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 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-naive 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. (C) 2016 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

Yazar Altunok, Elif Sargin
Sayan, Murat
Akhan, Sila
Aygen, Bilgehan
Yildiz, Orhan
Koruk, Suda Tekin
Mistik, Resit
Yayın Türü Article
Tek Biçim Adres https://hdl.handle.net/20.500.12628/3180
Tek Biçim Adres 10.1016/j.ijid.2016.07.003
Konu Başlıkları Baseline resistance
hepatitis C virus
mutation
protease inhibitors
Koleksiyonlar Araştırma Çıktıları | WoS | Scopus | TR-Dizin | PubMed | SOBİAD
PubMed İndeksli Yayınlar Koleksiyonu
WoS İndeksli Yayınlar Koleksiyonu
Dergi Adı INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
Dergi Cilt Bilgisi 50
Sayfalar 1 - 5
Yayın Yılı 2016
Eser Adı
[dc.title]
Protease Inhibitors Drug Resistance Mutations in Turkish Patients with Chronic Hepatitis C
Yazar
[dc.contributor.author]
Altunok, Elif Sargin
Yazar
[dc.contributor.author]
Sayan, Murat
Yazar
[dc.contributor.author]
Akhan, Sila
Yazar
[dc.contributor.author]
Aygen, Bilgehan
Yazar
[dc.contributor.author]
Yildiz, Orhan
Yazar
[dc.contributor.author]
Koruk, Suda Tekin
Yazar
[dc.contributor.author]
Mistik, Resit
Yayın Yılı
[dc.date.issued]
2016
Yayıncı
[dc.publisher]
ELSEVIER SCI LTD
Yayın Türü
[dc.type]
article
Özet
[dc.description.abstract]
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-naive 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. (C) 2016 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
Açıklama
[dc.description]
WOS: 000388326300001
Açıklama
[dc.description]
PubMed: 27401586
Kayıt Giriş Tarihi
[dc.date.accessioned]
2019-12-23
Açık Erişim Tarihi
[dc.date.available]
2019-12-23
Yayın Dili
[dc.language.iso]
eng
Konu Başlıkları
[dc.subject]
Baseline resistance
Konu Başlıkları
[dc.subject]
hepatitis C virus
Konu Başlıkları
[dc.subject]
mutation
Konu Başlıkları
[dc.subject]
protease inhibitors
Haklar
[dc.rights]
info:eu-repo/semantics/openAccess
ISSN
[dc.identifier.issn]
1201-9712
ISSN
[dc.identifier.issn]
1878-3511
Sponsor YAYINCI
[dc.description.sponsorship]
Department of Scientific Research Project of Kocaeli University; Turkish Society of Clinic Microbiology and Infectious Diseases
Sponsor YAYINCI
[dc.description.sponsorship]
This study was funded by Department of Scientific Research Project of Kocaeli University and Turkish Society of Clinic Microbiology and Infectious Diseases.
İlk Sayfa Sayısı
[dc.identifier.startpage]
1
Son Sayfa Sayısı
[dc.identifier.endpage]
5
Dergi Adı
[dc.relation.journal]
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
Dergi Cilt Bilgisi
[dc.identifier.volume]
50
Tek Biçim Adres
[dc.identifier.uri]
https://dx.doi.org/10.1016/j.ijid.2016.07.003
Tek Biçim Adres
[dc.identifier.uri]
https://hdl.handle.net/20.500.12628/3180
Görüntülenme Sayısı ( Şehir )
Görüntülenme Sayısı ( Ülke )
Görüntülenme Sayısı ( Zaman Dağılımı )
Görüntülenme
7
09.12.2022 tarihinden bu yana
İndirme
1
09.12.2022 tarihinden bu yana
Son Erişim Tarihi
06 Şubat 2024 22:06
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Tıklayınız
resistance patients treatment mutation detected mutations investigation Turkey responsible clinical included during variants frequently pattern revealed faldaprevir simeprevir boceprevir telaprevir studied rebound Background developed breakthrough develop Authors Published Elsevier natural behalf International Society Infectious Diseases
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