title: Analysis of drug resistance during HIV RNA viraemia in the MONET trial of darunavir/ritonavir monotherapy.
abstract: BACKGROUND
  When patients have HIV RNA suppressed to <50 copies/ml on current treatment, switching to darunavir (DRV)/ritonavir (DRV/r) monotherapy could prevent the development of resistance to other drug classes.
  
  
  METHODS
  In the MONET trial, 256 patients with HIV RNA<50 copies/ml on current highly active antiretroviral therapy (57% with protease inhibitors [PIs] and 43% with non-nucleoside reverse transcriptase inhibitors) and no history of virological failure were randomized to DRV/r 800/100 mg once daily, either as monotherapy (monotherapy arm) or with two nucleoside reverse transcriptase inhibitors (NRTIs; triple therapy arm). All samples with HIV RNA ≥ 50 copies/ml were genotyped, and a virtual phenotype was calculated (VircoType HIV-1 assays; Virco BVBA, Mechelen, Belgium).
  
  
  RESULTS
  A total of 63 patients had ≥ 1 HIV RNA result ≥ 50 copies/ml, of whom 38 were successfully genotyped. Most HIV RNA increases were transient and in the range of 50-200 copies/ml. Overall, 36 of the 38 (95%) successfully genotyped patients showed no International AIDS Society-USA major PI mutations, DRV mutations or NRTI mutations. Two patients showed some evidence of PI resistance during transient HIV RNA elevations: one patient in the monotherapy arm had a single DRV mutation (L33F) when HIV RNA was 63 copies/ml (the virus was phenotypically sensitive to DRV [fold change 0.8]) and one PI pretreated patient taking tenofovir disoproxil fumarate/emtricitabine/DRV/r had re-emergence of pre-existing NRTI (M184V) and PI (V82I and L90M) mutations after a short treatment interruption (this virus remained phenotypically sensitive to DRV/r). Both patients showed sustained HIV RNA suppression to week 48 remaining with the same treatment.
  
  
  CONCLUSIONS
  Emergence of drug resistance after changing a suppressive triple antiretroviral therapy to DRV/r with or without nucleoside analogues is uncommon.
authors.affiliation: HIV Unit, Hospital 12 de Octubre, Universidad Complutense de Madrid, Madrid, Spain. federicopulido@med.ucm.es
authors.forename: Federico
authors.initials: F
authors.lastname: Pulido
authors.forename: José R
authors.initials: JR
authors.lastname: Arribas
authors.forename: Andrew
authors.initials: A
authors.lastname: Hill
authors.forename: Yvon
authors.initials: Y
authors.lastname: Van Delft
authors.forename: Christiane
authors.initials: C
authors.lastname: Moecklinghoff
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D000069454:Darunavir; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000187:drug effects* / Q000235:genetics*; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D058889:Molecular Typing; D009154:Mutation; D063065:Organophosphonates / Q000008:administration & dosage / Q000627:therapeutic use; D012367:RNA, Viral / Q000032:analysis; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use; D000068698:Tenofovir; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D063065:Organophosphonates; D012367:RNA, Viral; D013449:Sulfonamides; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; D019438:Ritonavir; D000069454:Darunavir