Pegylated-interferon plus ribavirin treatment does not alter the prevalence of resistance-associated substitutions to direct-acting antivirals in HCV genotype 1a patients
Zhi-wei Chen,* Xi-chen Pang,* Zhao Li, Hong Ren, Peng Hu Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing M...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2017-08-01
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| Series: | Infection and Drug Resistance |
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| Online Access: | https://www.dovepress.com/pegylated-interferon-plus-ribavirin-treatment-does-not-alter-the-preva-peer-reviewed-article-IDR |
| _version_ | 1828769541946081280 |
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| author | Chen Z Pang X Li Z Ren H Hu P |
| author_facet | Chen Z Pang X Li Z Ren H Hu P |
| author_sort | Chen Z |
| collection | DOAJ |
| description | Zhi-wei Chen,* Xi-chen Pang,* Zhao Li, Hong Ren, Peng Hu Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China *These authors contributed equally to this work Background: Direct-acting antiviral (DAA) resistance-associated substitutions (RASs) can jeopardize the effectiveness of DAAs in patients with hepatitis C virus (HCV). The selection pressure by pegylated-interferon (Peg-IFN) plus ribavirin (P/R) treatment may enhance HCV genome variation. However, whether P/R treatment alters the rate of change of RASs is still unclear. Materials and methods: We retrieved the genomic sequences of HCV genotype (GT) 1a patients from GenBank, which included patients naïve to P/R (pre-IFN group) and those previously treated with P/R (post-IFN group). The sequences were aligned and analyzed by using MEGA 6.0 software. Clinically relevant RASs were summarized from the current medical literature. Results: In the cross-sectional study, the total prevalence of clinically relevant RASs was high, independent of the treatment group (pre-IFN: 219/403 [54.34%] vs post-IFN: 67/131 [51.15%]). The high prevalence was mainly detected in the NS3 region RAS at Q80 (40.69% vs 36.64%). The RASs in the NS5A region, such as M28, Q30, L31 and Y93, were uncommon (0%–5%). Similarly, all RASs showed no difference between the two groups. One exception was the RAS at I170 in the NS3 region, which was significantly higher in the post-IFN group than in the pre-IFN group. In the longitudinal study, similar results were observed. However, no difference in RAS at I170 was observed between the two groups. Finally, no clinically relevant RASs were detected in response to the DAA regimens approved for GT 1a patients treated with P/R. Conclusion: Our results suggest that previous P/R treatment failure was not favorably associated with an increase in DAAs RASs present in GT1a patients. Our results support the American Association for the Study of Liver Diseases’ recommendations of DAA intervention in P/R-treated GT1a patients. Keywords: pegylated-interferon, ribavirin, direct-acting antivirals, resistance-associated substitutions, prevalence |
| first_indexed | 2024-12-11T13:49:52Z |
| format | Article |
| id | doaj.art-303e7caa766e4f95b58d93296726944b |
| institution | Directory Open Access Journal |
| issn | 1178-6973 |
| language | English |
| last_indexed | 2024-12-11T13:49:52Z |
| publishDate | 2017-08-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Infection and Drug Resistance |
| spelling | doaj.art-303e7caa766e4f95b58d93296726944b2022-12-22T01:04:19ZengDove Medical PressInfection and Drug Resistance1178-69732017-08-01Volume 1027528134526Pegylated-interferon plus ribavirin treatment does not alter the prevalence of resistance-associated substitutions to direct-acting antivirals in HCV genotype 1a patientsChen ZPang XLi ZRen HHu PZhi-wei Chen,* Xi-chen Pang,* Zhao Li, Hong Ren, Peng Hu Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China *These authors contributed equally to this work Background: Direct-acting antiviral (DAA) resistance-associated substitutions (RASs) can jeopardize the effectiveness of DAAs in patients with hepatitis C virus (HCV). The selection pressure by pegylated-interferon (Peg-IFN) plus ribavirin (P/R) treatment may enhance HCV genome variation. However, whether P/R treatment alters the rate of change of RASs is still unclear. Materials and methods: We retrieved the genomic sequences of HCV genotype (GT) 1a patients from GenBank, which included patients naïve to P/R (pre-IFN group) and those previously treated with P/R (post-IFN group). The sequences were aligned and analyzed by using MEGA 6.0 software. Clinically relevant RASs were summarized from the current medical literature. Results: In the cross-sectional study, the total prevalence of clinically relevant RASs was high, independent of the treatment group (pre-IFN: 219/403 [54.34%] vs post-IFN: 67/131 [51.15%]). The high prevalence was mainly detected in the NS3 region RAS at Q80 (40.69% vs 36.64%). The RASs in the NS5A region, such as M28, Q30, L31 and Y93, were uncommon (0%–5%). Similarly, all RASs showed no difference between the two groups. One exception was the RAS at I170 in the NS3 region, which was significantly higher in the post-IFN group than in the pre-IFN group. In the longitudinal study, similar results were observed. However, no difference in RAS at I170 was observed between the two groups. Finally, no clinically relevant RASs were detected in response to the DAA regimens approved for GT 1a patients treated with P/R. Conclusion: Our results suggest that previous P/R treatment failure was not favorably associated with an increase in DAAs RASs present in GT1a patients. Our results support the American Association for the Study of Liver Diseases’ recommendations of DAA intervention in P/R-treated GT1a patients. Keywords: pegylated-interferon, ribavirin, direct-acting antivirals, resistance-associated substitutions, prevalencehttps://www.dovepress.com/pegylated-interferon-plus-ribavirin-treatment-does-not-alter-the-preva-peer-reviewed-article-IDRpegylated-interferonribavirindirect-acting antiviralsresistance associated substitutionsprevalence |
| spellingShingle | Chen Z Pang X Li Z Ren H Hu P Pegylated-interferon plus ribavirin treatment does not alter the prevalence of resistance-associated substitutions to direct-acting antivirals in HCV genotype 1a patients Infection and Drug Resistance pegylated-interferon ribavirin direct-acting antivirals resistance associated substitutions prevalence |
| title | Pegylated-interferon plus ribavirin treatment does not alter the prevalence of resistance-associated substitutions to direct-acting antivirals in HCV genotype 1a patients |
| title_full | Pegylated-interferon plus ribavirin treatment does not alter the prevalence of resistance-associated substitutions to direct-acting antivirals in HCV genotype 1a patients |
| title_fullStr | Pegylated-interferon plus ribavirin treatment does not alter the prevalence of resistance-associated substitutions to direct-acting antivirals in HCV genotype 1a patients |
| title_full_unstemmed | Pegylated-interferon plus ribavirin treatment does not alter the prevalence of resistance-associated substitutions to direct-acting antivirals in HCV genotype 1a patients |
| title_short | Pegylated-interferon plus ribavirin treatment does not alter the prevalence of resistance-associated substitutions to direct-acting antivirals in HCV genotype 1a patients |
| title_sort | pegylated interferon plus ribavirin treatment does not alter the prevalence of resistance associated substitutions to direct acting antivirals in hcv genotype 1a patients |
| topic | pegylated-interferon ribavirin direct-acting antivirals resistance associated substitutions prevalence |
| url | https://www.dovepress.com/pegylated-interferon-plus-ribavirin-treatment-does-not-alter-the-preva-peer-reviewed-article-IDR |
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