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

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

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

Bibliographical note

Funding Information:
This work was supported by Gilead Sciences.

Funding Information:
Lai Wei is consulting for AbbVie, Allegan, BMS, Gilead, MSD. Speaker for AbbVie, Ascletis, BMS, Kaiyin, Gilead, MSD, Research grant from AbbVie, BMS, and Roche.

Funding Information:
Young-Suk Lim is an advisory board member of Bayer Healthcare, Gilead Sciences, and Roche, and receives research funding from Bayer Healthcare and Gilead Sciences .

Publisher Copyright:
© 2018

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Virology

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