| dc.description | In addition to the authors, the POWER 1 study group included the following investigators and contributors to the design, conduct and analysis of the study. Australia: D. Cooper, J. Hoy, P. Martinez and C. Workman; Austria: A. Rieger; Belgium: N. Clumeck, C-M. Farber and F. van Wanzeele; Brazil: C.A. Da Cunha, R. Pedro, F. de Queiroz Telles, A. Timerman and J. Valdez-Madruga; Canada: P. Junod, D. Kilby, J. McLeod, R. O’Brien, A. Rachlis, C Tsoukas and S. Walmsely; France: J-F. Delfraissy, P-M. Girard, A. Lafeuillade, J-M. Molina, F. Raffi, J. Reynes, W. Rozenbaum and D. Vittecoq; Germany: K. Arasteh, H. Carls, S. Esser, H. Jaeger, J-A. Rump, C. K. Schewe, D. Schuster, S. Staszewski and A. Woehrmann; Hungary: D. Ba´nhegyi; Italy: A. Lazzarin, F. Mazzotta and V. Vullo; Poland: A. Boron-Kaczmarska; Portugal: T. Branco, R. Sarmento-e-Castro and J. Vera; Spain: K. Auirrebengoa, B. Clotet, J. Gonzalez-Lahoz, J. Iribarren, H. Knobel, M. J. Perez-Elias, J. J. Picazo and I. Santos; Switzerland: E. Bernasconi and M. Opravil; UK: C. Leen and E.Wilkins. | |
| dc.description | Background: The ongoing phase IIb POWER 1 (TMC114-C213) trial is designed to assess efficacy and safety of the protease inhibitor (PI) TMC114 (darunavir) in treatmentexperienced HIV-1-infected patients. Design: This randomized, partially blinded, 24-week dose-finding study compared efficacy and safety of four doses of TMC114 plus low-dose ritonavir (TMC114/r) with
investigator-selected control PI(s) (CPI[s]). Methods: Patients with one or more primary PI mutation and HIV RNA > 1000 copies/
ml received optimized background therapy, plus TMC114/r 400/100 mg once daily, 800/100 mg once daily, 400/100 mg twice daily or 600/100 mg twice daily, or CPI(s). The primary endpoint (intent-to-treat) compared proportions of patients achieving viral load reduction 1.0 log10 copies/ml from baseline. Results: In total, 318 patients were treated. Baseline mean viral load was 4.48 log10 copies/ml; median CD4 cell count was 179 cells/ml. In the CPI arm 62% of patients discontinued (virological failure: 54%); 10% of TMC114/r patients discontinued. More TMC114/r (69–77%) than CPI patients (25%) reached the primary endpoint (P < 0.001); 43–53% of TMC114/r patients and 18% ofthe CPIarm achievedviral load< 50 copies/ml (P < 0.001). TMC114/r demonstrated greater mean CD4 cell count increases versus CPI(s) (68–124 versus 20 cells/ml; P < 0.05). TMC114/r 600/100 mg twice daily demonstrated the highest virological and immunological responses. Adverse event incidence was similar between treatments; headache and diarrhoea were more common with CPI(s). Conclusions: TMC114/r demonstrated statistically higher 24-week virological response rates and CD4 cell count increases than CPI(s). TMC114/r 600/100 mg twice daily has received regulatory approval in treatment-experienced patients. | |
