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. 2015 Aug 28;10(8):e0134395.
doi: 10.1371/journal.pone.0134395. eCollection 2015.

Consideration of Viral Resistance for Optimization of Direct Antiviral Therapy of Hepatitis C Virus Genotype 1-Infected Patients

Julia Dietz  1 , Simone Susser  1 , Caterina Berkowski  1 , Dany Perner  1 , Stefan Zeuzem  1 , Christoph Sarrazin  1
Affiliations

Consideration of Viral Resistance for Optimization of Direct Antiviral Therapy of Hepatitis C Virus Genotype 1-Infected Patients

Julia Dietz et al. PLoS One. .

Abstract

Different highly effective interferon-free treatment options for chronic hepatitis C virus (HCV) infection are currently available. Pre-existence of resistance associated variants (RAVs) to direct antiviral agents (DAAs) reduces sustained virologic response (SVR) rates by 3-53% in hepatitis C virus (HCV) genotype 1 infected patients depending on different predictors and the DAA regimen used. Frequencies of single and combined resistance to NS3, NS5A and NS5B inhibitors and consequences for the applicability of different treatment regimens are unknown. Parallel population based sequencing of HCV NS3, NS5A and NS5B genes in 312 treatment-naïve Caucasian HCV genotype 1 infected patients showed the presence of major resistant variants in 20.5% (NS3), 11.9% (NS5A), and 22.1% (NS5B) with important differences for HCV subtypes. In NS3, Q80K was observed in 34.7% and 2.1% of subtype 1a and 1b patients, respectively while other RAVs to second generation protease inhibitors were detected rarely (1.4%). Within NS5A RAVs were observed in 7.1% of subtype 1a and 17.6% in subtype 1b infected patients. RAVs to non-nucleoside NS5B inhibitors were observed in 3.5% and 44.4% of subtype 1a and 1b patients, respectively. Considering all three DAA targets all subtype 1a and 98.6% of subtype 1b infected patients were wildtype for at least one interferon free DAA regimen currently available. In conclusion, baseline resistance testing allows the selection of at least one RAVs-free treatment option for nearly all patients enabling a potentially cost- and efficacy-optimized treatment of chronic hepatitis C.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exists.

Figures

Fig 1
Fig 1. Baseline NS3 RAVs in DAA-naïve patients.
A) GT1a- and B) GT1b-infected patients.
Fig 2
Fig 2. Occurrence of RAVs within NS5A in GT1a- (A) and GT1b- (B) infected patients.
Fig 3
Fig 3. Prevalence of NS5B RAVs in GT1a- (A) and GT1b- (B) infected patients.
Fig 4
Fig 4. Rate of patients with baseline RAVs for different DAA combination therapies.
See this image and copyright information in PMC

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