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).

Synthesis of Porous Biochar Containing Graphitic Carbon Derived From Lignin Content of Forestry Biomass and Its Application for the Removal of Diclofenac Sodium From Aqueous Solution.

Porous biochar containing graphitic carbon materials have received great attention from various disciplines, especially for environmental pollutant treatment, due to their cost-effective and specific textural properties. This study exhibited a two-step strategy to compose lignin-porous biochar containing graphitic carbon (LPGC) from pitch pine sawdust and investigated its adsorptive removal for diclofenac sodium (DCF) from an aqueous solution. Sulfuric acid (H2SO4) was utilized to obtain lignin content from biomass and potassium ferrate (K2FeO4) and was adopted to fulfill the synchronous carbonization and graphitization of LPGC. Through slow pyrolysis in atmospheric N2 (900°C - 2 h), the structure of the as-prepared sample was successfully modified. Using SEM images, a stripped layer structure was observed on the H2SO4-treated sample for both one-step and two-step activated samples, indicating the pronounced effect of H2SO4 in the layering of materials. K2FeO4 acted as an activator and catalyst to convert biomass into the porous graphitic structure. The BET surface area, XRD and Raman spectra analyses demonstrated that LPGC possessed a micro/mesoporous structure with a relatively large surface area (457.4 m2 g-1) as well as the presence of a graphitic structure. Further adsorption experiments revealed that LPGC exhibited a high DCF adsorption capacity (qmax = 159.7 mg g-1 at 298 K, pH = 6.5). The effects of ambient conditions such as contact time, solution pH, temperature, ionic strength, electrolyte background on the uptake of DCF were investigated by a batch adsorption experiment. Results indicated that the experimental data were best fitted with the pseudo second-order model and Langmuir isotherm model. Furthermore, the adsorption of DCF onto the LPGC process was spontaneous and endothermic. Electrostatic interaction, H-bonding interaction, and π-π interaction are the possible adsorption mechanisms. The porous biochar containing graphitic carbon obtained from the lignin content of pitch pine sawdust may be a potential material for eliminating organic pollutants from water bodies.

Impact of a methadone maintenance therapy pilot in Vietnam and its role in a scaled-up response.

BACKGROUND: As a dual response to the HIV epidemic and the high level of injecting drug use in Vietnam, the Ministry of Health (MOH) initiated a pilot methadone maintenance therapy (MMT) program in Hai Phong and Ho Chi Minh City (HCMC) in early 2009. The objectives of the pilot were to provide evidence on whether MMT could be successfully implemented in Vietnam and scaled up to other localities. METHODS: A prospective study was conducted among 965 opiate drug users admitted to the pilot. Data on demographic characteristics, sexual behaviors, substance use behaviors (including heroin use), and blood-borne virus infection (HIV, hepatitis B, and hepatitis C) were collected at treatment initiation and then again at 3-, 6-, 9-, 12-, 18-, and 24-month intervals thereafter. RESULTS: Twenty-four months after treatment initiation, heroin use as measured by urine test or self-report had reduced from 100 % of participants at both sites to 14.6 % in Hai Phong and 22.9 % in HCMC. When adjusted for multiple factors in Generalized Estimating Equations (GEE) logistic regression modeling, independent predictors of continued heroin use after 24 months of MMT in HCMC were the following: poor methadone adherence (adjusted odds ratio (AOR) = 3.7, 95 % confidence interval (CI) 1.8-7.8); currently on antiretroviral treatment (ART) (AOR = 1.8, 95 % CI 1.4-2.4); currently on TB treatment (AOR = 2.2, 95 % CI 1.4-3.4); currently experiencing family conflict (AOR = 1.6, 95 % CI 1.1-2.4); and currently employed (AOR = 0.8, 95 % CI 0.6-1.0). For Hai Phong participants, predictors were the following: currently on ART (AOR = 2.0, 95 % CI = 1.4-3.0); currently experiencing family conflict (AOR = 2.0, 95 % CI = 1.0-3.9); and moderate adherence to methadone (AOR = 2.1, 95 % CI = 1.2-1.9). In Hai Phong, the percentage of participants who were employed had also increased by end of study from 35.0 to 52.8 %, while in HCMC the level remained relatively unchanged, between 52.2 and 55.1 %. DISCUSSION: Study findings were used in multiple fora to convince policymakers and the public on the significant and vital role MMT can play in reducing heroin use and improving quality of life for individuals and families. Four years after this study was completed, Vietnam had expanded MMT to 162 clinics in 44 provinces serving 32,000 patients.