Signature nucleotide polymorphisms at positions 64 and 65 in reverse transcriptase favor the selection of the K65R resistance mutation in HIV-1 subtype C

J Infect Dis. 2009 Oct 15;200(8):1202-6. doi: 10.1086/605894.


Recently, we described a novel nucleotide template-based mechanism that may be the basis for the facilitated acquisition of the K65R resistance mutation in subtype C versus subtype B human immunodeficiency virus type 1 (HIV-1). In this article, we evaluated the effects of subtype C-specific silent polymorphisms in cell culture drug-selection experiments using nucleoside and nucleotide reverse-transcriptase inhibitors. The K65R pathway was selected more frequently in a subtype B virus that contained subtype C nucleotide polymorphisms at both positions 64 and 65 than in a wild-type NL4-3 subtype B virus. This is the first demonstration of the significance of silent nucleotide polymorphisms in the development of drug resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / pharmacology*
  • Cells
  • Drug Resistance, Viral / genetics*
  • HIV Reverse Transcriptase / genetics*
  • HIV-1 / classification*
  • HIV-1 / genetics*
  • Humans
  • Mutation
  • Polymorphism, Genetic*
  • Selection, Genetic
  • Time Factors


  • Anti-HIV Agents
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase