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

• 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
• 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

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： 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， 人们对青少年和年轻人的这些风险知之甚少，在以下情况下更是知之甚少： 尽管炎症与成人心血管疾病有关。 对于艾滋病毒，肠道完整性的改变和环境因素对代谢的作用 此外，还很少研究感染艾滋病毒的青少年的并发症。 撒哈拉以南非洲地区的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，已经在接受 ART 的青少年中进行了并发症治疗。 拟议的 R21 研究计划的总体目标是使用肠道替代标记 完整性、微生物易位和炎症，以了解其背后的机制 艾滋病毒感染者的肥胖和胰岛素抵抗，因此可以采取降低风险的治疗 未来可能会制定有针对性的新颖预防策略。 对 100 名艾滋病毒感染者和 100 名未感染者进行的横断面研究 控制，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，确定感染艾滋病毒的青少年存在“肠漏”的持续证据 与乌干达城市坎帕拉和农村地区古卢的艾滋病毒未感染对照相匹配。 我们将研究这些肠道完整性和细菌易位的测量是否相关 使用 DXA 扫描来测量肥胖和胰岛素抵抗的代谢疾病。 此外，我们将研究环境、营养和社会经济因素的作用 城市和农村环境及其与肠道标志物的关系可能有所不同 这项研究将提供肠道如何变化的全面视图。 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年轻人以及重要的环境和 乌干达城市和农村地区存在社会差异。 PI Dirajlal-Fargo 博士是一位杰出的候选人，他正在寻求成为一名 心脏代谢并发症领域国际公认的临床医生研究员 她还拥有在乌干达开展临床研究的丰富经验。 Dirajlal-Fargo 博士得到了凯斯西储大学和 她将可以前往彩虹婴儿和儿童医院的儿科。 丰富的资源将确保成功过渡到独立资助的调查人员。

项目成果

Increased monocyte and T-cell activation in treated HIV+ Ugandan children: associations with gut alteration and HIV factors.

接受艾滋病毒治疗的乌干达儿童单核细胞和 T 细胞活化增加：与肠道改变和艾滋病毒因素的关联。

• 发表时间: 2020
• 作者: Dirajlal;Albar, Zainab;Bowman, Emily;Labbato, Danielle;Sattar, Abdus;Karungi, Christine;Nazzinda, Rashida;Funderburg, Nicholas;Kityo, Cissy;Musiime, Victor;McComsey, Grace A
• 通讯作者: McComsey, Grace A

Cardiometabolic Complications in Youth With Perinatally Acquired HIV in the Era of Antiretroviral Therapy.

抗逆转录病毒治疗时代围产期感染艾滋病毒的青少年的心脏代谢并发症。

• 发表时间: 2021
• 影响因子: 4.6
• 作者: Dirajlal;McComsey, Grace A
• 通讯作者: McComsey, Grace A

Factors associated with insulin resistance in a longitudinal study of Ugandan youth with and without HIV.

对感染和未感染艾滋病毒的乌干达青年进行的纵向研究中与胰岛素抵抗相关的因素。

• 发表时间: 2024-02-01
• 作者: Dirajlal;Strah, Monika;Ailstock, Kate;Sattar, Abdus;Karungi, Christine;Nazzinda, Rashidah;Funderburg, Nicholas;Kityo, Cissy;Musiime, Victor;McComsey, Grace A
• 通讯作者: McComsey, Grace A