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%的人将经历与艾滋病毒相关的认知