Disclosures: R. Todd Frederick – Advisory Committees or Review Panels: Vital Therapies; Consulting: Salix, Gilead, Hyperion, Ocera The following people have nothing to disclose: Susan J. Ripper, Edward W. Holt, Stewart Cooper, Adil E. Wakil, Timothy
J. Davern, Raphael Merriman, Jennifer Guy Introduction: Plasma ribavirin (RBV) AG-014699 molecular weight concentration correlates with efficacy and toxicity in interferon-containing regimens, but the impact of RBV concentration on virological outcome in individuals who relapse following administration of sofosbuvir (SOF) and RBV has not been studied. This study examined the relationship between plasma RBV concentration and treatment outcome in treatment-naïve subjects who received SOF and RBV in the phase IIb QUANTUM study. Method: Stored plasma samples were retrieved for 47 subjects treated with SOF and weight-based RBV (800-1200mg/day) for 12 (51%, n=24) or 24 (49%, n=23) weeks. Week 4 plasma RBV concentration (mg/L) was quantified using validated High-Performance Liquid Chromatography assay with UV detection (HPLC-UV; λ 235 nm). Demographic and virological data were collected from baseline until date of last follow-up. Results: The trial Ferroptosis inhibitor population was predominantly male (57%, n=27) (median age 51 years, IQR 46-55) with GT1 HCV infection (79%, n=37). Only 1 patient has cirrhosis (2%). Median baseline body mass index was 27 kg/m2 (IQR 24-30). Median baseline
creati-nine was 101 mmol/L (IQR 88-116). Completion of allocated treatment
duration was high (98%, n=46). Sustained virolog-ical response (SVR12) was observed in 26 (55%) (GT1 51%, n=19; non-GT1 70%, n=7) with all treatment failure due to post-treatment relapse. Week 4 RBV concentration ranged from 0.62–6.44 mg/L (median 2.23 mg/L, IQR 1.69-2.87). Median week 4 RBV concentration was 2.25 mg/L (IQR 1.63-3.05) in those with SVR12 as compared to 2.07 mg/L (IQR 1.79-2.86) in those with treatment failure (OR 1.35; 95% CI 0.76-2.39; p=0.3). Similar results were seen when limiting analysis to those with GT1 (SVR12 2.25 mg/L, IQR 1.6-2.7; treatment failure 1.98 mg/L, IQR 1.7-2.86; OR 0.4; 95% CI 0.6-2.34; p=0.5). 38 subjects (83%) had undetectable HCV RNA at week 4 (RVR). In those with and without RVR, RBV concentrations medchemexpress were also similar (2.25 mg/L, IQR 1.79-2.87 vs 1.75 mg/L, IQR 1.64-2.69; OR 1.11; 95% CI 0.54-2.3; p=0.77). Limited haematological toxicity was noted, with median baseline and end-of-treatment haemoglobin 14 g/L (IQR 14-15) and 12 g/L (IQR 11-13), respectively, in those with SVR12 and 15 g/L (IQR 14-16) and 13 g/L (IQR 12-14), respectively, in those with treatment failure. Conclusion: In this study of predominantly GT1 treatment-naïve individuals treated with SOF and RBV, SVR12 was only 55% with all treatment failure related to relapse. Plasma RBV concentrations at week 4 were in the expected range.