Hepatitis C virus (HCV) protease variability and anti‐HCV protease inhibitor resistance in HIV/HCV‐coinfected patients

• Published in: HIV medicine Vol. 12; no. 8; pp. 506 - 509
• Main Authors: Trimoulet, P, Belzunce, C, Faure, M, Wittkop, L, Reigadas, S, Dupon, M, Ragnaud, J‐M, Fleury, H, Neau, D
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-09-2011; Wiley
• Subjects: Adult; Amino acid sequence; Amino acid substitution; Antiviral Agents; Antiviral Agents - therapeutic use; Coinfection; Data processing; Disease resistance; Drug Resistance, Viral; Drug Resistance, Viral - genetics; Female; Genotype; Genotypes; HCV protease; HCV protease inhibitor resistance; Hepacivirus; Hepacivirus - genetics; Hepatitis C; Hepatitis C - complications; Hepatitis C - drug therapy; Hepatitis C virus; HIV Infections; HIV Infections - complications; HIV Infections - drug therapy; HIV/HCV‐coinfected patients; Human immunodeficiency virus; Humans; Life Sciences; Male; Microbiology and Parasitology; Middle Aged; Mutation; Natural selection; Peptide Hydrolases; Peptide Hydrolases - genetics; Protease Inhibitors; Protease Inhibitors - therapeutic use; Proteinase inhibitors; Statistical analysis; Viral Nonstructural Proteins; Viral Nonstructural Proteins - genetics
• ISSN: 1464-2662; 1468-1293
• DOI: 10.1111/j.1468-1293.2011.00913.x

Objectives
Data on the natural selection of isolates harbouring mutations within the NS3 protease, conferring resistance to hepatitis C virus (HCV) protease inhibitors (PIs), are limited for HIV/HCV‐coinfected patients. The aim of this study was to describe the natural prevalence of mutations conferring resistance to HCV PIs in HIV/HCV‐coinfected patients compared with HCV‐monoinfected patients.
Methods
The natural prevalences of HCV PI resistance mutations in 120 sequences from HIV/HCV‐coinfected patients (58 genotype 1a, 18 genotype 1b and 44 genotype 4) and 501 sequences from HCV‐monoinfected patients (476 genotype 1 and 25 genotype 4), retrieved from GenBank as a control group, were compared.
Results
Of 76 sequences from HIV/HCV genotype 1‐coinfected patients, six (7.9%) showed amino acid substitutions associated with HCV PI resistance (V36L, n=1; V36M, n=2; T54S, n=2; R155K, n=1). In 31 of 476 (6.5%) HCV genotype 1 sequences retrieved from the GenBank database, HCV PI resistance mutations were found. The difference was not statistically significant (P=0.6). All of the sequences from HIV/HCV genotype 4‐coinfected patients and those retrieved from the GenBank database had amino acid changes at position 36 (V36L).
Conclusion
Our study suggests that the natural prevalence of strains resistant to HCV PIs does not differ between HCV‐monoinfected and HIV/HCV‐coinfected patients. Further studies on larger cohorts are needed to confirm these findings and to evaluate the impact of these mutations in clinical practice.