title: Emerging integrase inhibitor resistance mutations in raltegravir-treated HIV-1-infected patients with low-level viremia.
abstract: BACKGROUND
  The emergence of integrase strand-transfer inhibitor (INSTI) resistance-associated mutations was examined in patients with low-level viremia after switching from enfuvirtide to raltegravir in the ANRS 138-Easier trial.
  
  
  METHODS
  Integrase genes of plasma virus from raltegravir-treated patients in the Easier trial with low-level viremia (50-500 copies/ml) were sequenced to determine INSTI resistance-associated mutations. Baseline viral load, baseline and nadir CD4 cell count, antiretroviral treatment, genotypic susceptibility score, level of viremia and degree of treatment adherence during the study period were also analyzed.
  
  
  RESULTS
  Forty-nine patients experienced at least one episode of low-level viremia while receiving raltegravir; integrase genotyping was successful in samples from 39 individuals (80%). Among them, three [7.7%, 95% confidence interval (CI) 1.6-20.9%] had significant INSTI resistance mutations consisting of N155H in two and P145S in one. Absence of these mutations from proviral DNA at baseline suggested selection of INSTI resistance during episodes of low-level viremia. No specific factors significantly associated with emergence of INSTI resistance mutations during low-level viremia were identified.
  
  
  CONCLUSIONS
  Emergence of INSTI resistance mutations can occur during episodes of low-level viremia in patients receiving raltegravir-containing regimens.
authors.affiliation: Section of Retroviral Therapeutics, Brigham and Women's Hospital and Harvard Medical School, Boston, USA.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gallien
authors.forename: Constance
authors.initials: C
authors.lastname: Delaugerre
authors.forename: Isabelle
authors.initials: I
authors.lastname: Charreau
authors.forename: Joséphine
authors.initials: J
authors.lastname: Braun
authors.forename: Thomas
authors.initials: T
authors.lastname: Boulet
authors.forename: Aurélie
authors.initials: A
authors.lastname: Barrail-Tran
authors.forename: Nathalie
authors.initials: N
authors.lastname: de Castro
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kuritzkes
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics*; D019427:HIV Integrase / Q000235:genetics; D019428:HIV Integrase Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D011760:Pyrrolidinones / Q000627:therapeutic use*; D000068898:Raltegravir Potassium; D014766:Viremia / Q000235:genetics*
chemical_list: D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D019427:HIV Integrase