Pharmacokinetics (PK) and Pharmacodynamics (PD) of Etravirine (ETR) in Treatment-Experienced HIV-1 Infected Patients: Pooled 48-Week Results of DUET-1 and DUET-2

Background Etravirine (ETR; TMC125) is a next-generation NNRTI with potent activity against both wild-type and NNRTI-resistant HIV. DUET-1 and DUET-2 are identically designed, ongoing, Phase III, doubleblind, randomized trials of ETR versus placebo, both with an investigator-selected background regimen (BR) including ritonavir-boosted darunavir (DRV/r). The relationship between ETR pharmacokinetics and pharmacodynamics over 48 weeks from these trials was investigated. Methods Population pharmacokinetics for area under the plasma concentration-time curve (AUC) and predose plasma concentration (C0h) were estimated using Bayesian feedback. Analysis of covariance (ANCOVA) and logistic regression with generalized additive modeling (GAM) were used to analyze pharmacokinetic/pharmacodynamic (PK/PD) relationships with efficacy endpoints and safety.