title: Daclatasvir and Peginterferon/Ribavirin for Black/African-American and Latino Patients with HCV infection.
abstract: Background. Patient race and ethnicity have historically impacted HCV treatment response. This phase 3 study evaluated daclatasvir with peginterferon-alfa-2a/ribavirin (pegIFN alfa-2a/RBV) in treatment-naive black/African American (AA), Latino, and white non-Latino patients with chronic HCV genotype 1 infection.
  
  
  METHODS
  In this single-arm, open-label study, 246 patients received daclatasvir plus pegIFN alfa-2a and weight-based RBV. Patients with an extended rapid virologic response (eRVR; undetectable HCV-RNA at treatment weeks 4 and 12) received 24 weeks of treatment; those without eRVR received an additional 24 weeks of treatment with pegIFN alfa-2a/RBV. The primary endpoint was sustained virologic response at post-treatment week 12 (SVR12; HCV-RNA < 25 IU/mL) compared with the cohort historical rate.
  
  
  RESULTS
  Most patients were IL28B non-CC (84.4% black/AA; 77.6% Latino) genotype 1a-infected (72.7%; 81.3%), with HCV-RNA ≥ 800,000 IU/mL (81.3%; 64.5%). SVR12 rates were 50.8% (65/128; 95% confidence interval [CI], 42.1-59.4) for black/AA and 58.9% (63/107; 95% CI, 49.6-68.2) for Latino patients. The majority (55.5%; 58.9%) received 24 weeks treatment; rapid reductions (> 4-log10) in HCV-RNA levels were observed. Only 60.9% (78/128) of black/AA and 63.6% (68/107) of Latino patients completed treatment. On-treatment serious adverse events (SAEs) occurred in 21 patients. Discontinuations due to adverse events (AEs) occurred in 9 black/AA and 6 Latino patients.
  
  
  CONCLUSIONS
  SVR12 rates for black/AA (50.8%) and Latino (58.9%) cohorts treated with daclatasvir plus pegIFN alfa-2a/RBV and the lower bound of the 95% CIs were higher than the estimated historical control (black/AA, 26% SVR; Latino, 36% SVR) treated with pegIFN alfa-2a/RBV. These data support daclatasvir use in all-oral direct-acting antiviral combinations.
authors.affiliation: Fundación de Investigación, San Juan, Puerto Rico.
authors.forename: Maribel
authors.initials: M
authors.lastname: Rodriguez-Torres
authors.affiliation: Texas Liver Institute, University of Texas Health Science Center, San Antonio, Texas, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Lawitz
authors.affiliation: Infectious Disease Research Institute, Inc, Tampa, Florida, USA.
authors.forename: Bienvenido
authors.initials: B
authors.lastname: Yangco
authors.affiliation: Miami VA Medical Center, Miami, Florida, USA.
authors.forename: Lennox
authors.initials: L
authors.lastname: Jeffers
authors.affiliation: Pfleger Liver Institute, Los Angeles, California, USA.
authors.forename: Steven-Huy
authors.initials: SH
authors.lastname: Han
authors.affiliation: Mercy Medical Center, Baltimore, Maryland, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Thuluvath
authors.affiliation: Thomas Starzl Transplant Institute UPMC, Pittsburgh, Pennsylvania, USA.
authors.forename: Vinod
authors.initials: V
authors.lastname: Rustgi
authors.affiliation: Brooke Army Medical Center, San Antonio, Texas, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Harrison
authors.affiliation: North Texas Research Institute, Arlington, Texas, USA.
authors.forename: Reem
authors.initials: R
authors.lastname: Ghalib
authors.affiliation: Baylor College of Medicine, Houston, Texas, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Vierling
authors.affiliation: Virginia Commonwealth University School of Medicine and McGuire Research Institute, Richmond, Virginia, USA.
authors.forename: Velimir
authors.initials: V
authors.lastname: Luketic
authors.affiliation: Carolinas Medical Center, Charlotte, North Carolina, USA.
authors.forename: Philippe J
authors.initials: PJ
authors.lastname: Zamor
authors.affiliation: Digestive Disease Associates, Catonsville, Maryland, USA.
authors.forename: Natarajan
authors.initials: N
authors.lastname: Ravendhran
authors.affiliation: VA Long Beach Healthcare System, Long Beach, California, USA.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Morgan
authors.affiliation: Atlanta Medical Center, Atlanta, Georgia, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Pearlman
authors.affiliation: University of Miami Schiff Center for Liver Diseases, Miami, Florida, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: O'Brien
authors.affiliation: Florida Hospital Transplant Center, Orlando, Florida, USA.
authors.forename: Hicham
authors.initials: H
authors.lastname: Khallafi
authors.affiliation: Rutgers-New Jersey Medical School, Newark, New Jersey, USA.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Pyrsopoulos
authors.affiliation: Bristol-Myers Squibb Research and Development, Wallingford, Connecticut, USA.
authors.forename: George
authors.initials: G
authors.lastname: Kong
authors.affiliation: Bristol-Myers Squibb Research and Development, Wallingford, Connecticut, USA.
authors.forename: Fiona
authors.initials: F
authors.lastname: McPhee
authors.affiliation: Bristol-Myers Squibb Research and Development, Wallingford, Connecticut, USA.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Yin
authors.affiliation: Bristol-Myers Squibb Research and Development, Princeton, New Jersey, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Hughes
authors.affiliation: Bristol-Myers Squibb Research and Development, Princeton, New Jersey, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Treitel
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001741:Black or African American; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002219:Carbamates; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000208:ethnology / Q000821:virology; D006630:Hispanic or Latino; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D011647:Puerto Rico; D011759:Pyrrolidines; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D014633:Valine / Q000031:analogs & derivatives; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D002219:Carbamates; D007093:Imidazoles; D016898:Interferon-alpha; D011759:Pyrrolidines; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D014633:Valine; C549273:daclatasvir; C100416:peginterferon alfa-2a