Temporal dynamics of a predominant protease inhibitor-resistance mutation in a treatment-naive, hepatitis C virus-infected individual.
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.
Kim
Arthur Y
AY
Partners AIDS Research Center, Division of Infectious Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Timm
Joerg
J
Nolan
Brian E
BE
Reyor
Laura L
LL
Kane
Katherine
K
Berical
Andrew C
AC
Zachary
Kimon C
KC
Lauer
Georg M
GM
Kuntzen
Thomas
T
Allen
Todd M
TM
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
D011480:Protease Inhibitors; D012367:RNA, Viral