title: Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-1: 24-week results from a randomised, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Antiretroviral agents active against drug-resistant HIV-1 are needed for treatment-experienced patients. The aim of this trial was to assess the efficacy, safety, and tolerability of TMC125 (etravirine), a non-nucleoside reverse transcriptase inhibitor (NNRTI).
  
  
  METHODS
  DUET-1 is a continuing, multinational randomised, double-blind, placebo-controlled, phase III trial. Treatment-experienced adult patients with virological failure on stable antiretroviral therapy, documented genotypic evidence of NNRTI resistance, viral load over 5000 copies per mL, and three or more primary protease inhibitor mutations were randomly assigned to receive 200 mg TMC125 or placebo twice daily. All patients also received darunavir with low-dose ritonavir and investigator-selected nucleoside reverse transcriptase inhibitors. Enfuvirtide use was optional. The primary endpoint was a confirmed viral load below 50 copies per mL at week 24 (FDA time-to-loss of virological response algorithm). Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, with the number NCT00254046.
  
  
  RESULTS
  612 patients were randomised and treated (304 in the TMC125 group, 308 in the placebo group). By week 24, 42 (14%) patients in the TMC125 group and 56 (18%) in the placebo group had discontinued, mainly due to virological failure. At week 24, 170 (56%) patients in the TMC125 group and 119 (39%) patients in the placebo group achieved a confirmed viral load of less than 50 copies per mL (difference in response rates 17%; 95% CI 9-25; p=0.005). Most adverse events were mild or moderate in severity. The type and incidence of adverse events, including neuropsychiatric events, seen with TMC125 were generally comparable with placebo, with the exception of rash (61 [20%] patients on TMC125 vs 30 [10%] on placebo) and diarrhoea (36 [12%] patients on TMC125 vs 63 [20%] on placebo).
  
  
  CONCLUSIONS
  In treatment-experienced patients with NNRTI resistance, treatment with TMC125 achieved better virological suppression at week 24 than did placebo. The safety and tolerability profile of TMC125 was generally comparable with placebo.
authors.affiliation: Centro de Referência e Treinamento DST/AIDS, São Paulo, Brazil. valdezmr@uol.com.br
authors.forename: José Valdez
authors.initials: JV
authors.lastname: Madruga
authors.forename: Pedro
authors.initials: P
authors.lastname: Cahn
authors.forename: Beatriz
authors.initials: B
authors.lastname: Grinsztejn
authors.forename: Richard
authors.initials: R
authors.lastname: Haubrich
authors.forename: Jacob
authors.initials: J
authors.lastname: Lalezari
authors.forename: Anthony
authors.initials: A
authors.lastname: Mills
authors.forename: Gilles
authors.initials: G
authors.lastname: Pialoux
authors.forename: Timothy
authors.initials: T
authors.lastname: Wilkin
authors.forename: Monika
authors.initials: M
authors.lastname: Peeters
authors.forename: Johan
authors.initials: J
authors.lastname: Vingerhoets
authors.forename: Goedele
authors.initials: G
authors.lastname: de Smedt
authors.forename: Lorant
authors.initials: L
authors.lastname: Leopold
authors.forename: Roberta
authors.initials: R
authors.lastname: Trefiglio
authors.forename: Brian
authors.initials: B
authors.lastname: Woodfall
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000145:classification / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D011724:Pyridazines / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines; D012720:Severity of Illness Index
chemical_list: D019380:Anti-HIV Agents; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; C451734:etravirine