title: Emerging mutations and associated factors in patients displaying treatment failure on an etravirine-containing regimen.
abstract: BACKGROUND
  The aim of this study was to characterize the mutations selected upon failure on etravirine (ETR)-containing regimen in non-nucleoside reverse transcriptase inhibitors (NNRTIs)-experienced HIV-infected patients and the associated factors.
  
  
  METHODS
  Forty-two patients displaying virological failure after a 6 months ETR-containing regimen were studied. For each patient the reverse transcriptase (RT) sequence at failure was compared with all the RT sequences available before introduction of ETR. The effect of baseline and failure HIV-1 RNA, HIV-1 subtype, baseline number of NNRTI resistance mutations, protease inhibitor and nucleoside RT inhibitor genotypic sensitivity scores, number of new drugs used in the treatment, and previous use of efavirenz or nevirapine on the selection of NNRTI resistance mutations were investigated.
  
  
  RESULTS
  At failure, 12/42 (29%) patients showed development of at least 1 new NNRTI mutation (7 patients selected 1 mutation and 5 patients 2 mutations). NNRTI mutations selected were V179I (5 patients), V179L (1), V179F (2), L100I (1), K103N (2), Y181C (3), K101E (1), K101R (1) and H221Y (1). Univariate analysis showed that HIV-1 RNA level at failure (P=0.033) and past exposure to efavirenz (P<0.001) were associated with the occurrence of at least one NNRTI mutation. The multivariate model retained only past exposure to efavirenz. Among the 36 viruses classified as susceptible to ETR at baseline, 3 were classified as possibly resistant at failure.
  
  
  CONCLUSIONS
  In this study, 29% of viruses from patients experiencing ETR failure selected new NNRTI resistance mutations (at position V179 in 2/3 of cases) in a context of multiple NNRTI resistance mutations.
authors.affiliation: AP-HP, Pitie-Salpetriere Hospital, Pierre et Marie Curie University, INSERM U943, Paris, France. anne-genevieve.marcelin@psl.aphp.fr.
authors.forename: Anne-Genevieve
authors.initials: AG
authors.lastname: Marcelin
authors.forename: Diane
authors.initials: D
authors.lastname: Descamps
authors.forename: Catherine
authors.initials: C
authors.lastname: Tamalet
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Cottalorda
authors.forename: Jacques
authors.initials: J
authors.lastname: Izopet
authors.forename: Constance
authors.initials: C
authors.lastname: Delaugerre
authors.forename: Laurence
authors.initials: L
authors.lastname: Morand-Joubert
authors.forename: Mary-Anne
authors.initials: MA
authors.lastname: Trabaud
authors.forename: Dominique
authors.initials: D
authors.lastname: Bettinger
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rogez
authors.forename: Annick
authors.initials: A
authors.lastname: Ruffault
authors.forename: Cecile
authors.initials: C
authors.lastname: Henquell
authors.forename: Anne
authors.initials: A
authors.lastname: Signori-Schmuck
authors.forename: Magali
authors.initials: M
authors.lastname: Bouvier-Alias
authors.forename: Sophie
authors.initials: S
authors.lastname: Vallet
authors.forename: Bernard
authors.initials: B
authors.lastname: Masquelier
authors.forename: Philippe
authors.initials: P
authors.lastname: Flandre
authors.forename: Vincent
authors.initials: V
authors.lastname: Calvez
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D048588:Benzoxazines / Q000008:administration & dosage / Q000627:therapeutic use; D003521:Cyclopropanes; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D058889:Molecular Typing; D009154:Mutation; D019829:Nevirapine / Q000008:administration & dosage / Q000627:therapeutic use; D009570:Nitriles; D011724:Pyridazines / Q000008:administration & dosage* / Q000627:therapeutic use; D011743:Pyrimidines; D012367:RNA, Viral / Q000032:analysis; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D017211:Treatment Failure; D019562:Viral Load / Q000187:drug effects
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; C451734:etravirine; D019829:Nevirapine; D054303:HIV Reverse Transcriptase; C098320:efavirenz