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 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)1-11
Number of pages11
JournalHepatology International
DOIs
StateAccepted/In press - Feb 16 2017

Fingerprint

Ribavirin
Hepacivirus
Genotype
HIV
Safety
Therapeutics
HIV-1
BMS-790052
peginterferon alfa-2a
Viral Structural Proteins
Asthenia
Neutropenia
Drug Interactions
Fatigue
Headache
Anemia
Confidence Intervals
Weights and Measures

Keywords

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

ASJC Scopus subject areas

  • Hepatology

Cite this

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

In: Hepatology International, 16.02.2017, p. 1-11.

Research output: Contribution to journalArticle

Sulkowski, M, Fessel, WJ, Lazzarin, A, Berenguer, J, Zakharova, N, Cheinquer, H, Côté, P, Dieterich, D, Gadano, A, Matthews, G, Molina, JM, Moreno, C, Pineda, JA, Pulido, F, Rivero, A, Rockstroh, J, Hernandez, D, McPhee, F, Eley, T, Liu, Z, Mendez, P, Hughes, E, Noviello, S & 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, pp. 1-11. https://doi.org/10.1007/s12072-017-9788-z
Sulkowski, Mark ; Fessel, Walford J. ; Lazzarin, Adriano ; Berenguer, Juan ; Zakharova, Natalia ; Cheinquer, Hugo ; Côté, Pierre ; Dieterich, Douglas ; Gadano, Adrian ; Matthews, Gail ; Molina, Jean Michel ; Moreno, Christophe ; Pineda, Juan Antonio ; Pulido, Federico ; Rivero, Antonio ; Rockstroh, Jurgen ; Hernandez, Dennis ; McPhee, Fiona ; Eley, Timothy ; Liu, Zhaohui ; Mendez, Patricia ; Hughes, Eric ; Noviello, Stephanie ; Ackerman, Peter. / 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. In: Hepatology International. 2017 ; pp. 1-11.
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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.",
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T1 - Efficacy and safety of daclatasvir plus pegylated-interferon alfa 2a and ribavirin in previously untreated HCV subjects coinfected with HIV and HCV genotype-1

T2 - a Phase III, open-label study

AU - Sulkowski, Mark

AU - Fessel, Walford J.

AU - Lazzarin, Adriano

AU - Berenguer, Juan

AU - Zakharova, Natalia

AU - Cheinquer, Hugo

AU - Côté, Pierre

AU - Dieterich, Douglas

AU - Gadano, Adrian

AU - Matthews, Gail

AU - Molina, Jean Michel

AU - Moreno, Christophe

AU - Pineda, Juan Antonio

AU - Pulido, Federico

AU - Rivero, Antonio

AU - Rockstroh, Jurgen

AU - Hernandez, Dennis

AU - McPhee, Fiona

AU - Eley, Timothy

AU - Liu, Zhaohui

AU - Mendez, Patricia

AU - Hughes, Eric

AU - Noviello, Stephanie

AU - Ackerman, Peter

PY - 2017/2/16

Y1 - 2017/2/16

N2 - 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.

AB - 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.

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KW - HCV GT-1

KW - HIV/HCV coinfection

KW - Peginterferon alfa-2a/ribavirin

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