2/2 Alcohol associated Comorbidities and Microbiome Evaluation in HIV (ACME HIV)

2/2 HIV 中酒精相关合并症和微生物组评估 (ACME HIV)

• 批准号: 9408298
• 负责人: SHIRISH S BARVE
• 金额: $ 67.38万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-22 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9408298
• 关键词: Address; Adverse effects; Alcohol abuse; Alcohol consumption; Alcoholic beverage heavy drinker; Alcohols; Automobile Driving; Bacteria; Bacterial Genes; Behavior assessment; Biodiversity; Biological Markers; Brain; Chronic; Clinical; Cognition; Cognitive; Cohort Analysis; Cohort Studies; Collection; Comorbidity; Data; Development; Endotoxemia; Enrollment; Evaluation; Evaluation Studies; Florida; Functional disorder; Funding; Goals; HIV; HIV Infections; HIV-1; Heavy Drinking; Immune; Impaired cognition; Impairment; Individual; Infection; Inflammation; Inflammatory; Intervention; Intestines; Link; Longitudinal Studies; Measures; Neurobiology; Neurocognitive; Neurocognitive Deficit; Outcome; Participant; Pathogenesis; Pathogenicity; Pathologic; Peripheral; Permeability; Phylogeny; Prospective cohort study; Recruitment Activity; Research; Resolution; Resources; Role; Sample Size; Shotguns; Structure; Taxonomy; Testing; Virulence Factors; alcohol effect; alcohol measurement; alcohol research; clinically relevant; cognitive function; cognitive performance; cognitive testing; combinatorial; contingency management; cooking; drinking; gut microbiome; gut microbiota; immune activation; improved; metagenomic sequencing; microbial; microbial community; microbiome; microbiota; motivational enhancement therapy; neuroimaging; neuroinflammation; outcome prediction; payment; preclinical study; prospective; rRNA Genes; relating to nervous system; response; targeted treatment; whole genome

Heavy alcohol drinking and HIV-1 infection are independently associated with the development of abnormalities in the brain function and cognition, and increasing evidence indicates that the combinatorial effects of HIV infection and alcohol are likely to worsen these abnormalities. Significantly, both HIV- 1 infection and chronic alcohol abuse cause alterations in gut microbiome (dysbiosis) and increase intestinal permeability and microbial translocation (MT) which are major pathogenic factors driving local and systemic inflammation. The dysbiosis is characterized by loss of gut bacterial biodiversity, a reduction in beneficial bacteria, and/or an expansion of harmful or pro-inflammatory bacteria. However, there is limited understanding of (i) the interactive effects of heavy alcohol drinking and HIV-1 infection on gut dysbiosis and (ii) the longitudinal qualitative (microbial membership) and quantitative (relevant abundance) determinants of dysbiosis. The current proposal addresses these gaps with an overall goal to promote the development of rational therapies targeting gut dysbiosis. Accordingly, we pursue a unifying hypothesis that in HIV-infected individuals, heavy alcohol use compounds gut dysbiosis and consequent peripheral immune inflammation leading to exacerbation of neuro- inflammation and cognitive dysfunction. To test these hypotheses, we will enroll 100 HIV+ participants from “30-to-90-day challenge” Florida SHARC study (AA020797). This is a funded prospective cohort study in which enrolled heavy drinkers are challenged to stop drinking for 30 to 90 days, assisted by contingency management (CM) payments and motivational interviewing. This application, Alcohol associated Comorbidities and Microbiome Evaluation in HIV (ACME HIV 2/2) leverages the existing resources of “30-to-90-day challenge” Florida SHARC study: participant recruitment, measures of alcohol consumption, biospecimen and biomarker collection; expertise in alcohol, HIV and neuroimaging. New data include: longitudinal changes in gut dysbiosis, correlative changes in peripheral inflammation, and measures of cognition and neuroinflammation. In response to RFA-AA-17-014, we will partner with the St. PETER HIV study (ACME HIV 1/2) to corroborate our findings in Aims 1 and 2 and to conduct combined cross-cohort analyses. We will complete the following Specific Aims among HIV+ heavy drinkers: AIM 1: To assess longitudinal qualitative and quantitative changes in the gut microbiome (dysbiosis) associated with very heavy alcohol consumption. AIM 2: To determine the impact of HIV infection and alcohol abuse induced gut dysbiosis on intestinal permeability, microbial translocation (MT), and resultant peripheral endotoxemia, immune activation and inflammation. AIM 3: To investigate the impact of dysbiosis and peripheral inflammation on development of neuro-inflammation and cognitive function. Completion of these aims will lay groundwork for an intervention targeting alcohol-associated dysbiosis, which could profoundly reduce inflammation and improve cognitive functions in HIV+ heavy drinkers.

大量饮酒和HIV-1感染与艾滋病的发展独立相关