HIV clinic-based buprenorphine plus naloxone versus referral for methadone maintenance therapy for treatment of opioid use disorder in HIV clinics in Vietnam (BRAVO): an open-label, randomised, non-inferiority trial

Background: UNAIDS recommends integrating methadone or buprenorphine treatment of opioid use disorder with HIV care to improve HIV outcomes, but buprenorphine adoption remains limited in many countries. We aimed to assess whether HIV clinic-based buprenorphine plus naloxone treatment for opioid use disorder was non-inferior to referral for methadone maintenance therapy in achieving HIV viral suppression in Vietnam. Methods: In an open-label, non-inferiority trial (BRAVO), we randomly assigned people with HIV and opioid use disorder (1:1) by computer-generated random number sequence, in blocks of ten and stratified by site, to receive HIV clinic-based buprenorphine plus naloxone treatment or referral for methadone maintenance therapy in six HIV clinics in Vietnam. The primary outcome was HIV viral suppression at 12 months (HIV-1 RNA ≤200 copies per mL on PCR) by intention to treat (absolute risk difference [RD] margin ≤13%), compared by use of generalised estimating equations. Research staff actively queried treatment-emergent adverse events during quarterly study visits and passively collected adverse events reported during HIV clinic visits. This study is registered with ClinicalTrials.gov, NCT01936857, and is completed. Findings: Between July 27, 2015, and Feb 12, 2018, we enrolled 281 patients. At baseline, 272 (97%) participants were male, mean age was 38·3 years (SD 6·1), and mean CD4 count was 405 cells per μL (SD 224). Viral suppression improved between baseline and 12 months for both HIV clinic-based buprenorphine plus naloxone (from 97 [69%] of 140 patients to 74 [81%] of 91 patients) and referral for methadone maintenance therapy (from 92 [66%] of 140 to 99 [93%] of 107). Buprenorphine plus naloxone did not demonstrate non-inferiority to methadone maintenance therapy in achieving viral suppression at 12 months (RD −0·11, 95% CI −0·20 to −0·02). Retention on medication at 12 months was lower for buprenorphine plus naloxone than for methadone maintenance therapy (40% vs 65%; RD −0·53, 95% CI −0·75 to −0·31). Participants assigned to buprenorphine plus naloxone more frequently experienced serious adverse events (ten [7%] of 141 vs four of 140 [3%] assigned to methadone maintenance therapy) and deaths (seven of 141 [5%] vs three of 141 [2%]). Serious adverse events and deaths typically occurred in people no longer taking ART or opioid use disorder medications. Interpretation: Although integrated buprenorphine and HIV care may potentially increase access to treatment for opioid use disorder, scale-up in middle-income countries might require enhanced support for buprenorphine adherence to improve HIV viral suppression. The strength of our study as a multisite randomised trial was offset by low retention of patients on buprenorphine. Funding: National Institute on Drug Abuse (US National Institutes of Health).