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

项目摘要/摘要： 艾滋病毒携带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。与老年人所知的相比， 对青少年和年轻人中的这些风险知之甚少，在 撒哈拉以南非洲。尽管炎症与成年人的心血管疾病有关 HIV患者肠道完整性改变和环境因素对代谢的影响 对感染艾滋病毒的年轻人的并发症几乎没有进行过调查。此外， 在撒哈拉以南非洲，非艾滋病并存的情况可能会更严重，尽管没有对代谢的研究 在这种背景下，青少年对ART进行了复杂化处理。 这项拟议的R21研究计划的总体目标是使用肠道的替代标记 完整性、微生物易位和炎症，以了解潜在的机制 青年艾滋病毒携带者的肥胖和胰岛素抵抗，以便减少风险治疗 今后可能会制定适当的针对性和新颖的预防战略。在一个 100例青少年HIV感染者和100例非感染者的横断面研究 对照，该项目旨在测量肠道完整性和细菌易位的生物标记物 确定与年龄和性别相比较的青年艾滋病毒携带者“肠道渗漏”的持续证据 与坎帕拉(城市环境)和古鲁(乌干达农村环境)中未感染艾滋病毒的控制措施相匹配。 我们将调查这些衡量肠道完整性和细菌易位的指标是否相关 对于代谢性疾病，使用DXA扫描来测量肥胖和胰岛素抵抗。 此外，我们还将研究环境、营养和社会经济因素的作用。 这可能在城市和农村的环境以及它们与肠道标志的关联中有所不同 完整性和微生物移位。这项研究将提供关于GUT如何 完整性、细菌易位和炎症与代谢性疾病有关 感染艾滋病毒的青少年和青壮年以及重要的环境和 在乌干达，社会差异在城乡环境中发挥着作用。 PI，Dirajlal-Fargo博士，是一位特殊的候选人，他正在寻求成为一名 国际公认的心脏代谢并发症领域的临床医生和研究员 儿科艾滋病毒。她还拥有在乌干达进行临床研究的丰富经验。 Dirajlal-Fargo博士得到了凯斯西储大学和 彩虹婴幼儿医院儿科。她将有权访问 丰富的资源，将确保成功过渡到独立资助的调查员。

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.