Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-2: 24-week results from a randomised, double-blind, placebo-controlled trial

Adriano Lazzarin, Thomas Campbell, Bonaventura Clotet, Margaret Johnson, Christine Katlama, Arend Moll, William Towner, Benoit Trottier, Monika Peeters, Johan Vingerhoets, Goedele de Smedt, Benny Baeten, Greet Beets, Rekha Sinha, Brian Woodfall

Research output: Contribution to journalArticle

Abstract

Background: TMC125 (etravirine) is a non-nucleoside reverse-transcriptase inhibitor (NNRTI) with activity against NNRTI-resistant HIV-1 in phase IIb trials. The aim of DUET-2 is to examine the efficacy, tolerability, and safety of TMC125 in treatment-experienced patients. Methods: In this continuing randomised, double-blind, placebo-controlled, phase III trial, HIV-1-infected patients on failing antiretroviral therapy with evidence of resistance to currently available NNRTIs and at least three primary protease inhibitor mutations were eligible for enrolment if on stable (8 weeks unchanged) antiretroviral therapy with plasma HIV-1 RNA greater than 5000 copies per mL. Patients were randomly assigned to receive either TMC125 (200 mg) or placebo, each given twice daily with darunavir-ritonavir, investigator-selected nucleoside/nucleotide reverse transcriptase inhibitors, and optional enfuvirtide. The primary endpoint was the proportion of patients with confirmed viral load below 50 copies per mL at week 24 (FDA time-to-loss of virological response algorithm). Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00255099. Findings: 591 patients were randomised and treated (295 patients in the TMC125 group and 296 in the placebo group). By week 24, 51 (17%) patients in the TMC125 group and 73 (25%) in the placebo group had discontinued, mainly because of virological failure. 183 (62%) patients in the TMC125 group and 129 (44%) in the placebo group achieved confirmed viral load below 50 copies per mL at week 24 (difference 18%, 95% CI 11-26; p=0·0003). The type and frequency of adverse events were much the same in the two groups. Interpretation: In treatment-experienced patients, treatment with TMC125 led to better virological suppression at week 24 than did placebo. The safety and tolerability profile of TMC125 was generally comparable with placebo.

Original languageEnglish
Pages (from-to)39-48
Number of pages10
JournalLancet
Volume370
Issue number9581
DOIs
Publication statusPublished - Jul 7 2007

ASJC Scopus subject areas

  • Medicine(all)

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    Lazzarin, A., Campbell, T., Clotet, B., Johnson, M., Katlama, C., Moll, A., Towner, W., Trottier, B., Peeters, M., Vingerhoets, J., de Smedt, G., Baeten, B., Beets, G., Sinha, R., & Woodfall, B. (2007). Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-2: 24-week results from a randomised, double-blind, placebo-controlled trial. Lancet, 370(9581), 39-48. https://doi.org/10.1016/S0140-6736(07)61048-4