The impact of interleukin 28B rs12979860 single nucleotide polymorphism and liver fibrosis stage on response-guided therapy in HIV/HCV-coinfected patients

AIDS. 2013 Nov 13;27(17):2707-14. doi: 10.1097/01.aids.0000432460.44593.ef.

Abstract

Objective: According to the European AIDS Clinical Society (EACS) guidelines for response-guided therapy (RGT) of chronic hepatitis C virus (HCV) infection in HIV-positive patients, HCV-genotype (GT) and rapid virologic response (RVR) exclusively determine the duration of antiviral therapy with pegylated interferon and ribavirin (PEGIFN+RBV). The aim of this study was to investigate the impact of interleukin 28B rs12979860 single nucleotide polymorphism (IL28B) and liver fibrosis stage on RGT in HIV/HCV-coinfected patients.

Design: Four hundred and thirty HIV/HCV-coinfected patients treated with PEGIFN+RBV were included in this multinational, retrospective analysis.

Methods: Advanced liver fibrosis was defined as either METAVIR F3/F4 or liver stiffness more than 9.5 kPa.

Results: In patients with GT1/4 without RVR (GT1/4-noRVR), higher sustained virologic response (SVR) rates were observed in patients with extended treatment duration (48 weeks: 35% vs. 72 weeks: 60%; P = 0.008). In GT1/4-noRVR patients without advanced liver fibrosis (48 weeks: 45% vs. 72 weeks: 61%; P = 0.176), or with IL28B C/C (48 weeks: 48% vs. 72 weeks: 69%; P = 0.207), SVR rates did not vary significantly throughout the treatment duration subgroups. In contrast, in patients with advanced liver fibrosis (48 weeks: 11% vs. 72 weeks: 45%; P = 0.031), or IL28B non-C/C (48 weeks: 28% vs. 72 weeks: 56%; P = 0.011), extended treatment duration was associated with substantially higher SVR rates. GT2/3 patients with RVR (GT2/3-RVR) with shortened treatment duration (24 weeks) displayed SVR rates ranging from 83 to 100%, regardless of IL28B and liver fibrosis stage.

Conclusion: Our study confirms the concept of RGT in HIV/HCV coinfection and supports the extension of therapy duration to 72 weeks for patients with GT1/4-noRVR, especially in patients with IL28B non-C/C or advanced liver fibrosis. The results of our study strongly support the shortening of therapy duration to 24 weeks in GT2/3-RVR patients, regardless of IL28B and advanced liver fibrosis.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Antiviral Agents / administration & dosage*
  • Coinfection / drug therapy
  • Coinfection / genetics
  • Coinfection / pathology
  • Drug Therapy, Combination / methods
  • Female
  • HIV Infections / complications*
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Interferons / administration & dosage
  • Interleukins / genetics*
  • Liver Cirrhosis / genetics*
  • Liver Cirrhosis / pathology*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Retrospective Studies
  • Ribavirin / administration & dosage
  • Time Factors
  • Treatment Outcome

Substances

  • Antiviral Agents
  • interferon-lambda, human
  • Interleukins
  • Ribavirin
  • Interferons