Natural occurrence of NS5B inhibitor resistance-associated variants in Brazilian patients infected with HCV or HCV and HIV

Abstract

Resistance-associated variants (RAVs) represent a challenge to the success of new HCV therapies. The aim of this study was to describe the prevalence of naturally occurring NS5B RAVs in Brazilian direct acting antivirals (DAA)-naïve patients infected with HCV genotype 1, or co-infected with HIV. Patient enrollment and sample collection were performed between 2011 and 2013. Using Sanger-based sequencing, 244 sequences were obtained. RAVs detected in HCV-1a sequences were V321A (1.6 %), M414V (1.3 %), A421V (21.4-23.7 %), A421G (1.3 %) and Y448H (1.3 %); and in HCV-1b sequences were L159F (16.1 %), C316N (7.1-16.3 %) and A421V (3.2-6.3 %). Understanding the real RAVs scenario in patients is fundamental to establishing the most effective therapeutic strategy and in minimizing the risks for their selection.

Hepatitis C virus genotype 1 infection: Prevalence of NS5A and NS5B resistance‐associated substitutions in naïve patients from Argentina

“…Finally, NS5B S282T variant, a signature NS5B mutation known as being associated to resistance in in vitro SOF studies, was not detected in any patient at baseline. This finding is similar to data coming from the majority of previous in vivo studies …”

“…L159F and C316N were the most frequently identified NS5B substitutions at baseline. These findings appear to be in line with previous reports stating a high prevalence of L159F and C316N in Brazil (16%) and Italy (13%‐19%) . C316N and L159F were related to virologic failure after SOF/LDV and SOF/DCV treatment .…”

“…In this sense, the difference in prevalence between both subtypes tended to be significant ( P = .099). The value observed in this study was much lower than the one reported for Europe and Brazil but is in line with reports from Asiatic countries . L159F and C316N were the most frequently identified NS5B substitutions at baseline.…”

“…Up to date, similarly to NS5A, the prevalence of NS5B RASs has been well characterized in Europe, North America, and Asia, but less is known about their presence in other South American countries and, especially, in Argentina . A 6.3% of HCV‐1 infected patients were identified as presenting RASs in the analyzed NS5B region.…”

Avaliação da efetividade e segurança dos novos fármacos de ação direta indicados no tratamento da hepatite C

“…Em relação as mutações localizadas na região NS5B, em estudo realizado por Noble e colaboradores, identificou-se a presença de tais mutações em 20,1% dos pacientes com subgenótipo 1a, semelhante a frequência encontrada em nosso estudo, que foi de 19,7%; e em 16,3% dos pacientes com subgenótipo 1b, inferior ao encontrado em nosso estudo, que foi de 27,0%. As mutações observadas por Noble foram L159F, C316N e A421V, também observadas no presente estudo (NOBLE et al, 2017).…”