In vitro development of resistance to human immunodeficiency virus protease inhibitor GW640385.
Development of in vitro resistance to GW640385, a new human immunodeficiency virus type 1 protease inhibitor, was studied. Variants characterized included one with <4-fold resistance and amino acid substitutions Q58E/A71V (protease) and P452K (Gag) and one with >50-fold resistance and amino acid substitutions L10F/G16E/E21K/A28S/M46I/F53L/A71V (protease) and L449F/P453T (Gag). The A28S substitution substantially reduced replication capacity.
UK Virology, GlaxoSmithKline Inc., Gunnels Wood Road, Stevenage SG1 2NY, United Kingdom. pjy29430@gsk.com
P J
PJ
Yates
R
R
Hazen
M
M
St Clair
L
L
Boone
M
M
Tisdale
R C
RC
Elston
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D003001:Cloning, Molecular; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics*; D015750:Genes, gag; D014644:Genetic Variation; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D012641:Selection, Genetic; D014779:Virus Replication / Q000235:genetics*
D017320:HIV Protease Inhibitors; D016333:HIV Protease