title: Etravirine combined with antiretrovirals other than darunavir/ritonavir for HIV-1-infected, treatment-experienced adults: Week 48 results of a phase IV trial.
abstract: OBJECTIVE
  VIOLIN (TMC125IFD3002; NCT01422330) evaluated the safety, tolerability, and pharmacokinetics of etravirine with antiretrovirals other than darunavir/ritonavir in HIV-1-infected patients.
  
  
  METHODS
  In a 48-week, phase IV, single-arm, multicenter study, patients on prior antiretroviral therapy (⩾8 weeks) who needed to change regimen for virologic failure (viral load ⩾ 500 copies/mL) or simplification/adverse events (viral load < 50 copies/mL) received etravirine 200 mg bid with ⩾1 other active antiretroviral, excluding darunavir/ritonavir or only nucleoside/tide reverse transcriptase inhibitors.
  
  
  RESULTS
  Of 211 treated patients, 73% (n = 155) had baseline viral load ⩾ 50 copies/mL and 27% (n = 56) had baseline viral load < 50 copies/mL. Protease inhibitors were the most common background antiretrovirals (83%). Diarrhea was the most frequent adverse event (17%). Serious adverse events (no rash) occurred in 5% of patients; none were etravirine related. Overall, median etravirine AUC12hwas 5390 ng h/mL and C0hwas 353 ng/mL (N = 199). Week 48 virologic response rates (viral load < 50 copies/mL; Food and Drug Administration Snapshot algorithm) were 48% (74/155) (baseline viral load ⩾ 50 copies/mL) and 75% (42/56) (baseline viral load < 50 copies/mL). Virologic failure rates were 42% and 13%, respectively. The most frequently emerging etravirine resistance-associated mutations in virologic failures were Y181C, E138A, and M230L. Virologic response rates for patients with baseline viral load ⩾ 50 copies/mL were 38% (30/79) (non-adherent) versus 64% (44/69) (adherent subset).
  
  
  CONCLUSIONS
  Etravirine 200 mg bid in combination with antiretrovirals other than darunavir/ritonavir was well tolerated in the studied treatment-experienced HIV-1-infected population. The overall etravirine safety and tolerability profile and pharmacokinetics (specifically in those patients who were adherent) were similar to those previously observed for etravirine in HIV-1-infected adults. The relatively high level of non-adherence, also observed in the pharmacokinetic assessments, negatively impacted virologic response, especially in patients with ⩾50 copies/mL at baseline.
authors.affiliation: La Clinica Familiar de Luis Angel Garcia, Guatemala City, Guatemala.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Arathoon
authors.affiliation: Soweto Clinical Trials Centre, Johannesburg, South Africa.
authors.forename: Asad
authors.initials: A
authors.lastname: Bhorat
authors.affiliation: Infectious Diseases Hospital, Braşov, Romania.
authors.forename: Rodica
authors.initials: R
authors.lastname: Silaghi
authors.affiliation: Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Herta
authors.initials: H
authors.lastname: Crauwels
authors.affiliation: Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Ludo
authors.initials: L
authors.lastname: Lavreys
authors.affiliation: Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Lotke
authors.initials: L
authors.lastname: Tambuyzer
authors.affiliation: Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Ben
authors.initials: B
authors.lastname: Van Baelen
authors.affiliation: Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Simon
authors.initials: S
authors.lastname: Vanveggel
authors.affiliation: Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Magda
authors.initials: M
authors.lastname: Opsomer
keywords: Etravirine; efficacy; pharmacokinetics; safety; virology