Buprenorphine, often in combination with naloxone, is a critical treatment for opioid use disorder (OUD). Buprenorphine reduces opioid use, decreases overdose and all-cause mortality by half, reduces HIV risk behavior, and improves HIV-related treatment outcomes (Korthuis et al., 2011, Low et al., 2016, MacArthur et al., 2012, Mattick et al., 2014, Sordo et al., 2017). In many parts of the world buprenorphine treatment for OUD has been integrated into a variety of care models, including HIV clinics (Korthuis et al., 2017).

Buprenorphine is a partial agonist at the mu opioid receptor with antagonist effect at the kappa opioid receptor and less effect at delta and orphan opioid receptors. With low oral bioavailability, buprenorphine is mainly taken sublingually although transmucosal and subcutaneous formulations are also available for the treatment of OUD (Coe et al., 2019). Buprenorphine’s long half-life allows for once daily dosing and even every other day dosing can be effective. Buprenorphine undergoes both N-dealkylation and conjugation. Buprenorphine N-dealkylation is primarily through CYP3A4 and CYP2C8 enzymes and glucuronidation is principally by UGT1A3, UGT2B7, and UGT1A1 (Rouguieg et al., 2010). Norbuprenorphine, buprenorphine’s main metabolite, retains agonist effect at mu-opioid receptors but P-glycoprotein efflux transporters at the blood-brain barrier limit its overall clinical effect (Brown et al., 2012). Buprenorphine and its metabolites are mostly eliminated through the feces with approximately 20 % eliminated renally (Cone et al., 1984). Medications that induce CYP3A4 can increase buprenorphine clearance. Because buprenorphine has both high affinity at the mu opioid receptor and a long half-life, drug-drug interaction (DDI) with CYP3A4 inducers have little clinical impact on patient outcomes or dosing requirements. This contrasts with methadone where DDI can increase methadone clearance resulting in opioid withdrawal symptoms, need to increase methadone dose and dosing frequency (Bruce et al., 2013).

Previously, we used population pharmacokinetics (POPPK) to identify ethnic differences and the influence of both genetic variants and HIV antiretroviral therapy (ART) on methadone pharmacokinetics (Bart et al., 2021, Bart et al., 2014). Population pharmacokinetics uses sparse sampling to model pharmacokinetic parameters (Sheiner et al., 1977). This contrasts with traditional pharmacokinetic studies, which rely on dense sampling, a resource intensive approach that limits the size of study populations (often 8–12 participants total). With sparse sampling, POPPK allows for larger population sample sizes (generally over 50), making it easier than traditional pharmacokinetics to measure the effect of covariates on pharmacokinetic parameters. Here, we use POPPK to explore buprenorphine pharmacokinetics and the effect of HIV ART in patients with OUD taking buprenorphine in Vietnam.