title: Safety of enfuvirtide in combination with an optimized background of antiretrovirals in treatment-experienced HIV-1-infected adults over 48 weeks.
abstract: BACKGROUND
  Antiretroviral tolerability is a critical factor contributing to treatment outcome. The T-20 Versus Optimized Background Regimen Only (TORO) studies assessed the safety and efficacy of enfuvirtide in treatment-experienced HIV-1-infected patients.
  
  
  METHODS
  A total of 997 patients were randomized at a 2:1 ratio to an optimized background antiretroviral regimen plus enfuvirtide (n = 663) or an optimized background regimen alone (control group; n = 334). Control patients could switch to enfuvirtide on virologic failure.
  
  
  RESULTS
  In total, 26.5% of patients randomized to enfuvirtide and 36.6% to the control group discontinued study treatment before week 48; the percentage of patients withdrawn for safety reasons (including adverse events [AEs], deaths, and laboratory abnormalities) was 14.0% in the enfuvirtide group and 11.6% in the control group. Injection site reactions (ISRs) occurred in 98% of enfuvirtide patients and led to treatment discontinuation in 4.4%. Treatment-related (defined as possibly, probably, or remotely) AE rates per 100 patient-years were lower with enfuvirtide (96.2) than in the control group (149.9); diarrhea, nausea, and fatigue, the most frequently reported AEs, were significantly less frequent with enfuvirtide than in the control group. Pneumonia was significantly more frequent in patients treated with enfuvirtide (6.7 vs. 0.6 events per 100 patient-years), although the incidence was within expected ranges for this population. Lymphadenopathy was also higher in enfuvirtide-treated patients (7.1 vs. 1.2 events per 100 patient-years) for control patients.
  
  
  CONCLUSIONS
  The addition of enfuvirtide to an optimized background regimen does not exacerbate AEs commonly associated with antiretrovirals. ISRs limited treatment in <5% of patients.
authors.affiliation: Clinique Médicale l'Actuel, Montreal, Quebec, Canada. trottier@lactuel.ca
authors.forename: Benoit
authors.initials: B
authors.lastname: Trottier
authors.forename: Sharon
authors.initials: S
authors.lastname: Walmsley
authors.forename: Jacques
authors.initials: J
authors.lastname: Reynes
authors.forename: Peter
authors.initials: P
authors.lastname: Piliero
authors.forename: Mary
authors.initials: M
authors.lastname: O'Hearn
authors.forename: Mark
authors.initials: M
authors.lastname: Nelson
authors.forename: Julio
authors.initials: J
authors.lastname: Montaner
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.forename: Jacob
authors.initials: J
authors.lastname: Lalezari
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.forename: Keith
authors.initials: K
authors.lastname: Henry
authors.forename: David
authors.initials: D
authors.lastname: Cooper
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Keikawus
authors.initials: K
authors.lastname: Arastéh
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Delfraissy
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Stellbrink
authors.forename: Joep
authors.initials: J
authors.lastname: Lange
authors.forename: Daniel
authors.initials: D
authors.lastname: Kuritzkes
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Eron
authors.forename: Calvin
authors.initials: C
authors.lastname: Cohen
authors.forename: Tosca
authors.initials: T
authors.lastname: Kinchelow
authors.forename: Anne
authors.initials: A
authors.lastname: Bertasso
authors.forename: Emily
authors.initials: E
authors.lastname: Labriola-Tompkins
authors.forename: Anna
authors.initials: A
authors.lastname: Shikhman
authors.forename: Belinda
authors.initials: B
authors.lastname: Atkins
authors.forename: Laurence
authors.initials: L
authors.lastname: Bourdeau
authors.forename: Christopher
authors.initials: C
authors.lastname: Natale
authors.forename: Fiona
authors.initials: F
authors.lastname: Hughes
authors.forename: Jain
authors.initials: J
authors.lastname: Chung
authors.forename: Denise
authors.initials: D
authors.lastname: Guimaraes
authors.forename: Claude
authors.initials: C
authors.lastname: Drobnes
authors.forename: Silvia
authors.initials: S
authors.lastname: Bader-Weder
authors.forename: Ralph
authors.initials: R
authors.lastname: Demasi
authors.forename: Lynn
authors.initials: L
authors.lastname: Smiley
authors.forename: Miklos P
authors.initials: MP
authors.lastname: Salgo
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D003967:Diarrhea; D004359:Drug Therapy, Combination; D000077560:Enfuvirtide; D005221:Fatigue; D015700:HIV Envelope Protein gp41 / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D023581:HIV Fusion Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D008206:Lymphatic Diseases; D009325:Nausea; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011014:Pneumonia
chemical_list: D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D000077560:Enfuvirtide