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

Abstract

Background: 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–naïve 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 failure analysis and 92.3% in the on-treatment analysis; no patient developed genotypic or phenotypic resistance to NRTIs or non-nucleoside reverse transcriptase inhibitors (NNRTIs) after virologic failure. Seventy-one subjects had evaluable etravirine pharmacokinetics. The median (interquartile range) of etravirine AUC₂₄ and C₀ were 12,447 (8,261–15,652) ng•h/mL and 330 (188–472) ng/mL, respectively. There was no correlation between etravirine exposure and virologic response or adverse events.Conclusions: In the SENSE trial, etravirine 400 mg once daily achieved similar exposures to historical reference data on etravirine when dosed at 200 mg twice daily. There was no apparent relationship between the pharmacokinetics of etravirine and virologic response or adverse events.

Keywords:

• antiretroviral treatment
• etravirine
• non-nucleoside reverse transcriptase inhibitors
• pharmacokinetics