Influence of IL28B polymorphisms on response to a lower-than-standard dose peg-IFN-α 2a for genotype 3 chronic hepatitis C in HIV-coinfected patients

PLoS One. 2012;7(1):e28115. doi: 10.1371/journal.pone.0028115. Epub 2012 Jan 3.


Background: Data on which to base definitive recommendations on the doses and duration of therapy for genotype 3 HCV/HIV-coinfected patients are scarce. We evaluated the efficacy of a lower peginterferon-α 2a dose and a shorter duration of therapy than the current standard of care in genotype 3 HCV/HIV-coinfected patients.

Methods and findings: Pilot, open-label, single arm clinical trial which involved 58 Caucasian HCV/HIV-coinfected patients who received weekly 135 µg peginterferon-α 2a plus ribavirin 400 mg twice daily during 20 weeks after attaining undetectable viremia. The relationships between baseline patient-related variables, including IL28B genotype, plasma HCV-RNA, ribavirin dose/kg, peginterferon-α 2a and ribavirin levels with virological responses were analyzed. Only 4 patients showed lack of response and 5 patients dropped out due to adverse events related to the study medication. Overall, sustained virologic response (SVR) rates were 58.3% by intention-to-treat and 71.4% by per protocol analysis, respectively. Among patients with rapid virologic response (RVR), SVR and relapses rates were 92.6% and 7.4%, respectively. No relationships were observed between viral responses and ribavirin dose/kg, peginterferon-α 2a concentrations, ribavirin levels or rs129679860 genotype.

Conclusions: Weekly 135 µg pegIFN-α 2a could be as effective as the standard 180 µg dose, with a very low incidence of severe adverse events. A 24-week treatment duration appears to be appropriate in patients achieving RVR, but extending treatment up to just 20 weeks beyond negativization of viremia is associated with a high relapse rate in those patients not achieving RVR. There was no influence of IL28B genotype on the virological responses.

Trial registration: NCT00553930.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Dose-Response Relationship, Drug
  • Female
  • Genotype*
  • HIV Infections / complications*
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / metabolism
  • Humans
  • Interferon-alpha / adverse effects
  • Interferon-alpha / pharmacokinetics
  • Interferon-alpha / therapeutic use*
  • Interferons
  • Interleukins / genetics*
  • Male
  • Middle Aged
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / pharmacokinetics
  • Polyethylene Glycols / therapeutic use*
  • Polymorphism, Single Nucleotide*
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / pharmacokinetics
  • Recombinant Proteins / therapeutic use
  • Ribavirin / pharmacokinetics
  • Ribavirin / therapeutic use
  • Safety
  • Treatment Outcome


  • IFNL3 protein, human
  • Interferon-alpha
  • Interleukins
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • Interferons
  • peginterferon alfa-2a

Associated data