Protease Inhibitors Drug Resistance Mutations in Turkish Patients with Chronic Hepatitis C
Background: Drug resistance development is an expected problem during treatment with protease inhibitors (PIs), this is largely due to the fact that Pls are low-genetic barrier drugs. Resistance-associated variants (RAVs) however may also occur naturally, and prior to treatment with Pls, the clinica...
Main Authors: | , , , , , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2016-09-01
|
Series: | International Journal of Infectious Diseases |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S1201971216311109 |
id |
doaj-746674f3f2674d80aa0bd064e45cced1 |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Elif Sargin Altunok Murat Sayan Sila Akhan Bilgehan Aygen Orhan Yildiz Suda Tekin Koruk Resit Mistik Nese Demirturk Onur Ural Şükran Kose Aynur Aynioglu Fatime Korkmaz Gülden Ersoz Nazan Tuna Celal Ayaz Faruk Karakecili Derya Keten Dilara Inan Saadet Yazici Safiye Koculu Taner Yildirmak |
spellingShingle |
Elif Sargin Altunok Murat Sayan Sila Akhan Bilgehan Aygen Orhan Yildiz Suda Tekin Koruk Resit Mistik Nese Demirturk Onur Ural Şükran Kose Aynur Aynioglu Fatime Korkmaz Gülden Ersoz Nazan Tuna Celal Ayaz Faruk Karakecili Derya Keten Dilara Inan Saadet Yazici Safiye Koculu Taner Yildirmak Protease Inhibitors Drug Resistance Mutations in Turkish Patients with Chronic Hepatitis C International Journal of Infectious Diseases Baseline resistance hepatitis C virus mutation protease inhibitors |
author_facet |
Elif Sargin Altunok Murat Sayan Sila Akhan Bilgehan Aygen Orhan Yildiz Suda Tekin Koruk Resit Mistik Nese Demirturk Onur Ural Şükran Kose Aynur Aynioglu Fatime Korkmaz Gülden Ersoz Nazan Tuna Celal Ayaz Faruk Karakecili Derya Keten Dilara Inan Saadet Yazici Safiye Koculu Taner Yildirmak |
author_sort |
Elif Sargin Altunok |
title |
Protease Inhibitors Drug Resistance Mutations in Turkish Patients with Chronic Hepatitis C |
title_short |
Protease Inhibitors Drug Resistance Mutations in Turkish Patients with Chronic Hepatitis C |
title_full |
Protease Inhibitors Drug Resistance Mutations in Turkish Patients with Chronic Hepatitis C |
title_fullStr |
Protease Inhibitors Drug Resistance Mutations in Turkish Patients with Chronic Hepatitis C |
title_full_unstemmed |
Protease Inhibitors Drug Resistance Mutations in Turkish Patients with Chronic Hepatitis C |
title_sort |
protease inhibitors drug resistance mutations in turkish patients with chronic hepatitis c |
publisher |
Elsevier |
series |
International Journal of Infectious Diseases |
issn |
1201-9712 1878-3511 |
publishDate |
2016-09-01 |
description |
Background: Drug resistance development is an expected problem during treatment with protease inhibitors (PIs), this is largely due to the fact that Pls are low-genetic barrier drugs. Resistance-associated variants (RAVs) however may also occur naturally, and prior to treatment with Pls, the clinical impact of this basal resistance remains unknown. In Turkey, there is yet to be an investigation into the hepatitis C (HCV) drug associated resistance to oral antivirals.
Materials and methods: 178 antiviral-naïve patients infected with HCV genotype 1 were selected from 27 clinical centers of various geographical regions in Turkey and included in the current study. The basal NS3 Pls resistance mutations of these patients were analyzed.
Results: In 33 (18.5%) of the patients included in the study, at least one mutation pattern that can cause drug resistance was identified. The most frequently detected mutation pattern was T54S while R109K was the second most frequently detected. Following a more general examination of the patients studied, telaprevir (TVR) resistance in 27 patients (15.2%), boceprevir (BOC) resistance in 26 (14.6%) patients, simeprevir (SMV) resistance in 11 (6.2%) patients and faldaprevir resistance in 13 (7.3%) patients were detected. Our investigation also revealed that rebound developed in the presence of a Q80K mutation and amongst two V55A mutations following treatment with TVR, while no response to treatment was detected in a patient with a R55K mutation.
