Metabolic impact of ART on women living with HIV and their infants

ART 对艾滋病毒感染者及其婴儿的代谢影响

• 批准号: 10527632
• 负责人: Jim Aizire
• 金额: $ 39.99万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10527632
• 关键词: Address; Adult; Affect; Africa South of the Sahara; Appetite Regulation; Appetite Stimulants; Biological; Body Composition; Body Weight; Body Weight decreased; Breastfed infant; Conduct Clinical Trials; Control Groups; Data; Desire for food; Dietary Fiber; Dual-Energy X-Ray Absorptiometry; Energy Intake; Energy Metabolism; Enrollment; Expenditure; Fatty acid glycerol esters; Formulation; Future; Gold; Growth; HIV; HIV-exposed uninfected infant; Health; Infant; Intake; Integrase; Intervention; Investigation; Knowledge; Lactation; Length; Limb structure; Link; Maternal Physiology; Measures; Metabolic; Metabolic Pathway; Mothers; Obesity; Outcome; Overweight; Peptides; Persons; Phenotype; Physiological; Physiology; Population; Postpartum Period; Postpartum Women; Pregnancy; Probiotics; Prospective cohort study; Questionnaires; Randomized; Regimen; Regulation; Research; Resistance; Risk; Special Population; Therapeutic; Thinness; Time; Treatment Protocols; Uganda; Universities; Volatile Fatty Acids; Weight; Weight Gain; Woman; adverse birth outcomes; antiretroviral therapy; base; clinical research site; clinically significant; cohort; comorbidity; dietary; disorder risk; doubly-labeled water; efavirenz; high risk; improved; increased appetite; inhibitor; insight; maternal risk; metabolic profile; metabolome; microbiome; non-nucleoside reverse transcriptase inhibitors; peptide hormone; pill; postpartum weight; prospective; scale up; standard of care

Project Summary People living with HIV in Sub-Saharan Africa and elsewhere have weight gain with integrase strand transfer inhibitor (INSTI)-based treatment regimens. Weight gain with Dolutegravir (DTG), an INSTI, has also been observed in postpartum women although how DTG-regimens affects postpartum weight is not known. Understanding the impact of maternal DTG-regimens on the physiology of postpartum body weight regulation has clinical significance as postpartum weight retention is known to increase future maternal risk of overweight, obesity and non-communicable diseases (NCD). With the ongoing scale-up of DTG in Sub-Saharan Africa for HIV management, our understanding of how DTG regimens affect the physiology of postpartum body weight regulation could help identify potential interventions to reduce future overweight and NCD risk in this population. To address this research gap, in aim 1 of this study, we propose to initiate a prospective cohort study in Uganda of postpartum women with HIV on DTG and non-DTG based regimens, as well as a control group without HIV. In this cohort, we will study how DTG-regimens, as compared to non-DTG regimens or women without HIV, affects the macro-phenotype (i.e. energy intake and expenditure) and micro-phenotype (i.e. metabolic profile) of the physiology of body weight regulation in postpartum women. Metabolic profile includes assessment of orexigenic and anti-orexigenic peptides and hormones, short-chain fatty acids, and unbiased `omics' approaches. Aim 2 of this study will leverage the postpartum cohort to also follow their breastfeeding infants for similar investigations of how maternal DTG-regimens affects infant energy intake, expenditure and metabolic profile. Further, by comparing to infants born to mothers without HIV, our study will help us understand the physiology of growth deficits observed in infants born to mothers with HIV (and on non-DTG regimens), one of the most clinically significant outcomes in this population; and to understand whether DTG impacts are similar to other ARTs. Our overall hypothesis is that maternal DTG-based ART regimens will result in increased maternal and infant energy intake, with increased appetite and a dysregulated metabolic profile. Through these two aims, we address an urgent need to understand how maternal HIV and DTG impacts the physiology of body weight regulation in postpartum women and their HIV-exposed uninfected (HEU) infants. These maternal-infant populations have a unique physiological profile with increased energy demands on the lactating mother and breastfeeding infant to sustain growth. In addition to improving our understanding of the physiology, our detailed metabolic assessments will further help identify potential therapeutics (e.g. related to intake/appetite, expenditure, or metabolic pathways) for management of postpartum weight and infant growth in maternal-infant populations with HIV.

项目概要 撒哈拉以南非洲和其他地区的艾滋病毒感染者因整合酶链转移而体重增加 基于抑制剂（INSTI）的治疗方案。多替拉韦 (DTG)（一种 INSTI）的体重增加也已被证实 尽管 DTG 方案如何影响产后体重尚不清楚，但在产后妇女中观察到了这一情况。 了解母亲 DTG 方案对产后体重调节生理学的影响 具有临床意义，因为众所周知，产后体重滞留会增加未来母亲超重的风险， 肥胖和非传染性疾病（NCD）。随着 DTG 在撒哈拉以南非洲地区的不断扩大 HIV 管理，我们对 DTG 方案如何影响产后体重生理学的理解 监管可以帮助确定潜在的干预措施，以减少该人群未来的超重和非传染性疾病风险。 为了弥补这一研究空白，在本研究的目标 1 中，我们建议在乌干达启动一项前瞻性队列研究 接受 DTG 和非 DTG 治疗方案的感染 HIV 的产后妇女，以及未感染 HIV 的对照组。 在这个队列中，我们将研究 DTG 方案与非 DTG 方案或没有 HIV 的女性相比如何 影响宏观表型（即能量摄入和支出）和微观表型（即代谢特征） 产后妇女体重调节的生理学。代谢概况包括评估 促进食欲和抗食欲肽和激素、短链脂肪酸和公正的“组学” 接近。这项研究的目标 2 将利用产后队列来跟踪母乳喂养的婴儿 关于母亲 DTG 方案如何影响婴儿能量摄入、消耗和代谢的类似研究 轮廓。此外，通过与没有感染艾滋病毒的母亲所生的婴儿进行比较，我们的研究将帮助我们了解 在感染 HIV 的母亲（以及采用非 DTG 方案）所生婴儿中观察到的生长缺陷的生理学，其中之一 该人群中最具临床意义的结果；并了解 DTG 影响是否相似 到其他艺术。我们的总体假设是，基于 DTG 的孕产妇 ART 方案将导致孕产妇死亡率增加 和婴儿能量摄入，食欲增加和代谢失调。通过这两个目标， 我们迫切需要了解孕产妇 HIV 和 DTG 如何影响体重生理学 对产后妇女及其暴露于艾滋病毒的未感染（HEU）婴儿的监管。这些母婴 人群具有独特的生理特征，对哺乳期母亲的能量需求增加， 母乳喂养婴儿以维持生长。除了提高我们对生理学的理解之外，我们详细的 代谢评估将进一步帮助确定潜在的治疗方法（例如与摄入量/食欲相关， 支出或代谢途径）用于管理母婴产后体重和婴儿生长 艾滋病毒感染者。