Journal Article

Safety, Tolerability, and Preliminary Efficacy of 48 Weeks of Etravirine Therapy in a Phase IIb Dose-Ranging Study Involving Treatment-Experienced Patients with HIV-1 Infection

Julio Montaner, Patrick Yeni, Nathan N. Clumeck, Gerd Fätkenheuer, Jose Gatell, Phillip Hay, Elena Seminari, Monika P. Peeters, Monika Schöller-Gyüre, Myriam Simonts and Brian Woodfall

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 47, issue 7, pages 969-978
Published in print October 2008 | ISSN: 1058-4838
Published online October 2008 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/591705
Safety, Tolerability, and Preliminary Efficacy of 48 Weeks of Etravirine Therapy in a Phase IIb Dose-Ranging Study Involving Treatment-Experienced Patients with HIV-1 Infection

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  • Infectious Diseases
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  • Microbiology

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Background. Etravirine (ETR; also known as TMC125) is a new nonnucleoside reverse-transcriptase inhibitor with activity against wild-type and nonnucleoside reverse-transcriptase inhibitor–resistant human immunodeficiency virus type 1 (HIV-1).

Methods. This randomized, phase IIb, placebo-controlled, 2-stage, dose-escalating trial evaluated the safety, tolerability, and preliminary efficacy of 3 twice-daily doses of ETR (experimental formulation TF035; compared with placebo), administered with an individually optimized background regimen, in treatment-experienced HIV-1–infected patients. In stage 1 of the trial, 166 patients received ETR (400 mg or 800 mg twice daily) or placebo. In stage 2 of the trial, 74 patients received ETR (800 mg or 1200 mg twice daily) or placebo. The primary objective was to assess the safety and tolerability of the regimens over 48 weeks.

Results. Neuropsychiatric adverse events (AEs) of interest occurred in 46.6% of patients in the combined ETR group and in 45.5% of patients in the combined placebo group (P=.89). Clinically relevant hepatic AEs occurred in 3.4% of patients who received ETR and in 6.1% of patients who received placebo (P=.47), and rash occurred in 19.5% and 12.1%, respectively (P=.25). In general, there was no evidence of a relationship between ETR dose and specific AEs. Most AEs were severity grade 1 or 2; the incidence of grade 3 or 4 AEs was comparable between groups (27.0% in the combined ETR group vs. 27.3% in the placebo group). Plasma preparation tubes were used for viral load measurement. In stage 1, there was no statistically significant difference in efficacy between ETR and placebo. In stage 2, the decrease in log10 plasma viral load between baseline and week 24 was statistically significantly greater in patients who received ETR, compared with patients who received placebo; a trend in favor of ETR persisted until week 48.

Conclusions. ETR was generally safe and well tolerated during long-term administration in treatment-experienced, HIV-1–infected patients, and it had a safety profile comparable to that of placebo.

Journal Article.  4560 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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