Naturally occurring hepatitis C virus (HCV) NS3/4A protease inhibitor resistance-related mutations in HCV genotype 1-infected subjects in Italy

Autor: Francesco Saladini, C. Caudai, Andrea De Luca, Simona Di Giambenedetto, Francesco Pippi, Genny Meini, Barbara Rossetti, Ilaria Vicenti, Maurizio Zazzi, P. Almi, Andrea Rosi, Letizia Sidella
Rok vydání: 2012
Předmět:
Microbiology (medical)
Genotype
Hepatitis C virus
Molecular Sequence Data
Mutation
Missense
Hepacivirus
Biology
Viral Nonstructural Proteins
medicine.disease_cause
Settore MED/17 - MALATTIE INFETTIVE
Antiviral Agents
Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA
Telaprevir
resistance
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Boceprevir
Drug Resistance
Viral
medicine
Prevalence
Humans
Pharmacology (medical)
Protease inhibitor (pharmacology)
Protease Inhibitors
030304 developmental biology
Pharmacology
0303 health sciences
NS3
Mutation
Intracellular Signaling Peptides and Proteins
virus diseases
Sequence Analysis
DNA
Hepatitis C
Chronic
medicine.disease
Virology
digestive system diseases
3. Good health
Infectious Diseases
chemistry
Italy
Immunology
HCV
Coinfection
RNA
Viral
030211 gastroenterology & hepatology
Carrier Proteins
medicine.drug
Zdroj: Journal of Antimicrobial Chemotherapy; Vol 67
ISSN: 1460-2091
Popis: To assess the prevalence of hepatitis C virus (HCV) NS3/4A protease inhibitor (PI) resistance mutations in HCV genotype 1-infected PI-naive individuals in Italy.One hundred and twelve patients infected with HCV genotype 1a or 1b (based on Versant HCV Genotype 2.0 or 5'UTR/core sequencing) and never treated with any HCV PI were evaluated. The whole NS3 region was analysed by population sequencing and mutations related to resistance to linear and macrocyclic PIs were recorded.Forty-six HCV-monoinfected and 66 HCV/HIV-coinfected subjects were studied. Complete NS3 sequence information was obtained for 109 (97.3%) samples: 67 subtype 1a and 42 subtype 1b. Subtype assignment by NS3 sequencing was concordant in 100.0% and 83.9% of cases with the original 5'UTR sequencing and Versant result, respectively. At least one mutation related to PI resistance was detected in 21 (19.3%) isolates. However, 11 of these had only Q80K, expected to confer resistance to one investigational macrocyclic compound, and were detected only in subtype 1a. Boceprevir and telaprevir resistance-related mutations were detected in 10 (9.2%) isolates and included V36L, T54S and V55A. Only one isolate harboured two mutations (V36L and T54S). There was no association between HCV PI resistance and HIV coinfection or exposure to HIV PIs.A minority of untreated HCV genotype 1 patients in Italy harbour a virus population carrying HCV PI resistance-related mutations. The clinical implications of this finding warrant further analysis.
Databáze: OpenAIRE
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