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Impact of antiretroviral therapy on the variability of the HCV NS5B polymerase in HIV/HCV co-infected patients.
MedLine Citation:
PMID:  21954459     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
ObjectivesAssessment of the impact of antiretroviral drugs on the variability of hepatitis C virus (HCV) NS5B polymerase in HIV/HCV co-infected individuals.MethodsHCV NS5B polymerase was sequenced from plasma at baseline and at the end of follow-up in HIV/HCV co-infected individuals on a stable antiretroviral regimen seen at two outpatient clinics for at least 2 years. The presence of mutations associated with drug resistance to experimental HCV polymerase inhibitors was examined.ResultsSixty-one HIV/HCV co-infected patients (34% HCV-1a, 25% HCV-1b, 18% HCV-3 and 23% HCV-4) were analysed. The mean time on antiretroviral therapy was 52 months. All patients received HIV nucleoside analogues; 66% along with non-nucleoside analogues. The median HCV RNA was 6.1 log at baseline and 6 log IU/mL at the end of follow-up. The median HIV RNA was 4.4 log at baseline and 1.5 log copies/mL at the end of follow-up. No evidence of selection of NS5B polymerase inhibitor resistance mutations was seen when comparing samples collected at baseline and at the end of follow-up from the same individuals. All NS5B sequences from HCV-1a and HCV-3 showed V499A, associated with resistance to HCV non-nucleoside site-1 inhibitors (NNI-1). In addition, HCV-3 showed I482L, associated with resistance to NNI-2, and HCV-4 showed M414L, I482L and V499A, associated with resistance to NNI-3, 2 and 1, respectively. Two HCV-1b patients showed C316N, related with resistance to NNI-4.ConclusionsThe use of antiretroviral drugs does not increase the rate of primary drug resistance mutations to HCV NS5B polymerase inhibitors in HIV/HCV co-infected patients. However, natural polymorphisms associated with reduced susceptibility to some HCV NNIs are common, particularly in HCV variants other than HCV-1b.
Authors:
Zulema Plaza; Vincent Soriano; Maria Del Mar Gonzalez; Federico A Di Lello; Juan Macias; Pablo Labarga; Juan Antonio Pineda; Eva Poveda
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-27
Journal Detail:
Title:  The Journal of antimicrobial chemotherapy     Volume:  -     ISSN:  1460-2091     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7513617     Medline TA:  J Antimicrob Chemother     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
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