Dolutegravir resistance mutation R263K cannot coexist in combination with many classical integrase inhibitor resistance substitutions

J Virol. 2015 Apr;89(8):4681-4. doi: 10.1128/JVI.03485-14. Epub 2015 Feb 4.

Abstract

The new integrase strand transfer inhibitor (INSTI) dolutegravir (DTG) displays limited cross-resistance with older drugs of this class and selects for the R263K substitution in treatment-experienced patients. We performed tissue culture selections with DTG, using viruses resistant to older INSTIs and infectivity and resistance assays, and showed that the presence of the E92Q or N155H substitution was compatible with the emergence of R263K, whereas the G140S Q148R, E92Q N155H, G140S, Y143R, and Q148R substitutions were not.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution / genetics*
  • Drug Resistance / genetics*
  • HIV Integrase / genetics*
  • HIV Integrase Inhibitors / pharmacology*
  • HIV-1 / genetics*
  • Heterocyclic Compounds, 3-Ring / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Mutagenesis, Site-Directed
  • Oxazines
  • Piperazines
  • Pyridones

Substances

  • HIV Integrase Inhibitors
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • dolutegravir
  • HIV Integrase