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

HIV Medicine
Early View (Articles online in advance of print)

P Trimoulet 1,†, C Belzunce 2,†, M Faure 1, L Wittkop 3, S Reigadas 1, M Dupon 2, J-M Ragnaud 2, H Fleury 1, D Neau 2

Article first published online: 16 MAR 2011
DOI: 10.1111/j.1468-1293.2011.00913.x
© 2011 British HIV Association

Author Information

1 Virology Laboratory, Bordeaux University Hospital, Bordeaux, France
2 Department of Tropical and Infectious Diseases, Bordeaux University Hospital, Bordeaux, France
3 INSERM U897 Center of Epidemiology and Biostatistics, ISPED Bordeaux School of Public Health, University of Bordeaux 2, Bordeaux, France

* Correspondence: Dr Pascale Trimoulet, Laboratoire de Virologie, Hôpital Pellegrin Tripode, Place Amélie Raba-Léon, EA 2968, Bordeaux University Hospital, Bordeaux Cedex 33076, France. Tel: +33 5 56 79 55 10; fax: +33 5 56 79 56 73; e-mail: pascale.trimoulet@chu-bordeaux.fr

†† The first two authors contributed equally to the study

Abstract

Keywords: HCV protease inhibitor resistance; HCV protease; HIV/HCV-coinfected patients

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.

Source