Strategies for assignment of HIV-HCV genotype-1-coinfected patients to either dual-therapy or direct-acting antiviral agent-based triple-therapy

Antivir Ther. 2014;19(4):407-14. doi: 10.3851/IMP2717. Epub 2013 Dec 17.

Abstract

Background: The aim of this study was to evaluate strategies for assignment of HIV-HCV genotype-1-coinfected patients (HIV-HCV-GT1) to either dual-therapy or direct-acting antiviral agent (DAA)-based triple-therapy.

Methods: A total of 148 treatment-naive HIV-HCV-GT1 who received antiviral therapy with pegylated interferon/ribavirin were included in this multinational, retrospective analysis. Patients with rapid virological response (RVR) were treated for 48 weeks, while patients without RVR received either 48 or 72 weeks of treatment. IL28B rs12979860 (IL28B) non-C/C, advanced liver fibrosis and high HCV RNA were considered as established risk factors for treatment failure.

Results: A trend toward higher sustained virological response (SVR) rates in patients with IL28B C/C (65% [37/57] versus 51% [40/79]; P=0.097) was observed. Higher SVR rates were observed in patients without advanced liver fibrosis (61% [47/77] versus 42% [22/52]); P=0.036) and without high HCV RNA (73% [35/48] versus 49% [49/100]; P=0.006), as well as in patients with RVR (90% [35/39] versus 45% [49/109]; P<0.001). SVR rates varied statistically significantly between the risk factors for treatment failure subgroups (86% [6/7] versus 69% [34/49] versus 48% [21/44] versus 20% [4/20] for zero, one, two and three risk factors, respectively; P<0.001). In patients without RVR, higher rates of SVR were observed in those treated for 72 weeks (62% [23/37]), when compared to patients treated for 48 weeks (36% [26/72]; P=0.01).

Conclusions: RVR had an excellent positive predictive value for the response to dual-therapy in HIV-HCV-GT1, emphasizing the utility of a lead-in phase for assigning these patients to dual-therapy or DAA-based triple-therapy. The use of an IL28B-guided approach was suboptimal, while a combination of established baseline predictors may provide guidance for individual treatment decisions prior to the initiation of antiviral therapy. However, the extension of treatment duration to 72 weeks in HIV-HCV-GT1 without RVR should be strongly considered if triple-therapy is not available.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Antiretroviral Therapy, Highly Active
  • Antiviral Agents / therapeutic use*
  • CD4 Lymphocyte Count
  • Coinfection*
  • Drug Therapy, Combination
  • Female
  • Genotype
  • HIV Infections / drug therapy*
  • HIV Infections / genetics
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1 / genetics*
  • Hepacivirus / genetics*
  • Hepatitis C / complications
  • Hepatitis C / drug therapy*
  • Hepatitis C / genetics
  • Hepatitis C / immunology
  • Hepatitis C / virology
  • Humans
  • Interferon-alpha / therapeutic use
  • Interferons
  • Interleukins / genetics
  • Liver Cirrhosis / etiology
  • Male
  • Middle Aged
  • Odds Ratio
  • Polyethylene Glycols / therapeutic use
  • Recombinant Proteins / therapeutic use
  • Retrospective Studies
  • Treatment Failure
  • Treatment Outcome
  • Viral Load
  • Young Adult

Substances

  • Antiviral Agents
  • interferon-lambda, human
  • Interferon-alpha
  • Interleukins
  • Recombinant Proteins
  • Polyethylene Glycols
  • Interferons
  • peginterferon alfa-2a