title: Simeprevir (TMC435) with pegylated interferon/ribavirin in patients coinfected with HCV genotype 1 and HIV-1: a phase 3 study.
abstract: BACKGROUND
  Simeprevir is an oral, once-daily, hepatitis C virus (HCV) NS3/4A protease inhibitor for the treatment of chronic HCV genotype 1 infection. Human immunodeficiency virus (HIV) coinfection accelerates progression of liver disease. This uncontrolled, open-label trial explored the safety and efficacy of simeprevir in patients with HCV genotype 1/HIV type 1 (HIV-1) coinfection.
  
  
  METHODS
  Patients received simeprevir (150 mg once daily) with pegylated interferon alfa-2a/ribavirin (peg-IFN/RBV) for 12 weeks. Noncirrhotic HCV treatment-naive patients and prior relapsers received response-guided therapy (RGT) with peg-IFN/RBV for 24 or 48 weeks. Prior null responders, prior partial responders, and patients with cirrhosis received peg-IFN/RBV for 48 weeks. The primary endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12).
  
  
  RESULTS
  One hundred and six patients (93 on antiretroviral therapy) were enrolled and treated. SVR12 rates were 79.2% in HCV treatment-naive patients, 57.1% in prior null responders, 86.7% in prior relapsers, and 70.0% in prior partial responders. Fifty-four of 61 eligible patients (88.5%) met RGT criteria for 24 weeks of peg-IFN/RBV, of whom 87.0% (47/54) achieved SVR12. SVR12 rates were 80.0% (36/45) and 63.6% (14/22) for patients with METAVIR scores of F0-F2 and F3-F4, respectively. Common adverse event (AE) rates were consistent with peg-IFN/RBV therapy (fatigue, headache, nausea, neutropenia). Most AEs were grade 1/2; serious AEs occurred in 5.7% of patients, none of which were fatal.
  
  
  CONCLUSIONS
  Simeprevir was generally well tolerated with safety similar to that observed in HCV-monoinfected patients and high SVR12 rates in HCV treatment-naive patients, prior relapsers, prior partial responders, and prior null responders with HIV-1 coinfection.
  
  
  BACKGROUND
  NCT01479868.
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Douglas
authors.initials: D
authors.lastname: Dieterich
authors.affiliation: Medizinische Universitätsklinik I-Immunologische Ambulanz, Bonn, Germany.
authors.forename: Jürgen Kurt
authors.initials: JK
authors.lastname: Rockstroh
authors.affiliation: Royal London Hospital, United Kingdom.
authors.forename: Chloe
authors.initials: C
authors.lastname: Orkin
authors.affiliation: Hospital General de Elche and Universidad Miguel Hernández, Alicante, Spain.
authors.forename: Félix
authors.initials: F
authors.lastname: Gutiérrez
authors.affiliation: McGill University Health Centre, Montreal, Canada.
authors.forename: Marina B
authors.initials: MB
authors.lastname: Klein
authors.affiliation: Centre Hospitalier Universitaire Gui De Chauliac, Montpellier, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Reynes
authors.affiliation: Janssen Global Services, Titusville.
authors.forename: Umesh
authors.initials: U
authors.lastname: Shukla
authors.affiliation: Janssen Research and Development, Raritan, New Jersey.
authors.forename: Alan
authors.initials: A
authors.lastname: Jenkins
authors.affiliation: Janssen Infectious Diseases BVBA.
authors.forename: Oliver
authors.initials: O
authors.lastname: Lenz
authors.affiliation: Janssen Research and Development, Beerse, Belgium.
authors.forename: Sivi
authors.initials: S
authors.lastname: Ouwerkerk-Mahadevan
authors.affiliation: Janssen Infectious Diseases BVBA.
authors.forename: Monika
authors.initials: M
authors.lastname: Peeters
authors.affiliation: Janssen Global Services, Titusville.
authors.forename: Guy
authors.initials: G
authors.lastname: De La Rosa
authors.affiliation: Janssen Infectious Diseases BVBA.
authors.forename: Lotke
authors.initials: L
authors.lastname: Tambuyzer
authors.affiliation: Janssen Infectious Diseases BVBA.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Jessner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006575:Heterocyclic Compounds, 3-Ring / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D000069616:Simeprevir; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D006575:Heterocyclic Compounds, 3-Ring; D016898:Interferon-alpha; D011994:Recombinant Proteins; D013449:Sulfonamides; D011092:Polyethylene Glycols; D012254:Ribavirin; D000069616:Simeprevir; C100416:peginterferon alfa-2a
keywords: coinfection; hepatitis C virus; human immunodeficiency virus type 1; simeprevir