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

Katlama, Christine; Haubrich, Richard; Lalezari, Jacob; Lazzarin, Adriano; Madruga, Jose V.; Molina, Jean-Michel; Schechter, Mauro; Peeters, Monika; Picchio, Gaston; Vingerhoets, Johan; Woodfall, Brian; De Smedt, Goedele; DUET-1; DUET-2 study groups

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

Date

2009

Authors

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.

Keywords

Etravirine, Treatment-experienced, HIV-1, Randomized Controlled Trials, Pooled Analysis

Citation

Katlama, C., Haubrich, R., Lalezari, J., Lazzarin, A., Madruga, J. V., Molina, J.-M., ... De Smedt, G. (2009). Efficacy and safety of etravirine in treatment-experienced, HIV-1 patients: Pooled 48 week analysis of two randomized, controlled trials. AIDS, 23(17), 2289–2300. doi:10.1097/qad.0b013e3283316a5e