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.

Abstract

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.

• Authors: Julio Montaner, Patrick Yeni, Nathan N Clumeck, Gerd Fätkenheuer, Jose Gatell, Phillip Hay, Elena Seminari, Monika P Peeters, Monika Schöller-Gyüre, Myriam Simonts, Brian Woodfall, TMC125-C203 Study Group
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 47 Issue 7 Pg. 969-78 (Oct 01 2008) ISSN: 1537-6591 [Electronic] United States
• PMID: 18764771 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• Nitriles
• Pyridazines
• Pyrimidines
• etravirine

Topics

• Adult
• Aged
• Anti-HIV Agents (administration & dosage, adverse effects, therapeutic use)
• CD4 Lymphocyte Count
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• HIV Infections (drug therapy)
• HIV-1
• Humans
• Male
• Middle Aged
• Nitriles
• Pyridazines (administration & dosage, adverse effects, therapeutic use)
• Pyrimidines