Slow-release naltrexone implant versus oral naltrexone for improving treatment outcomes in people with HIV who are addicted to opioids: a double-blind, placebo-controlled, randomised trial.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: National Institutes of Health, National Institute on Drug Abuse, Penn Centre for AIDS Research, and Penn Mental Health AIDS Research Centre.

Naltrexone implant for the treatment of polydrug dependence: a randomized controlled trial.

OBJECTIVE: The majority of drug addicts are polydrug dependent, and no effective pharmacological treatment is currently available for them. The authors studied the overall real-world effectiveness of naltrexone implant in this patient population. METHOD: The authors assessed the effectiveness of a naltrexone implant in the treatment of coexisting heroin and amphetamine polydrug dependence in 100 heroin- and amphetamine-dependent outpatients in a 10-week randomized, double-blind, placebo-controlled trial. The main outcome measures were retention in the study, proportion of drug-free urine samples, and improvement score on the Clinical Global Impressions Scale (CGI). Analyses were conducted in an intent-to-treat model. RESULTS: At week 10, the retention rate was 52% for patients who received a naltrexone implant and 28% for those who received a placebo implant; the proportions of drug-free urine samples were 38% and 16%, respectively, for the two groups. On the CGI improvement item, 56% of the patients in the naltrexone group showed much or very much improvement, compared with 14% of those in the placebo group (number needed to treat=3). CONCLUSIONS: Naltrexone implants resulted in higher retention in the study, decreased heroin and amphetamine use, and improved clinical condition for patients, thus providing the first evidence of an effective pharmacological treatment for this type of polydrug dependence.