Safety and Effectiveness of Medications for Alcohol Use Disorder among HIV+/-

HIV 酒精使用障碍药物的安全性和有效性 /-

• 批准号: 10686388
• 负责人: E. Jennifer Edelman
• 金额: $ 53.08万
• 依托单位: YALE UNIVERSITY
• 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/10686388
• 关键词: Address; Adoption; Adverse event; Aging; Alcohol consumption; Alcoholic Liver Diseases; Alcohols; Artificial Intelligence; Baclofen; Big Data; Biological; CD4 Lymphocyte Count; Cirrhosis; Clinical Pharmacists; Clinical Trials; Collaborations; Communication; Complex; Coupled; Data; Data Analytics; Disulfiram; Effectiveness; Electronic Health Record; Evaluation; Event; Exposure to; FDA approved; Family; Genes; Genetic; Genetic Epistasis; Genetic Variation; Goals; HIV; Health Personnel; Health behavior; Healthcare; Individual; Injury; Intervention; Intervention Studies; Link; Liver; Liver diseases; Mediating; Metformin; Methods; Morbidity - disease rate; Naltrexone; National Institute on Alcohol Abuse and Alcoholism; Older Population; Outcome; Patients; Persons; Pharmaceutical Preparations; Pharmacists; Pharmacy facility; Physiological; Pilot Projects; Pioglitazone; Polypharmacy; Prazosin; Productivity; Provider; Recording of previous events; Risk; Risk Assessment; Safety; Series; Spironolactone; Systems Biology; Time; United States Food and Drug Administration; Variant; Verapamil; Veterans Health Administration; Viral Load result; acamprosate; adverse outcome; alcohol abuse therapy; alcohol intervention; alcohol research; alcohol use disorder; artificial intelligence method; biomarker evaluation; candidate identification; cohort; comparative effectiveness study; data cleaning; drinking; drug repurposing; electronic health data; frailty; gabapentin; gene network; genetic element; genetic variant; genome-wide; improved; indexing; innovation; liver injury; medication safety; mortality; novel; organ injury; personalized medicine; pilot trial; pre-clinical; programs; protective effect; racial diversity; random forest; reduced alcohol use; routine care; treatment response; uptake

HARP PROJECT 2 SUMMARY Although rarely addressed by HIV healthcare providers, alcohol use disorder (AUD) is a major cause of morbidity and mortality among people aging with HIV (PAH). There are only three Food and Drug Administration-approved medications for AUD and these have had limited acceptability and uptake for several reasons. HIV providers are unfamiliar with AUD medications and reticent to add an unfamiliar medication in the complex context of pre-existing polypharmacy and physiologic frailty. Even in less complex contexts, the effectiveness of these medications is modest on average, likely due in part to variations in genetic liability. Further, despite PAH’s excess liability for hepatic injury from alcohol-associated liver disease (AALD), we lack medications to mitigate this injury. As more people are aging with HIV and they continue to drink alcohol, there is growing need to identify and evaluate candidate AUD and AALD medications that will be safe and effective in the context of polypharmacy and physiologic frailty. Analyses of large scale, real-world data may help us identify and evaluate candidate medications for repurposing (i.e., medications commonly used for other purposes that may also decrease drinking or hepatic injury). Building on our strong collaborative history and supported by the larger HIV and Alcohol Research center focused on Polypharmacy (HARP) Program, we will apply innovative approaches to enhance timely discovery and initial evaluation of candidate repurposed medications for AUD and AALD. In Aim 1 we apply Explainable Artificial Intelligence methods and systems biology to data from the national Veterans Administration Healthcare (VA) electronic health record linked to genetic data and public data to identify candidate repurposed AUD and AALD medications in the context of gene networks, which may provide mechanistic details at the biological level. In Aim 2 we use data from the well-characterized VA family of cohorts encompassing >60,000 PAH and millions of uninfected controls, to conduct propensity score matched analyses to examine the safety and effectiveness of four candidate medications (prazosin, pioglitazone, and verapamil for AUD and metformin for AALD) among PAH and uninfected individuals. In Aim 3, informed by these analyses, our prior alcohol interventions in HIV treatment settings, and in collaboration with the Risk Communication and Administrative/Data Analytic Cores, we will conduct three pilot studies employing clinical pharmacist-delivered personalized risk messaging and identified candidate medications to generate time sensitive data on the feasibility, acceptability, and efficacy of these medications to address AUD or AALD. Together, these studies will collectively expedite the pipeline from discovery to evaluation of novel medications to address AUD and AALD among PAH.

竖琴项目2总结