title: Efficacy and safety of raltegravir in treatment-experienced HIV-1-infected patients switching from enfuvirtide-based regimens: 48 week results of the randomized EASIER ANRS 138 trial.
abstract: OBJECTIVE
  To assess the sustainable efficacy and safety of a switch from enfuvirtide to raltegravir in patients with multidrug-resistant HIV infection.
  
  
  METHODS
  One hundred and seventy patients with multidrug-resistant HIV infection and suppressed plasma HIV RNA levels < 400 copies/mL under an enfuvirtide-based regimen were randomized to maintain their regimen or to switch to a raltegravir-based regimen (immediate group) in a 48 week prospective, randomized, open-label trial. At week 24, patients in the maintenance arm also switched to raltegravir (deferred group). Baseline genotypic susceptibility scores (GSSs) were calculated using available historical resistance tests. Efficacy was assessed by the cumulative proportion of patients with virological failure, defined as a confirmed plasma HIV RNA ≥ 400 copies/mL up to week 48. The EASIER ANRS 138 trial is registered at ClinicalTrials.gov (NCT00454337).
  
  
  RESULTS
  At baseline, 86% of patients had plasma HIV RNA levels <50 copies/mL and 86% had a GSS ≥ 1. Through to week 48, in the on-treatment analysis, only one patient in the immediate group, with a GSS of 0, developed virological failure. At week 48, 90% of patients in both the immediate and deferred groups had plasma HIV-1 RNA levels <50 copies/mL. Median CD4 cell counts remained stable during follow-up. Of note, 12 of 66 (18.2%) patients receiving a regimen combining raltegravir and ritonavir-boosted tipranavir experienced alanine aminotransferase elevations, which led to a switch from tipranavir to darunavir in 8 cases, without discontinuation of raltegravir.
  
  
  CONCLUSIONS
  In well-suppressed patients with multidrug-resistant HIV infection, a switch from enfuvirtide to raltegravir is generally well tolerated and has sustained antiviral efficacy when combined with a potent background regimen.
authors.affiliation: Department of Infectious Diseases, Assistance Publique Hôpitaux de Paris, Saint-Louis Hospital, Paris, France. sebastien.gallien@sls.aphp.fr
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gallien
authors.forename: Joséphine
authors.initials: J
authors.lastname: Braun
authors.forename: Constance
authors.initials: C
authors.lastname: Delaugerre
authors.forename: Isabelle
authors.initials: I
authors.lastname: Charreau
authors.forename: Jacques
authors.initials: J
authors.lastname: Reynes
authors.forename: François
authors.initials: F
authors.lastname: Jeanblanc
authors.forename: Renaud
authors.initials: R
authors.lastname: Verdon
authors.forename: Pierre
authors.initials: P
authors.lastname: de Truchis
authors.forename: Thierry
authors.initials: T
authors.lastname: May
authors.forename: Isabelle
authors.initials: I
authors.lastname: Madelaine-Chambrin
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Aboulker
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D018791:CD4 Lymphocyte Count; D024921:Drug Resistance, Multiple, Viral; D023381:Endpoint Determination; D000077560:Enfuvirtide; D005260:Female; D005602:France; D005838:Genotype; D015700:HIV Envelope Protein gp41 / Q000627:therapeutic use*; D023581:HIV Fusion Inhibitors; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D019428:HIV Integrase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010446:Peptide Fragments / Q000627:therapeutic use*; D010865:Pilot Projects; D011446:Prospective Studies; D011760:Pyrrolidinones / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D000068898:Raltegravir Potassium; D016896:Treatment Outcome
chemical_list: D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D019428:HIV Integrase Inhibitors; D010446:Peptide Fragments; D011760:Pyrrolidinones; D012367:RNA, Viral; D000077560:Enfuvirtide; D000068898:Raltegravir Potassium; D000410:Alanine Transaminase