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.

Alcohol use and HIV risk behaviors among HIV-infected hospitalized patients in St. Petersburg, Russia.

PURPOSE: Russia has high per capita alcohol consumption and an injection-drug-use-driven HIV epidemic. However, the role of alcohol in the spread of HIV infection in Russia is largely unexplored. Thus, we assessed recent alcohol use and associated HIV risk behaviors among HIV-infected persons in St. Petersburg, Russia. METHODS: We recruited HIV-infected hospitalized patients from the Botkin Infectious Disease Hospital between June 2001 and March 2002. Interviewers assessed alcohol and drug use with the addiction severity index (ASI) and sex- and drug-risk behaviors with the risk assessment battery (RAB). Lifetime abuse or dependence diagnoses for alcohol and drugs were established by a physician with addiction medicine training. RESULTS: Among 201 subjects, diagnoses of abuse or dependence (AB/DEP) were common: 9% (19/201) had only alcohol AB/DEP; 39% (78/201) had alcohol and drug AB/DEP; 47% (95/201) had only drug AB/DEP; and 4% (9/201) had no diagnosis of alcohol or drug AB/DEP. Sex- and drug-risk behaviors varied significantly by substance use diagnosis. Subjects with any alcohol AB/DEP had higher sex-risk RAB scores than those with drug only AB/DEP (6.1 versus 3.9, p<.0001). Among subjects with any diagnosis of drug AB/DEP, having in addition an alcohol diagnosis was associated with unclean needle use in the last six months (33% (26/78) versus 21% (20/95), p=0.08). CONCLUSIONS: Lifetime alcohol diagnoses of abuse or dependence were present in nearly one-half of hospitalized HIV-infected patients in St. Petersburg, Russia and were associated with significantly higher sex-risk behaviors and borderline significantly higher drug-risk behaviors. As HIV infection spreads rapidly in Russia and Eastern Europe, these data support the need for HIV risk-reduction interventions in alcohol abusing populations and raise the potential of benefit by addressing alcohol use in HIV-infected populations.