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

描述（由申请人提供）：艾滋病患者阿片类药物成瘾的复发会导致寻求药物的行为，抗逆转录病毒治疗（ART）的不依从性，治疗失败和病毒耐药性的发展。成功的成瘾治疗应该起到相反的作用。接受抗逆转录病毒治疗的阿片类药物成瘾患者通常使用美沙酮或丁丙诺啡维持治疗，但这些药物受到监管限制，并不总能停止阿片类药物的使用，在许多情况下无法获得，也不是所有患者都能接受。纳曲酮维持是另一种有用的选择，因为它可以阻断阿片类药物的作用，并防止复发，如果按照指示服用。它已成为50毫克片剂，每天服用，最初受到临床医生的热烈欢迎；然而，当大多数患者停止服用并复发时，热情就减弱了。开发可能克服这些问题的长效制剂的努力直到最近才实现，现在有了缓释制剂，并重新引起了将其用于阿片类药物成瘾治疗的兴趣。这些配方还可以通过防止复发来促进阿片类药物成瘾患者坚持抗逆转录病毒治疗。因此，本项目旨在测试一种缓慢释放纳曲酮并阻断阿片类药物作用3个月（IN）的可植入制剂是否比50mg /天口服纳曲酮（ON）更有效，以改善开始第一次ART治疗的阿片类药物成瘾患者的ART依从性和治疗结果。俄罗斯是一个理想的地方，因为它有一种批准的产品，大多数艾滋病患者是海洛因成瘾者，俄罗斯法律不允许激动剂治疗，患者对纳曲酮的兴趣很高，巴甫洛夫医科大学的合作研究团队在IN和ON方面有丰富的经验。为了验证IN比ON的HIV治疗效果更好的假设，我们提出了一项为期48周的随机、双盲、双虚拟试验，对圣彼得堡200名最近开始第一次抗逆转录病毒治疗的海洛因成瘾者进行IN和ON的比较。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会比ON更有效，因为它会减少复发和更多的依从性。公共卫生相关性：本研究将评估在俄罗斯圣彼得堡开始抗逆转录病毒治疗的阿片类药物成瘾患者中，口服纳曲酮50mg /天与缓释纳曲酮植入物对抗逆转录病毒治疗（ART）反应的影响。该研究将随机抽取260名刚开始抗逆转录病毒治疗的阿片类药物成瘾者，进行为期48周的药物咨询，每两周服用口服纳曲酮50mg /天+安慰剂纳曲酮植入物，或安慰剂片+纳曲酮植入物。主要结果将是通过病毒载量的减少来衡量对ART的反应。

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.