Naltrexone and Behavioral Drug and HIV Risk Reduction Counseling in Russia

描述（由申请方提供）：俄罗斯联邦估计有160万至400万阿片类药物使用者（大多数为注射毒品使用者）和94万多艾滋病毒感染者（80%与注射毒品有关），正面临艾滋病毒爆发性流行的前景。目前在俄罗斯，住院戒毒后口服纳洛酮维持（NMT）是阿片类药物依赖的唯一药物治疗。减少艾滋病毒传播和戒毒后复吸的循证咨询服务并不普遍或经常提供。NMT是使用医疗模式提供的，医生只提供简短的医疗管理（MM）。几个考虑因素，包括我们初步研究的数据，表明NMT的疗效可能会提高使用缓释纳洛酮（XR/NTX），而不是口服纳洛酮（O/NTX），并结合NMT与行为药物和艾滋病毒风险降低咨询（BDRC）。[By减少依从性问题和治疗损耗，XR/NTX可以提高临床有效性（即，减少复发风险，IDU和其他与药物使用相关的风险行为）。BDRC还可以改善药物依从性，促进行为改变，从而降低复发风险，IDU和其他与药物和性相关的HIV风险行为。然而，尚未系统评价纳洛酮制剂（O/NTX与XR/NTX）和咨询（仅MM或与BDRC联合）的各种组合减少药物和性相关HIV风险行为以及增加阿片类药物戒断持续时间的疗效和成本效益。因此，我们提出了一项2x2析因随机临床试验，评估两种药物制剂（O/NTX和XR/NTX）和两种手动指导咨询条件（仅MM或MM+BDRC）的疗效和成本效益以及药物和咨询条件之间的潜在相互作用。脱毒后，阿片类药物依赖受试者（N=320）将被随机分配至4个治疗组之一，接受6个月的治疗：O/NTX+MM、XR/NTX+MM、O/NTX+MM+BDRC或XR/NTX+MM+BDRC。[主要结果指标包括性和药物相关的艾滋病毒风险行为的减少，[非法阿片类药物使用的减少]和治疗保留。其他结果指标包括阿片类药物或其他药物使用频率的减少，健康状况和医疗保健利用，犯罪行为和逮捕，以及职业和家庭功能和生活质量的改善。所有研究受试者将在基线时和6个月治疗期内每月进行一次评估，并在活性治疗期后持续6个月。数据分析将侧重于意向治疗样本。研究结果将允许评价XR/NTX是否具有比O/NTX更上级的功效或更具成本效益，BDRC加MM是否具有比仅MM更上级的功效或更具成本效益，以及药物和咨询的特定组合是否具有比其它组合更上级的功效或更具成本效益。 公共卫生相关性：这项研究的长期目标是促进循证行为和药理学治疗的发展和传播，以减少俄罗斯的艾滋病毒传播、注射毒品使用（IDU）和海洛因使用。本研究将探讨行为疗法与纳洛酮药物疗法相结合治疗阿片类药物依赖和降低阿片类药物依赖者艾滋病毒感染风险的效果。具体地说，该研究将确定延长释放注射纳洛酮是否具有更大的疗效并且比口服纳洛酮维持更具成本效益，行为药物和HIV风险降低咨询（BDRC）结合简短的医学管理（MM）是否具有更大的疗效并且比仅MM更具成本效益，以及药物制剂和咨询的特定组合（仅MM或MM加BDRC）是否比其他组合具有更大的功效或更具成本效益。

DESCRIPTION (provided by applicant): With an estimated 1.6-4 million opiate users (majority with injection drug use (IDU)) and more than 940,000 HIV infected individuals (80% linked to IDU), the Russian Federation is facing the prospect of an explosive HIV epidemic. Currently in Russia, inpatient detoxification followed by oral naltrexone maintenance (NMT) is the only pharmacologic treatment for opiate dependence. Evidence-based counseling to reduce HIV transmission and relapse following detoxification is not widely available or routinely provided. NMT is offered using a medical model, with physicians providing only brief medical management (MM). Several considerations, including data from our preliminary studies, suggest that the efficacy of NMT may be improved by using extended-release naltrexone (XR/NTX) instead of oral naltrexone (O/NTX) and by combining NMT with behavioral drug and HIV risk reduction counseling (BDRC). [By reducing adherence problems and treatment attrition, XR/NTX may improve clinical effectiveness (i.e., reduce relapse risk, IDU, and other risk behaviors associated with drug use).] BDRC may also improve medication adherence and promote behavioral change leading to reduced relapse risk, IDU, and other drug- and sex-related HIV risk behaviors. However, the efficacy and cost-effectiveness for reducing drug- and sex-related HIV risk behaviors and increasing duration of opioid abstinence of the various combinations of naltrexone formulation (O/NTX vs. XR/NTX) and counseling (MM only or combined with BDRC) have not been systematically evaluated. Consequently, we are proposing a 2x2 factorial randomized clinical trial evaluating the efficacy and cost-effectiveness of two medication formulations (O/NTX and XR/NTX) and two manual-guided counseling conditions (MM only or MM+BDRC) and the potential interactions between medications and counseling conditions. Following detoxification, opiate dependent subjects (N=320) will be randomly assigned to 6 months of treatment in one of four treatment groups: O/NTX+MM, XR/NTX+MM, O/NTX+MM+BDRC, or XR/NTX+MM+BDRC. [Primary outcome measures include reductions in sex- and drug-related HIV risk behaviors, [reductions in illicit opiate use], and treatment retention. Other outcome measures include reductions in frequency of opiate or other drug use, health status and healthcare utilization, criminal behavior and arrests, and improvements in vocational and family functioning and quality of life.] All study participants will be assessed at baseline and monthly during the 6 month treatment phase and for 6 months following the active treatment phase. Data analyses will focus on the intention-to treat sample. The study results will allow evaluation of whether XR/NTX has superior efficacy or is more cost-effective than O/NTX, whether BDRC plus MM has superior efficacy or is more cost- effective than MM only, and whether particular combinations of medications and counseling have superior efficacy or are more cost-effective than other combinations. PUBLIC HEALTH RELEVANCE: The long-term goals of this study are to foster development and dissemination of evidence-based behavioral and pharmacological treatments to reduce HIV transmission, injection drug use (IDU), and heroin use in Russia. This study will examine the effects of combining behavioral therapy with naltrexone pharmacotherapy for the treatment of opiate dependence and reduction of HIV risks in opiate dependent individuals. Specifically the study will determine whether extended-release injection naltrexone has greater efficacy and is more cost- effective than oral naltrexone maintenance, whether behavioral drug and HIV risk reduction counseling (BDRC) combined with brief, medical management (MM) has greater efficacy and is more cost-effective than MM only, and whether particular combinations of medication formulation and counseling (MM only or MM plus BDRC) have greater efficacy or are more cost-effective than other combinations.