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.

Figure 1

Maximum-likelihood phylogenetic trees analyses of the NS5A and NS5B genes of HCV strains circulating in Uruguay. Reference strains in the tree are shown by genotype_country_accession number. Numbers at the branches indicate bootstrap values. The bar at the bottom of the tree denotes distance. Uruguayan strains genotype 1a are shown in red and genotype 1b in blue. (a) NS5A region (953 nucleotides); (b) NS5B region (361 nucleotides).

Figure 2

Maximum-likelihood phylogenetic tree analysis of the NS5A of HCV-1a strains circulating in Uruguay. The maximum-likelihood phylogenetic tree shows the evolutionary relationships between the Uruguayan, Brazilian, and worldwide HCV-1a isolates sequences. Uruguayan strains are shown in red. The bar at the bottom of the tree denotes distance. Sequence names have been removed for clarity.