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复发会导致寻药行为、不坚持抗逆转录病毒治疗 (ART)、治疗失败以及病毒耐药性的产生。成功的成瘾治疗应该起到相反的作用。接受 ART 的阿片类药物成瘾患者通常维持使用美沙酮或丁丙诺啡，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，在许多情况下并不可用，并且并非所有患者都能接受。纳曲酮维持治疗是另一种有用的选择，因为如果按指示服用，它可以阻止阿片类药物的作用并防止复发。它已推出每日服用 50 毫克的片剂，最初受到了临床医生的热情欢迎；然而，当大多数患者停止服用该药并病情复发时，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得以实现，并且缓释制剂现已上市，并且人们对将其用于阿片类药物成瘾治疗重新产生了兴趣。这些制剂还可以通过防止复发来促进阿片类药物成瘾患者坚持 ART。因此，该项目旨在测试缓慢释放纳曲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 毫克/天口服纳曲酮 (ON) 更有效地改善开始首次 ART 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 的理想地点，因为该国拥有已获批准的产品，大多数 HIV 患者都是海洛因成瘾者，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 方面拥有丰富的经验。为了检验 IN 比 ON 带来更好的 HIV 治疗结果这一假设，我们提出了一项为期 48 周的随机、双盲、双模拟试验，在圣彼得堡开始首次 ART 的 200 名最近戒毒的海洛因成瘾者中比较 IN 和 ON。主要结果是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 效果更好，因为它会减少复发和提高依从性。公共卫生相关性：本研究将评估俄罗斯圣彼得堡开始 ART 的阿片类药物成瘾患者每天口服 50 毫克纳曲酮与缓释纳曲酮植入剂对抗逆转录病毒治疗 (ART) 反应的影响。它将随机将 260 名最近戒毒的阿片类药物成瘾者开始 ART 进行为期 48 周的双周药物咨询课程，其中包括口服纳曲酮 50 毫克/天安慰剂纳曲酮植入物或安慰剂片剂纳曲酮植入物。主要结果是通过病毒载量减少来衡量对 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.