UCLA

Opioid use disorder (OUD), hepatitis C (HCV), and HIV are components of a syndemic and public health emergency in the US. Effective treatments exist for all three conditions, but adherence to these treatments can be difficult, particularly for those with OUD. Evidence from real world data is lacking on the complex interactions between treatment for OUD and infections such as HIV and HCV. The studies within this dissertation investigate factors related to medication adherence among patients living with OUD and HCV or HIV using real-world data from a large administrative claims database of privately and publicly insured people. The goal of this dissertation was three-fold. First, we described demographic, pharmaceutical, HCV treatment adherence, and healthcare utilization characteristics of those using both opioid agonist therapy (OAT), a treatment for OUD, and direct acting-antivirals (DAA) for the treatment of HCV (Aim 1). Second, we compared the effects of co-prescription of buprenorphine, a form of OAT, and ART protease inhibitors (PIs) on buprenorphine adherence (Aim 2). Lastly, using growth mixture modeling, we identified OAT long-term adherence trajectories and analyzed the predictors of OAT long-term adherence patterns (Aim 3). All aims were completed using a large administrative claims database of publicly and privately insured people in the US between 2015-2019. Aim 1 was completed using a retrospective cohort of over 2,000 insured adults on OAT who initiated HCV DAA therapy between 2015 and 2019. Over time, the median age of cohort entrants decreased (2015: 49 (interquartile range (IQR): 30-57); 2019: 37 (IQR:31-46)), the prevalence of additional substance use diagnoses at baseline increased (2015: 58%; 2019: 70%), and the cohort transitioned from mostly initiating ledipasvir/sofosbuvir (proprietary name: Harvoni) in 2015 (59%) to mostly initiating glecaprevir/pibrentasvir (proprietary name: Mavyret) by 2019 (77%). Among the youngest cohort entrants (18-35 years old), 13% discontinued HCV DAA therapy early. Among the oldest cohort entrants (51-64), 9% discontinued early. Twelve percent of people with an additional substance use diagnosis at baseline discontinued their HCV DAA therapy early. In contrast, 10% of people with OUD alone discontinued their HCV DAA therapy early. These proportions remained similar regardless of commercial or Medicaid insurance source. Despite having high levels of potential risk factors for early discontinuation such as psychiatric comorbidity and substance use, the overall proportion of people who discontinued HCV DAA therapy before eight weeks was like that observed in populations without OUD. This suggests that OUD should not be used as exclusionary criterion for payer authorization of these life-saving medications. Aim 2 used a cohort of 255 people living with and receiving pharmacotherapy for HIV and OUD. There were small to no marked differences in buprenorphine adherence and persistence across protease inhibitor vs. non-protease inhibitor forms of ART. These results remained the same in the crude, adjusted, and sensitivity analyses. Future quantitative bias analysis can illuminate the level of misclassification needed on factors such as IDU, cocaine use, and psychiatric disorders to meaningfully change confounding control and thus the results of the present study. Future studies with a larger sample size can stratify analysis by the type of PI to avoid collapsing all PIs into a single category. Collapsing all PIs may have drowned the effects of potent PI-induced enzyme inhibition among PIs with weaker enzyme inhibition potential in our study. For Aim 3, we identified three well-separated OAT adherence trajectories among 5,495 people living with HCV and OUD. We also examined the extent to which baseline demographic, clinical, and healthcare utilization characteristics predicted OAT adherence trajectory membership. Notably, 60% of the cohort was classified into sub-therapeutic adherence groups. Both the low and moderate OAT adherence trajectory groups had a mean proportion of days covered per month of less than 50% (<15 days). Additionally, we found that at baseline, having OUD without additional substance use diagnoses, initiating buprenorphine instead of methadone, older age, being female, a greater number of outpatient visits, and no overdoses were reliably associated with higher adherence during follow-up. Conversely, black race was associated with low adherence group membership. The findings of this dissertation can be used to improve clinical guidelines for HIV treatment choice among those with OUD and help to target additional support for patients at increased risk of treatment non-adherence among people with OUD and HCV. Our results provide vital and novel information on strategies to address the public health emergency that is the OUD, HCV, and HIV syndemic.