First Pavlov State Medical University of Saint Petersburg, Saint Petersburg, Russia; VM Bekhterev National Medical Research Centre for Psychiatry and Neurology, Saint Petersburg, Russia.
First Pavlov State Medical University of Saint Petersburg, Saint Petersburg, Russia.
Lancet HIV. 2019 Apr;6(4):e221-e229. doi: 10.1016/S2352-3018(18)30362-X. Epub 2019 Mar 14.
Untreated opioid addiction in people with HIV is associated with poor HIV treatment outcomes. Slow-release, long-acting, implantable naltrexone might improve these outcomes. Here, we present results of a study aimed to test this hypothesis.
We did a 48 week double-blind, double-dummy, placebo-controlled, phase 3, randomised trial with men and women addicted to opioids who were starting antiretroviral therapy (ART) for HIV and whose viral loads were higher than 1000 copies per mL. Participants were seeking treatment at two HIV and two narcology programme centres in Saint Petersburg, Russia, and the surrounding Leningrad region. The Pavlov statistical department created a table with stratification on gender distribution, viral load, and CD4 cell count. We stratified participants according to gender, viral load, and CD4 cells per μL, and randomly assigned (1:1) them to addiction treatment with a naltrexone implant and oral naltrexone placebo (implant group) or oral naltrexone and placebo implant (oral group). The primary outcome was plasma viral load of less than 400 copies per mL at 24 weeks and 48 weeks. We included all randomly assigned participants in outcome analyses (intention to treat). Treatment staff and patients were masked to group assignment. The study is complete and registered at ClinicalTrials.gov, NCT01101815.
Between July 14, 2011, and April 14, 2014, 238 potential participants were recruited and screened, 35 were excluded for not meeting inclusion criteria, three declined to participate, and 200 were randomly assigned to treatment (100 to each group). At week 24, 38 (38) participants in the implant group and 35 (35%) in the oral group had viral loads less than 400 copies per mL (risk ratio 1·1, 95% CI 0·76-1·56; p=0·77). At week 48, 66 participants in the implant group and 50 in the oral group had viral loads less than 400 copies per mL (risk ratio 1·32, 95% CI 1·04-1·68; p=0·045). There were seven serious adverse events: three deaths in the implant group (one due to heart disease, one trauma, and one AIDS), and four in the oral group (two overdoses, one pancreatic cancer, and one AIDS). The overdose deaths occurred 9-10 months after the last naltrexone dose.
The longer the blockade of opioid effects, the more protection an individual gets from missed ART doses and impulsive behaviours that lead to relapse and poor, even fatal, outcomes. Commercial development of implants could result in a meaningful addition to addiction treatment options.
National Institutes of Health, National Institute on Drug Abuse, Penn Centre for AIDS Research, and Penn Mental Health AIDS Research Centre.
未经治疗的艾滋病毒感染者阿片类药物成瘾与艾滋病毒治疗结局不佳有关。缓释、长效、可植入的纳曲酮可能改善这些结果。在此，我们介绍了一项旨在检验这一假设的研究结果。
我们进行了一项为期 48 周的双盲、双模拟、安慰剂对照、3 期、随机试验，纳入了开始接受抗逆转录病毒治疗（ART）的艾滋病毒感染且病毒载量高于 1000 拷贝/毫升的阿片类药物成瘾的男性和女性。参与者在俄罗斯圣彼得堡和周边列宁格勒地区的两家 HIV 和两家戒毒方案中心寻求治疗。巴甫洛夫统计部门根据性别分布、病毒载量和 CD4 细胞计数制定了一个分层表格。我们根据性别、病毒载量和每微升 CD4 细胞数对参与者进行分层，并将其随机（1:1）分配到纳曲酮植入和口服纳曲酮安慰剂（植入组）或口服纳曲酮和安慰剂植入（口服组）的成瘾治疗中。主要结局是在 24 周和 48 周时血浆病毒载量小于 400 拷贝/毫升。我们对所有随机分配的参与者进行了意向治疗（ITT）结局分析。治疗人员和患者对分组情况不知情。该研究已完成并在 ClinicalTrials.gov 注册，编号为 NCT01101815。
2011 年 7 月 14 日至 2014 年 4 月 14 日期间，共招募了 238 名潜在参与者并进行了筛查，35 名参与者因不符合纳入标准而被排除，3 名参与者拒绝参与，200 名参与者被随机分配到治疗组（每组 100 名）。在第 24 周，植入组有 38 名（38%）参与者和口服组有 35 名（35%）参与者的病毒载量小于 400 拷贝/毫升（风险比 1.1，95%CI 0.76-1.56；p=0.77）。在第 48 周，植入组有 66 名（66%）参与者和口服组有 50 名（50%）参与者的病毒载量小于 400 拷贝/毫升（风险比 1.32，95%CI 1.04-1.68；p=0.045）。有 7 例严重不良事件：植入组有 3 例死亡（1 例死于心脏病，1 例创伤，1 例艾滋病），口服组有 4 例（2 例过量用药，1 例胰腺癌，1 例艾滋病）。过量用药死亡发生在最后一次纳曲酮剂量后 9-10 个月。
阻断阿片类药物作用的时间越长，个体因错过 ART 剂量和冲动行为而导致复发和不良甚至致命结局的保护作用就越大。植入物的商业开发可能会为成瘾治疗选择增加一个有意义的手段。
美国国立卫生研究院、国立药物滥用研究所、宾夕法尼亚艾滋病研究中心和宾夕法尼亚心理健康艾滋病研究中心。
