Presentation Abstract

Session: 195-HIV Clinical Trials
Tuesday, Sep 14, 2010, 1:30 PM - 4:00 PM
Presentation Title: H-1810 -
Characterization of the Resistance Profile of TMC278: 48-week Analysis of the Phase 3 Studies ECHO and THRIVE
Location: Ballroom East
Presentation Number: H-1810
Pres. Time: Tuesday, Sep 14, 2010, 2:00 PM - 2:15 PM
Category: H
Keywords: TMC278; phase III; virology
Author(s): Laurence Rimsky - Tibotec R&D 1, Joseph Eron - Professor of Medicine2, Bonaventura Clotet - _ 3, Johan Vingerhoets - Tibotec R&D 1, Hilde Azijn - Tibotec R&D 1, Simon Vanveggel - Tibotec R&D 1, Annemie Hoogstoel - Tibotec R&D 1, Marita Stevens - Tibotec R&D 1, Katia Boven - Tibotec R&D 4, Gaston Picchio - Sr. Director Clinical Virology 4;
1Tibotec, Mechelen, Belgium, 2UNC, Chapel Hill, NC, 3irsiCaixa Fndn., Barcelona, Spain, 4Tibotec, Titusville, NJ.
Financial Disclosures:  L. Rimsky,
Tibotec Role(s): Employee, Received: Salary.
J. Eron,
Boehringer Ingelheim Pharmaceuticals Role(s): Investigator, Received: Research Grant.
GlaxoSmithKline Role(s): Consultant, Investigator, Received: Research Grant.
Merck & Co, Inc Role(s): Consultant, Investigator, Speaker's Bureau, Received: Research Grant.
Avexa Ltd Role(s): Consultant.
Bristol-Myers Squibb Role(s): Consultant, Speaker's Bureau.
Chimerix Inc Role(s): Consultant.
Pfizer Inc Role(s): Consultant.
Tibotec Role(s): Consultant, Speaker's Bureau.
Tobira Therapeutics Inc Role(s): Consultant.
Virco Lab, Inc. Role(s): Consultant, Speaker's Bureau.
B. Clotet,
Abbott, Boehringer Ingelheim, Gilead, GlaxoSmithKline, Janssen-Cilag, Merck Sharp & Dohme, Panacos, Pfizer, Roche, Tibotec Role(s): Investigator, Scientific Advisor (Review Panel or Advisory Committee), Received: Research Grant, Speaker Honorarium, Consulting Fee.
J. Vingerhoets,
Tibotec Role(s): Employee, Received: Salary.
H. Azijn,
Tibotec Role(s): Employee, Received: Salary.
S. Vanveggel,
Tibotec Role(s): Employee, Received: Salary.
A. Hoogstoel,
Tibotec Role(s): Employee, Received: Salary.
M. Stevens,
Tibotec Role(s): Employee, Received: Salary.
K. Boven,
Tibotec Role(s): Employee, Received: Salary.
G. Picchio,
Tibotec Role(s): Employee, Received: Salary.
Abstract: Background: ECHO (C209) and THRIVE (C215) are ongoing, 96-week, Phase 3 trials to compare the efficacy, safety and tolerability of TMC278 (25mg qd) vs. efavirenz (EFV) (600mg qd) plus fixed N(t)RTI background regimens in HIV-1 infected treatment-naïve patients. Patients experiencing virologic failure (VF) were analyzed for the emergence of viral genotypic and phenotypic changes. Methods: The primary endpoint was the proportion of patients achieving <50 HIV RNA copies/mL at Week 48 (ITT-TLOVR analysis). Resistance analyses were conducted in the intent to treat population. The pooled (ECHO+THRIVE) analyses are presented. Results: 686 and 682 patients were randomized and treated with TMC278 and EFV, respectively. TLOVR response rates were 84.3% for TMC278 and 82.3% for EFV confirming the non-inferiority of the TMC278 regimen. A total of 72/686 (10.5%) and 39/682 (5.7%) patients met the definitions of VF in the TMC278 and EFV arms, respectively (p=0.005); of these 62 (86%) and 28 (72%) had successful resistance tests. The proportions of VF patients who had emergent NNRTI resistance associated mutations (RAMs) were 63% and 54% in the TMC278 and EFV arms, respectively (p=0.49). The proportion of VF patients with emerging IAS-USA N(t)RTI RAMs was 68% in the TMC278 arm and 32% in the EFV arm (p=0.003). The 3 most frequent emerging RAMs in the TMC278 VFs were M184I (n=29), E138K (n=28) and M184V (n=14). E138K and M184I were usually observed together. K103N was the most common mutation in EFV VFs (n=11). Fifty percent of TMC278 and 43% of EFV VFs developed phenotypic resistance to the NNRTI in the regimen. Conclusions: These results confirm that TMC278, in combination with a N(t)RTI background regimen, was effective and non inferior to EFV. VFs were uncommon but more frequent in the TMC278 group where they were characterized mainly by the emergence of E138K and M184I/V.

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