title: Impact of antiretroviral therapy on the variability of the HCV NS5B polymerase in HIV/HCV co-infected patients.
abstract: OBJECTIVE
  Assessment of the impact of antiretroviral drugs on the variability of hepatitis C virus (HCV) NS5B polymerase in HIV/HCV co-infected individuals.
  
  
  METHODS
  HCV 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.
  
  
  RESULTS
  Sixty-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.
  
  
  CONCLUSIONS
  The 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.affiliation: Department of Infectious Diseases,  Hospital Carlos III, Madrid,  Spain.
authors.forename: Zulema
authors.initials: Z
authors.lastname: Plaza
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
authors.forename: Maria del Mar
authors.initials: Mdel M
authors.lastname: Gonzalez
authors.forename: Federico A
authors.initials: FA
authors.lastname: Di Lello
authors.forename: Juan
authors.initials: J
authors.lastname: Macias
authors.forename: Pablo
authors.initials: P
authors.lastname: Labarga
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Pineda
authors.forename: Eva
authors.initials: E
authors.lastname: Poveda
mesh_terms: D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D024882:Drug Resistance, Viral; D005260:Female; D014644:Genetic Variation; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000150:complications / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000821:virology; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D017422:Sequence Analysis, DNA; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase