title: Prevalence of resistance mutations related to integrase inhibitor S/GSK1349572 in HIV-1 subtype B raltegravir-naive and -treated patients.
abstract: OBJECTIVE
  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.
authors.affiliation: Laboratoire de Virologie, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, UPMC Université Paris 06, INSERM U943, Paris, France. isabelle.malet@psl.aphp.fr
authors.forename: Isabelle
authors.initials: I
authors.lastname: Malet
authors.forename: Marc
authors.initials: M
authors.lastname: Wirden
authors.forename: Slim
authors.initials: S
authors.lastname: Fourati
authors.forename: Daniele
authors.initials: D
authors.lastname: Armenia
authors.forename: Bernard
authors.initials: B
authors.lastname: Masquelier
authors.forename: Lavinia
authors.initials: L
authors.lastname: Fabeni
authors.forename: Sophie
authors.initials: S
authors.lastname: Sayon
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.forename: Carlo Federico
authors.initials: CF
authors.lastname: Perno
authors.forename: Vincent
authors.initials: V
authors.lastname: Calvez
authors.forename: Anne-Geneviève
authors.initials: AG
authors.lastname: Marcelin
authors.forename: Francesca
authors.initials: F
authors.lastname: Ceccherini-Silberstein
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000873:Anthracenes / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D019427:HIV Integrase / Q000235:genetics; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006575:Heterocyclic Compounds, 3-Ring; D006801:Humans; D020125:Mutation, Missense; D010078:Oxazines; D010879:Piperazines; D015995:Prevalence; D011728:Pyridones; D011760:Pyrrolidinones / Q000008:administration & dosage; D000068898:Raltegravir Potassium; D017422:Sequence Analysis, DNA; D014764:Viral Proteins / Q000235:genetics*; D000099226:Dolutegravir
chemical_list: D000873:Anthracenes; D019380:Anti-HIV Agents; D019427:HIV Integrase; D006575:Heterocyclic Compounds, 3-Ring; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D014764:Viral Proteins; D000099226:Dolutegravir; C514801:p31 integrase protein, Human immunodeficiency virus 1