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

• 批准号: 8071255
• 负责人: Lynn Elizabeth Fiellin
• 金额: $ 4.59万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 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/8071255
• 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

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）：很少有治疗方法被评估以减少大量饮酒、酒精滥用和对艾滋病毒感染者的依赖的影响。这些水平的酒精消费与高活性抗逆转录病毒治疗（HAART）依从性降低、病毒突变可能性增加、疾病进展加快、促进肝损伤和性风险增加有关。纳曲酮与咨询相结合，是一种有效的治疗酗酒、酒精滥用和酒精依赖的方法，但没有关于其在艾滋病毒感染患者中的使用或疗效的数据。在一项为期24周的随机双盲安慰剂对照临床试验中，研究人员将纳曲酮与安慰剂进行了比较，试验对象是在HIV诊所中重度饮酒、酒精滥用或依赖haart治疗的HIV感染患者（N=154）。为了确定治疗的长期影响，所有患者将在9个月和12个月进行随访。随机分配到纳曲酮组的患者最初将接受每日口服制剂，如果耐受，将转移到每月缓释制剂。所有患者将接受药物管理（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，旨在近似于适合在艾滋病毒初级保健环境中实施的治疗类型。它的重点是通过由受过医学培训的提供者提供的一系列简短干预措施，减少酗酒和改善服药依从性。将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HAART药物的依从性。次要研究结果包括大量饮酒的频率、HIV病毒突变（使用标准测定和超深度测序）、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。这一建议的新颖方面包括：1)综合现场酒精和艾滋病毒治疗；2)使用缓释纳曲酮，这可能会改善这类患者的依从性，对他们来说，药物依从性是具有挑战性的；3)使用包括药房补充数据在内的几种衡量HAART依从性的措施；4)使用复杂的技术来检查新病毒突变的发展，包括检测新的次要变异；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，将有助于确定纳曲酮和循证咨询在酒精问题的haart非依从性受试者中的作用。