Pharmacokinetics and Pharmacodynamics of Etravirine 400 mg Once Daily in Treatment-Naïve Patients

AbstractBackground: Etravirine is currently approved for HIV treatment–experienced patients at a dose of 200 mg twice daily. The long terminal elimination half-life of etravirine should support once-daily dosing.Methods: In the double-blind 48-week SENSE trial, 157 antiretroviral treatment–naive patients were randomly assigned to receive etravirine 400 mg once daily (n = 79) or efavirenz 600 mg once daily (n = 78), plus 2 nucleoside reverse transcriptase inhibitors (NRTIs). Sparse sampling for etravirine plasma concentrations was conducted during the 48-week trial. Area under the curve over the dosing interval (AUC24) and trough concentration (C0) were estimated using a population pharmacokinetic model and compared with previous results using the 200-mg twice-daily dosage. The relationship between etravirine AUC24 and C0 with efficacy and safety was also assessed.Results: By week 48, the percentage of patients in the etravirine arm with HIV RNA <50 copies/ mL was 75.9% in the intent-to-treat switch equals...