دورية أكاديمية
NS5A resistance-associated substitutions in patients with genotype 1 hepatitis C virus: Prevalence and effect on treatment outcome
| العنوان: | NS5A resistance-associated substitutions in patients with genotype 1 hepatitis C virus: Prevalence and effect on treatment outcome |
|---|---|
| المساهمون: | Stefan Zeuzem, Masashi Mizokami, Stephen Pianko, Alessandra Mangia, Kwang-Hyub Han, Ross Martin, Evguenia Svarovskaia, Hadas Dvory-Sobol, Brian Doehle, Charlotte Hedskog, Chohee Yun, Diana M Brainard, Steven Knox, John G McHutchison, Michael D Miller, Hongmei Mo, Wan-Long Chuang, Ira Jacobson, Gregory J Dore, Mark Sulkowski, Han, Kwang Hyub |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Adolescent, Adult, Aged, 80 and over, Antiviral Agents / therapeutic use, Benzimidazoles / therapeutic use, Drug Resistance, Viral, Female, Fluorenes / therapeutic use, Genotype, Hepatitis C, Chronic / drug therapy, Chronic / virology, Humans, Male, Middle Aged, Treatment Outcome, Viral Nonstructural Proteins / antagonists & inhibitors, Viral Nonstructural Proteins / genetics, Young Adult, HCV genotype 1, Ledipasvir, NS5A RAS, Sofosbuvir, Sustained virologic response |
| الوصف: | Background & aims: The efficacy of NS5A inhibitors for the treatment of patients chronically infected with hepatitis C virus (HCV) can be affected by the presence of NS5A resistance-associated substitutions (RASs). We analyzed data from 35 phase I, II, and III studies in 22 countries to determine the pretreatment prevalence of various NS5A RASs, and their effect on outcomes of treatment with ledipasvir-sofosbuvir in patients with genotype 1 HCV. Methods: NS5A gene deep sequencing analysis was performed on samples from 5397 patients in Gilead clinical trials. The effect of baseline RASs on sustained virologic response (SVR) rates was assessed in the 1765 patients treated with regimens containing ledipasvir-sofosbuvir. Results: Using a 15% cut-off, pretreatment NS5A and ledipasvir-specific RASs were detected in 13% and 8% of genotype 1a patients, respectively, and in 18% and 16% of patients with genotype 1b. Among genotype 1a treatment-naïve patients, SVR rates were 91% (42/46) vs. 99% (539/546) for those with and without ledipasvir-specific RASs, respectively. Among treatment-experienced genotype 1a patients, SVR rates were 76% (22/29) vs. 97% (409/420) for those with and without ledipasvir-specific RASs, respectively. Among treatment-naïve genotype 1b patients, SVR rates were 99% for both those with and without ledipasvir-specific RASs (71/72 vs. 331/334), and among treatment-experienced genotype 1b patients, SVR rates were 89% (41/46) vs. 98% (267/272) for those with and without ledipasvir-specific RASs, respectively. Conclusions: Pretreatment ledipasvir-specific RASs that were present in 8-16% of patients have an impact on treatment outcome in some patient groups, particularly treatment-experienced patients with genotype 1a HCV. Lay summary: The efficacy of treatments using NS5A inhibitors for patients with chronic hepatitis C virus (HCV) infection can be affected by the presence of NS5A resistance-associated substitutions (RASs). We reviewed results from 35 clinical trials where patients with genotype 1 ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0168-8278 1600-0641 |
| العلاقة: | JOURNAL OF HEPATOLOGY; J01441; OAK-2017-1215; https://ir.ymlib.yonsei.ac.kr/handle/22282913/195775Test; https://core.ac.uk/reader/77006799?utm_source=linkoutTest; T992017183; JOURNAL OF HEPATOLOGY, Vol.66(5) : 910-918, 2017-05 |
| DOI: | 10.1016/j.jhep.2017.01.007 |
| الإتاحة: | https://doi.org/10.1016/j.jhep.2017.01.007Test https://ir.ymlib.yonsei.ac.kr/handle/22282913/195775Test https://core.ac.uk/reader/77006799?utm_source=linkoutTest |
| حقوق: | CC BY-NC-ND 2.0 KR |
| رقم الانضمام: | edsbas.F83FCBA6 |
| قاعدة البيانات: | BASE |
| تدمد: | 01688278 16000641 |
|---|---|
| DOI: | 10.1016/j.jhep.2017.01.007 |