Prevalence of hepatitis C virus-resistant association substitutions to direct-acting antiviral agents in treatment-naïve hepatitis C genotype 1b-infected patients in western China

Abstract

BackgroundDirect-acting antivirals (DAAs) against hepatitis C virus (HCV) are potent and highly efficacious. However, resistance-associated substitutions (RASs) relevant to DAAs can impair treatment effectiveness even at baseline. Moreover, the prevalence of baseline RASs in HCV genotype 1b-infected patients in western China is still unclear.Materials and methodsDirect sequencing of the HCV NS3, NS5A, and NS5B regions was performed in baseline serum samples of 70 DAAs treatment-naïve HCV 1b-infected patients in western China. The sequences were analyzed with MEGA version 5.05 software. Evolutionary patterns of RASs and amino-acid covariance patterns in the NS3, NS5A, and NS5B genes were analyzed by MEGA and Cytoscape (version 3.2.1), respectively.ResultsThe presence of at least one RAS in the NS3 region (C16S, T54S, Q80R/L, A87T, R117H, S122G, V132I, V170I) was observed in 85.48% (53 of 62) of patients, RASs in the NS5A region (L28M, R30Q, Q54H, P58S/T, Q62H/R, Y93H) were observed in 42.42% (28 of 66) of patients, and RASs in the NS5B region (N142S, A300T, C316N, A338V, S365A, L392I, M414L, I424V, A442T, V499A, S556G) were observed in 100% (44 of 44) of patients. Evolutionary patterns of RASs and amino-acid covariance patterns for the NS3, NS5A, and NS5B genes are reported.ConclusionThe prevalence of RASs relevant to DAAs detected in the NS3, NS5A, and NS5B regions of HCV 1b from DAA treatment-naïve patients is high. Therefore, more attention should be paid to RASs associated with DAAs in the upcoming DAA-treatment era in China.

Hepatitis C Virus among Female Sex Workers: A Cross-Sectional Study Conducted along Rivers and Highways in the Amazon Region

“…In this study, this rate was even higher as 6 of 26 (23.1%) HCV-infected FSWs had RASs for grazoprevir. The S122G and Y56F substitutions were identified, and have already been described in the scientific literature [61][62][63]. On the other hand, there is no scientific report of the association of N174S with resistance in non-responders to viral therapy, but there are reports of its presence in patients infected with HCV subtype 1a [64].…”

<p>Computational analysis of naturally occurring resistance-associated substitutions in genes <em>NS3</em>, <em>NS5A</em>, and <em>NS5B</em> among 86 subtypes of hepatitis C virus worldwide</p>

“…Several studies have assessed the prevalence of naturally occurring RASs in HCV genes NS3, NS5A, and/or NS5B from DAA-naïve patients but have focused on particular subtypes21–25 or have used HCV sequence databases26–28 containing a relatively small number of sequences covering very few subtypes. Welzel et al29 performed the largest study to date including 46 subtypes across 5 geographic regions, but the RAS distributions determined in that study were based on clinical trials from regional medical centers in primarily developed countries and thus may not reflect the global HCV RAS landscape.…”

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

“…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.…”