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

随着艾滋病毒携带者(PLWH)寿命的延长，大约50%的人将经历与艾滋病毒相关的认知 功能障碍，这可能会影响日常活动，导致发病率和死亡率，并增加 艾滋病病毒传播的可能性。PLWH人群饮酒可能会进一步加剧长期认知 功能障碍，推测的机制涉及肠道微生物群，微生物易位，全身 炎症，最终是神经性炎症。然而，我们对这一问题的认识还存在许多差距。 具体的病理生理机制，以及提供有效和可接受的干预措施的必要性 帮助PLWH减少饮酒或保护他们免受与酒精有关的伤害。的首要目标是 本P01将确定并最终实施新的/改进的、有针对性的干预措施，这些干预措施将会改善 与饮酒的艾滋病毒携带者的认知和大脑功能障碍有关的结果。建议的P01 活动将扩展我们目前的研究路线，形成南方艾滋病毒和酒精研究的核心 财团(SHARC)。本P01的具体目的是：1)提高我们对具体情况的理解 HIV感染者肠道微生物群与认知和大脑健康结果之间的联系机制；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的研究活动与培训方案和 SHARC中的社区参与活动。我们的P01将使用两个内核，为两个 研究组成部分(RC1、RC2)。两个RC将总共招募200名有风险饮酒的PLWH进入临床 共享共同时间点和结果评估的试验。Rc1将比较两种扩展策略 应急管理时间延长至60天，使用呼气测定仪和手腕佩戴的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道-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，被假设为刺激自主神经 系统，从而减少炎症和改善认知。另一种干预是益生菌 旨在改善艾滋病毒携带者和饮酒者肠道微生物群的补充剂。全 RC2组和RC1组的参与者将在两个时间点进行神经成像。数据科学 CORE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P01收集，以识别与以下因素相关的因素 干预的成败。行政核心将提供科学领导、临床研究和 招聘基础设施，以及与优秀培训方案、发展机会、 和SHARC提供的社区参与。我们的社区与不同的人群接触， 和从临床试验参与者那里收集可接受性数据，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.