کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8292774 | 1536738 | 2018 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Prevalence of NS5A resistance associated variants in NS5A inhibitor treatment failures and an effective treatment for NS5A-P32 deleted hepatitis C virus in humanized mice
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کلمات کلیدی
DAAsledipasvirLDVSOFSofosbuvirASVPiBuPAdcvSCIDSVRGLEasunaprevir - آسونپروویرResistance-associated variants - انواع مرتبط با مقاومتdirect-acting antivirals - داروهای ضد ویروسی مستقیمdaclatasvir - داکلاتاشیرurokinase-type plasminogen activator - فعال کننده پلاسمینوژن نوع urokinaseHepatitis C virus - هپاتیت سیHCV - هپاتیت سیpolymerase chain reaction - واکنش زنجیره ای پلیمرازPCR - واکنش زنجیرهٔ پلیمرازsustained virological response - پاسخ ویروسی بالقوهsevere combined immunodeficiency - کمبود شدید مصدوم
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Prevalence of NS5A resistance associated variants in NS5A inhibitor treatment failures and an effective treatment for NS5A-P32 deleted hepatitis C virus in humanized mice Prevalence of NS5A resistance associated variants in NS5A inhibitor treatment failures and an effective treatment for NS5A-P32 deleted hepatitis C virus in humanized mice](/preview/png/8292774.png)
چکیده انگلیسی
Patients with chronic hepatitis C virus (HCV) infection who have failed to respond to direct-acting antiviral (DAA) treatment often acquire drug resistance-associated variants (RAVs). The NS5A-P32 deletion (P32del) RAV confers potent resistance to NS5A inhibitors; therefore, patients who acquire this deletion are likely to fail to respond to DAA re-treatment. We investigated the prevalence of N55A-P32del in patients who failed to respond to prior NS5A inhibitor treatment using direct sequencing and analyzed the efficacy of DAA combination treatment in the presence of NS5A-P32del RAVs using human hepatocyte transplanted mice. NS5A-P32del was detected in one of 23 (4.3%) patients who had failed to respond to prior NS5A inhibitor treatment. Although four weeks of NS3/4A protease inhibitor glecaprevir plus NS5A inhibitor pibrentasvir treatment effectively suppressed HCV replication in wild-type HCV-infected mice, serum HCV RNA never became negative in P32del HCV-infected mice. When P32del HCV-infected mice were treated with four weeks of glecaprevir plus pibrentasvir combined with the NS5B polymerase inhibitor sofosbuvir, serum HCV RNA became negative, and the virus was eliminated from the liver in three out of four mice. We conclude that the combination of sofosbuvir and glecaprevir plus pibrentasvir may be an effective new treatment option for patients with NS5A-P32del.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 500, Issue 2, 2 June 2018, Pages 152-157
Journal: Biochemical and Biophysical Research Communications - Volume 500, Issue 2, 2 June 2018, Pages 152-157
نویسندگان
Yuji Teraoka, Takuro Uchida, Michio Imamura, Mitsutaka Osawa, Masataka Tsuge, Hiromi Abe-Chayama, C. Nelson Hayes, Grace Naswa Makokha, Hiroshi Aikata, Daiki Miki, Hidenori Ochi, Yuji Ishida, Chise Tateno, Kazuaki Chayama,