title: Impact of prior virological failure and nucleos(t)ide genotypic resistance mutations on the efficacy of switching from ritonavir-boosted protease inhibitors to raltegravir.
abstract: BACKGROUND
  The virological efficacy of switching from a ritonavir-boosted protease inhibitor (PI/r)- to a raltegravir (RAL)-containing regimen remains controversial according to the results of SWITCHMRK and SPIRAL studies. The aim of this analysis is to assess the impact of prior resistance mutations to nucleos(t)ides and other potential factors on the virological outcome.
  
  
  METHODS
  This was a substudy of the prospective, open-label, multicentre SPIRAL study. Demographic, virological variables, prior episodes of virological failures (VF) and archived resistance mutations to nucleos(t)ides were identified from databases and its impact measured by genotypic sensitive scores (GSS) according to the genotypic resistance interpretation algorithm from the Stanford HIV Drug Resistance Database on outcome was analysed.
  
  
  RESULTS
  Of 250 patients (128 RAL and 122 PI/r) included in the main SPIRAL study, 74 (30%) had previous VF with prior genotypic resistance tests (GRT). Median time of virological suppression prior to inclusion in SPIRAL study was 63.5 months. GSS for backbone nucleos(t)ides was <1 in 15/38 (39%) in the RAL arm and in 9/36 (25%) in the PI/r arm (P=0.13). Among those with nucleos(t)ides GSS <1, 0/15 (0%) in the RAL versus 2/9 (22%) in the PI/r arm developed VF (P=0.13). Moreover 0/11 subjects with null or residual (GSS≤0.5) backbone activity developed VF in the RAL arm.
  
  
  CONCLUSIONS
  The 48-week virological efficacy of switching from a PI/r to RAL in subjects with long-term virological suppression was not compromised by a reduction of the nucleos(t)ide backbone activity.
authors: Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Spain. jlblanco@clinic.ub.es.
authors: José L
authors: JL
authors: Blanco
authors: Ana
authors: A
authors: Gonzalez-Cordón
authors: Josep M
authors: JM
authors: Llibre
authors: Marta
authors: M
authors: Calvo
authors: Felix
authors: F
authors: Gutierrez
authors: Daniel
authors: D
authors: Podzamczer
authors: Montserrat
authors: M
authors: Laguno
authors: Emilio
authors: E
authors: Fumero
authors: Javier
authors: J
authors: Murillas
authors: Josep
authors: J
authors: Mallolas
authors: Maria
authors: M
authors: Martinez-Rebollar
authors: Montserrat
authors: M
authors: Lonca
authors: Iñaki
authors: I
authors: Perez
authors: Josep M
authors: JM
authors: Gatell
authors: Esteban
authors: E
authors: Martinez
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D019428:HIV Integrase Inhibitors / Q000627:therapeutic use*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D011446:Prospective Studies; D000068898:Raltegravir Potassium / Q000627:therapeutic use*; D019438:Ritonavir / Q000627:therapeutic use*; D019562:Viral Load / Q000187:drug effects
chemical_list: D019428:HIV Integrase Inhibitors; D017320:HIV Protease Inhibitors; D000068898:Raltegravir Potassium; D019438:Ritonavir