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.
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.


RESULTS
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.


CONCLUSIONS
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.
Lazzarin
Adriano
A
Vita-Salute, San Raffaele University, Milan, Italy. lazzarin.adriano@hsr.it
Campbell
Thomas
T
Clotet
Bonaventura
B
Johnson
Margaret
M
Katlama
Christine
C
Moll
Arend
A
Towner
William
W
Trottier
Benoit
B
Peeters
Monika
M
Vingerhoets
Johan
J
de Smedt
Goedele
G
Baeten
Benny
B
Beets
Greet
G
Sinha
Rekha
R
Woodfall
Brian
B
D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000627:therapeutic use; D023581:HIV Fusion Inhibitors / Q000627:therapeutic use; D015658:HIV Infections / Q000145:classification / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010446:Peptide Fragments / Q000627:therapeutic use; D011724:Pyridazines / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines; D019562:Viral Load
D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D009570:Nitriles; D010446:Peptide Fragments; D011724:Pyridazines; D011743:Pyrimidines; C451734:etravirine; D000077560:Enfuvirtide