title: Dynamics of enfuvirtide resistance mutations in enfuvirtide-experienced patients remaining in virological failure under salvage therapy.
abstract: BACKGROUND
  Evaluation of the dynamics of enfuvirtide (ENF) resistance mutations after ENF withdrawal in patients with virological failure under salvage therapy may be helpful to optimize the management of ENF in human immunodeficiency virus (HIV)-infected patients.
  
  
  METHODS
  Seven patients with a failing ENF-containing regimen, initiated for at least 3 months (median 6.4 months, range 3-14), were included and followed up prospectively at the time of virological failure. Genotypic analysis of the gp41 region by bulk sequencing and clonal analysis was performed in plasma and/or peripheral blood mononuclear cells to detect ENF resistance mutations.
  
  
  RESULTS
  Genotypic profiles of ENF-resistant variants at ENF discontinuation were as follows: V38A in 3 patients, V38A+N42T+N43D in 1 patient, N43D in 2 patients, and N43K in 1 patient. Clonal analysis showed that maintaining ENF treatment after virological failure has an impact on both (1) the number of resistance profiles detected, and (2) the time of persistence of ENF-resistant variants. ENF-resistant variants were archived in HIV DNA in 5/7 patients. At 1 month after ENF withdrawal, no significant increase in HIV-1 viral load was observed.
  
  
  CONCLUSIONS
  The persistence of ENF-resistant variants was found to be correlated to exposure time to failing drug. ENF withdrawal should be considered in patients with virological failure to preserve the possible efficacy of ENF recycling or upcoming entry inhibitors.
authors.affiliation: Laboratoire de Virologie, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Charpentier
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Jenabian
authors.forename: Christophe
authors.initials: C
authors.lastname: Piketty
authors.forename: Marina
authors.initials: M
authors.lastname: Karmochkine
authors.forename: Pascaline
authors.initials: P
authors.lastname: Tisserand
authors.forename: Didier
authors.initials: D
authors.lastname: Laureillard
authors.forename: Laurent
authors.initials: L
authors.lastname: Bélec
authors.forename: Ali
authors.initials: A
authors.lastname: Si-Mohamed
authors.forename: Laurence
authors.initials: L
authors.lastname: Weiss
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics*; D000077560:Enfuvirtide; D019143:Evolution, Molecular; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D015700:HIV Envelope Protein gp41 / Q000494:pharmacology* / Q000627:therapeutic use; D023581:HIV Fusion Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D016879:Salvage Therapy; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D012367:RNA, Viral; D000077560:Enfuvirtide