In vitro evolution of the human immunodeficiency virus type 1 gag-protease region and maintenance of reverse transcriptase resistance following prolonged drug exposure

J Clin Microbiol. 2001 Mar;39(3):1124-9. doi: 10.1128/JCM.39.3.1124-1129.2001.

Abstract

We studied the human immunodeficiency virus type 1 phenotypic and genotypic profiles of a dual drug-resistant isolate (isolate 14aPost-DR) selected for zidovudine (ZDV) and lamivudine (3TC) resistance and then cultured in the presence of 3TC and a protease inhibitor: indinavir (IDV), ritonavir, or KNI-272. The IDV-treated virus was highly resistant to 3TC, ZDV, and IDV and accumulated protease mutations at positions M46I and V82F. A change from alanine to valine was observed in 4 of 10 clones in the P2 position of the p7-p1 Gag-protease cleavage site, linked to position M46I in the dominant viral quasispecies. Previous 3TC resistance did not impair the development of additional mutations in the protease and Gag-protease cleavage regions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Resistance, Microbial
  • Drug Resistance, Multiple
  • Evolution, Molecular*
  • Gene Products, gag / genetics*
  • HIV Infections / virology
  • HIV Protease / genetics*
  • HIV Protease Inhibitors / pharmacology
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • HIV-1 / genetics
  • HIV-1 / growth & development
  • Humans
  • Indinavir / pharmacology
  • Lamivudine / pharmacology
  • Microbial Sensitivity Tests
  • Molecular Sequence Data
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Zidovudine / pharmacology

Substances

  • Gene Products, gag
  • HIV Protease Inhibitors
  • Reverse Transcriptase Inhibitors
  • Lamivudine
  • Zidovudine
  • Indinavir
  • HIV Protease

Associated data

  • GENBANK/AF152964
  • GENBANK/AF152965
  • GENBANK/AF152966
  • GENBANK/AF152967
  • GENBANK/AF152968
  • GENBANK/AF152969
  • GENBANK/AF152970
  • GENBANK/AF152971
  • GENBANK/AF152972
  • GENBANK/AF152973
  • GENBANK/AF152974
  • GENBANK/AF152975
  • GENBANK/AF152976
  • GENBANK/AF152977
  • GENBANK/AF152978
  • GENBANK/AF152979
  • GENBANK/AF152980
  • GENBANK/AF152981
  • GENBANK/AF152982
  • GENBANK/AF152983
  • GENBANK/AF152984
  • GENBANK/AF152985
  • GENBANK/AF152986
  • GENBANK/AF152987
  • GENBANK/AF152988
  • GENBANK/AF152989
  • GENBANK/AF152990
  • GENBANK/AF152991
  • GENBANK/AF152992
  • GENBANK/AF152993
  • GENBANK/AF152994
  • GENBANK/AF152995