title: 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.
abstract: 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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Divisions of Infectious Diseases and Gastroenterology/Hepatology, Johns Hopkins Hospital, The Johns Hopkins University School of Medicine , Baltimore, MD, USA. msulkowski@jhmi.edu.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sulkowski
authors.affiliation: Kaiser Permanente San Francisco Medical Center, San Francisco, CA, USA.
authors.forename: Walford J
authors.initials: WJ
authors.lastname: Fessel
authors.affiliation: Unit of Infectious Diseases, Clinica Malattie Infettive, Institute of Hospitalisation and Scientific Care, Milan, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.affiliation: Unidad de Enfermedades Infecciosas/VIH (4100), Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Berenguer
authors.affiliation: St Petersburg AIDS Center, SPT AIDS C 179A OBVODNIY CANAL, Saint Petersburg, Russian Federation.
authors.forename: Natalia
authors.initials: N
authors.lastname: Zakharova
authors.affiliation: Servico De Gastroentereologia, Hospital De Clinicas De Porto Alegre, Porto Alegre, Rio Grande Do Sul, Brazil.
authors.forename: Hugo
authors.initials: H
authors.lastname: Cheinquer
authors.affiliation: Clinique Medicale Du Quartier Latin, Montreal, QC, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Côté
authors.affiliation: Institute for Liver Disease, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Dieterich
authors.affiliation: Hospital Italiano De Buenos Aires, Buenos Aires, Argentina.
authors.forename: Adrian
authors.initials: A
authors.lastname: Gadano
authors.affiliation: St Vincent's Hospital (NSW), Darlinghurst, NSW, Australia.
authors.forename: Gail
authors.initials: G
authors.lastname: Matthews
authors.affiliation: Hopital Saint Louis, Paris, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
authors.affiliation: Hospital Erasme, Brussels, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Moreno
authors.affiliation: Infectious Diseases and Microbiology Unit, Hospital Universitario de Valme, Seville, Spain.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Pineda
authors.affiliation: Hospital Universitario 12 De Octubre, Madrid, Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: Pulido
authors.affiliation: Hospital Universitario Reina Sofia, Cordoba, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rivero
authors.affiliation: Universitaetsklinikum Bonn, Medizinische Klinik, Bonn, Germany.
authors.forename: Jurgen
authors.initials: J
authors.lastname: Rockstroh
authors.affiliation: Department of Virology Discovery Biology, Bristol-Myers Squibb Research and Development, Wallingford, CT, USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Hernandez
authors.affiliation: Department of Virology Discovery Biology, Bristol-Myers Squibb Research and Development, Wallingford, CT, USA.
authors.forename: Fiona
authors.initials: F
authors.lastname: McPhee
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Eley
authors.affiliation: Bristol-Myers Squibb, Hopewell, Pennington, NJ, USA.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Mendez
authors.affiliation: Bristol-Myers Squibb, Lawrenceville, NJ, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Hughes
authors.affiliation: Bristol-Myers Squibb, Lawrenceville, NJ, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Noviello
authors.affiliation: Bristol-Myers Squibb, Wallingford, CT, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Ackerman
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002219:Carbamates; D060085:Coinfection / Q000188:drug therapy* / Q000821:virology; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011759:Pyrrolidines; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D016898:Interferon-alpha; D011759:Pyrrolidines; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D014633:Valine; C549273:daclatasvir; C100416:peginterferon alfa-2a
keywords: Daclatasvir; HCV GT-1; HIV/HCV coinfection; Peginterferon alfa-2a/ribavirin