title: HIV-1 drug resistance mutations emerging on darunavir therapy in PI-naive and -experienced patients in the UK.
abstract: Darunavir is considered to have a high genetic barrier to resistance. Most darunavir-associated drug resistance mutations (DRMs) have been identified through correlation of baseline genotype with virological response in clinical trials. However, there is little information on DRMs that are directly selected by darunavir in clinical settings.
  
  
  
  We examined darunavir DRMs emerging in clinical practice in the UK.
  
  
  
  Baseline and post-exposure protease genotypes were compared for individuals in the UK Collaborative HIV Cohort Study who had received darunavir; analyses were stratified for PI history. A selection analysis was used to compare the evolution of subtype B proteases in darunavir recipients and matched PI-naive controls.
  
  
  
  Of 6918 people who had received darunavir, 386 had resistance tests pre- and post-exposure. Overall, 2.8% (11/386) of these participants developed emergent darunavir DRMs. The prevalence of baseline DRMs was 1.0% (2/198) among PI-naive participants and 13.8% (26/188) among PI-experienced participants. Emergent DRMs developed in 2.0% of the PI-naive group (4 mutations) and 3.7% of the PI-experienced group (12 mutations). Codon 77 was positively selected in the PI-naive darunavir cases, but not in the control group.
  
  
  
  Our findings suggest that although emergent darunavir resistance is rare, it may be more common among PI-experienced patients than those who are PI-naive. Further investigation is required to explore whether codon 77 is a novel site involved in darunavir susceptibility.
authors.affiliation: Research Department of Infection and Population Health, University College London, London, UK k.elbouzidi@ucl.ac.uk.|Research Department of Infection, Division of Infection and Immunity, University College London, London, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: El Bouzidi
authors.affiliation: MRC Clinical Trials Unit at UCL, London, UK.
authors.forename: Ellen
authors.initials: E
authors.lastname: White
authors.affiliation: Virus Reference Department, Centre of Infections, Public Health England, London, UK.
authors.forename: Jean L
authors.initials: JL
authors.lastname: Mbisa
authors.affiliation: Research Department of Infection and Population Health, University College London, London, UK.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Sabin
authors.affiliation: Research Department of Infection and Population Health, University College London, London, UK.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Phillips
authors.affiliation: Department of HIV Medicine, Imperial College Healthcare NHS Trust, London, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Mackie
authors.affiliation: Department of Medicine, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK.
authors.forename: Anton L
authors.initials: AL
authors.lastname: Pozniak
authors.affiliation: MRC Clinical Trials Unit at UCL, London, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Tostevin
authors.affiliation: Research Department of Infection, Division of Infection and Immunity, University College London, London, UK.|Wellcome Trust Africa Centre for Health and Population Sciences, University of KwaZulu Natal, Mtubatuba, South Africa.
authors.forename: Deenan
authors.initials: D
authors.lastname: Pillay
authors.affiliation: MRC Clinical Trials Unit at UCL, London, UK.
authors.forename: David T
authors.initials: DT
authors.lastname: Dunn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D000069454:Darunavir / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D006113:United Kingdom; D055815:Young Adult
chemical_list: D017320:HIV Protease Inhibitors; D000069454:Darunavir