Faldaprevir and pegylated interferon α-2a/ribavirin in individuals co-infected with hepatitis C virus genotype-1 and HIV

AIDS. 2015 Mar 13;29(5):571-81. doi: 10.1097/QAD.0000000000000579.

Abstract

Objective: Faldaprevir is a potent, once-daily hepatitis C virus (HCV) NS3/4A protease inhibitor. STARTVerso4 assessed the efficacy and safety of faldaprevir and response-guided pegylated interferon α-2a/ribavirin (PegIFN/RBV) in individuals with HCV/HIV co-infection.

Design: A phase 3 open-label study (NCT01399619).

Methods: Individuals (N = 308) co-infected with HCV genotype 1 (treatment-naive or prior interferon relapsers) and HIV [96% on antiretroviral therapy (ART)] received faldaprevir 120 mg (N = 123) or 240 mg (N = 185) and PegIFN/RBV. Those receiving a protease inhibitor or efavirenz ART were assigned to faldaprevir 120 or 240 mg, respectively. Individuals achieving early treatment success (ETS; HCV RNA <25 IU/ml at week 4 and undetectable at week 8) were randomized to 24 or 48 weeks of PegIFN/RBV. The primary endpoint was sustained virologic response 12 weeks after treatment (SVR12).

Results: SVR12 was achieved in 221 (72%) individuals, and the rates were comparable across faldaprevir doses. ETS was achieved in 80%, and of these 86% achieved SVR12, with comparable rates with 24 and 48 weeks of PegIFN/RBV (87 and 94%, respectively). In multivariate analysis, age below 40 years, IL28B CC genotype, and baseline HCV RNA below 800 000 IU/ml were associated with SVR12 (P = 0.027, P < 0.0001, and P = 0.0002, respectively), whereas treatment (ART regimen and faldaprevir dose), liver cirrhosis, and genotype 1 subtype were not. The safety profile was comparable to that of faldaprevir in HCV-monoinfected individuals.

Conclusions: High SVR12 rates were achieved with faldaprevir and PegIFN/RBV in HIV/HCV co-infected individuals, regardless of faldaprevir dose and background ART, HCV genotype 1 subtype, or cirrhosis status. SVR rates mirrored those obtained with similar regimens in HCV monoinfected individuals.

Trial registration: ClinicalTrials.gov NCT01343888 NCT01399619 NCT01343888.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-Retroviral Agents / therapeutic use
  • Antiviral Agents / therapeutic use*
  • Drug Therapy, Combination / methods
  • HIV Infections / complications*
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Interferon-alpha / therapeutic use*
  • Middle Aged
  • Oligopeptides / therapeutic use*
  • Polyethylene Glycols / therapeutic use*
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use*
  • Thiazoles / therapeutic use*
  • Treatment Outcome
  • Viral Load
  • Viremia / diagnosis
  • Young Adult

Substances

  • Anti-Retroviral Agents
  • Antiviral Agents
  • Interferon-alpha
  • Oligopeptides
  • Recombinant Proteins
  • Thiazoles
  • Polyethylene Glycols
  • Ribavirin
  • faldaprevir
  • peginterferon alfa-2a

Associated data

  • ClinicalTrials.gov/NCT01343888
  • ClinicalTrials.gov/NCT01399619
  • ClinicalTrials.gov/NCT01343888