Cross-resistance profile of the novel integrase inhibitor Dolutegravir (S/GSK1349572) using clonal viral variants selected in patients failing raltegravir

J Infect Dis. 2011 Dec 1;204(11):1811-5. doi: 10.1093/infdis/jir636. Epub 2011 Oct 7.

Abstract

Novel integrase inhibitors are in advanced clinical development, and cross-resistance data are needed to consider the possibility to plan a sequential usage within this class of antiretroviral drugs. Ex vivo phenotypic assays were conducted on 11 wild-type and 27 fully replicating recombinant viruses obtained from 11 patients failing previous raltegravir-containing regimens. Dolutegravir maintained its activity in vitro on viruses with mutations in position 143 and 155. However, viruses with mutation Q148R associated with secondary mutations and the combination Q148H+G140S were instead associated with a reduced level of susceptibility to dolutegravir in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution / genetics
  • Anti-HIV Agents / pharmacology*
  • Drug Resistance, Viral / genetics*
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Integrase / genetics
  • HIV Integrase Inhibitors / pharmacology*
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • HIV-1 / genetics*
  • Heterocyclic Compounds, 3-Ring / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Microbial Sensitivity Tests
  • Mutation
  • Oxazines
  • Phenotype
  • Piperazines
  • Pyridones
  • Pyrrolidinones / pharmacology
  • Raltegravir Potassium

Substances

  • Anti-HIV Agents
  • HIV Integrase Inhibitors
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • Pyrrolidinones
  • Raltegravir Potassium
  • dolutegravir
  • HIV Integrase