Susceptibilities of human immunodeficiency virus type 1 enzyme and viral variants expressing multiple resistance-engendering amino acid substitutions to reserve transcriptase inhibitors

Antimicrob Agents Chemother. 1994 Jun;38(6):1404-7. doi: 10.1128/aac.38.6.1404.

Abstract

To evaluate the potential that multiply resistant human immunodeficiency virus type 1 variants may arise during combination nucleoside and nonnucleoside reverse transcriptase inhibitor therapy, we constructed a series of mutant reverse transcriptase enzymes and viruses that coexpressed various combinations of resistance-associated amino acid substitutions. Substitutions at residues 100 (Leu-->Ile) and 181 (Tyr-->Cys), which mediate resistance to the nonnucleosides, suppressed resistance to 3'-azido-3'-deoxythymidine (AZT) when coexpressed with AZT-specific substitutions. However, a number of viral variants that exhibited significantly reduced susceptibilities to both classes of inhibitors were constructed.

MeSH terms

  • Drug Resistance, Microbial
  • HIV Reverse Transcriptase
  • HIV-1 / drug effects*
  • Mutation
  • Reverse Transcriptase Inhibitors*
  • Structure-Activity Relationship
  • Zidovudine / pharmacology

Substances

  • Reverse Transcriptase Inhibitors
  • Zidovudine
  • HIV Reverse Transcriptase