Abstract
Background
This crossover, open-label clinical study evaluated the potential for clinically relevant drug interactions between ritonavir-boosted elvitegravir (elvitegravir/r), an HIV integrase inhibitor, and etravirine, a non-nucleoside reverse transcriptase inhibitor.
Methods
Healthy volunteers were randomized into one of two groups, each with two arms. Group 1 (n=20) followed a sequence of 10-day dosing of elvitegravir/r (150/100 mg once daily) and elvitegravir/r plus etravirine (200 mg twice daily) or the reverse (n=10 per sequence). Group 2 (n=14) followed a sequence of 10-day dosing of etravirine and etravirine plus elvitegravir/r or the reverse (n=7 per sequence), all under fed conditions. Elvitegravir, ritonavir and etravirine pharmacokinetics were determined on days 10 and 20 using non-compartmental analyses. Lack of pharmacokinetic alteration bounds for 90% confidence intervals (CI) about the geometric mean ratio (GMR; coadministration versus alone) were 70–143% for elvitegravir and ritonavir pharmacokinetics (maximum concentration [Cmax], concentration at the end of the dosing interval [Ctau] and area under the plasma concentration–time curve [AUCtau; 0–24 h] and 80–125% for etravirine pharmacokinetics (AUCtau 0–12 h).
Results
Of the 34 enrolled participants, 31 completed the study. There were three discontinuations, but none were caused by adverse events (AEs). The most common treatment-emergent AE was headache. Elvitegravir pharmacokinetic GMR was 6–7% higher following elvitegravir/r plus etravirine dosing versus elvitegravir/r. The GMR for etravirine and ritonavir AUCtau were 2.4% and 12.3% lower, respectively. Importantly, the 90% CI for elvitegravir and etravirine pharmacokinetics and AUCtau and Cmax for ritonavir were within the lack of alteration bounds.
Conclusions
Elvitegravir/r and etravirine do not undergo clinically relevant drug interactions and can be coadministered without dose adjustment.