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Abstract Details
Treatment outcomes in hepatitis C virus genotype 1a infected patients with and without baseline NS5A resistance-associated substitutions
Julia Dietz1, Johannes Vermehren1, Katrin Matschenz2, Peter Buggisch2, Hartwig Klinker3, Julian Schulze Zur Wiesch4, Holger Hinrichsen5, Kai-Henrik Peiffer1, Christiana Graf1, Thomas Discher6, Janina Trauth6, Jörn M Schattenberg7, Felix Piecha4, Stefan Mauss8, Claus Niederau9, Tobias Müller10, Christoph Neumann-Haefelin11, Christoph P Berg12, Stefan Zeuzem1, Christoph Sarrazin113, European HCV Resistance Study Group
Author information
1Department of Internal Medicine 1, University Hospital, Goethe University, Frankfurt, Germany; German Center for Infection Research (DZIF), External Partner Site Frankfurt, Germany.
2Institute for Interdisciplinary Medicine IFI, Hamburg, Germany.
3Department of Internal Medicine II, Division of Infectious Diseases, University Hospital Würzburg, Germany.
4I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Germany.
5Gastroenterologisch-Hepatologisches Zentrum Kiel, Kiel, Germany.
6Department of Internal Medicine II, Section of Infectious Diseases, Justus-Liebig-University Giessen, Giessen, Germany.
7Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
8Center for HIV and Hepatogastroenterology, Düsseldorf, Germany.
10Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany.
11Department of Medicine II, Medical Center, Faculty of Medicine, University of Freiburg, Germany.
12Department of Internal Medicine I, University of Tübingen, Tübingen, Germany.
13Medizinische Klinik 2, St. Josefs-Hospital, Wiesbaden, Germany.
Abstract
Background&aims: The presence of baseline resistance-associated substitutions (RASs) reduced sustained virologic response (SVR) rates in chronic hepatitis C virus (HCV) genotype 1a infected patients treated with Elbasvir/Grazoprevir (EBR/GZR). This study aimed to evaluate the frequency of NS5A RASs and treatment outcomes in patients for whom EBR/GZR was intended.
Methods: We sequenced NS5A in 832 samples from German genotype1a-infected DAA-naïve patients population-based, which were collected in the European Resistance Database. Treatment outcomes and clinical parameters were evaluated in 519 of these patients retrospectively.
Results: Overall, 6.5% of patients harbored EBR-specific NS5A RASs at baseline, including Q30H/R (3.3%), L31M (1.8%), Y93H (1.6%) and other individual variants. Antiviral treatment, including EBR/GZR, was initiated in 88% of patients. In the absence of RASs, the majority of patients received EBR/GZR for 12 weeks (57%) and the SVR rate was 97% compared to 99% SVR achieved using other DAA regimens (LDV/SOF±RBV, G/P, PrOD+RBV, VEL/SOF). Various regimens were used in the presence of RASs and SVR rates were high following treatment with LDV/SOF (100%), G/P (83%), PrOD/RBV (100%), VEL/SOF (100%), SMV/SOF (100%) and EBR/GZR+RBV for 16 weeks (100%). However, two patients received EBR/GZR for 16 weeks without RBV and one relapsed.
Conclusions: EBR/GZR treatment with or without RBV for 12 or 16 weeks according to a baseline RAS analysis was highly effective with ≥97% SVR in patients with genotype 1a. EBR/GZR without RBV should be avoided in patients with RASs. High SVR rates were also achieved using other 8 or 12 weeks DAA regimens.