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

HIV Med. 2011 Sep;12(8):506-9. doi: 10.1111/j.1468-1293.2011.00913.x. Epub 2011 Mar 16.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use
  • Coinfection
  • Drug Resistance, Viral / genetics*
  • Female
  • Genotype
  • HIV Infections / complications*
  • HIV Infections / drug therapy*
  • Hepacivirus / genetics
  • Hepatitis C / complications*
  • Hepatitis C / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Peptide Hydrolases / genetics
  • Protease Inhibitors / therapeutic use*
  • Viral Nonstructural Proteins / genetics*

Substances

  • Antiviral Agents
  • NS3 protein, hepatitis C virus
  • Protease Inhibitors
  • Viral Nonstructural Proteins
  • Peptide Hydrolases