Conclusion: We are of the opinion that drug resistance analyses can be beneficial and necessary in revealing which variants are responsible for pre-treatment natural resistance and which mutations are responsible for the viral breakthrough that may develop during the treatment. |
topic |
Baseline resistance hepatitis C virus mutation protease inhibitors |
url |
http://www.sciencedirect.com/science/article/pii/S1201971216311109 |
work_keys_str_mv |
AT elifsarginaltunok proteaseinhibitorsdrugresistancemutationsinturkishpatientswithchronichepatitisc AT muratsayan proteaseinhibitorsdrugresistancemutationsinturkishpatientswithchronichepatitisc AT silaakhan proteaseinhibitorsdrugresistancemutationsinturkishpatientswithchronichepatitisc AT bilgehanaygen proteaseinhibitorsdrugresistancemutationsinturkishpatientswithchronichepatitisc AT orhanyildiz proteaseinhibitorsdrugresistancemutationsinturkishpatientswithchronichepatitisc AT sudatekinkoruk proteaseinhibitorsdrugresistancemutationsinturkishpatientswithchronichepatitisc AT resitmistik proteaseinhibitorsdrugresistancemutationsinturkishpatientswithchronichepatitisc AT nesedemirturk proteaseinhibitorsdrugresistancemutationsinturkishpatientswithchronichepatitisc AT onurural proteaseinhibitorsdrugresistancemutationsinturkishpatientswithchronichepatitisc AT sukrankose proteaseinhibitorsdrugresistancemutationsinturkishpatientswithchronichepatitisc AT aynuraynioglu proteaseinhibitorsdrugresistancemutationsinturkishpatientswithchronichepatitisc AT fatimekorkmaz proteaseinhibitorsdrugresistancemutationsinturkishpatientswithchronichepatitisc AT guldenersoz proteaseinhibitorsdrugresistancemutationsinturkishpatientswithchronichepatitisc AT nazantuna proteaseinhibitorsdrugresistancemutationsinturkishpatientswithchronichepatitisc AT celalayaz proteaseinhibitorsdrugresistancemutationsinturkishpatientswithchronichepatitisc AT farukkarakecili proteaseinhibitorsdrugresistancemutationsinturkishpatientswithchronichepatitisc AT deryaketen proteaseinhibitorsdrugresistancemutationsinturkishpatientswithchronichepatitisc AT dilarainan proteaseinhibitorsdrugresistancemutationsinturkishpatientswithchronichepatitisc AT saadetyazici proteaseinhibitorsdrugresistancemutationsinturkishpatientswithchronichepatitisc AT safiyekoculu proteaseinhibitorsdrugresistancemutationsinturkishpatientswithchronichepatitisc AT taneryildirmak proteaseinhibitorsdrugresistancemutationsinturkishpatientswithchronichepatitisc |
_version_ |
1725275767964696576 |
spelling |
doaj-746674f3f2674d80aa0bd064e45cced12020-11-25T00:44:12ZengElsevierInternational Journal of Infectious Diseases1201-97121878-35112016-09-0150C1510.1016/j.ijid.2016.07.003Protease Inhibitors Drug Resistance Mutations in Turkish Patients with Chronic Hepatitis CElif Sargin Altunok0Murat Sayan1Sila Akhan2Bilgehan Aygen3Orhan Yildiz4Suda Tekin Koruk5Resit Mistik6Nese Demirturk7Onur Ural8Şükran Kose9Aynur Aynioglu10Fatime Korkmaz11Gülden Ersoz12Nazan Tuna13Celal Ayaz14Faruk Karakecili15Derya Keten16Dilara Inan17Saadet Yazici18Safiye Koculu19Taner Yildirmak20Infectious Diseases and Clinical Microbiology, Bitlis Public Hospital, Bitlis 13000, TurkeyClinical Laboratory, Kocaeli University Faculty of Medicine, Kocaeli 41380, TurkeyInfectious Diseases And Clinical Microbiology, Kocaeli University Faculty of Medicine, Kocaeli 41380, TurkeyInfectious Diseases And Clinical Microbiology, Erciyes University Faculty of Medicine, Kayseri 38030, TurkeyInfectious Diseases And Clinical Microbiology, Erciyes University Faculty of Medicine, Kayseri 