Baseline resistance-guided therapy does not enhance the response to interferon-free treatment of HCV infection in real life

Luis M Real,Carlos Galera,Dolores Merino,Nicolás Merchante,María J Ríos,Juan Macías,Juan A Pineda,Luis Morano,Rafael Granados,Marcial Delgado,Ana B Pérez,Miguel G Deltoro,Federico García

doi:10.1038/s41598-018-33367-1

Abstract

Hepatitis C virus (HCV) response to direct-acting antivirals (DAAs) may be influenced by the presence of resistance-associated substitutions (RASs). This study aimed to assess if NS5A baseline RAS-guided treatment enhances the rate of sustained viral response (SVR) in naïve HCV-infected patients in clinical practice. All HCV-infected patients who initiated treatment with interferon (IFN)-free DAA-based regimens between March 2016 and May 2017 in 17 Spanish hospitals and who had evaluable SVR 12 weeks (SVR12) after the end of therapy were included. Patients had to be DAA naïve, with the exception of sofosbuvir with/without IFN. In one hospital, participants received therapy guided by the presence of NS5A-RASs (RGT population). Patients enrolled in the remaining hospitals, without baseline RASs testing, constituted the control population. A total of 120 and 512 patients were included in the RGT and control populations, respectively. Nine (7.5%) individuals in the RGT population showed baseline NS5A-RASs. All of them achieved SVR12. The SVR12 rate in the RGT population was 97.2% (three relapses) whereas it was 98.8% (six relapses) in the control population (p = 0.382). Our findings suggest that testing for baseline NS5A-RASs in naïve HCV-infected patients does not enhance the rate of SVR to DAA-based IFN-free therapy in clinical practice.

Highlights

Treatment of hepatitis C virus (HCV) infection using direct-acting antiviral (DAA) combinations achieves high cure rates
Our results suggest that routine testing of baseline resistance-associated substitutions (RASs) in naïve Hepatitis C virus (HCV)-infected patients does not enhance the rate of sustained virological response (SVR) to all oral DAA-based therapy in daily clinical practice
The rate of SVR achieved by non-guided treatment is so high, that no benefit is added by RAS testing

Summary

Introduction

Treatment of hepatitis C virus (HCV) infection using direct-acting antiviral (DAA) combinations achieves high cure rates. According to data generated in phase 2 and 3 clinical trials, resistance of HCV to DAAs due to the presence of resistance-associated substitutions (RASs) in the viral genome, mainly those within the NS5A gene, can influence treatment response[7,8] For this reason, the AASLD-IDSA guidelines recommend testing for baseline NS5A RASs in specific DAA-naïve HCV-infected populations who are going to be treated with DAA-combinations containing a NS5A inhibitor[4]. Cento et al.[9] reported 100% sustained virological response (SVR) rate in DAA-naïve patients undergoing treatment guided by baseline RASs in clinical practice. They did not compare with a control population without RAS-guided treatment. We aimed to assess whether baseline RASs guided treatment increases the rate of SVR in naïve HCV-infected patients in daily clinical practice

Objectives

Methods

Results

Conclusion