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：
8127683
负责人：
Lynn Elizabeth Fiellin
金额：
$ 73.88万
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/8127683
关键词：
AIDS prevention AIDS/HIV problem Address Adherence Adverse effects Affect Alcohol abuse Alcohol consumption Alcohol dependence 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）：很少评估治疗方法，以减少饮酒，酗酒和对感染HIV感染患者的依赖的影响。这些水平的饮酒水平与依从性降低了高度活跃的抗逆转录病毒疗法（HAART），病毒突变的可能性增加，疾病进展增强，促进肝损伤以及增加性风险的增加。纳曲酮与咨询相结合，是对大量饮酒，酗酒和依赖性的有效治疗方法，但尚无有关其在HIV感染患者中使用或功效的数据。拟议的研究将Naltrexone与安慰剂与安慰剂进行了24周的随机双盲安慰剂对照临床试验，该试验在HAART-NON-NON辅助感染的HIV感染的HIV感染患者中，患有大量饮酒，酒精滥用或依赖性（n = 154）。为了确定治疗的长期影响，所有患者将在9和12个月的时间进行随访。随机分配给纳曲酮的患者最初将接受口服配方，如果可以容忍，将转移到每月延长的释放配方中。所有患者将获得药物管理（MM）的咨询平台，并结合药物教练（MC）（MM/MC）。 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。它着重于减少大量饮酒（MM）和改善药物依从性（MC），这是由受过医学训练的提供商提供的一系列简短干预措施。数据分析将针对治疗随机分配的患者的样本进行纳曲酮 + mm/mc与安慰剂 + mm/mc的样本。主要的研究结果是遵守HAART药物。二级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测序），CD4淋巴细胞计数和HIV RNA的变化，酒精 - 饮酒肝毒性和性风险行为。该提案的新方面包括：1）综合现场酒精和艾滋病毒治疗； 2）使用扩展释放纳曲酮，这可能会改善该药物依从性挑战的患者人群的依从性； 3）使用多种措施来遵守包括药房补充数据； 4）使用复杂技术来检查新的病毒突变的发展，包括检测新的次要变体； 5）收集有关治疗的肝作用的详细数据。由经验丰富的艾滋病毒和成瘾研究人员团队进行的拟议研究将有助于定义纳曲酮和基于证据的咨询在患有酒精问题的哈特 - 非戒律受试者中的作用。公共卫生相关性：该项目对改善艾滋病毒患者的护理具有直接影响。目标是通过减少饮酒，改善药物依从性，降低艾滋病毒耐药性，改善HIV免疫标记物以及通过针对大量饮酒患者靶向性风险行为来预防HIV传播，来优化艾滋病毒疾病的治疗。在这类干预研究中，该患者人群的代表性不足。当前的项目将有助于推进这一研究领域，并扩大感染HIV感染的患者接受的护理类型。