Efficacy and safety of etravirine in treatment-experienced, HIV-1 patients: pooled 48 week analysis of two randomized, controlled trials

AIDS. 2009 Nov 13;23(17):2289-300. doi: 10.1097/QAD.0b013e3283316a5e.

Abstract

Objective: To evaluate the efficacy, safety and virologic resistance profile of etravirine (TMC125), a next-generation nonnucleoside reverse transcriptase inhibitor, over 48 weeks in treatment-experienced adults infected with HIV-1 strains resistant to a nonnucleoside reverse transcriptase inhibitor and other antiretrovirals.

Design: DUET-1 (NCT00254046) and DUET-2 (NCT00255099) are two identically designed, randomized, double-blind phase III trials.

Methods: Patients received twice-daily etravirine 200 mg or placebo, each plus a background regimen of darunavir/ritonavir, investigator-selected nucleoside/nucleotide reverse transcriptase inhibitors and optional enfuvirtide. Eligible patients had documented nonnucleoside reverse transcriptase inhibitor resistance, at least three primary protease inhibitor mutations at screening and were on a stable but virologically failing regimen for at least 8 weeks, with plasma viral load more than 5000 copies/ml. Pooled 48-week data from the two trials are presented.

Results: Patients (1203) were randomized and treated (n = 599, etravirine; n = 604, placebo). Significantly more patients in the etravirine than in the placebo group achieved viral load less than 50 copies/ml at week 48 (61 vs. 40%, respectively; P < 0.0001). Significantly fewer patients in the etravirine group experienced at least one confirmed or probable AIDS-defining illness/death (6 vs. 10%; P = 0.0408). Safety and tolerability in the etravirine group was comparable to the placebo group. Rash was the only adverse event to occur at a significantly higher incidence in the etravirine group (19 vs. 11%, respectively, P < 0.0001), occurring primarily in the second week of treatment.

Conclusion: At 48 weeks, treatment-experienced patients receiving etravirine plus background regimen had statistically superior and durable virologic responses (viral load less than 50 copies/ml) than those receiving placebo plus background regimen, with comparable tolerability and no new safety signals reported since week 24.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antiretroviral Therapy, Highly Active
  • Double-Blind Method
  • Drug Resistance, Multiple, Viral
  • Female
  • HIV Infections / drug therapy*
  • HIV-1 / drug effects*
  • Humans
  • Male
  • Middle Aged
  • Nitriles
  • Pyridazines / pharmacology*
  • Pyridazines / therapeutic use
  • Pyrimidines
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Treatment Outcome
  • Viral Load
  • Young Adult

Substances

  • Nitriles
  • Pyridazines
  • Pyrimidines
  • Reverse Transcriptase Inhibitors
  • etravirine

Associated data

  • ClinicalTrials.gov/NCT00254046
  • ClinicalTrials.gov/NCT00255099