The primary aim of this study was to determine the bioequivalence of boceprevir, an HCV protease inhibitor and etravirine, an HIV non-nucleoside reverse transcriptase inhibitor; area under the concentration time curve (AUC0,τ); maximum concentration (Cmax); and trough concentration (C8 or Cmin) when administered in combination versus alone.Open-label crossover study in healthy volunteers.Boceprevir, etravirine, and the combination were administered for 11-14 days with intensive sampling between days 11 and 14 of each sequence. Boceprevir and etravirine were quantified using validated liquid chromatography coupled with tandem mass spectrometry and high-performance liquid chromatography/ultraviolet assays, respectively and pharmacokinetics determined using noncompartmental methods. Geometric mean ratios (GMRs) and 90% confidence interval (CI) for the combination versus each drug alone were evaluated using 2 one-sided t tests. The hypothesis of equivalence was rejected if 90% GMR CI was not contained in the interval (0.8-1.25).Twenty subjects completed study. GMRs (90% CI) for etravirine AUCo,τ, Cmax, and Cmin were 0.77 (0.66 to 0.91), 0.76 (0.68 to 0.85), and 0.71 (0.54 to 0.95), respectively, in combination versus alone. Boceprevir GMRs (90% CI) for AUCo,τ, Cmax, and C8 were 1.10 (0.94 to 1.28), 1.10 (0.94 to 1.29), and 0.88 (0.66 to 1.17), respectively, in combination versus alone. All adverse events (n = 112) were mild or moderate. Six subjects discontinued: 4 due to rash, 1 due to central nervous system effects, and 1 for a presumed viral illness.Etravirine AUCo,τ, Cmax, and Cmin decreased 23%, 24%, and 29%, respectively, with boceprevir. Boceprevir AUC0,τ and Cmax increased 10% and C8 decreased 12% by etravirine. Additional research is needed to elucidate the mechanism(s) and therapeutic implications of the observed interaction. [ABSTRACT FROM AUTHOR]