有机会获得丰富的资源，将确保成功过渡到独立资助的调查。