38030, TurkeyInfectious Diseases and Clinical Microbiology, Koc University Faculty of Medicine, İstanbul 34010, TurkeyInfectious Diseases and Clinical Microbiology, Uludag University Faculty of Medicine, Bursa, TurkeyInfectious Diseases and Clinical Microbiology, Afyon Kocatepe University Faculty of Medicine, Afyonkarahisar, TurkeyInfectious Diseases and Clinical Microbiology, Selçuk University Faculty of Medicine, Konya, TurkeyInfectious Diseases and Clinical Microbiology, Tepecik Training and Research Hospital, İzmir, TurkeyInfectious Diseases and Clinical Microbiology, Zonguldak Ataturk Public Hospital, Zonguldak, TurkeyInfectious Diseases and Clinical Microbiology, Konya Training and Research Hospital, Konya, TurkeyInfectious Diseases And Clinical Microbiology, Mersin University Faculty of Medicine, Mersin, TurkeyInfectious Diseases and Clinical Microbiology, Sakarya University Faculty of Medicine, Sakarya, TurkeyInfectious Diseases and Clinical Microbiology, Dicle University Faculty of Medicine, Diyarbakir, TurkeyInfectious Diseases and Clinical Microbiology, Erzincan University Faculty of Medicine, Erzincan, TurkeyInfectious Diseases and Clinical Microbiology, Necip Fazil City Hospital, Kahramanmaraş, TurkeyInfectious Diseases and Clinical Microbiology, Akdeniz University Faculty of Medicine, Antalya, TurkeyInfectious Diseases and Clinical Microbiology, Göztepe Training and Research Hospital, İstanbul, TurkeyInfectious Diseases and Clinical Microbiology, Giresun Public Hospital, Giresun, TurkeyInfectious Diseases and Clinical Microbiology, Okmeydanı Training and Research Hospital, İstanbul, TurkeyBackground: Drug resistance development is an expected problem during treatment with protease inhibitors (PIs), this is largely due to the fact that Pls are low-genetic barrier drugs. Resistance-associated variants (RAVs) however may also occur naturally, and prior to treatment with Pls, the clinical impact of this basal resistance remains unknown. In Turkey, there is yet to be an investigation into the hepatitis C (HCV) drug associated resistance to oral antivirals. Materials and methods: 178 antiviral-naïve patients infected with HCV genotype 1 were selected from 27 clinical centers of various geographical regions in Turkey and included in the current study. The basal NS3 Pls resistance mutations of these patients were analyzed. Results: In 33 (18.5%) of the patients included in the study, at least one mutation pattern that can cause drug resistance was identified. The most frequently detected mutation pattern was T54S while R109K was the second most frequently detected. Following a more general examination of the patients studied, telaprevir (TVR) resistance in 27 patients (15.2%), boceprevir (BOC) resistance in 26 (14.6%) patients, simeprevir (SMV) resistance in 11 (6.2%) patients and faldaprevir resistance in 13 (7.3%) patients were detected. Our investigation also revealed that rebound developed in the presence of a Q80K mutation and amongst two V55A mutations following treatment with TVR, while no response to treatment was detected in a patient with a R55K mutation. Conclusion: We are of the opinion that drug resistance analyses can be beneficial and necessary in revealing which variants are responsible for pre-treatment natural resistance and which mutations are responsible for the viral breakthrough that may develop during the treatment.http://www.sciencedirect.com/science/article/pii/S1201971216311109Baseline resistancehepatitis C virusmutationprotease inhibitors |