A mutation in the 3' region of the human immunodeficiency virus type 1 reverse transcriptase (Y318F) associated with nonnucleoside reverse transcriptase inhibitor resistance

J Virol. 2002 Jul;76(13):6836-40. doi: 10.1128/jvi.76.13.6836-6840.2002.


The Y318F substitution in the 3' region of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) has been linked to nonnucleoside RT inhibitor (NNRTI) resistance in vitro. A systematic search of a large phenotypic-genotypic database (Virco) linked the Y318F substitution with a >10-fold decrease in NNRTI susceptibility in >85% of clinically derived isolates. There was a significant association between Y318F and use of delavirdine (P = 10(-11)) and nevirapine (P = 10(-6)) but not efavirenz (P = 0.3). Site-directed HIV-1 Y318F mutants in an HXB2 background displayed 42-fold-decreased susceptibility to delavirdine but <3-fold-decreased susceptibility to nevirapine or efavirenz. Combinations of Y318F with K103N, Y181C, or both resulted in decreased efavirenz susceptibility of 43-, 3.3-, and 84-fold, respectively, as well as >100- and >60-fold decreases in delavirdine and nevirapine susceptibility, respectively. These results indicate the importance of the Y318F substitution in HIV-1 drug resistance.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Anti-HIV Agents / pharmacology*
  • Drug Resistance, Viral / genetics*
  • HIV Reverse Transcriptase / chemistry
  • HIV Reverse Transcriptase / genetics*
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • HIV-1 / genetics
  • Humans
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Mutation
  • Reverse Transcriptase Inhibitors / pharmacology*


  • 3' Untranslated Regions
  • Anti-HIV Agents
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase