title: Temporal dynamics of a predominant protease inhibitor-resistance mutation in a treatment-naive, hepatitis C virus-infected individual.
abstract: The dramatic antiviral activities of drugs that specifically inhibit hepatitis C virus replication can be tempered by baseline mutations that confer resistance. We describe the kinetics of an R155K mutation in hepatitis C virus (HCV) NS3 protease known to confer resistance to specific protease inhibitors in an individual coinfected with human immunodeficiency virus-1 and HCV. Longitudinal sequences revealed changes in the relative frequency with which this variant was observed independent of HCV replication levels, illustrating that this mutation coexists with wild-type strains in vivo in the absence of drugs. The persistence of drug-resistance mutations argues for baseline resistance genotyping at the time therapy is initiated to accurately predict the efficacy of treatment.
authors.affiliation: Partners AIDS Research Center, Division of Infectious Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Arthur Y
authors.initials: AY
authors.lastname: Kim
authors.forename: Joerg
authors.initials: J
authors.lastname: Timm
authors.forename: Brian E
authors.initials: BE
authors.lastname: Nolan
authors.forename: Laura L
authors.initials: LL
authors.lastname: Reyor
authors.forename: Katherine
authors.initials: K
authors.lastname: Kane
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Berical
authors.forename: Kimon C
authors.initials: KC
authors.lastname: Zachary
authors.forename: Georg M
authors.initials: GM
authors.lastname: Lauer
authors.forename: Thomas
authors.initials: T
authors.lastname: Kuntzen
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
mesh_terms: D000328:Adult; D024882:Drug Resistance, Viral / Q000235:genetics*; D015658:HIV Infections / Q000150:complications; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics*; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D008297:Male; D009154:Mutation; D010802:Phylogeny; D011480:Protease Inhibitors / Q000494:pharmacology*; D012367:RNA, Viral; D013997:Time Factors; D014779:Virus Replication / Q000235:genetics
chemical_list: D011480:Protease Inhibitors; D012367:RNA, Viral