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Naturally occurring substitutions conferring resistance to hepatitis C virus polymerase inhibitors in treatment-naive patients infected with genotypes 1-5

Abstract :

BACKGROUND: The hepatitis C virus (HCV) RNA-dependent RNA polymerase, NS5B, is essential for virus RNA replication. It is thus an attractive therapeutic target. Several compound nucleoside analogues, non-nucleoside inhibitors and cyclosporine analogues are being developed to inhibit NS5B activity. However, nucleotide changes in the NS5B gene can confer resistance to them.METHODS: We investigated the prevalence of known substitutions conferring resistance in HCV polymerase in 124 treatment-naive French patients infected with HCV genotypes 1, 2, 3, 4 or 5 by sequencing the NS5B gene. RESULTS: None of the 124 HCV NS5B sequences analysed contained substitutions conferring resistance to nucleoside analogues; however, NS5B polymerases containing substitutions conferring resistance to non-nucleoside inhibitors were frequent within genotype 1 strains (17%) and very common in non-genotype 1 strains. Similarly, substitutions conferring resistance to cyclosporine analogues were more prevalent within the various genotypes. CONCLUSIONS: Naturally occurring substitutions conferring resistance to NS5B inhibitors are common in treatment-naive patients infected with HCV genotype 1, 2, 3, 4 or 5. Their influence on treatment outcome should be assessed.

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Journal articles
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https://hal.univ-angers.fr/hal-03268565
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Submitted on : Wednesday, June 23, 2021 - 12:11:46 PM
Last modification on : Monday, July 4, 2022 - 9:46:20 AM

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  • HAL Id : hal-03268565, version 1
  • OKINA : ua3543

Citation

Florence Abravanel, Cécile Henquell, Hélène Le Guillou-Guillemette, Viorica Balan, Audrey Mirand, et al.. Naturally occurring substitutions conferring resistance to hepatitis C virus polymerase inhibitors in treatment-naive patients infected with genotypes 1-5. Antiviral Therapy, International Medical Press, 2009, 14 (5), pp.723 - 730. ⟨hal-03268565⟩

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