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.
Bibliographical noteFunding Information:
This work was supported by Gilead Sciences.
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.
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