title: Antiviral Activity of Pocapavir in a Randomized, Blinded, Placebo-Controlled Human Oral Poliovirus Vaccine Challenge Model.
abstract: BACKGROUND
  Immunodeficient individuals who excrete vaccine-derived polioviruses threaten polio eradication. Antivirals address this threat.
  
  
  METHODS
  In a randomized, blinded, placebo-controlled study, adults were challenged with monovalent oral poliovirus type 1 vaccine (mOPV1) and subsequently treated with capsid inhibitor pocapavir or placebo. The time to virus negativity in stool was determined.
  
  
  RESULTS
  A total of 144 participants were enrolled; 98% became infected upon OPV challenge. Pocapavir-treated subjects (n = 93) cleared virus a median duration of 10 days after challenge, compared with 13 days for placebo recipients (n = 48; P = .0019). Fifty-two of 93 pocapavir-treated subjects (56%) cleared virus in 2-18 days with no evidence of drug resistance, while 41 of 93 (44%) treated subjects experienced infection with resistant virus while in the isolation facility, 3 (3%) of whom were infected at baseline, before treatment initiation. Resistant virus was also observed in 5 placebo recipients (10%). Excluding those with resistant virus, the median time to virus negativity was 5.5 days in pocapavir recipients, compared with 13 days in placebo recipients (P < .0001). There were no serious adverse events and no withdrawals from the study.
  
  
  CONCLUSIONS
  Treatment with pocapavir was safe and significantly accelerated virus clearance. Emergence of resistant virus and transmission of virus were seen in the context of a clinical isolation facility.
  
  
  BACKGROUND
  EudraCT 2011-004804-38.
authors.affiliation: ViroDefense, Chevy Chase, Maryland.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Collett
authors.affiliation: ViroDefense, Chevy Chase, Maryland.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Hincks
authors.affiliation: Center for Infectious Diseases Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands; and.
authors.forename: Kimberley
authors.initials: K
authors.lastname: Benschop
authors.affiliation: Center for Infectious Diseases Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands; and.
authors.forename: Erwin
authors.initials: E
authors.lastname: Duizer
authors.affiliation: Center for Infectious Diseases Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands; and.
authors.forename: Harrie
authors.initials: H
authors.lastname: van der Avoort
authors.affiliation: Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, and.
authors.forename: Eric
authors.initials: E
authors.lastname: Rhoden
authors.affiliation: Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, and.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Liu
authors.affiliation: Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, and.
authors.forename: M Steven
authors.initials: MS
authors.lastname: Oberste
authors.affiliation: Task Force for Global Health, Decatur, Georgia.
authors.forename: Mark A
authors.initials: MA
authors.lastname: McKinlay
authors.affiliation: Clinical Trial Center, Sahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: Marianne
authors.initials: M
authors.lastname: Hartford
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010647:Phenyl Ethers / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011051:Poliomyelitis / Q000517:prevention & control*; D011055:Poliovirus Vaccine, Oral / Q000008:administration & dosage*; D016037:Single-Blind Method; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects; D017201:Virus Shedding; D057646:Virus Uncoating / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D010647:Phenyl Ethers; D011055:Poliovirus Vaccine, Oral; C000619933:pocapavir
keywords: Polio; antiviral; clinical efficacy; clinical trial design; drug resistance; pocapavir; poliovirus; transmission; virus challenge; virus eradication.