title: Virological responses during treatment for recent hepatitis C virus:  potential benefit for ribavirin use in HCV/HIV co-infection.
abstract: OBJECTIVE
  The role of ribavirin (RBV) in the treatment of recent hepatitis C virus (HCV) (acute/early chronic) is unclear, particularly in HIV-infected individuals. This study evaluated early virological decline during recent HCV therapy in HIV-uninfected individuals receiving pegylated interferon (PEG-IFN) monotherapy and HIV-infected individuals receiving PEG-IFN/RBV.
  
  
  METHODS
  The Australian Trial in Acute Hepatitis C was a nonrandomized prospective study of patients with recent HCV.
  
  
  METHODS
  All participants received PEG-IFN (24 weeks); HCV/HIV participants also received RBV. Early HCV RNA decline was assessed among adherent participants (≥80% PEG-IFN, ≥80% treatment). Logistic regression identified predictors of rapid virological response (RVR) (<10 IU/ml).
  
  
  RESULTS
  Of 109 treated, 82% were adherent (HCV, n=57; HCV/HIV, n=32). Overall, RVR was 51% (HCV: 55% vs. HCV/HIV: 43%; P=0.323). Factors independently associated with RVR included duration of infection less than 26 weeks, HCV RNA below 5.6 log(10) IU/ml at baseline and HCV genotype 2/3 infection. Between baseline and week 12, mean decline in HCV RNA was greater in HCV/HIV participants (PEG-IFN/RBV) compared to HCV participants (PEG-IFN) (4.19 vs. 3.32 log(10) IU/ml; P=0.029). Greater HCV RNA decline was observed in those treated with RBV, particularly amongst those with an estimated duration of infection at least 26 weeks and those with unfavourable IL28B genotypes. Adherent HIV-uninfected and infected participants had similar early virological response (76 vs. 90%; P=0.102) and sustained virological response (63 vs. 75%; P=0.253), respectively. RVR was highly predictive of sustained virological response (adjusted odds ratio 4.09; 1.49, 11.25).
  
  
  CONCLUSIONS
  The results of this study suggest a potential benefit for PEG-IFN and RBV combination therapy in maximizing virological responses in HCV/HIV participants with recent HCV, particularly those with a longer duration of HCV infection and unfavourable IL28B genotypes.
authors.affiliation: The Kirby Institute for Infection and Immunity in Society, University of New South Wales (UNSW), Sydney, Australia. jgrebely@kirby.unsw.edu.au
authors.forename: Jason
authors.initials: J
authors.lastname: Grebely
authors.forename: Margaret
authors.initials: M
authors.lastname: Hellard
authors.forename: Tanya
authors.initials: T
authors.lastname: Applegate
authors.forename: Kathy
authors.initials: K
authors.lastname: Petoumenos
authors.forename: Barbara
authors.initials: B
authors.lastname: Yeung
authors.forename: Jordan J
authors.initials: JJ
authors.lastname: Feld
authors.forename: William
authors.initials: W
authors.lastname: Rawlinson
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Lloyd
authors.forename: Jacob
authors.initials: J
authors.lastname: George
authors.forename: John M
authors.initials: JM
authors.lastname: Kaldor
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dore
authors.forename: Gail V
authors.initials: GV
authors.lastname: Matthews
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001315:Australia / Q000453:epidemiology; D060085:Coinfection; D005260:Female; D005838:Genotype; D006678:HIV / Q000187:drug effects* / Q000235:genetics; D006679:HIV Seropositivity / Q000188:drug therapy* / Q000453:epidemiology; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D016015:Logistic Models; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012367:RNA, Viral / Q000187:drug effects; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D012367:RNA, Viral; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda