No influence of antiretroviral therapy on the mutation rate of the HCV NS5B polymerase in HIV/HCV-coinfected patients.
OBJECTIVE
To assess the impact of antiretroviral treatment (ART), including nucleoside analogues retrotranscriptase inhibitors (NRTIs), on the mutation rate of hepatitis C virus (HCV) NS5B polymerase and on the ratio of substitution at synonymous and nonsynonymous sites (dN/dS) this polymerase in HIV/HCV-coinfected patients.


METHODS
Sixty-one patients on defined ART were included in this study. The NS5B polymerase of HCV was sequenced at baseline and after at least two years of ART. The mutation rate and the dN/dS were calculated at both times.


RESULTS
The NS5B gene from forty-nine (80.3%) patients including; 19 HCV-1a (38.8%), 13 HCV-1b (26.5%), 8 HCV-3a (16.3%) and 9 HCV-4d (18.4%), could be sequenced. Thirty-two (65.3%) patients received non-nucleoside analogues and 41 (83.7%) received protease inhibitor. The mean estimated substitution rates at baseline and at the end of follow-up were from 1.38 to 3.5×10(-3)substitution/site/year (s/s/y) and from 1.39 to 3.18×10(-3)s/s/y, respectively, varying according to HCV genotype. All HCV genotypes at baseline and the end time point had values of dN/dS <1. At the end of follow-up, most of sites experienced negative selection and positive selection occurred only in a few sites.


CONCLUSIONS
The mutation rate of NS5B in HIV/HCV-coinfected patients is within the range previously reported in studies in HCV-monoinfected patients. Additionally, the use of ART, including NRTIs, in these patients does not affect neither mutation rate nor the dN/dS of the HCV NS5B protein, suggesting that its use would not generate new resistance mutants to the polymerase inhibitors of HCV.
Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Instituto de Biomedicina de Sevilla, Avenida de Bellavista s/n, 41014 Seville, Spain.
Federico Alejandro
FA
Di Lello
Juan
J
Macias
Zulema
Z
Plaza
Silvia
S
García-Rey
Vicente
V
Soriano
Celia
C
Cifuentes
Maria del Mar
Mdel M
González
Manuel
M
Parra-Sánchez
Pablo
P
Labarga
Eva
E
Recio
Eva
E
Poveda
Juan Antonio
JA
Pineda
D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D016174:Hepacivirus / Q000201:enzymology*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D059645:Mutation Rate; D020125:Mutation, Missense; D017354:Point Mutation; D012367:RNA, Viral / Q000235:genetics; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D012324:RNA-Dependent RNA Polymerase
D044966:Anti-Retroviral Agents; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase