Reducing Heavy Drinking to Optimize HIV/AIDS Treatment and Prevention

减少酗酒以优化艾滋病毒/艾滋病的治疗和预防

基本信息

批准号：
7943140
负责人：
Lynn Elizabeth Fiellin
金额：
$ 75.09万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7943140
关键词：
AIDS prevention AIDS/HIV problem Address Adherence Adverse effects Affect Alcohol abuse Alcohol consumption Alcohols Area Behavior Therapy Behavioral Biological Assay CD4 Lymphocyte Count Caring Clinic Collection Controlled Clinical Trials Counseling Data Data Analyses Dependence Detection Development Disease Disease Progression Double-Blind Method Drug Formulations Frequencies Funding Goals HIV HIV drug resistance Heavy Drinking Hepatic Hepatotoxicity Highly Active Antiretroviral Therapy Immune system Immunologic Markers Individual Injury Intention Intervention Studies Lead Liver Liver Function Tests Measures Medical Medication Management Minor Mutation Naltrexone National Institute on Alcohol Abuse and Alcoholism Oral Outcome Outcome Study Patients Pharmaceutical Preparations Pharmacotherapy Pharmacy facility Placebo Control Placebos Prevention Provider RNA Randomized Reporting Research Research Personnel Risk Risk-Taking Role Sampling Series Site Substance Use Disorder Techniques Training Variant Viral Viral Markers Woman addiction brief intervention comparative efficacy drinking effective therapy evidence base experience follow-up immune function improved medication compliance meetings men novel patient population placebo controlled study primary care setting public health relevance response sex risk therapy adherence therapy design transmission process treatment effect

项目摘要

DESCRIPTION (provided by applicant): Few treatments have been evaluated to reduce the impact of heavy drinking, alcohol abuse and dependence on HIV-infected patients. These levels of alcohol consumption are associated with decreased adherence to highly active antiretroviral therapy (HAART), an increased likelihood of viral mutations, enhanced disease progression, promotion of liver injury, and increased sexual risk taking. Naltrexone, when combined with counseling, is an effective treatment for heavy drinking, alcohol abuse and dependence yet there are no data on its use or efficacy in HIV-infected patients. The proposed study compares naltrexone to placebo in a 24- week randomized double-blind placebo-controlled clinical trial in HAART-non-adherent HIV-infected patients with heavy drinking, alcohol abuse or dependence (N=154 ) in an HIV clinic. To determine the long-term impact of treatment, all patients will undergo follow-up at 9 and 12 months. Patients randomized to naltrexone will initially receive the oral daily formulation and, if tolerated, will be transferred to the monthly extended release formulation. All patients will receive the counseling platform of Medication Management (MM) combined with Medication Coaching (MC) (MM/MC). MM/MC is a compound manualized treatment intended to approximate the type of treatment that would be suitable for implementation in an HIV primary care setting. It focuses on reducing heavy drinking (MM) and improving medication adherence (MC) through a series of brief interventions delivered by a medically trained provider. Data analyses will be conducted on the intention to treat sample of patients randomly assigned to receive naltrexone + MM/MC versus placebo + MM/MC. The primary study outcome is adherence to HAART medications. Secondary study outcomes include frequency of heavy drinking, HIV viral mutations (using standard assays and ultra-deep sequencing), change in CD4 lymphocyte counts and HIV RNA, alcohol-HAART hepatotoxicity, and sexual risk behaviors. The novel aspects of this proposal include: 1) Integrated on-site alcohol and HIV treatment; 2) The use of extended release naltrexone which is likely to improve adherence in this patient population for whom medication adherence is challenging; 3) The use of several measures for HAART adherence including pharmacy refill data; 4) The use of sophisticated techniques for examining the development of new viral mutations including the detection of new minor variants; and 5) Collection of detailed data on the hepatic effects of treatment. The proposed study, conducted by an experienced team of HIV and addiction researchers, will help define the role of naltrexone and evidence-based counseling in HAART-non-adherent subjects with alcohol problems. PUBLIC HEALTH RELEVANCE: This project has direct implications for improving the care of individuals with HIV. The goals are to optimize the treatment of HIV disease by decreasing alcohol consumption, improving medication adherence, reducing the risk of HIV drug resistance, improving HIV immune markers, and promoting the prevention of HIV transmission by targeting sexual risk behaviors in patients with heavy drinking. This patient population has been under-represented in these types of intervention studies. The current project will serve to advance this area of research and expand the types of care that HIV-infected patients receive.

描述（由申请人提供）：很少有治疗方法能够减少酗酒、酗酒和对艾滋病毒感染者的依赖的影响。这些饮酒水平与高效抗逆转录病毒治疗 (HAART) 的依从性降低、病毒突变的可能性增加、疾病进展加剧、肝损伤加剧以及性行为风险增加有关。纳曲酮与咨询相结合，是治疗酗酒、酒精滥用和酒精依赖的有效方法，但尚无关于其在艾滋病毒感染者中的使用或疗效的数据。这项拟议的研究在一项为期 24 周的随机双盲安慰剂对照临床试验中对纳曲酮与安慰剂进行了比较，试验对象是 HIV 诊所中未接受 HAART 治疗、酗酒、酗酒或依赖酒精的 HIV 感染患者 (N=154)。为了确定治疗的长期影响，所有患者都将在 9 个月和 12 个月时接受随访。随机接受纳曲酮的患者最初将接受每日口服制剂，如果耐受，将转为每月缓释制剂。所有患者都将接受药物管理（MM）结合药物指导（MC）（MM/MC）的咨询平台。 MM/MC 是一种复合手动治疗，旨在近似适合在 HIV 初级保健环境中实施的治疗类型。它的重点是通过经过医学培训的提供者提供的一系列简短干预措施来减少酗酒 (MM) 和提高药物依从性 (MC)。将针对随机分配接受纳曲酮 + MM/MC 与安慰剂 + MM/MC 的患者样本的治疗意向进行数据分析。主要研究结果是坚持使用 HAART 药物。次要研究结果包括大量饮酒的频率、HIV 病毒突变（使用标准检测和超深度测序）、CD4 淋巴细胞计数和 HIV RNA 的变化、酒精-HAART 肝毒性和性危险行为。该提案的新颖之处包括：1）综合现场酒精和艾滋病毒治疗； 2) 使用缓释纳曲酮可能会提高药物依从性具有挑战性的患者群体的依从性； 3) 使用多种衡量 HAART 依从性的措施，包括药房补充数据； 4) 使用复杂的技术来检查新病毒突变的发展，包括检测新的微小变异； 5) 收集治疗对肝脏影响的详细数据。这项拟议的研究由经验丰富的艾滋病毒和成瘾研究人员团队进行，将有助于明确纳曲酮和循证咨询在患有酒精问题的非 HAART 受试者中的作用。公共卫生相关性：该项目对于改善艾滋病毒感染者的护理具有直接影响。目标是通过减少饮酒、提高用药依从性、降低艾滋病毒耐药性风险、改善艾滋病毒免疫标志物以及通过针对酗酒患者的性危险行为来促进预防艾滋病毒传播来优化艾滋病毒疾病的治疗。在这些类型的干预研究中，这一患者群体的代表性不足。当前的项目将有助于推进这一领域的研究并扩大艾滋病毒感染者接受的护理类型。