Adherence to HIV Therapy in Heroin Addicts: Oral vs Extended Release Naltrexone

描述（由申请人提供）：HIV患者阿片类药物成瘾的复发有助于寻求药物的行为，不依从抗逆转录病毒治疗（ART），治疗失败和病毒耐药性的发展。成功的成瘾治疗应该做相反的事情。接受ART的阿片类药物成瘾患者通常维持美沙酮或丁丙诺啡，但这些药物受到监管限制，并不总是停止阿片类药物的使用，在许多情况下不可用，并不是所有患者都能接受。纳洛酮维持是另一种可能有用的选择，因为它可以阻止阿片类药物的作用，并防止复发，如果按指示服用。它已经作为每天服用的50 mg片剂提供，最初受到临床医生的热情;然而，当大多数患者停止服用并复发时，热情减弱。开发可能克服这些问题的长效制剂的努力只是最近才得以实现，缓释制剂现已上市，并重新引起了人们对将其用于类阿片成瘾治疗的兴趣。这些制剂还可以通过预防复发来促进阿片类药物成瘾患者对ART的依从性。因此，该项目旨在测试一种缓慢释放纳洛酮并阻断阿片类药物作用3个月（IN）的植入式制剂是否比50 mg/天口服纳洛酮（ON）更有效，以改善正在开始其第一次ART发作的阿片类药物成瘾患者的ART依从性和治疗结果。俄罗斯是研究IN的理想场所，因为它有批准的产品，大多数HIV患者是海洛因成瘾者，俄罗斯法律不允许激动剂治疗，患者对纳洛酮的兴趣很高，并且巴甫洛夫医科大学的合作研究小组对IN和ON具有丰富的经验。为了检验IN比ON导致更好的HIV治疗结果的假设，我们提出了一个48周的随机双盲，在彼得堡，200名刚戒毒的海洛因成瘾者开始了他们的第一次ART治疗。主要结果将是24周和48周时病毒载量<400拷贝的患者比例。我们假设IN比ON更有效，因为它与更少的复发和更多的依从性相关。公共卫生相关性：这项研究将评估口服纳洛酮50 mg/天与缓释纳洛酮植入物对俄罗斯彼得堡开始抗逆转录病毒治疗（ART）的阿片类药物成瘾患者对抗逆转录病毒治疗（ART）的反应的影响。它将随机分配260名最近脱毒的阿片类药物成瘾者开始ART，接受为期48周的双周药物咨询，口服纳洛酮50 mg/天+安慰剂纳洛酮植入物，或安慰剂片剂+纳洛酮植入物。主要结果将是对ART的反应，通过病毒载量的减少来衡量。

DESCRIPTION (provided by applicant): Relapse to opioid addiction in patients with HIV contributes to drug-seeking behavior, non-adherence to antiretroviral therapy (ART), treatment failure, and the development of viral resistance. Successful addiction treatment should do the opposite. Opioid addicted patients receiving ART are often maintained on methadone or buprenorphine, but these medications are subject to regulatory limitations, do not always stop opioid use, are not available in many settings, and not acceptable to all patients. Naltrexone maintenance is another option that could be useful as it blocks opioid effects and prevents relapse if taken as directed. It has been available as a 50 mg tablet that is taken daily and was initially met with enthusiasm by clinicians; however enthusiasm waned when most patients stopped taking it and relapsed. Efforts to develop long-acting formulations that might overcome these problems were realized only very recently, and sustained release formulations are now available and have renewed interest in using it for opioid addiction treatment. These formulations may also facilitate adherence to ART in opioid addicted patients by preventing relapse. Accordingly, this project aims to test whether an implantable formulation that slowly releases naltrexone and blocks opioid effects for 3 months (IN) is more effective than 50 mg/day oral naltrexone (ON) for improving ART adherence and treatment outcome in opioid addicted patients who are beginning their first episode of ART. Russia is an ideal place to study IN since it has an approved product, most HIV patients are heroin addicts, Russian law does not permit agonist treatment, patient interest in naltrexone is high, and the collaborating research team at Pavlov Medical University has extensive experience with IN and ON. To test the hypothesis that IN results in better HIV treatment outcome than ON, we propose a 48-week, randomized, double blind, double- dummy trial comparing IN with ON in 200 recently detoxified heroin addicts beginning their first episode of ART in St. Petersburg. The primary outcomes will be the proportion of patients with a viral load of <400 copies at 24 and 48 weeks. We hypothesize that IN will work better than ON because it will be associated with less relapse and more adherence. PUBLIC HEALTH RELEVANCE: This study will assess the impact of oral naltrexone 50 mg/day vs. a sustained-release naltrexone implant on response to antiretroviral therapy (ART) in opioid addicted patients beginning ART in St. Petersburg, Russia. It will randomize 260 recently detoxified opioid addicts beginning ART to a 48-week course of biweekly drug counseling with oral naltrexone 50 mg/day + placebo naltrexone implant, or placebo tablet + naltrexone implant. The primary outcome will be response to ART as measured by reduction in viral load.