Efficacy and safety of daclatasvir plus pegylated-interferon alfa 2a and ribavirin in previously untreated HCV subjects coinfected with HIV and HCV genotype-1: a Phase III, open-label study

Mark S. Sulkowski, Walford J. Fessel, Adriano Lazzarin, Juan Berenguer, Natalia Zakharova, Hugo Cheinquer, Pierre Côté, Douglas Dieterich, Adrian Gadano, Gail Matthews, Jean Michel Molina, Christophe Moreno, Juan Antonio Pineda, Federico Pulido, Antonio Rivero, Jurgen Rockstroh, Dennis Hernandez, Fiona McPhee, Timothy Eley, Zhaohui LiuPatricia Mendez, Eric Hughes, Stephanie Noviello, Peter Ackerman

Research output: Contribution to journalArticle

Abstract

Background: Daclatasvir (DCV) is a potent, pangenotypic, hepatitis C virus (HCV) non-structural protein 5A inhibitor with low potential for drug interactions with antiretroviral therapy (ART). We evaluated the safety and efficacy of DCV plus peginterferon alfa-2a/ribavirin (PegIFN/RBV) in HIV-1/HCV genotype-1-coinfected patients. Methods: AI444043 (NCT01471574), an open-label, Phase III, single-arm, response-guided treatment (RGT) study included 301 patients. They received DCV doses of 30, 60 or 90 mg once daily (depending on concomitant ART), plus weight-based RBV (<75 kg, 1000 mg/day; or ≥75 kg, 1200 mg/day), and once-weekly PegIFN 180 μg, for 24 weeks. If required by RGT, PegIFN/RBV without DCV was extended for an additional 24 weeks of therapy. The primary endpoint was the proportion of patients with sustained virologic response at post-treatment Week 12 (SVR12). Results: Overall, 224 (74%) patients achieved SVR12 and the lower bound of the 95% confidence interval was higher than the historic SVR rate with PegIFN/RBV alone (70 vs. 29%). Most common adverse events (AEs) were fatigue, neutropenia, anemia, asthenia and headache. On-treatment serious AEs occurred in 24/301 (8%) patients; 18/301 (6%) discontinued treatment due to AE. Conclusions: DCV + PegIFN/RBV led to sustained HCV virologic response in the majority of HIV-1-HCV-coinfected patients, regardless of concomitant ART. HIV control was not compromised and no new safety signals were identified. This study supports DCV use in HIV-1-HCV-coinfected patients, while allowing the vast majority of patients to remain on their existing ART regimen.

Original languageEnglish (US)
Pages (from-to)188-198
Number of pages11
JournalHepatology International
Volume11
Issue number2
DOIs
StatePublished - Mar 1 2017

Keywords

  • Daclatasvir
  • HCV GT-1
  • HIV/HCV coinfection
  • Peginterferon alfa-2a/ribavirin

ASJC Scopus subject areas

  • Hepatology

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    Sulkowski, M. S., Fessel, W. J., Lazzarin, A., Berenguer, J., Zakharova, N., Cheinquer, H., Côté, P., Dieterich, D., Gadano, A., Matthews, G., Molina, J. M., Moreno, C., Pineda, J. A., Pulido, F., Rivero, A., Rockstroh, J., Hernandez, D., McPhee, F., Eley, T., ... Ackerman, P. (2017). Efficacy and safety of daclatasvir plus pegylated-interferon alfa 2a and ribavirin in previously untreated HCV subjects coinfected with HIV and HCV genotype-1: a Phase III, open-label study. Hepatology International, 11(2), 188-198. https://doi.org/10.1007/s12072-017-9788-z