Lai Wei1, Masao Omata2, Young-Suk Lim3, Qing Xie4, Jin Lin Hou5, Jidong Jia6, Charlotte Hedskog7, Ross Martin7, Brian Doehle7, Jenny Yang7, Shampa De-Oertel7, Benedetta Massetto7, Kathryn Kersey7, Diana M Brainard7, Evguenia Svarovskaia7, Hongmei Mo7, Kwang-Hyub Han8, Masashi Mizokami9, Zhongping Duan10. 1. Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory for Hepatitis C and Immunologic Liver Disease, Beijing, China. 2. Yamanashi Prefectural Hospital Organization, Yamanashi, Japan. Electronic address: momata-tky@umin.ac.jp. 3. Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. 4. Shanghai Jiaotong University Ruijin Hospital, Shanghai, China. 5. Nanfang Hospital of Southern Medical University, Guangzhou, China. 6. Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing, China. 7. Gilead Sciences, Inc, Foster City, CA, USA. 8. Yonsei University College of Medicine Seoul, South Korea. 9. Kohnodai Hospital, National Center for Global Health and Medicine, Chiba, Japan. 10. Beijing Youan Hospital Affiliated to Capital Medical University, Beijing, 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.
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.