Personalized treatment of hepatitis C genotype 1a in Norway and Sweden 2014–2016: a study of treatment outcome in patients with or without resistance-based DAA-therapy

Abstract

Objectives: Resistance-associated substitutions (RASs) may impair treatment response to direct-acting antivirals (DAA) in hepatitis C virus (HCV) treatment. We investigated the effects of baseline NS3-RASs (Q80K and R155K) and clinically relevant NS5A-RASs in patients with HCV genotype (GT) 1a infection on treatment outcome, with or without resistance-based DAA-treatment. This multi-center study was carried out between 2014 and 2016.

Patients/methods: Treatment in the intervention group (n = 92) was tailored to baseline resistance. Detection of NS3-RAS led to an NS5A-inhibitor-based regimen and detection of NS5A-RAS to a protease-inhibitor regimen. Patients without baseline RAS in the intervention group and all patients in the control group (n = 101) received recommended standard DAA-treatment.

Results: The sustained virologic response rates (SVR) in the intervention and control groups were 97.8% (90/92) and 93.1% (94/101), respectively (p = .174). A trend toward higher SVR-rate in cirrhotic patients (p = .058) was noticed in the intervention group compared to the control group with SVR-rates 97.5% (39/40) and 83.3% (35/42), respectively. All patients with baseline NS3 (Q80K/R155K) or NS5A-RASs in the intervention group achieved SVR with personalized resistance-based treatment. In the control group, five patients with Q80K or R155K at baseline were treated with simeprevir + sofosbuvir and treatment failed in two of them. Furthermore, one of three patients who failed ledipasvir + sofosbuvir treatment had NS5A-RASs at baseline.

Conclusions: In line with the findings of the OPTIMIST-2 trial for Q80K and the EASL-guidelines 2016 for NS5A-RASs, baseline RASs appeared to have an impact on treatment outcome albeit a statistical significance was not observed in this low-prevalence population.

Keywords:

• Baseline resistance
• hepatitis C virus
• NS5A
• Q80K
• resistance-associated substitution
• sustained virologic response

Acknowledgments

A. L. received Clinical Research Support (ALF) from Uppsala County Council and Uppsala University. The authors would like to thank Navaneethan Palanisamy for grammatical assistance. Anders Bergqvist, Christina Öhrmalm and Kåre Bondeson are thanked for their help with the resistance analysis.

Disclosure statement

J.L. has received an unrestricted research grant from Medivir, but this company was not involved in any parts of this study. The other authors report no conflicts of interest.

Additional information

Funding

J. L. received financial support for this study from the Uppsala-Örebro Regional Research Council, the Selander Foundation and Scandinavian Society for Antimicrobial Chemotherapy.