Prevalence of baseline NS3 resistance-associated substitutions (RASs) on treatment with protease inhibitors in patients infected with HCV genotype 1 - 08/11/19
, Nathália Delvaux a, Carlos Eduardo Brandão-Mello b, Estevão Portela Nunes c, Paulo Sérgio Fonseca de Sousa a, Lia Laura Lewis Ximenez de Souza Rodrigues a, Elisabeth Lampe a, Francisco Campello do Amaral Mello aBienvenue sur EM-consulte, la référence des professionnels de santé.
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Highlights |
• | Overall RAS prevalence in this study was 13.7% (10/73). RAS prevalence for HCV subtype 1b was 17.4% (4/23) while for HCV subtype 1a was 12% (6/50). |
• | Primary mutations V36M/L and R155K were observed only in HCV subtype 1a, whereas T54S and Q80K were identified only in HCV subtype 1b. RAS V36M, which is related to reduction of susceptibility to second-generation PIs, was the most frequent in the study (6.9%; 5/73). |
• | Our results indicated that Brazilian isolates of HCV present a distinct pattern of RAS depending on the infecting viral subtype. In contrast to data from other countries, RAS Q80K prevalence in Brazil is low in HCV subtype 1a. |
• | Our observations suggested that naturally occurring NS3 substitutions did not seem to negatively impact treatment outcome and the use of simeprevir, paritaprevir and grazopevir has a high probability of being effective for treating HCV chronic carriers infected with subtypes 1a and 1b. |
Summary |
Background and aims |
Treatment for hepatitis C has evolved significantly with the licensing of direct-acting antiviral drugs (DAAs). However, one of the limiting factors of the effectiveness of antiviral therapy with protease inhibitors (PIs) is the emergence of resistance caused by point mutations. The aim of this study was to determine the prevalence of resistance-associated substitutions (RASs) in HCV NS3 gene in patients infected with genotype 1 before therapy with simeprevir.
Methods |
A total of 73 serum samples from 15 treatment-experienced patients with boceprevir/telaprevir and 58 DAA-naïve patients were collected before therapy with DAAs simeprevir, daclatasvir and/or sofosbuvir. Presence of baseline resistance-associated substitutions (RAS) in the serine protease domain of HCV NS3 was analyzed by nucleotide sequencing followed by amino acid deduction.
Results |
Overall RAS prevalence in this study was 13.7% (10/73). RAS prevalence for HCV subtype 1b was 17.4% (4/23) while for HCV subtype 1a was 12% (6/50). Primary mutations V36M/L and R155K were observed only in HCV subtype 1a, whereas T54S and Q80K were identified only in HCV subtype 1b. RAS V36M, which is related to reduction of susceptibility to second-generation PIs, was the most frequent in the study (6.9%; 5/73).
Conclusions |
Our results indicated that Brazilian isolates of HCV present a distinct pattern of RAS depending on the infecting viral subtype. In contrast to data from other countries, RAS Q80K prevalence in Brazil is low in HCV subtype 1a. This study improves the knowledge of genetic barrier for resistance to PIs involving RASs in chronically infected patients and its possible impact on an unsuccessful treatment outcome, information that might be crucial to upcoming decisions of incorporation of new DAAs in Brazilian guidelines of antiviral therapy against HCV infection.
Le texte complet de cet article est disponible en PDF.Keywords : HCV, RAS, Protease inhibitors
Plan
Vol 43 - N° 6
P. 700-706 - novembre 2019 Retour au numéro
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