title: Association of a novel human immunodeficiency virus type 1 protease substrate cleft mutation, L23I, with protease inhibitor therapy and in vitro drug resistance.
abstract: 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.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, California 94305, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Johnston
authors.forename: Mark A
authors.initials: MA
authors.lastname: Winters
authors.forename: Soo-Yon
authors.initials: SY
authors.lastname: Rhee
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Merigan
authors.forename: Celia A
authors.initials: CA
authors.lastname: Schiffer
authors.forename: Robert W
authors.initials: RW
authors.lastname: Shafer
mesh_terms: 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
chemical_list: D017320:HIV Protease Inhibitors; D009842:Oligopeptides; C073773:HIV protease nonapeptide substrate; D016333:HIV Protease