| Workshop 16 (JSH・JSGE) |
| Fri. November 2nd 9:40 - 12:00 Room 8: Portopia Hotel Main Building Kairaku 1+2 |
| Prevalence and effect on treatment outcome of 4 NS5B substitutions A207T, A218S, C316N and Q464E in genotype 1b patients | |||
| Hadas Dvory-Sobol1, Takuma Matsuda1, Diana M. Brainard1 | |||
| 1Gilead Sciences, Inc. | |||
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| Background and Aims: The error-prone and absent proofreading activity of the HCV NS5B enzyme together with the high replication rate leads to high sequence variability of HCV. In real world practice in Japan, 4 NS5B variants A207T, A218S, C316N and Q464E were detected in patients experiencing virologic failure after ledipasvir-sofosbuvir (LDV/SOF) therapy. Here we evaluate the baseline prevalence and the effect of these variants on treatment outcome among patients from different geographic regions. Method: NS5B gene deep sequencing was performed on samples from 3023 patients with genotype 1b HCV infection including DAA-naive and DAA experienced patients in Gilead clinical trials (Japan n=422, Other Asia n=996, Europe n=575, North America n=946, Oceania n=84). Results are reported using a 15% cutoff. Results: The 4 NS5B variants A207T, A218S, C316N and Q464E alone and together were highly prevalent among patients from Japan, China or total Asia, compared to patients from Europe, North America and Oceania. The prevalence of the 4 NS5B variants together in Japan, China, total Asia, Europe, North America, and Oceania were 28%, 18%, 20%, 2%, 1%, 4%, respectively. All Japanese patients with the 4 NS5B variants alone or together achieved SVR12 following treatment with LDV/SOF for 12 weeks. In vitro replicon assays demonstrated no change in susceptibility to SOF of the variants alone or together. Conclusion: A207T, A218S, C316N and Q464E are natural polymorphisms in the NS5B gene. These substitutions were highly prevalent in Japan and didn’t have impact on treatment outcome with LDV/SOF. |
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Index Term 1: NS5B variants Index Term 2: Sofosbuvir |
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