title: Abacavir coadministration does not interfere with the suppressive activity of ribavirin in an HCV replicon system.
abstract: BACKGROUND
  HCV is a major cause of morbidity and mortality in HIV-coinfected patients. Several observational studies have suggested that HCV response to pegylated interferon and ribavirin is lower in HIV-coinfected patients treated with abacavir. It has been postulated that abacavir could compete with ribavirin to be phosphorylated, leading to a reduction in the active form of the drug (triphosphorylated ribavirin). Here, we studied the effect of abacavir, tenofovir or lamivudine addition on the suppressive activity of ribavirin in an HCV RNA replicon system.
  
  
  METHODS
  We used the human hepatoma HuH-7 cell clone 9B containing the HCV genotype 1b replicon I389/NS3-3'. Cells were treated for 24 h with ribavirin (0, 10 and 50 μM) plus abacavir, tenofovir or lamivudine at doses of 0, 10 and 50 μM and HCV RNA production was quantified by real-time PCR in triplicate assays. Results were expressed as mean±SD of the HCV RNA produced per cell (log(10) IU/cell). Means were compared using the Student's t-test.
  
  
  RESULTS
  Ribavirin treatment produced a dose-dependent suppression of HCV RNA production by the replicon system. Combination of ribavirin and interferon resulted in an additive antiviral activity. The addition of abacavir did not modify the suppressive activity of ribavirin on the replicon HCV RNA expression. Similar results were obtained when ribavirin was used in combination with tenofovir or lamivudine.
  
  
  CONCLUSIONS
  In a subgenomic HCV RNA replicon system, the antiviral effect of ribavirin was not modified by the addition of abacavir, tenofovir or lamivudine.
authors: Infectious Diseases Department, Vall d'Hebron Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain. evavandeneynde@yahoo.com
authors: Eva
authors: E
authors: Van den Eynde
authors: Josep
authors: J
authors: Quer
authors: María
authors: M
authors: Cubero
authors: Adriá
authors: A
authors: Curran
authors: María
authors: M
authors: Homs
authors: Damir
authors: D
authors: Garcia-Cehic
authors: Vicenç
authors: V
authors: Falco
authors: Esteban
authors: E
authors: Ribera
authors: Juan I
authors: JI
authors: Esteban
authors: Albert
authors: A
authors: Pahissa
authors: Manuel
authors: M
authors: Crespo
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015224:Dideoxynucleosides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D012367:RNA, Viral / Q000378:metabolism; D012093:Replicon; D012254:Ribavirin / Q000494:pharmacology*; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D000998:Antiviral Agents; D015224:Dideoxynucleosides; D007372:Interferons; D012367:RNA, Viral; D012254:Ribavirin; D000099227:Abacavir