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.
aUniversité Pierre et Marie Curie, Paris VI and Hôpital Pitié-Salpêtrière, Paris, France
bUniversity of California San Diego, San Diego, California, USA
cQuest Clinical Research, San Francisco, California, USA
dVita-Salute, San Raffaele University, Milan, Italy
eCentro de Referência e Treinamento DST/AIDS, São Paulo, Brazil
fDepartment of Infectious Diseases, Saint-Louis Hospital, University of Paris, Diderot Paris 7, France
gProjeto Praça Onze, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
hTibotec BVBA, Mechelen, Belgium
iTibotec, Inc., Yardley, Pennsylvania, USA.
* DUET-1 and DUET-2 study groups detailed in Acknowledgment section.
Received 8 May, 2009
Revised 29 July, 2009
Accepted 30 July, 2009
Correspondence to Professor Christine Katlama, MD, Hôpital Pitié-Salpêtrière, Paris, France. Tel: +33 1 42 16 01 42; fax: +33 1 42 16 01 26; e-mail: email@example.com