Highlights
- •In patients with GT1-6 HCV infection, 28% had detectable NS5A class RASs at baseline.
- •High SVR rate was observed in patients treated with SOF/VEL irrespective of baseline NS5A RASs.
- •Single NS5A class resistance was observed at virologic failure post SOF/VEL treatment.
Background & Aims
The fixed-dose combination of sofosbuvir/velpatasvir was highly efficacious in patients
infected with genotype (GT)1–6 hepatitis C virus (HCV) in the ASTRAL studies. This
analysis evaluated the impact of baseline resistance-associated substitutions (RASs)
on treatment outcome and emergence of RASs in patients infected with HCV GT1-6 who
were treated with sofosbuvir/velpatasvir.
Methods
Non-structural protein 5A and 5B (NS5A and NS5B) deep sequencing was performed at baseline and at the time of relapse for all patients
treated with sofosbuvir/velpatasvir for 12 weeks (n = 1,778) in the ASTRAL-1–3, ASTRAL-5
and POLARIS-2–3 studies.
Results
Patients with 37 known and 19 novel HCV subtypes were included in these analyses.
Overall, 28% (range 9% to 61% depending on genotype) had detectable NS5A class RASs
at baseline, using a 15% sequencing assay cut-off. There was no significant effect
of baseline NS5A class RASs on sustained virologic response at week 12 (SVR12) with
sofosbuvir/velpatasvir; the SVR12 rate in the presence of NS5A class RASs was 100%
and 97%, in patients with GT1a and GT1b infection, respectively, and 100% in patients
with GT2 and GT4–6 infections. In GT3 infection, the SVR rate was 93% and 98% in patients
with and without baseline NS5A class RASs, respectively. The overall virologic failure
rate was low (20/1,778 = 1.1%) in patients treated with sofosbuvir/velpatasvir. Single
NS5A class resistance was observed at virologic failure in 17 of the 20 patients.
Conclusions
Sofosbuvir/velpatasvir taken for 12 weeks once daily resulted in high SVR rates in
patients infected with GT1–6 HCV, irrespective of baseline NS5A RASs. NS5A inhibitor
resistance, but not sofosbuvir resistance, was detected in the few patients with virologic
failure. These data highlight the high barrier to resistance of this regimen for the
treatment of chronic HCV across all genotypes in the vast majority of patients.
Lay summary
Sofosbuvir/velpatasvir taken once daily for 12 weeks resulted in high sustained virologic
response rates in patients infected with HCV, irrespective of the presence of NS5A
resistance-associated variants prior to treatment. Single class NS5A inhibitor resistance,
but not sofosbuvir resistance, was detected in the few patients with virologic failure.
These data highlight the high barrier to resistance of this regimen for the treatment
of chronic HCV across all genotypes in the vast majority of patients.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: December 05, 2017
Accepted:
November 27,
2017
Received in revised form:
November 9,
2017
Received:
June 9,
2017
Identification
Copyright
© 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
