HCV phylogenetic signature and prevalence of pretreatment NS5A and NS5B NI-Resistance associated substitutions in HCV-Infected patients in Mainland China

Lai Wei, Masao Omata, Young Suk Lim, Qing Xie, Jin Lin Hou, Jidong Jia, Charlotte Hedskog, Ross Martin, Brian Doehle, Jenny Yang, Shampa De-Oertel, Benedetta Massetto, Kathryn Kersey, Diana M. Brainard, Evguenia Svarovskaia, Hongmei Mo, Kwang Hyub Han, Masashi Mizokami, Zhongping Duan

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Abstract

Background & aims: Resistance associated substitutions (RAS) can reduce the efficacy of some direct-acting antiviral HCV regimens. Here, prevalence of RAS in genotype (GT) 1b, 2, 3, and 6 HCV-infected patients from Asian counties, North America and Europe are described and compared. Methods: Pretreatment HCV RAS were assessed with 15% cutoff from patients enrolled in clinical trials of sofosbuvir-containing regimens in Mainland China, Japan, Korea, and India. Phylogenetic analyses were performed to investigating subtype diversity. Results: In GT1b patients, the prevalence of NS5A RAS, including Y93H, was similar across Asian countries (18–21%), and North America (15%) or Europe (19%). The prevalence of NS5B NI RAS, including L159F, was lower in Asian countries (1–5%) compared to North America (4%) or Europe (20%). The prevalence of NS3 RAS in patients from China (22%) and North America (28%) were lower than in Europe (40%). For GT2 patients in China, 100% had GT2a subtype with high prevalence of NS5A L31M. For GT3, the prevalence of GT3b was substantially higher in China (54%) than in North America or Europe (<1%); 99% of GT3b patients in China had NS5A RAS A30K+L31M, which confers high levels of resistance to NS5A inhibitors. In GT3a patients in China, the prevalence of NS5A RAS was lower (5%) than in North America and Europe (14–16%). Prevalence of NS5B NI RAS in GT2 and GT3 patients was rare across regions (<2%). Conclusions: Differences in the prevalence of GT2 and GT3 subtypes and NS5A RAS were observed between Asian and Western countries.

Original languageEnglish
Pages (from-to)178-184
Number of pages7
JournalAntiviral Research
Volume158
DOIs
Publication statusPublished - 2018 Oct

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China
North America
Korea
Antiviral Agents
India
Japan
Genotype
Clinical Trials

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Virology

Cite this

Wei, Lai ; Omata, Masao ; Lim, Young Suk ; Xie, Qing ; Hou, Jin Lin ; Jia, Jidong ; Hedskog, Charlotte ; Martin, Ross ; Doehle, Brian ; Yang, Jenny ; De-Oertel, Shampa ; Massetto, Benedetta ; Kersey, Kathryn ; Brainard, Diana M. ; Svarovskaia, Evguenia ; Mo, Hongmei ; Han, Kwang Hyub ; Mizokami, Masashi ; Duan, Zhongping. / HCV phylogenetic signature and prevalence of pretreatment NS5A and NS5B NI-Resistance associated substitutions in HCV-Infected patients in Mainland China. In: Antiviral Research. 2018 ; Vol. 158. pp. 178-184.
@article{c8510e96471740de9b2caf65a0dd8275,
title = "HCV phylogenetic signature and prevalence of pretreatment NS5A and NS5B NI-Resistance associated substitutions in HCV-Infected patients in Mainland China",
abstract = "Background & aims: Resistance associated substitutions (RAS) can reduce the efficacy of some direct-acting antiviral HCV regimens. Here, prevalence of RAS in genotype (GT) 1b, 2, 3, and 6 HCV-infected patients from Asian counties, North America and Europe are described and compared. Methods: Pretreatment HCV RAS were assessed with 15{\%} cutoff from patients enrolled in clinical trials of sofosbuvir-containing regimens in Mainland China, Japan, Korea, and India. Phylogenetic analyses were performed to investigating subtype diversity. Results: In GT1b patients, the prevalence of NS5A RAS, including Y93H, was similar across Asian countries (18–21{\%}), and North America (15{\%}) or Europe (19{\%}). The prevalence of NS5B NI RAS, including L159F, was lower in Asian countries (1–5{\%}) compared to North America (4{\%}) or Europe (20{\%}). The prevalence of NS3 RAS in patients from China (22{\%}) and North America (28{\%}) were lower than in Europe (40{\%}). For GT2 patients in China, 100{\%} had GT2a subtype with high prevalence of NS5A L31M. For GT3, the prevalence of GT3b was substantially higher in China (54{\%}) than in North America or Europe (<1{\%}); 99{\%} of GT3b patients in China had NS5A RAS A30K+L31M, which confers high levels of resistance to NS5A inhibitors. In GT3a patients in China, the prevalence of NS5A RAS was lower (5{\%}) than in North America and Europe (14–16{\%}). Prevalence of NS5B NI RAS in GT2 and GT3 patients was rare across regions (<2{\%}). Conclusions: Differences in the prevalence of GT2 and GT3 subtypes and NS5A RAS were observed between Asian and Western countries.",
author = "Lai Wei and Masao Omata and Lim, {Young Suk} and Qing Xie and Hou, {Jin Lin} and Jidong Jia and Charlotte Hedskog and Ross Martin and Brian Doehle and Jenny Yang and Shampa De-Oertel and Benedetta Massetto and Kathryn Kersey and Brainard, {Diana M.} and Evguenia Svarovskaia and Hongmei Mo and Han, {Kwang Hyub} and Masashi Mizokami and Zhongping Duan",
year = "2018",
month = "10",
doi = "10.1016/j.antiviral.2018.08.001",
language = "English",
volume = "158",
pages = "178--184",
journal = "Antiviral Research",
issn = "0166-3542",
publisher = "Elsevier",

