title: Efficacy and safety of 48 weeks of enfuvirtide 180 mg once-daily dosing versus 90 mg twice-daily dosing in HIV-infected patients.
abstract: OBJECTIVE
  To evaluate the safety and antiviral activity of once-daily (qd) enfuvirtide (ENF) compared with twice daily (bid) ENF.
  
  
  METHODS
  T20-401 was a phase 2, open-label, randomized, 48-week pilot study comparing ENF 180 mg qd versus ENF 90 mg bid, added to an optimized background (OB) regimen. Patients were randomized 1:1 to receive ENF 180 mg qd given as two 90-mg injections (n = 30) or one 90-mg injection bid (n = 31), plus OB. The primary efficacy endpoint was the proportion of patients achieving a HIV-1 RNA viral load <400 copies/mL. Adherence, pharmacokinetics, safety, and tolerability parameters, including injection site reactions (ISRs), were compared between treatment arms.
  
  
  RESULTS
  At Week 48, 23.3% of patients on once daily versus 22.6% on twice daily (p = .969) reached <400 copies/mL and 13.3% and 22.6% (p = .323), respectively, reached <50 copies/mL. The proportion reporting 1 adverse event or ISRs was comparable between arms, despite an increased incidence of grade 4 erythema (13% vs. 0%), induration (33% vs. 12%), and ecchymosis (7% vs. 0%) on twice daily versus once daily. ENF adherence (95% of prescribed doses) was higher on once daily (80.0%) versus twice daily (58.1%).
  
  
  CONCLUSIONS
  The antiviral efficacy, safety, and tolerability of 180 mg ENF qd appeared comparable with that of 90 mg ENF bid at Week 48, although the study was not powered to demonstrate the noninferiority of once daily versus twice daily.
authors.affiliation: Central Texas Clinical Research LLC, Austin, Texas 78705, USA. dwight@seton.org
authors.forename: David
authors.initials: D
authors.lastname: Wright
authors.forename: Allen
authors.initials: A
authors.lastname: Rodriguez
authors.forename: Eliot
authors.initials: E
authors.lastname: Godofsky
authors.forename: Sharon
authors.initials: S
authors.lastname: Walmsley
authors.forename: Emily
authors.initials: E
authors.lastname: Labriola-Tompkins
authors.forename: Lucille
authors.initials: L
authors.lastname: Donatacci
authors.forename: Anna
authors.initials: A
authors.lastname: Shikhman
authors.forename: Ernestine
authors.initials: E
authors.lastname: Tucker
authors.forename: Yu-Yuan
authors.initials: YY
authors.lastname: Chiu
authors.forename: Jain
authors.initials: J
authors.lastname: Chung
authors.forename: Lucy
authors.initials: L
authors.lastname: Rowell
authors.forename: Ralph
authors.initials: R
authors.lastname: Demasi
authors.forename: Neil
authors.initials: N
authors.lastname: Graham
authors.forename: Miklos
authors.initials: M
authors.lastname: Salgo
mesh_terms: D000328:Adult; D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D023581:HIV Fusion Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D010865:Pilot Projects; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D012367:RNA, Viral; D000077560:Enfuvirtide