title: Resistant minority species are rarely observed in patients on darunavir/ritonavir monotherapy.
abstract: OBJECTIVE
  To analyse the emergence of resistant viruses in patients failing darunavir monotherapy, including minority species, and to investigate the impact of baseline reverse transcriptase (RT), protease (PR) and gag resistance mutations on virological failure (VF) occurrence.
  
  
  METHODS
  Nine of the 225 HIV-1-infected patients enrolled in the MONOI trial (darunavir/ritonavir monotherapy or darunavir/ritonavir + two nucleoside reverse transcriptase inhibitors in a switch strategy) experienced VF, defined as two plasma HIV-1 viral loads >400 copies/mL at least 2 weeks apart. Among these nine patients with VF, five were in the darunavir/ritonavir monotherapy arm and four were in the darunavir/ritonavir triple therapy arm. Bulk sequences of the PR, RT and gag genes at baseline (on DNA) and at the time of VF (on RNA) were determined for all patients with two viral loads >50 copies/mL at least 2 weeks apart (n = 47). PR and gag gene clonal analysis was performed on plasma samples of the nine patients with VF.
  
  
  RESULTS
  There was no association between mutations in RT, PR and gag genes in DNA and VF occurrence. None of the patients demonstrated selection of darunavir resistance mutations among the 47 patients with a viral load >50 copies/mL at least 2 weeks apart. The virus of one of the nine patients with VF presented minority variants with darunavir resistance mutations at positions 32, 47 and 50. Clonal analysis of the gag region for the nine patients with VF did not show any selection of minority variants.
  
  
  CONCLUSIONS
  In patients with failure on darunavir/ritonavir monotherapy we did not find any selection of darunavir resistance mutations using standard genotype testing. However, the virus of one patient among nine failures presented minority variants plus darunavir resistance mutations.
authors.affiliation: AP-HP, Pitié-Salpêtrière Hospital, INSERM U 943 and Pierre et Marie Curie University, Paris, France. sidonie.lambert@psl.aphp.fr
authors.forename: Sidonie
authors.initials: S
authors.lastname: Lambert-Niclot
authors.forename: Philippe
authors.initials: P
authors.lastname: Flandre
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Valantin
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
authors.forename: Sophie
authors.initials: S
authors.lastname: Sayon
authors.forename: Laurence
authors.initials: L
authors.lastname: Morand-Joubert
authors.forename: Constance
authors.initials: C
authors.lastname: Delaugerre
authors.forename: Michele
authors.initials: M
authors.lastname: Algarte-Genin
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.forename: Vincent
authors.initials: V
authors.lastname: Calvez
authors.forename: Anne-Genevieve
authors.initials: AG
authors.lastname: Marcelin
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000494:pharmacology; D000069454:Darunavir; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D012367:RNA, Viral / Q000235:genetics; D019438:Ritonavir / Q000008:administration & dosage* / Q000494:pharmacology; D012641:Selection, Genetic; D013449:Sulfonamides / Q000008:administration & dosage* / Q000494:pharmacology; D017211:Treatment Failure; D019562:Viral Load; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D013449:Sulfonamides; D054301:gag Gene Products, Human Immunodeficiency Virus; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; D019438:Ritonavir; D000069454:Darunavir