title: Safety and Efficacy of Pegylated Interferon Lambda, Ribavirin, and Daclatasvir in HCV and HIV-Coinfected Patients.
abstract: To evaluate the efficacy and safety of pegylated interferon-lambda-1a (Lambda)/ribavirin (RBV)/daclatasvir (DCV) for treatment of patients coinfected with chronic hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Treatment-naive patients were assigned to cohort A [HCV genotype (GT)-2 or -3] or cohort B [HCV GT-1(a or b) or -4]. All patients received Lambda/RBV/DCV for the first 12 weeks; cohort A received Lambda/RBV for an additional 12 weeks, followed by 24 weeks of follow-up, and cohort B received response-guided therapy. The primary endpoint was the proportion of patients who achieved a sustained virologic response at post-treatment week 12 (SVR12). In cohort A (n = 104), 84.6% achieved SVR12 (95.0% in GT-2; 83.1% in GT-3). In cohort B (n = 196), 76.0% achieved SVR12 (71.7% in GT-1a; 86.0% in GT-1b; 70.7% in GT-4). Rates of discontinuation due to adverse events (AEs) (3.8% and 6.1%) and serious AEs (5.8% and 6.1%) were low in cohorts A and B, respectively. In addition, treatment with Lambda/RBV/DCV had little impact on CD4 counts. SVR12 rates with Lambda/RBV/DCV in an HCV/HIV-coinfected population ranged from 71.7% to 95.0%. Treatment was generally well tolerated, with a low proportion of patients discontinuing due to AEs. Clinical trial registration NCT01866930.
authors.affiliation: 1 Chelsea and Westminster Hospital , London, United Kingdom .
authors.forename: Mark
authors.initials: M
authors.lastname: Nelson
authors.affiliation: 2 Hospital Universitario 12 Octubre , Centro de Actividades Ambulatorias, Madrid, Spain .
authors.forename: Rafael
authors.initials: R
authors.lastname: Rubio
authors.affiliation: 3 Scientific Institute Ospedale , San Raffaele, Milan, Italy .
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.affiliation: 4 State Research Center-Institute of Biophysics , Russian Ministry of Health, Moscow, Russia .
authors.forename: Svetlana
authors.initials: S
authors.lastname: Romanova
authors.affiliation: 5 Zuckerberg San Francisco General, University of California , San Francisco, San Francisco, California.
authors.forename: Annie
authors.initials: A
authors.lastname: Luetkemeyer
authors.affiliation: 6 Vancouver Infectious Diseases Centre , Vancouver, Canada .
authors.forename: Brian
authors.initials: B
authors.lastname: Conway
authors.affiliation: 7 Department of Infectious Diseases, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, University of Paris Diderot , Paris, France .
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
authors.affiliation: 8 Bristol-Myers Squibb , Wallingford, Connecticut.
authors.forename: Dong
authors.initials: D
authors.lastname: Xu
authors.affiliation: 8 Bristol-Myers Squibb , Wallingford, Connecticut.
authors.forename: Subasree
authors.initials: S
authors.lastname: Srinivasan
authors.affiliation: 9 Shionogi Inc. , Florham Park, New Jersey.
authors.forename: Simon
authors.initials: S
authors.lastname: Portsmouth
mesh_terms: D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D002219:Carbamates; D060085:Coinfection; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007372:Interferons / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives; D019562:Viral Load; D007378:Interleukins; D000095022:Interferon Lambda
chemical_list: D002219:Carbamates; D007093:Imidazoles; D007372:Interferons; D011759:Pyrrolidines; D012254:Ribavirin; D014633:Valine; C000624353:interferon-lambda, human; D007378:Interleukins; D000095022:Interferon Lambda; C549273:daclatasvir
keywords: IFN receptors; IFNs and cytokines; antiviral actions; infectious disease