title: High frequency of integrase Q148R minority variants in HIV-infected patients naive of integrase inhibitors.
abstract: BACKGROUND
  Integrase positions 148 and 155 represent main determinants of resistance to integrase inhibitors. We assessed the prevalence of minority variants harboring such mutations in integrase-naive HIV-infected patients.
  
  
  METHODS
  Two groups of patients were studied: 40 heavily antiretroviral-experienced patients, initiating a raltegravir-based therapy and 51 antiretroviral-naive patients. Allele-specific real-time PCR (AS-PCR) systems, developed for Q148H, Q148R and N155H mutations, were performed at baseline for antiretroviral-experienced patients. Samples from antiretroviral-naive patients were tested with the Q148R AS-PCR assay.
  
  
  RESULTS
  The limits of detection of AS-PCR systems were 0.10, 0.10 and 0.05% for Q148H, Q148R and N155H mutations, respectively. AS-PCR systems were successful in 79 of 91 samples. In antiretroviral-experienced patients, Q148R minority variants were frequently detected (26/32 patients, 81%) at low-level frequency (median = 0.40%), whereas no minority variants exhibiting Q148H or N155H mutation were found. Twenty-four of 26 patients exhibiting Q148R variants were virological responders but four of them displayed a delayed virological response occurring between W18 and W36. Two patients exhibited virological failure under raltegravir, both harboring Q148R minority variants at baseline. However, we did not find any association between the presence of Q148R minority variants and an increased risk of virological failure. Q148R minority variants were also found in 86% of antiretroviral-naive patients, a prevalence significantly higher than that of K103N minority variants (26%).
  
  
  CONCLUSIONS
  Q148R variants were frequently detected, always at low-level, in antiretroviral-experienced and naive patients. Although their presence was not consistently associated with virological failure, their impact on long-term viral suppression needs to be further investigated.
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Européen Georges Pompidou, Laboratoire de Virologie, France. charlotte.charpentier@egp.aphp.fr
authors.forename: Charlotte
authors.initials: C
authors.lastname: Charpentier
authors.forename: Didier
authors.initials: D
authors.lastname: Laureillard
authors.forename: Christophe
authors.initials: C
authors.lastname: Piketty
authors.forename: Pascaline
authors.initials: P
authors.lastname: Tisserand
authors.forename: Dominique
authors.initials: D
authors.lastname: Batisse
authors.forename: Marina
authors.initials: M
authors.lastname: Karmochkine
authors.forename: Ali
authors.initials: A
authors.lastname: Si-Mohamed
authors.forename: Laurence
authors.initials: L
authors.lastname: Weiss
mesh_terms: D000328:Adult; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D019427:HIV Integrase / Q000187:drug effects / Q000235:genetics*; D019428:HIV Integrase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000187:drug effects / Q000235:genetics*; D011110:Polymorphism, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D019562:Viral Load
chemical_list: D019428:HIV Integrase Inhibitors; D019427:HIV Integrase