Pretreatment Hepatitis C Virus NS5A/NS5B Resistance-Associated Substitutions in Genotype 1 Uruguayan Infected Patients

Abstract

Hepatitis C Virus (HCV) infection treatment has dramatically changed with the advent of direct-acting antiviral agents (DAAs). However, the efficacy of DAAs can be attenuated by the presence of resistance-associated substitutions (RASs) before and after treatment. Indeed, RASs detected in DAA treatment-naïve HCV-infected patients could be useful for clinical management and outcome prediction. Although the frequency of naturally occurring HCV NS5A and NS5B RASs has been addressed in many countries, there are only a few reports on their prevalence in the South American region. The aim of this study was to investigate the presence of RASs to NS5A and NS5B inhibitors in a DAA treatment naïve cohort of Uruguayan patients infected with chronic hepatitis C and compare them with reports from other South American countries. Here, we found that naturally occurring substitutions conferring resistance to NS5A and NS5B inhibitors were present in 8% and 19.2%, respectively, of treatment-naïve HCV genotype 1 infected patients. Importantly, the baseline substitutions in NS5A and NS5B herein identified differ from the studies previously reported in Brazil. Furthermore, Uruguayan strains subtype 1a clustered within all major world clades, showing that HCV variants currently circulating in this country are characterized by a remarkable genetic diversity.

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 …”

“…In the present study, RASs were present in 25.8% of the NS5A sequences analyzed from Buenos Aires, Argentina. Even when RASs frequencies informed in the literature comprise wide values ranging between less than 10% to more than 40%, the prevalence observed in this study is higher when compared to most regional and worldwide studies . Differences in sample characteristics such as cohort size, positions analyzed, applied detection methods, uncertainty about prior exposure to DAA, and acting viral genotypes/subtypes can affect the rate of RASs, hindering comparison among different studies.…”

“…While several works had determined the worldwide prevalence of NS5A/B RASs, the information coming from South América is very scarce . It is known that RASs prevalence in both proteins varies by geographic region.…”

Comment on “Pretreatment Hepatitis C Virus NS5A/NS5B Resistance-Associated Substitutions in Genotype 1 Uruguayan Infected Patients”

“…We very much enjoyed reading the recently published article by Aldunate et al [1] in which the authors evaluated the presence of naturally occurring NS5A and NS5B resistance-associated substitutions (RASs) among drug-naïve patients who were chronically infected with Hepatitis C virus (HCV) genotype 1 in Montevideo, Uruguay. The frequency of targeted RASs in this study is estimated based on 31 HCV patients conveniently recruited from referees to a gastroenterology clinic in Montevideo, Uruguay.…”

“…This happens because nucleotide sequences will tend to make cluster according to the degree of similarity in their base composition, irrespective of their true evolutionary relationships [2]. Aldunate et al [1] have not tested the data for substitution saturation. If substitution saturation is substantial in their data, then the genotype assignments as well as the evolutionary relationships reconstructed by the authors might be incorrect.…”