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

Abstract

Background: Untreated opioid addiction in persons with HIV is associated with poor outcome. Slow release, long-acting, implantable naltrexone may improve outcomes. Methods: We conducted a 48-week outcome study beween July 2011 and April 2015 of opioid addicted males and females starting antiretroviral treatment (ART) for HIV whose viral loadwas ≥1000 copies per mL and were seeking treatment at HIV and Narcology programs in St. Petersburg and the surrounding Leningrad Region, Russian Federation. We stratified participants according to gender, viral load (VL) and CD4 cells per μL, and randomized them to addiction treatment with a naltrexone implant and oral naltrexone placebo (NI), or oral naltrexone and placebo implant (ON). The primary outcome was plasma viral load of ≤400 copies per mL at 24 and 48 weeks. We included all randomized participants in outcome analyses. Treatment staff was blinded to group assignment. The study is complete and registered at ClinicalTrials.gov, NCT01101815 Findings: 238 potential subjects were screened, 35 excluded for not meeting inclusion criteria, 3 declined to participate and 200 were randomized. There was no difference between NI and ON in the number of participants with VL≤400 copies per mL at week 24 (38 [38%] vs 35 [35%] p=0•77) but more NI than ON participants had a VL≤400 copies per mL at week 48 (66 [66%] vs 50 [50%] RR: 1•32 [95% CI: 1•04−1•68] p=0•0451). There were seven serious adverse events: three deaths in NI (one heart disease, one trauma, one AIDS), and four in ON (two overdoses, one pancreatic cancer, one AIDS). The overdose deaths occurred 9-10 months after the last naltrexone dose. Interpretation: The longer the blockade, the more protection from missed doses and the impulsive behaviors that lead to relapse and poor, even fatal outcomes. Commercial development of implants could result in a meaningful addition to current addiction treatment options.

Gender difference in all‐cause mortality of people living with HIV in Iran: findings from a 20‐year cohort study

“…This finding is in line with a few previous reports from Iran [58] and other countries [59]. However, another study reported otherwise [60].…”

HIV clinic‐based extended‐release naltrexone versus treatment as usual for people with HIV and opioid use disorder: a non‐blinded, randomized non‐inferiority trial

“…In a trial in Russia, people with OUD and untreated HIV were randomized to receive long‐acting naltrexone implants or daily oral naltrexone dosing. At 24 weeks, 38% of those assigned to long‐acting naltrexone and 35% of those assigned to oral naltrexone achieved an HIV viral load < 400 copies/ml [15]. HIV viral suppression rates of 52.7% at 24 weeks among those randomized to XR‐NTX in the CHOICES trial exceeds viral suppression observed in these prior studies, as well as a systematic review of 32 mainly observational studies that reported a 45% increase in HIV viral suppression attributed to opioid agonist treatment [4].…”

“…Our results suggest that initiating XR‐NTX in a non‐addiction specialty outpatient setting facilitates HIV viral suppression on a level comparable to initiating opioid agonist treatment. While OUD treatment adherence most probably mediates the effect of XR‐NTX on HIV viral suppression [15], XR‐NTX may also mitigate risky decision‐making and improve treatment adherence through central effects on the reward pathway [28].…”

“…In incarcerated individuals with OUD and HIV, XR‐NTX initiated prior to release increased HIV viral suppression at 6 months compared with those randomized to placebo [14]. Similarly, a long‐acting naltrexone implant achieved greater HIV suppression compared to oral naltrexone in a trial in Russia [15].…”

Goofballing of Opioid and Methamphetamine: The Science Behind the Deadly Cocktail

“…Oral treatment of naltrexone for opioid dependence is ineffective due to poor treatment adherence ( Minozzi et al, 2011 ). Naltrexone implant, on the other hand, has produced some positive results in the treatment of opioid or polydrug abuse ( Kelty et al, 2019 ; Krupitsky et al, 2019 ). Nevertheless, the clinical efficacy of the implant in the long-term has not been reported and the potential opioid overdose associated with naltrexone implant has not been sufficiently explored ( Saucier et al, 2018 ).…”