The real-world impact of dosing of methadone and buprenorphine in retention on opioid agonist therapies in Ukraine.

Abstract

Ukraine's HIV epidemic remains concentrated among opioid-dependent people who inject drugs (PWID) where opioid agonist therapies (OAT) like methadone (MMT) and buprenorphine (BMT) maintenance treatments are the most cost-effective HIV prevention strategies, but remain under-scaled. This study aimed to measure the association between dose and type of OAT prescribed and treatment retention. Observational longitudinal cohort study. Patients (n=15 290) prescribed OAT throughout Ukraine from 2004 through 2016. Data were analyzed using time-event strategies to estimate cumulative treatment retention, defined as time to OAT discontinuation. Cumulative retention proportions at 1, 12 and 36months were assessed for outcomes. Cox regression with log-rank likelihood assessed independent predictors of treatment discontinuation. The proportion prescribed high (MMT: >85mg; BMT: ≥16mg), medium (MMT: >40-85mg; BMT: >6-15mg) and low (MMT: ≤40mg; BMT: ≤6mg) dosages was 25, 43 and 32%, respectively. Retention was significantly higher for BMT than MMT both at 12 (89 versus 75%) and 36months (80 versus 56%). Although dosing levels for BMT did not influence retention, increasing dosages for MMT were significantly associated with higher retention rates at 1 (90, 96, 99%), 12 (59, 78, 91%) and 36 (34, 59, 79%) months, respectively. Independent predictors associated with 12-month OAT discontinuation were medium [adjusted hazard ratio (aHR)=2.23; 95% confidence limit (CL)=1.95-2.54] and low (aHR=4.96; 95% CL=4.37-5.63) OAT dosage relative to high dosage, male sex (aHR=1.27; 95% CL=1.14-1.41), MMT relative to BMT prescription (aHR=1.57; 95% CL=1.32-1.87) and receiving OAT in general (aHR=1.22; 95% CL=1.02-1.46) or tuberculosis (aHR=1.43; 95% CL=1.10-1.85) hospitals, relative to specialty addiction treatment and AIDS center settings. Lower dosages contributed more to dropout especially at 1month (aHR 3.12; 95% CL=2.21-4.41 and aHR 7.71; 95% CL=5.51-10.79 for medium and low dosages, respectively). Younger age was significantly associated with OAT discontinuation only at 36months (aHR=1.08; 95% CI=1.02-1.15). Higher dosages of opioid agonist therapies, especially for methadone maintenance treatment patients, appear to be associated with higher levels of treatment retention in Ukraine.