Strategic treatment optimization for HCV (STOPHCV1): a randomised controlled trial of ultrashort duration therapy for chronic hepatitis C.

Background:  The World Health Organization (WHO) has identified the need for a better understanding of which patients with hepatitis C virus (HCV) can be cured with ultrashort course HCV therapy. Methods:  A total of 202 individuals with chronic HCV were randomised to fixed-duration shortened therapy (8 weeks) vs variable-duration ultrashort strategies (VUS1/2). Participants not cured following first-line treatment were retreated with 12 weeks' sofosbuvir/ledipasvir/ribavirin. The primary outcome was sustained virological response 12 weeks (SVR12) after first-line treatment and retreatment. Participants were factorially randomised to receive ribavirin with first-line treatment. Results:  All evaluable participants achieved SVR12 overall (197/197, 100% [95% CI 98-100]) demonstrating non-inferiority between fixed-duration and variable-duration strategies (difference 0% [95% CI -3.8%, +3.7%], 4% pre-specified non-inferiority margin). First-line SVR12 was 91% [86%-97%] (92/101) for fixed-duration vs 48% [39%-57%] (47/98) for variable-duration, but was significantly higher for VUS2 (72% [56%-87%] (23/32)) than VUS1 (36% [25%-48%] (24/66)). Overall, first-line SVR12 was 72% [65%-78%] (70/101) without ribavirin and 68% [61%-76%] (69/98) with ribavirin (p=0.48). At treatment failure, the emergence of viral resistance was lower with ribavirin (12% [2%-30%] (3/26)) than without (38% [21%-58%] (11/29), p=0.01). Conclusions:  Unsuccessful first-line short-course therapy did not compromise retreatment with sofosbuvir/ledipasvir/ribavirin (100% SVR12). SVR12 rates were significantly increased when ultrashort treatment varied between 4-7 weeks rather than 4-6 weeks. Ribavirin significantly reduced resistance emergence in those failing first-line therapy. ISRCTN Registration : 37915093 (11/04/2016).
Competing Interests: Competing interests: GC has received fees from MSD and Gilead unrelated to this work. SR has carried out consultancy work for Gilead SM has received fees from Abbvie, MSD and Gilead unrelated to this work. SLP has received grants from Gilead Sciences and ViiV Healthcare unrelated to this work. DF has received research funding from Gilead and advised and/or spoken for Gilead, Merck and Abbvie unrelated to this work. RG reports grants from abbvie and Gilead unrelated to this work. MN, SMcP and MW report personal fees from MSD, abbvie and Gilead unrelated to this work. SBarclay reports personal fees from abbvie and Gilead unrelated to this work. SBhagani reports personal fees from abbive, Gilead and MSD. All other authors report no conflicts of interest.
(Copyright: © 2021 Cooke GS et al.)