Background: People who use drugs (PWUD) are at high risk of hepatitis C virus (HCV) infection. HCV patients often have psychiatric disorders requiring antipsychotic based treatment which can interact with HCV treatment-related metabolic pathways producing drug-drug interactions (DDIs). Our study evaluated potential DDIs between direct-acting antivirals (DAAs) and concomitant medications used in PWUD/antipsychotics-treated HCV patients in the Unites States, specially in the co-use of quetiapine and methadone, both with known risk in QTc prolongation.

Methods: This retrospective cohort study examined patients treated for HCV with SOF/VEL or GLE/PIB using IQVIA PharMetrics Plus claims data from July 2015 to June 2023. The use of antipsychotic drugs as co-medications during HCV therapy was analyzed. The PWUD population and the use of opioid substitution therapy (OST) for each DAA was subsequently identified, evaluating the risk of DDIs using the Liverpool DDI tracker.

Results: Patients on antipsychotics represented 3.7% (420/11,324) of the total cohort, 3.9% (267/6,784) treated with SOF/VEL and 3.4% (153/4,540) with GLE/PIB. Out of 178 PWUD patients on antipsychotics (42.4%), 106 (60%) were treated with SOF/VEL and 72 (40%) with GLE/PIB. Among the 106 patients on SOF/VEL, DDI risk was present in 14 patients (11.3%; 1 for clinically significant DDIs -CSDDI- and 1.9% for weak DDIs -WDDI). For the 72 GLE/PIB treated patients, 100% were on DDI risk (57 for CSDDI and 15 for WDDI). Quetiapine was the most common antipsychotic involved in the DDI risk with GLE/PIB (42), followed by aripiprazole (9) and Lurasidone (9). Interestingly, 8 patients receiving quetiapine were also on methadone as OST, with 4 on SOF/VEL and 4 on GLE/PIB.

Conclusion: Antipsychotic use in PWUD population in the US represents a similar proportion compared to previous non-US studies. Despite HCV treatment guidelines recommendations, the use of Protease Inhibitors-based DAA shows an increased risk of DDIs commonly used in US patients, specially with the use of QTc prolongation based medications like quetiapine and methadone.