Prevalence of resistance mutations related to integrase inhibitor S/GSK1349572 in HIV-1 subtype B raltegravir-naive and -treated patients

J Antimicrob Chemother. 2011 Jul;66(7):1481-3. doi: 10.1093/jac/dkr152. Epub 2011 Apr 7.

Abstract

Objectives: To compare the frequency of previously in vitro-selected integrase mutations (T124A, T124A/S153F, S153Y, T124A/S153Y and L101I/T124A/S153Y) conferring resistance to S/GSK1349572 between HIV-1 subtype B integrase inhibitor (INI)-naive and raltegravir-treated patients.

Methods: Integrase sequences from 650 INI-naive patients and 84 raltegravir-treated patients were analysed.

Results: The T124A mutation alone and the combination T124A/L101I were more frequent in raltegravir-failing patients than in INI-naive patients (39.3% versus 24.5%, respectively, P = 0.005 for T124A and 20.2% versus 10.0%, respectively, P = 0.008 for T124A/L101I). The S153Y/F mutations were not detected in any integrase sequence (except for S153F alone, only detected in one INI-naive patient).

Conclusions: T124A and T124A/L101I, more frequent in raltegravir-treated patients, could have some effect on raltegravir response and their presence could play a role in the selection of other mutations conferring S/GSK1349572 resistance. The impact of raltegravir-mediated changes such as these on the virological response to S/GSK1349572 should be studied further.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution / genetics
  • Anthracenes / pharmacology*
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / pharmacology*
  • Drug Resistance, Viral*
  • Genotype
  • HIV Infections / drug therapy
  • HIV Infections / virology*
  • HIV Integrase / genetics
  • HIV-1 / classification
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • HIV-1 / isolation & purification
  • Heterocyclic Compounds, 3-Ring
  • Humans
  • Mutation, Missense*
  • Oxazines
  • Piperazines
  • Prevalence
  • Pyridones
  • Pyrrolidinones / administration & dosage
  • Raltegravir Potassium
  • Sequence Analysis, DNA
  • Viral Proteins / genetics*

Substances

  • Anthracenes
  • Anti-HIV Agents
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • Pyrrolidinones
  • Viral Proteins
  • Raltegravir Potassium
  • dolutegravir
  • HIV Integrase
  • p31 integrase protein, Human immunodeficiency virus 1