NDLI: Specific Detection of Naturally Occurring Hepatitis C Virus Mutants with Resistance to Telaprevir and Boceprevir (Protease Inhibitors) among Treatment-Naïve Infected Individuals

Content Provider	PubMed Central
Author	Salvador, Fonseca-coronado Alejandro, Escobar-gutiérrez Karina, Ruiz-tovar Cruz-rivera, Mayra Yolanda Pilar, Rivera-osorio Mauricio, Vazquez-pichardo Carlos, Carpio-pedroza Juan Alberto, Ruíz-pacheco Juan Cazares, Fernando Vaughan, Gilberto
Copyright Year	2012
Abstract	The use of telaprevir and boceprevir, both protease inhibitors (PI), as part of the specifically targeted antiviral therapy for hepatitis C (STAT-C) has significantly improved sustained virologic response (SVR) rates. However, different clinical studies have also identified several mutations associated with viral resistance to both PIs. In the absence of selective pressure, drug-resistant hepatitis C virus (HCV) mutants are generally present at low frequency, making mutation detection challenging. Here, we describe a mismatch amplification mutation assay (MAMA) PCR method for the specific detection of naturally occurring drug-resistant HCV mutants. MAMA PCR successfully identified the corresponding HCV variants, while conventional methods such as direct sequencing, endpoint limiting dilution (EPLD), and bacterial cloning were not sensitive enough to detect circulating drug-resistant mutants in clinical specimens. Ultradeep pyrosequencing was used to confirm the presence of the corresponding HCV mutants. In treatment-naïve patients, the frequency of all resistant variants was below 1%. Deep amplicon sequencing allowed a detailed analysis of the structure of the viral population among these patients, showing that the evolution of the NS3 is limited to a rather small sequence space. Monitoring of HCV drug resistance before and during treatment is likely to provide important information for management of patients undergoing anti-HCV therapy.
Related Links	http://dx.doi.org/10.1128/jcm.05842-11
Ending Page	287
Page Count	7
Starting Page	281
File Format	PDF
ISSN	00951137
e-ISSN	1098660X
Journal	Journal of Clinical Microbiology
Issue Number	2
Volume Number	50
Language	English
Publisher	American Society for Microbiology
Publisher Date	2012-02-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Microbiology (medical) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Microbiology (medical)

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