2.1 Study design and data sources
This is an observational study among OAT patients from 2013 to 2017 in Norway. Data were extracted from The Norwegian Prescription Database (NorPD) from January 1, 2013 to March 31, 2018. The database covers the entire Norwegian population and records all drugs dispensed from pharmacies in Norway, hence leaving only over-the-counter drugs and drugs administered at hospitals and nursing homes. All drugs are classified according to The Anatomical Therapeutic Chemical (ATC) classification system [39]. Defined daily doses (DDDs) according to 2018 [40] were employed to quantify the dispensed OAT and HCV medications respectively. The DDDs are the assumed average maintenance dose per day for a drug used for its main indication [41].
Data from The Norwegian Centre for Addiction Research were used for estimating the prevalence of chronic HCV among OAT patients, whereas incidence data among Norwegian PWIDs was gathered from The Norwegian Institute of Public Health and Meijerink et al. [14] The former publish annual status reports on prevalence, whereas the latter have demonstrated the incidence in a compartmental model for HCV infections from 1973-2030 in Norway. These data were not linked on an individual level.
2.2 Study population and definitions
The study population included all individuals with at least one dispensed prescription of buprenorphine (ATC code N07BC01), methadone (N07BC02), buprenorphine-naloxone (N07BC51), and levomethadone (N07BC05). Other opioids are very rarely used for OAT in Norway and considered outside national guidelines [42]. Patients <18 years and with other indications than OAT were excluded from the study on the basis of formulation, chronic pain and palliative care reimbursement codes (Figure S1).
Exposure to HCV treatment was defined as being dispensed either pegylated interferon alpha (L03AB05 and L03AB11) and ribavirin (J05AP01) or DAAs (group J05AP) during the study period. Thus, definition of treatment uptake was any individual on OAT who has been dispensed HCV treatment. Any individual who died was censored in the calendar year they passed away. Rates were calculated by dividing number of individuals with dispensed HCV treatment by individuals on OAT, stratified by each calendar year. The cumulative frequency, which is the addition of successive years of treatment uptake, was then calculated. HCV treatment was stratified as overall treatment with any chronic HCV medication and treatment with solely DAAs.
HCV treatment coverage was defined as individuals on OAT identified in NorPD annually, adjusted for death, HCV prevalence, and new cases of chronic HCV each year, which had received treatment for chronic HCV during the study period. Mean prevalence during the study period among patients enrolled in OAT ranged from 51% in 2013 to 43% in 2017 [5, 17-20] and proportional prevalence among OAT individuals were calculated per calendar year. Incidence was around 400 per year for PWIDs during the study period [14]. It proved methodologically challenging to estimate the HCV incidence among OAT individuals from PWIDs due to lack of reliable evidence from the literature, and for this reason expert opinion were obtained from clinicians in addiction medicine and set to 0.70 (70%). We developed the following basic model for our coverage calculation:

where HCV cov is HCV coverage, t_HCV = number of OAT patients with dispensed HCV treatment, p_HCV = number of OAT patients with chronic HCV and i_HCV = number of new cases of chronic HCV among OAT patients. Coverage was calculated annually for Norway and by Health County, and as cumulative frequencies.
We defined adherence to DAA as having collected prescriptions equivalent to three months of treatment or more. DAAs for adults, which in Norway is prescribed only by specialists in either infectious medicine or gastroenterology, are collected for one-month-at-a-time basis where a typical DAA treatment course is 12 weeks, i.e. three dispensed prescriptions and ≥84 DDDs. The exception is the drug combination ledipasvir/sofosbuvir, which may be prescribed for eight weeks (two collections and ≥54 DDD) for cases of previously untreated genotype 1 infections. This allowed us to examine adherence based on number of dispensed prescriptions and DDDs. Impending factors associated with treatment adherence to DAAs were identified a priori and included gender, age, and OAT continuity, and subject to multivariate analyzes in a step-by-step model.
Finally, OAT continuity was defined according to dispensed DDDs and stratified into three categories, ranging from a high level of OAT continuity in category I (>2 DDD), medium in category II (2-1 DDD), and to a low level of OAT continuity in category III (<12 DDD). One DDD for methadone and buprenorphine is 25mg and 8mg respectively.
2.3 Statistical analyzes and strategy
Descriptive data are presented as frequencies, percentages, means, and with corresponding 95% confidence intervals where appropriate. Logistic regression on factors associated with adherence are presented as adjusted odds ratio (aOR) when adjusted for age, gender and OAT continuity.
The initial processing of the received encrypted file from NorPD was completed in SPSS version 24. Secondly, the file was converted and subsequently analyzed in Stata SE version 15 (StataCorp, TX, USA). Map figures were made in R.
2.4 Data handling and ethical considerations
Since all data was analyzed anonymously no written consent was obtained from any of the individuals in the study. This study was approved by the regional committee for ethics in medical research (no. 2018/939/REK Vest). It was conducted in accordance with the Helsinki Declaration and as an observational study in accordance with international accepted STROBE guidelines [43].