Association of a novel human immunodeficiency virus type 1 protease substrate cleft mutation, L23I, with protease inhibitor therapy and in vitro drug resistance.
We observed a previously uncharacterized mutation in the protease substrate cleft, L23I, in 31 of 4,303 persons undergoing human immunodeficiency virus type 1 genotypic resistance testing. In combination with V82I, L23I was associated with a sevenfold reduction in nelfinavir susceptibility and a decrease in replication capacity. In combination with other drug resistance mutations, L23I was associated with multidrug resistance and a compensatory increase in replication capacity.
Johnston
Elizabeth
E
Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, California 94305, USA.
Winters
Mark A
MA
Rhee
Soo-Yon
SY
Merigan
Thomas C
TC
Schiffer
Celia A
CA
Shafer
Robert W
RW
D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000821:virology*; D016333:HIV Protease / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D009842:Oligopeptides / Q000235:genetics*; D011487:Protein Conformation
D017320:HIV Protease Inhibitors; D009842:Oligopeptides; C073773:HIV protease nonapeptide substrate; D016333:HIV Protease