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https://www.arca.fiocruz.br/handle/icict/10556
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Mar. 2016
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- IOC - Artigos de Periódicos [12490]
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NS5A INHIBITOR RESISTANCE-ASSOCIATED POLYMORPHISMS IN BRAZILIAN TREATMENT-NAIVE PATIENTS INFECTED WITH GENOTYPE 1 HEPATITIS C VIRUS
Affilliation
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatites Virais. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatites Virais. Rio de Janeiro, RJ, Brasil / UNIRIO. Hospital Universitário Gaffrée Guinle. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatites Virais. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatites Virais. Rio de Janeiro, RJ, Brasil / UNIRIO. Hospital Universitário Gaffrée Guinle. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatites Virais. Rio de Janeiro, RJ, Brasil.
Abstract
Objectives: Several promising NS5A protein inhibitors for hepatitis Cvirus (HCV) treatment, showing good antiviral
activity, are currently being evaluated in clinical trials. However, viral breakthroughs associated with resistant variants
have been observed, especially in patients infected with HCV-1a. We aimed to evaluate the occurrence of
potential resistance mutations in the NS5A gene of HCV among Brazilian treatment-naive patients.
Methods: Direct sequencing of the HCV NS5A gene was performed in serum samples of 106 treatment-naive
patients infected with subtypes 1a (n¼52) and 1b (n¼54). The sequence variability, signature patterns in
amino acid sequences and variants associated with NS5A inhibitors were evaluated.
Results: The M28T and Y93H mutations were found in the subtype 1a sequences of two (3.85%) patients, and
seven (13.46%) other patients presented the secondary mutation(s) H58P, E62D or H58P-E62D. For subtype 1b,
the Y93H mutation was found in two (3.70%) patients and the substitutions R30Q, L31M, P58S and I280V were
found in eight (14.81%) patients. Two distinct HCV-1a clades were distinguished by a phylogenetic analysis performed
along with representative HCV-1a sequences and sequences containing HCV NS5A inhibitor resistance
mutations retrieved from the Los Alamos database. All Brazilian sequences formed a large group of related
sequences inside clade 1. It is noteworthy that 65.85% of sequences with substitution at sites 28, 30, 31 and
93 were found in clade 1.
Conclusion: Brazilian HCV-1a sequences presented a peculiar pattern of amino acid composition, mutations and
frequencies, which is distinct from other previously characterized sequences from other locations. The association
of these findings with the outcome of treatment with NS5A inhibitors awaits further analysis.
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