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

随着艾滋病毒感染者（PLWH）寿命的延长，大约50%的人将经历与艾滋病毒相关的认知障碍。 功能障碍，可能影响日常活动，导致发病率和死亡率，并增加 艾滋病病毒的传播。PLWH中的酒精消费可能会进一步加剧长期认知 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，我们对以下问题的理解存在许多差距： 具体的病理生理机制，以及需要提供有效和可接受的干预措施 帮助PLWH减少饮酒或保护他们免受与酒精相关的伤害。的首要目标 本P01旨在确定并最终实施新的/改进的、有针对性的干预措施， 结果与饮酒的HIV感染者的认知和脑功能障碍有关。建议P01 活动将扩展我们目前的研究路线，形成了南方艾滋病毒和酒精研究的核心 财团（SHARC）。本P01的具体目标是：1）提高我们对特定 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;以及3）将P01的研究活动与培训计划联系起来并加以扩展， 在SHARC的社区参与活动。我们的P01将利用两个内核，为两个 研究组件（RC 1、RC 2）。两个RC将共同招募200名有饮酒风险的PLWH进入临床 具有共同时间点和结局评估的试验。RC 1将比较两种策略， 应急管理到60天，使用呼气测醉器和腕戴式生物传感器监测饮酒情况。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。一次发言 是一种可穿戴的经皮迷走神经刺激器，假设其刺激自主神经 系统，从而减少炎症和改善认知。另一种是益生菌 补充剂旨在改善HIV和酒精消费者的肠道微生物组。所有 RC 2中的参与者和RC 1中的一部分参与者将在两个时间点进行神经成像。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 使用机器学习和人工智能方法从该P01中收集，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，并连接到优秀的培训计划，发展机会， 以及SHARC提供的社区参与。我们与不同人群的社区接触， 以及从临床试验参与者中收集可接受性数据，将有助于我们准备扩大 最有希望的干预措施，并在我们的研究的下一阶段走向实施。

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.