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.

随着艾滋病毒感染者 (PLWH) 寿命的延长，大约 50% 的人会经历与艾滋病毒相关的认知 功能障碍，可能影响日常活动，导致发病率和死亡率，并增加可能性 艾滋病毒传播。感染者饮酒可能进一步加剧长期认知障碍 功能障碍，推测机制涉及肠道微生物组、微生物易位、全身性 炎症，最终是神经炎症。然而，我们对这方面的认识还存在很多差距。 具体的病理生理机制，以及提供有效且可接受的干预措施的必要性 帮助感染者减少饮酒或保护他们免受酒精相关伤害。总体目标是 这个 P01 是确定并最终实施新的/改进的、有针对性的干预措施，以改善 与饮酒的艾滋病毒感染者的认知和大脑功能障碍相关的结果。拟议的P01 活动将扩展我们目前的研究范围，构成南方艾滋病毒和酒精研究的核心 联盟（SHARC）。本 P01 的具体目标是： 1）提高我们对具体问题的理解 将肠道微生物组与艾滋病毒感染者的认知和大脑健康结果联系起来的机制； 2） 评估旨在减少酒精对大脑和认知健康影响的干预措施 艾滋病毒感染者； 3) 将本 P01 的研究活动与培训计划联系起来并加以扩展， SHARC 的社区参与活动。我们的 P01 将利用两个核心，为两个核心提供基础设施 研究组件（RC1、RC2）。两个RC将共同招募200名有饮酒危险的艾滋病病毒感染者进入临床 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 60 天的应急管理，使用呼吸分析仪和腕戴式生物传感器来监测饮酒情况。 RC2 使用混合试验设计来评估两种针对肠脑轴的生物医学干预措施。一次干预 是一种可穿戴的经皮迷走神经刺激器，假设可以刺激自主神经 系统，从而减少炎症并提高认知能力。另一种干预措施是益生菌 旨在改善艾滋病毒感染者和饮酒者的肠道微生物组的补充剂。全部 RC2 中的参与者和 RC1 中的一部分参与者将在两个时间点进行神经影像检查。数据科学 Core将提供数据管理和分析支持，并对现有数据和数据进行分析 使用机器学习和人工智能方法从 P01 中收集数据，以确定与 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，以及与优秀培训计划、发展机会的联系， 以及 SHARC 提供的社区参与。我们的社区与不同人群的互动， 以及从临床试验参与者那里收集可接受性数据，将有助于我们做好扩大规模的准备 最有希望的干预措施，并在我们下一阶段的研究中迈向实施。