Association of a novel human immunodeficiency virus type 1 protease substrate cleft mutation, L23I, with protease inhibitor therapy and in vitro drug resistance

Antimicrob Agents Chemother. 2004 Dec;48(12):4864-8. doi: 10.1128/AAC.48.12.4864-4868.2004.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Drug Resistance, Viral
  • HIV Infections / virology*
  • HIV Protease / metabolism*
  • HIV Protease Inhibitors / therapeutic use*
  • HIV-1 / drug effects*
  • Humans
  • Models, Molecular
  • Mutation / genetics
  • Oligopeptides / genetics*
  • Protein Conformation


  • HIV Protease Inhibitors
  • Oligopeptides
  • HIV protease nonapeptide substrate
  • HIV Protease