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

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.

• Authors: Christine Katlama, Richard Haubrich, Jacob Lalezari, Adriano Lazzarin, José V Madruga, Jean-Michel Molina, Mauro Schechter, Monika Peeters, Gaston Picchio, Johan Vingerhoets, Brian Woodfall, Goedele De Smedt, DUET-1, DUET-2 study groups
• Journal: AIDS (London, England) (AIDS) Vol. 23 Issue 17 Pg. 2289-300 (Nov 13 2009) ISSN: 1473-5571 [Electronic] England
• PMID: 19710593 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, therapeutic use)
• Pyrimidines
• Reverse Transcriptase Inhibitors (pharmacology, therapeutic use)
• Treatment Outcome
• Viral Load
• Young Adult