Trial of Human Milk Oligosaccharide-based synbiotics for HIV-exposed uninfected children

基于母乳寡糖的合生元对暴露于艾滋病毒的未感染儿童的试验

• 批准号: 10414997
• 负责人: Rupak Shivakoti
• 金额: $ 64.34万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10414997
• 关键词: Address; Africa South of the Sahara; Age; Area; Biological; Biological Factors; Breast Feeding; Breastfed infant; Child; Clinical; Counseling; Fermentation; Growth; HIV; HIV Infections; HIV-exposed uninfected infant; Health; High Prevalence; Human Milk; Infant; Inflammation; Inflammatory; Intervention; Intervention Trial; Lead; Mediating; Metabolic Pathway; Metabolism; Morbidity - disease rate; Mothers; Observational Study; Oligosaccharides; Outcome; Pathway interactions; Pharmaceutical Preparations; Placebos; Population; Prevalence; Probiotics; Randomized; Research; Risk; Rural; Sampling; South Africa; Testing; Time; Vertical Disease Transmission; Visit; Volatile Fatty Acids; Woman; adverse outcome; antiretroviral therapy; arm; base; child bearing; cohort; comparison group; experience; follow-up; gut microbiota; health disparity; high risk; improved; infant gut microbiome; infant outcome; inflammatory marker; microbiome; microbiome composition; microbiota; mortality; mortality risk; novel; optimism; pandemic disease; prevent; randomized placebo controlled trial; randomized trial; recruit; rural South Africa; social factors; socioeconomics; success; transmission process

Project Summary HIV-exposed uninfected (HEU) infants have higher rates of mortality, infectious morbidity and growth deficits compared to HIV-unexposed uninfected (HUU) infants despite the success of maternal antiretroviral therapy (ART) in reducing vertical transmission. Our group has observed that human milk oligosaccharide (HMO) composition of breastmilk, and its relationships to the infant gut microbiome maturity and composition, may account for some of the increased risks seen in HEU infants. Currently, no specific interventions have been shown to correct for disparities in health outcomes experienced by HEU infants. To address this gap, we propose a proof-of-concept, randomized, placebo-controlled trial of a synbiotic in breast-fed HEU infants. The synbiotic is composed of 2'-fucosyllactose (2'FL) HMO and B. infantis probiotic. 2'FL is associated with reductions in mortality, infectious morbidity and growth deficits. B. infantis is included to support 2'FL fermentation and thereby maximize benefits from the 2'FL intervention. We will randomize 120 breast-fed HEU infants at 4 weeks of age 1:1 to receive synbiotic or placebo through 24 weeks of age, with a follow-up through 48 weeks of age. We will also recruit 60 breast-fed HUU infants as a comparator group and they will be followed for the same duration with no intervention. This study will be conducted in rural South Africa, in a region with high maternal HIV prevalence and high rates of infectious morbidity and growth deficits in infants. In specific aim 1, we will evaluate whether the synbiotic i) reduces infectious morbidity and growth faltering, and ii) influences biological pathways related to infant gut microbiome, metabolism, and inflammation while the intervention is in place during the first 24 weeks of age. In specific aim 2, we will evaluate whether effects persist after the intervention is discontinued through 48 weeks of age. Specific aim 3 will compare HEU and HUU cohorts and investigate biological pathways associated with infectious morbidity and growth. Overall, we hypothesize that the synbiotic will reduce infectious morbidity and improve growth in HEU infants. Our study will provide novel information on whether some of the excess risks in HEU infants can be ameliorated through interventions targeting breastfeeding-mediated microbiome and inflammatory pathways.

项目摘要 未感染艾滋病毒(HEU)的婴儿死亡率、感染性发病率和生长缺陷较高 尽管母亲抗逆转录病毒治疗成功，但与未接触艾滋病毒的未感染(HUU)婴儿相比 (ART)在减少垂直传播方面。我们小组观察到，人乳低聚糖(HMO) 母乳的组成及其与婴儿肠道微生物组成熟度和组成的关系可能 这是导致HEU婴儿患病风险增加的部分原因。目前，还没有具体的干预措施 被证明纠正了HEU婴儿经历的健康结果的差异。为了解决这一差距，我们 建议一项概念验证、随机、安慰剂对照试验，用于母乳喂养的HEU婴儿中的合生元。这个 合生素由2‘-岩藻糖基乳糖(2’FL)HMO和婴儿芽孢杆菌益生菌组成。2‘FL与 减少死亡率、传染病发病率和增长赤字。B.包括婴儿以支持2‘FL 发酵，从而最大限度地受益于2‘FL干预。我们将随机选择120名母乳喂养的HEU 4周龄1：1的婴儿接受联合生物制剂或安慰剂治疗至24周龄，并进行随访 48周大。我们还将招募60名母乳喂养的HUU婴儿作为对照组，他们将 在相同的持续时间内，不进行任何干预。这项研究将在南非农村地区进行， 该区域产妇艾滋病毒感染率高，婴儿感染率和生长缺陷发生率高。 在具体目标1中，我们将评估合生元I)是否减少感染发病率和生长停滞， 和ii)影响与婴儿肠道微生物群、新陈代谢和炎症有关的生物途径，而 干预措施在出生后头24周内到位。在具体目标2中，我们将评估 持续到48周后停止干预。具体目标3将比较高浓缩铀和 Huu对与感染发病率和生长相关的生物学途径进行了研究。总体而言，我们 假设合生元将降低感染发病率并改善HEU婴儿的生长发育。我们的研究 将提供新的信息，说明是否可以通过以下方式改善HEU婴儿的一些额外风险 针对母乳喂养介导的微生物和炎症途径的干预。