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Wei, L, Omata, M, Lim, YS, Xie, Q, Hou, JL, Jia, J, Hedskog, C, Martin, R, Doehle, B, Yang, J, De-Oertel, S, Massetto, B, Kersey, K, Brainard, DM, Svarovskaia, E, Mo, H, Han, KH, Mizokami, M & Duan, Z 2018, 'HCV phylogenetic signature and prevalence of pretreatment NS5A and NS5B NI-Resistance associated substitutions in HCV-Infected patients in Mainland China', Antiviral Research, vol. 158, pp. 178-184. https://doi.org/10.1016/j.antiviral.2018.08.001

HCV phylogenetic signature and prevalence of pretreatment NS5A and NS5B NI-Resistance associated substitutions in HCV-Infected patients in Mainland China. / Wei, Lai; Omata, Masao; Lim, Young Suk; Xie, Qing; Hou, Jin Lin; Jia, Jidong; Hedskog, Charlotte; Martin, Ross; Doehle, Brian; Yang, Jenny; De-Oertel, Shampa; Massetto, Benedetta; Kersey, Kathryn; Brainard, Diana M.; Svarovskaia, Evguenia; Mo, Hongmei; Han, Kwang Hyub; Mizokami, Masashi; Duan, Zhongping.

In: Antiviral Research, Vol. 158, 10.2018, p. 178-184.

Research output: Contribution to journalArticle

TY - JOUR

T1 - HCV phylogenetic signature and prevalence of pretreatment NS5A and NS5B NI-Resistance associated substitutions in HCV-Infected patients in Mainland China

AU - Wei, Lai

AU - Omata, Masao

AU - Lim, Young Suk

AU - Xie, Qing

AU - Hou, Jin Lin

AU - Jia, Jidong

AU - Hedskog, Charlotte

AU - Martin, Ross

AU - Doehle, Brian

AU - Yang, Jenny

AU - De-Oertel, Shampa

AU - Massetto, Benedetta

AU - Kersey, Kathryn

AU - Brainard, Diana M.

AU - Svarovskaia, Evguenia

AU - Mo, Hongmei

AU - Han, Kwang Hyub

AU - Mizokami, Masashi

AU - Duan, Zhongping

PY - 2018/10

Y1 - 2018/10

N2 - Background & aims: Resistance associated substitutions (RAS) can reduce the efficacy of some direct-acting antiviral HCV regimens. Here, prevalence of RAS in genotype (GT) 1b, 2, 3, and 6 HCV-infected patients from Asian counties, North America and Europe are described and compared. Methods: Pretreatment HCV RAS were assessed with 15% cutoff from patients enrolled in clinical trials of sofosbuvir-containing regimens in Mainland China, Japan, Korea, and India. Phylogenetic analyses were performed to investigating subtype diversity. Results: In GT1b patients, the prevalence of NS5A RAS, including Y93H, was similar across Asian countries (18–21%), and North America (15%) or Europe (19%). The prevalence of NS5B NI RAS, including L159F, was lower in Asian countries (1–5%) compared to North America (4%) or Europe (20%). The prevalence of NS3 RAS in patients from China (22%) and North America (28%) were lower than in Europe (40%). For GT2 patients in China, 100% had GT2a subtype with high prevalence of NS5A L31M. For GT3, the prevalence of GT3b was substantially higher in China (54%) than in North America or Europe (<1%); 99% of GT3b patients in China had NS5A RAS A30K+L31M, which confers high levels of resistance to NS5A inhibitors. In GT3a patients in China, the prevalence of NS5A RAS was lower (5%) than in North America and Europe (14–16%). Prevalence of NS5B NI RAS in GT2 and GT3 patients was rare across regions (<2%). Conclusions: Differences in the prevalence of GT2 and GT3 subtypes and NS5A RAS were observed between Asian and Western countries.

AB - Background & aims: Resistance associated substitutions (RAS) can reduce the efficacy of some direct-acting antiviral HCV regimens. Here, prevalence of RAS in genotype (GT) 1b, 2, 3, and 6 HCV-infected patients from Asian counties, North America and Europe are described and compared. Methods: Pretreatment HCV RAS were assessed with 15% cutoff from patients enrolled in clinical trials of sofosbuvir-containing regimens in Mainland China, Japan, Korea, and India. Phylogenetic analyses were performed to investigating subtype diversity. Results: In GT1b patients, the prevalence of NS5A RAS, including Y93H, was similar across Asian countries (18–21%), and North America (15%) or Europe (19%). The prevalence of NS5B NI RAS, including L159F, was lower in Asian countries (1–5%) compared to North America (4%) or Europe (20%). The prevalence of NS3 RAS in patients from China (22%) and North America (28%) were lower than in Europe (40%). For GT2 patients in China, 100% had GT2a subtype with high prevalence of NS5A L31M. For GT3, the prevalence of GT3b was substantially higher in China (54%) than in North America or Europe (<1%); 99% of GT3b patients in China had NS5A RAS A30K+L31M, which confers high levels of resistance to NS5A inhibitors. In GT3a patients in China, the prevalence of NS5A RAS was lower (5%) than in North America and Europe (14–16%). Prevalence of NS5B NI RAS in GT2 and GT3 patients was rare across regions (<2%). Conclusions: Differences in the prevalence of GT2 and GT3 subtypes and NS5A RAS were observed between Asian and Western countries.

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