Interventions to improve alcohol-related comorbidities along the gut-brain axis in persons with HIV infection

改善 HIV 感染者沿肠-脑轴的酒精相关合并症的干预措施

• 批准号: 10682449
• 负责人: RONALD A COHEN
• 金额: $ 132.07万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-10 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10682449
• 关键词: Advisory Committees; Affect; Age; Alcohol consumption; Alcohols; Autonomic nervous system; Biological; Biosensor; Brain; Cephalic; Charge; Clinical; Clinical Data; Clinical Research; Clinical Trials; Cognition; Cognitive; Collection; Communities; Data; Data Analytics; Data Science; Data Science Core; Development; Enrollment; Ethnic Origin; Failure; Feedback; Florida; Future; Gender; Goals; Grant; HIV; HIV Infections; HIV-associated cognitive impairment; Health; Hybrids; Impaired cognition; Individual; Inflammation; Infrastructure; Intervention; Leadership; Learning; Link; Machine Learning; Monitor; Morbidity - disease rate; National Institute on Alcohol Abuse and Alcoholism; Nerve; Nervous System; Neurologic; Outcome; Outcome Assessment; Participant; Persons; Phase; Population; Population Heterogeneity; Productivity; Public Health; Quality of life; Race; Randomized; Readiness; Research; Research Activity; Research Infrastructure; Structure; Training Programs; Training Support; Training and Infrastructure; U-Series Cooperative Agreements; Vagus nerve structure; Variant; Work; Wrist; alcohol research; behavior change; brain dysfunction; brain health; brain pathway; clinical trial participant; cognitive function; community engagement; comorbidity; contingency management; cooking; data management; data sharing; drinking; dysbiosis; effective intervention; experience; future implementation; gut bacteria; gut microbiome; gut-brain axis; hazardous drinking; high risk drinking; improved; improved outcome; incentive strategies; individual response; microbial; mortality; neuroimaging; neuroinflammation; payment; prevent; probiotic supplementation; programs; recruit; scale up; success; systemic inflammatory response; transmission process; trial design

As persons living with HIV (PLWH) live longer, approximately 50% will experience HIV-related cognitive dysfunction, which may affect daily activities, contribute to morbidity and mortality, and increase the likelihood of HIV transmission. Alcohol consumption among PLWH may further exacerbate long-term cognitive dysfunction, with the presumed mechanism involving the gut microbiome, microbial translocation, systemic inflammation, and ultimately neuroinflammation. However, there are many gaps in our understanding regarding the specific pathophysiological mechanisms, and a need to offer interventions that are effective and acceptable in helping PLWH to reduce drinking or to protect them against alcohol-related harm. The overarching goal of this P01 is to identify and ultimately implement new/improved, targeted interventions that will improve outcomes related to cognitive and brain dysfunction in persons with HIV who drink alcohol. The proposed P01 activity will extend our current line of research that forms the core of the Southern HIV & Alcohol Research Consortium (SHARC). The specific aims of this P01 are to: 1) improve our understanding of the specific mechanisms that connect the gut microbiome to cognitive and brain health outcomes in persons with HIV; 2) evaluate interventions that are intended to reduce the impact of alcohol on brain and cognitive health in persons with HIV; and 3) connect and extend the research activity from this P01 with the training programs and community engagement activity in the SHARC. Our P01 will utilize two cores that provide infrastructure to two Research Components (RC1, RC2). The two RC will together enroll 200 PLWH with at-risk drinking into clinical trials that share common timepoints and outcome assessments. RC1 will compare two strategies to extend contingency management to 60 days, using breathalyzers and wrist-worn biosensors to monitor drinking. RC2 uses a hybrid trial design to evaluate two biomedical interventions targeting the gut-brain axis. One intervention is a wearable, transcutaneous vagus nerve stimulator that is hypothesized to stimulate the autonomic nervous system, resulting in decreased inflammation and improved cognition. The other intervention is a probiotic supplement intended to improve the gut microbiome in persons with HIV and alcohol consumption. All participants in RC2, and a subset of those in RC1 will have neuroimaging at two timepoints. The Data Science Core will provide data management and analytical support, and will analyze existing data and the data collected from this P01 using a machine learning and AI approach to identify factors associated with intervention success or failure. The Administrative Core will provide scientific leadership, clinical research and recruitment infrastructure, and connection to the outstanding training programs, development opportunities, and community engagement provided by the SHARC. Our community engagement with diverse populations, and collection of acceptability data from clinical trial participants, will facilitate our readiness to scale up the most promising interventions and move towards implementation in the next phase of our research.

随着患有艾滋病毒（PLWH）的人的寿命更长，大约50％会经历与HIV相关的认知 功能障碍可能会影响日常活动，导致发病率和死亡率，并增加可能性 艾滋病毒传播。 PLWH中的饮酒可能会进一步加剧长期认知 功能障碍，具有涉及肠道微生物组，微生物易位，全身性的假定机制 炎症，最终是神经炎症。但是，我们关于 特定的病理生理机制，以及需要提供有效且可接受的干预措施 帮助PLWH减少饮酒或保护其免受与酒精有关的伤害。总体目标 该P01是识别并最终实施新/改进的针对性干预措施，以改善 与艾滋病毒饮酒患者的认知和脑功能障碍有关的结果。拟议的P01 活动将扩展我们当前的研究线，构成南方艾滋病毒和酒精研究的核心 财团（Sharc）。该P01的具体目的是：1）提高我们对特定的理解 将肠道微生物组与艾滋病毒患者中的认知和脑健康结局相关的机制； 2） 评估旨在减少酒精对大脑和认知健康影响的干预措施 艾滋病毒的人； 3）将研究活动从该P01连接并扩展到培训计划以及 Sharc的社区参与活动。我们的P01将利用两个核心，这些核心为两个提供基础设施 研究组件（RC1，RC2）。这两个RC将共同招募200 PLWH，危险饮酒进入临床 具有共同时间点和结果评估的试验。 RC1将比较两种策略来扩展 应急管理到60天，使用呼吸分析仪和腕上的生物传感器来监测饮酒。 RC2 使用混合试验设计来评估针对肠道轴的两种生物医学干预措施。一种干预 是一种可穿戴的经皮神经刺激器，假设刺激自主神经 系统，导致炎症减少和认知改善。另一个干预措施是益生菌 旨在改善艾滋病毒和饮酒患者的肠道微生物组的补充剂。全部 RC2的参与者以及RC1中的一部分将在两个时间点具有神经影像学。数据科学 核心将提供数据管理和分析支持，并将分析现有数据和数据 使用机器学习和AI方法从该P01收集，以识别与 干预成功或失败。行政核心将提供科学领导，临床研究和 招聘基础设施，以及与杰出的培训计划，发展机会的联系， 以及Sharc提供的社区参与。我们社区与不同人群的参与， 并收集临床试验参与者的可接受性数据，将有助于我们准备扩大规模 在我们研究的下一阶段，最有希望的干预措施并朝着实施迈进。