Reducing Heavy Drinking to Optimize HIV/AIDS Treatment and Prevention

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，酒精滥用和依赖艾滋病毒感染患者的影响。这些饮酒水平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、肝损伤加重和性风险增加有关。纳洛酮，当与咨询相结合时，是一种有效的治疗酗酒，酒精滥用和依赖，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。该研究在一项为期24周的随机双盲安慰剂对照临床试验中比较了纳洛酮与安慰剂，该试验在HIV诊所的HAART非依从性HIV感染患者（N=154）中进行，这些患者患有大量饮酒，酒精滥用或依赖。为了确定治疗的长期影响，所有患者将在9个月和12个月时接受随访。随机接受纳曲酮治疗的患者最初将接受每日口服制剂，如果耐受，将转入每月缓释制剂。所有患者将接受药物管理（MM）与药物指导（MC）（MM/MC）相结合的咨询平台。MM/MC是一种复合手动治疗，旨在接近适合在艾滋病毒初级保健环境中实施的治疗类型。它的重点是减少大量饮酒（MM）和改善药物依从性（MC）通过一系列简短的干预措施提供了一个受过医学训练的提供者。将对随机分配接受纳洛酮+ MM/MC与安慰剂+ MM/MC的患者的意向治疗样本进行数据分析。主要研究结果是坚持HAART药物治疗。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），CD 4淋巴细胞计数和HIV RNA的变化，酒精-HAART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HIV治疗; 2）使用缓释纳洛酮，这可能会改善药物依从性具有挑战性的患者人群的依从性; 3）使用几种HAART依从性指标，包括药房再填充数据; 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;和5）收集关于治疗的肝脏影响的详细数据。这项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确定纳洛酮的作用，并在有酒精问题的HAART非依从性受试者中进行循证咨询。 公共卫生相关性：该项目对改善艾滋病毒感染者的护理有直接影响。其目标是通过减少饮酒，提高药物依从性，降低艾滋病毒耐药性的风险，改善艾滋病毒免疫标志物，并通过针对大量饮酒患者的性风险行为来促进预防艾滋病毒传播，从而优化艾滋病毒疾病的治疗。在这些类型的干预研究中，该患者人群的代表性不足。目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得到的护理种类。

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.