Fluvastatin as an adjuvant to pegylated interferon and ribavirin in HIV/hepatitis C virus genotype 1 co-infected patients: an open-label randomized controlled study

J Antimicrob Chemother. 2010 Apr;65(4):735-40. doi: 10.1093/jac/dkq002. Epub 2010 Jan 30.

Abstract

Objectives: Recent reports demonstrated in vitro the efficacy of fluvastatin in inhibiting hepatitis C virus (HCV) replication and a synergistic effect in association with interferon-alpha (IFN-alpha). In vivo the inhibition of HCV replication by statins has not been demonstrated. We evaluated in this open-label, randomized controlled study the efficacy of fluvastatin as adjuvant to pegylated-(PEG)-IFN and ribavirin in HIV/HCV genotype 1 co-infected patients.

Patients and methods: Forty-four HIV/HCV co-infected patients were randomized to receive, in addition to PEG-IFN-alpha 2b and ribavirin, 80 mg of fluvastatin once daily or no medication. Primary and secondary endpoints were the achievement of sustained virological response (SVR) and rapid virological response (RVR), respectively.

Results: By intent-to-treat analysis, 25% of the patients achieved an SVR. An SVR was observed in 8/21 patients in the fluvastatin arm and in 3/23 patients in the standard therapy arm (P = 0.08). A significantly higher RVR rate was obtained in the fluvastatin arm compared with the standard therapy [7/21 (33%) and 1/23 (4%), respectively; P = 0.02]. Baseline alanine aminotransferase (ALT) values and fluvastatin treatment arm were the only predictors of RVR at the univariate analysis; however, no predictors were independently associated with RVR or SVR at the multivariate analysis.

Conclusions: Fluvastatin addition to standard therapy did not significantly increase the SVR rate in HIV/HCV genotype 1 co-infected patients; however, it did significantly improve the RVR. Further studies are needed to confirm these promising results and to investigate the mechanisms of action of statins in HCV infection.

Publication types

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

MeSH terms

  • Adult
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / therapeutic use*
  • Drug Therapy, Combination
  • Fatty Acids, Monounsaturated / administration & dosage
  • Fatty Acids, Monounsaturated / therapeutic use*
  • Female
  • Fluvastatin
  • Genotype
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • Hepacivirus / genetics
  • Hepacivirus / isolation & purification
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Indoles / administration & dosage
  • Indoles / therapeutic use*
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / therapeutic use*
  • Male
  • Middle Aged
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / therapeutic use*
  • Recombinant Proteins
  • Ribavirin / administration & dosage
  • Ribavirin / therapeutic use*
  • Treatment Outcome
  • Viral Load

Substances

  • Antiviral Agents
  • Fatty Acids, Monounsaturated
  • Indoles
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • Fluvastatin
  • peginterferon alfa-2b