Naltrexone and Behavioral Drug and HIV Risk Reduction Counseling in Russia

描述(由申请人提供)：俄罗斯联邦估计有160-400万鸦片吸毒者(大多数为注射吸毒者)和940,000多名艾滋病毒感染者(80%与注射吸毒者有关)，俄罗斯联邦正面临艾滋病毒爆炸性流行的前景。目前在俄罗斯，住院戒毒后口服纳曲酮维持(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发的循证咨询并没有广泛获得或常规提供。NMT是使用医疗模式提供的，医生只提供简单的医疗管理(MM)。一些考虑因素，包括我们初步研究的数据表明，使用缓释纳曲酮(XR/NTX)代替口服纳曲酮(O/NTX)，并将NMT与行为药物和HIV风险降低咨询(BDRC)相结合，可以提高NMT的疗效。[通过减少依从性问题和治疗磨耗，XR/NTX可能会提高临床有效性(即减少复发风险、IDU和其他与药物使用有关的危险行为)。]BDRC还可以提高服药依从性，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艾滋病毒危险行为。然而，在减少与药物和性相关的艾滋病毒危险行为和延长阿片类药物戒断持续时间方面，纳曲酮制剂(O/NTX与XR/NTX)和咨询(仅MM或与BDRC合并)的各种组合的有效性和成本效益尚未得到系统评估。因此，我们提出了一项2x2因子随机临床试验，评估两种药物配方(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-效果，以及药物和咨询条件之间的潜在相互作用。脱毒后，阿片依赖者(N=320)随机分为四个治疗组：O/NTX+MM、XR/NTX+MM、O/NTX+MM+BDRC或XR/NTX+MM+BDRC。[主要结果衡量标准包括减少与性和毒品有关的艾滋病毒危险行为、[减少非法鸦片使用]和保留治疗。其他成果措施包括减少鸦片或其他药物的使用频率、健康状况和保健利用、犯罪行为和逮捕，以及改善职业和家庭功能以及生活质量。]所有研究参与者将在6个月的治疗阶段和积极治疗阶段之后的6个月内，在基线和月度进行评估。数据分析将重点放在意向上--处理样本。研究结果将允许评估XR/NTX是否比O/NTX更有效或更具成本效益，BDRC+MM是否比MM更有效或更具成本效益，以及特定的药物和咨询组合是否比其他组合更有效或更具成本效益。 公共卫生相关性：这项研究的长期目标是促进以证据为基础的行为和药物治疗的开发和传播，以减少俄罗斯的艾滋病毒传播、注射毒品使用和海洛因使用。这项研究将考察行为疗法和纳曲酮药物疗法在治疗阿片类药物依赖和降低阿片类药物依赖者的艾滋病毒风险方面的效果。具体地说，这项研究将确定缓释注射用纳曲酮是否比口服纳曲酮维持治疗更有效和更具成本效益，行为药物和艾滋病毒风险降低咨询(BDRC)与简要、医疗管理(MM)相结合是否比仅MM更有效和更具成本效益，以及特定的药物配方和咨询组合(仅MM或MM+BDRC)是否比其他组合更有效或更具成本效益。

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.