A liberalized approach to directly observed therapy for HCV retains excellent cure rates among PWID in Vienna.

Introduction: Directly observed therapy (DOT) is an effective strategy to optimize hepatitis C virus (HCV) cure rates in people who inject drugs (PWID) on stable opioid agonist therapy (OAT). While adherence to daily DOT is excellent, it remains unclear if extended DOT distribution intervals result in similar sustained virologic response (SVR) rates. Methods: PWID undergoing DOT with direct-acting antiviral agents (DAA) alongside OAT for HCV infection at a low-threshold institution were included. Social distancing requirements during the COVID19 pandemic led to an extension in DOT dispensation intervals; therefore, the study population was classified according to "tight period" (DAA start 2014-2020) and "liberal period" (DAA start 2020-2023) cohorts. Socioeconomic characteristics, DOT distribution schedules, and rates of SVR at week 12 after end of therapy (SVR12) were compared between groups. Results: We included 719 consecutive PWID (male: 76.5 %; median age: 39 years), 441 (61.3 %) were treated in the "tight period" and 278 (38.7 %) in the "liberal period". Baseline characteristics were comparable between cohorts, however, socioeconomic features of the "liberal period" group showed more problematic features (unemployment: 83.1 % vs. 67.3 %; lack of housing: 38.5 % vs. 35.1 %; ongoing injection drug use: 64.0 % vs. 57.8 %; each p < 0.001).While the "tight period" group had their DAA most commonly dispensed on a daily basis (78.9 %), the "liberal period" group received their DAA/OAT mostly once weekly (45.0 %) or 2-3x/week (24.1 %; p < 0.001). The number of missed DAA ingestions (0.3 % vs. 0.4 %; p = 0.239) and SVR12 rates by modified intention to treat analysis (exclusion of PWID who were lost to follow-up [FU] or died) were similar (401/404, 99.3 % vs. 194/195, 99.5 %; p = 1.000) between tight and liberal period, respectively.Loss of FU after end of DAA treatment was more common during the "liberal period" (28.8 % vs. 7.9 %; p < 0.001), yet no treatment interruptions or early discontinuations occurred. Conclusion: DOT originally aimed to address non-adherence among PWID by strict control through daily supervised OAT and DAA ingestion. While this approach inherently manifests a position of advanced distrust towards PWID, our findings suggest that a strategy of advanced trust and liberalization of DOT alongside effective harm reduction measures yields excellent adherence and results in similarly high HCV cure rates.