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
N1 - 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.
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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U2 - 10.1016/j.antiviral.2018.08.001
DO - 10.1016/j.antiviral.2018.08.001
M3 - Article
C2 - 30120954
AN - SCOPUS:85052111416
VL - 158
SP - 178
EP - 184
JO - Antiviral Research
JF - Antiviral Research
SN - 0166-3542
ER -