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

BACKGROUND AND AIMS: 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. DESIGN: Observational longitudinal cohort study. PARTICIPANTS AND SETTING: Patients (n = 15 290) prescribed OAT throughout Ukraine from 2004 through 2016. MEASUREMENTS: 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 36 months were assessed for outcomes. Cox regression with log-rank likelihood assessed independent predictors of treatment discontinuation. FINDINGS: The proportion prescribed high (MMT: > 85 mg; BMT: ≥ 16 mg), medium (MMT: > 40-85 mg; BMT: > 6-15 mg) and low (MMT: ≤ 40 mg; BMT: ≤ 6 mg) dosages was 25, 43 and 32%, respectively. Retention was significantly higher for BMT than MMT both at 12 (89 versus 75%) and 36 months (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 1 month (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 36 months (aHR = 1.08; 95% CI = 1.02-1.15). CONCLUSIONS: Higher dosages of opioid agonist therapies, especially for methadone maintenance treatment patients, appear to be associated with higher levels of treatment retention in Ukraine.

Cdk1: unsung hero of S phase?

Cdk2 has been viewed as a key cell cycle regulator that is essential for S phase progression. The recent discovery that Cdk2 is not required for cell proliferation in mice now shows that other factors must be able to replace Cdk2 in stimulating DNA replication. Experiments performed in Xenopus egg extracts identify the mitotic protein kinases Cdk1/Cyclin B and Cdk1/Cyclin A as likely candidates. These observations raise the intriguing possibility that Cdk1 normally participates in genome duplication in wild type cells.