title: Analysis of Mutations in the Gene Encoding Cytomegalovirus DNA Polymerase in a Phase 2 Clinical Trial of Brincidofovir Prophylaxis.
abstract: Brincidofovir is an oral antiviral in development for prevention of cytomegalovirus disease. Cytomegalovirus genotyping results from a phase 2 trial comparing brincidofovir to placebo for prophylaxis against cytomegalovirus infection in hematopoietic cell transplant recipients provided initial data on the clinical resistance profile for brincidofovir. In this study, no known resistance-associated mutations were detected in brincidofovir-treated subjects; identified genotypic substitutions did not confer resistance to cytomegalovirus antivirals in vitro, suggesting that these changes represent polymorphisms unrelated to brincidofovir resistance. Lack of evidence for genotypic resistance during prophylaxis suggests that first-line use of brincidofovir for prevention of cytomegalovirus infection may preserve downstream options for patients.
authors.affiliation: Chimerix, Durham, North Carolina.
authors.forename: E Randall
authors.initials: ER
authors.lastname: Lanier
authors.affiliation: Chimerix, Durham, North Carolina.
authors.forename: Scott
authors.initials: S
authors.lastname: Foster
authors.affiliation: Chimerix, Durham, North Carolina.
authors.forename: Tom
authors.initials: T
authors.lastname: Brundage
authors.affiliation: Division of Infectious Diseases, Oregon Health and Science University Department of Veterans Affairs Medical Center, Portland, Oregon.
authors.forename: Sunwen
authors.initials: S
authors.lastname: Chou
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham.
authors.forename: Mark N
authors.initials: MN
authors.lastname: Prichard
authors.affiliation: Viracor-IBT Laboratories, Lee's Summit, Missouri.
authors.forename: Steven
authors.initials: S
authors.lastname: Kleiboeker
authors.affiliation: Chimerix, Durham, North Carolina.
authors.forename: Chad
authors.initials: C
authors.lastname: Wilson
authors.affiliation: Chimerix, Durham, North Carolina.
authors.forename: Donella
authors.initials: D
authors.lastname: Colville
authors.affiliation: Chimerix, Durham, North Carolina.
authors.forename: Herve
authors.initials: H
authors.lastname: Mommeja-Marin
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D003587:Cytomegalovirus / Q000235:genetics; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D003596:Cytosine / Q000627:therapeutic use*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D009154:Mutation / Q000187:drug effects*; D066027:Transplant Recipients; D014481:United States
chemical_list: D000998:Antiviral Agents; D003596:Cytosine; D004259:DNA-Directed DNA Polymerase
keywords: CMV; CMV (DNA) polymerase; CMV phosphotransferase; UL54; UL97; brincidofovir; cytomegalovirus; stem cell transplantation