To print: Select File and then Print from your browser's menu --------------------------------------------------------------------------------------- Title: Trial Results Show Etravirine Safe and Effective in HIV-1 for Treatment-Resistant Patients: Presented at CROI URL: http://www.pslgroup.com/dg/21CA3A.htm Doctor's Guide February 7, 2008
By Maria Bishop BOSTON, MA -- February 7, 2008 -- Etravirine provides safe and durable efficacy and has superior virologic and immunologic benefits in patients with HIV-1 who are treatment experienced and resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIs), researchers reported here at the 15th Conference on Retroviruses and Opportunistic Infections (CROI). The ongoing, 96-week, phase 3 DUET-1 trial was led by Richard H. Haubrich, MD, Professor of Medicine, Department of Medicine, Division of Infectious Diseases, University of California San Diego, San Diego, California. Dr. Haubrich and colleagues randomized 612 treatment-experienced patients with HIV-1 in a double-blind fashion to etravirine 200 mg or placebo. Subjects in the DUET-1 trial had documented resistance to NNRTIs and at least 3 primary protease inhibitor (PI) mutations. Both study arms received a background regimen of ritonavir-boosted darunavir (DRV/r) plus an optimized, investigator-selected nucleoside reverse transcriptase inhibitor and optional enfuvirtide. Of patients with a low viral load (<50 copies/mL), 94% of patients in the etravirine arm maintained a viral load of less than 50 copies/mL at week 24 versus 89% of patients in the placebo arm at week 48. Except for mild to moderate rash, the tolerability of etravirine was similar to placebo. In a separate, identically designed analysis, the ongoing, 96-week, phase 3, DUET-2 trial revealed similar results in its 591-patient cohort. Of those patients with a low viral load (<50 copies/mL) at week 24, 90% in the etravirine arm maintained a viral load of less than 50 copies/mL versus 88% in the placebo arm at week 48. Lead author of DUET-2, Margaret Johnson, MD, Head of Clinical Service, Royal Free Hospital, London, United Kingdom, noted that adverse events in DUET-2 were mostly similar to placebo, with no new safety concerns. Cases of rash were mild to moderate, occurred early, and resolved with continued treatment. Treatment was discontinued due to rash in 2.4% of the etravirine arm and 0% of the placebo arm, respectively. Rates of nervous system and psychiatric disorders with etravirine were comparable with those seen with placebo. Finally, a pooled analysis of 24-week results from both the DUET-1 and -2 trials was presented with a focus on pharmacokinetics and pharmacodynamics by lead author Thomas N. Kakuda, PharmD, Director of Clinical Pharmacology, Tibotec Inc, Yardley, Pennsylvania. Despite pharmacokinetic variability, no dose adjustments are needed for etravirine based on covariate analysis and the lack of pharmacokinetic/pharmacodynamic relationships, stated Dr. Kakuda. Pharmacokinetic data from 574 etravirine subjects in DUET-1 and DUET-2 were available from the pool of 599 subjects randomized to the study drug. The US Food and Drug Administration granted approval last year to the etravirine tablet formulation, the first NNRTI to show antiviral activity in treatment-experienced adults with HIV resistance to an NNRTI and other antiretroviral agents. [Presentation titles: DUET-1: Week 48 Results of a Phase III Randomized Double-Blind Trial to Evaluate the Efficacy and Safety of TMC125 vs Placebo in 612 Treatment-Experienced HIV-1-Infected Patients. Abstract 790. DUET-2: Week-48 Results of a Phase III Randomized Double-Blind Trial to Evaluate the Efficacy and Safety of TMC125 Vs Placebo in 591 Treatment-Experienced HIV-1-Infected Patients. Abstract 791. Pharmacokinetics and Pharmacodynamics of the NNRTI TMC125 in Treatment-Experienced HIV-1-Infected Patients: Pooled 24-Week Results of DUET-1 and DUET-2. Abstract 762] --------------------------------------------------------------------------------------------- Copyright © 1999 P\S\L Consulting Group Inc. All rights reserved. Republication or redistribution of P\S\L content is expressly prohibited without the prior written consent of P\S\L. P\S\L shall not be liable for any errors, omissions or delays in this content or any other content on its sites, newsletters or other publications, nor for any decisions or actions taken in reliance on such content. --------------------------------------------------------------------------------------------- This news story was printed from *Doctor's Guide to the Internet* located at http://www.docguide.com --------------------------------------------------------------------------------------- Return to News Story Page This site is maintained by webmaster@pslgroup.com Please contact us with any comments, problems or bugs. All contents Copyright (c) 1998 P\S\L Consulting Group Inc. All rights reserved.