Pooled week 48 efficacy and safety results from ECHO and THRIVE, two double-blind, randomised, phase III trials comparing TMC278 versus efavirenz in treatment-naïve, HIV-1-infected patients
C. Cohen1, J.-M. Molina2, P. Cahn3, B. Clotet4, J. Fourie5, B. Grinsztejn6, W. Hao7, M. Johnson8, M. Saag9, K. Supparatpinyo10, H. Crauwels11, L. Rimsky11, S. Vanveggel11, P. Williams11, K. Boven12
1Community Research Initiative of New England, Boston, United States, 2Saint-Louis Hospital and University of Paris, Department of Infectious Diseases, Paris, France, 3Hospital Juan A Fernández and Fundación Huesped, Buenos Aires, Argentina, 4Hospital Universitari Germans Trias i Pujol and irsiCaixa Foundation, Barcelona, Spain, 5Dr J Fourie Medical Centre, KwaZulu Natal, South Africa, 6Instituto de Pesquisa Clínica Evandro Chagas-Fiocruz, Rio de Janeiro, Brazil, 7Beijing You'an Hospital, Beijing, China, 8Royal Free Hospital, London, United Kingdom, 9University of Alabama at Birmingham, Infectious Diseases, Birmingham, United States, 10Chiang Mai University, Section of Infectious Disease, Chiang Mai, Thailand, 11Tibotec BVBA, Mechelen, Belgium, 12Tibotec Inc, Titusville, United States
Background: Pooled 48-week primary analysis results of two Phase III trials with TMC278, ECHO (TMC278-C209, NCT00540449) and THRIVE (TMC278-C215, NCT00543725), are presented.
Methods: These international trials include treatment-naïve adult patients receiving (1:1) TMC278 25mg qd or efavirenz 600mg qd, plus either tenofovir disoproxil fumarate (TDF)/emtricitabine (ECHO) or TDF/emtricitabine, lamivudine/zidovudine or abacavir/lamivudine (THRIVE). The primary objective was to demonstrate non-inferiority of TMC278 to efavirenz in confirmed virologic response (viral load [VL] < 50 copies/mL ITT-TLOVR algorithm) at Week 48.
Results: A total of 1368 patients were randomised and treated. Median baseline VL was 5.00 log10 copies/mL and median CD4 256 cells/mm3. TMC278 showed non-inferior efficacy versus efavirenz (Table). The virologic failure rate was 9.0% in the TMC278 group and 4.8% in the efavirenz group. There were lower incidences with TMC278 of adverse events (AEs) leading to discontinuation, and grade 2-4 AEs at least possibly related to treatment, rash, dizziness and abnormal dreams/nightmare (Table). Grade 3/4 laboratory abnormalities for cholesterol (0.1% vs. 2.5%), LDL-cholesterol (0.7% vs. 4.1%) and triglycerides (0.3% vs. 2.2%) were lower with TMC278 versus efavirenz, respectively (p≤0.001). There was no difference in QTc interval between groups.
Conclusions: Response rates were among the highest observed in recent treatment-naïve trials. TMC278 demonstrated non-inferior efficacy versus efavirenz, when administered with NRTIs. The virologic failure rate was higher with TMC278. Incidences of AEs leading to discontinuation, grade 2-4 AEs at least possibly related to treatment, rash, dizziness and abnormal dreams/nightmare, and grade 3/4 laboratory abnormalities for lipids were significantly lower with TMC278.
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