Short Communication: Bioequivalence of Tenofovir and Emtricitabine After Coencapsulation with the Proteus Ingestible Sensor

Abstract

Adherence to tenofovir disoproxil fumarate/emtricitabine (TDF/FTC, Truvada®) is the primary determinant of HIV pre-exposure prophylaxis (PrEP) efficacy. Despite its importance, limitations exist in current methods of adherence quantification, restricting their implementation in the clinic. Proteus Discover (Proteus Digital Health®) can measure the time of each dose using an ingestible sensor that is coencapsulated with medication. In this study, the bioequivalence of coencapsulated TDF/FTC with the Proteus sensor was compared relative to unencapsulated drug. This was a 1:1 randomized cross-over study in which healthy participants received a single dose of unencapsulated and coencapsulated TDF/FTC. A 14-day washout separated each period. Blood was collected at predose and at 0.25, 0.5, 1, 2, 4, 6, 10, 24, 48, and 72 h postdose. Plasma concentrations were determined by LC-MS/MS methods, with a 10 ng/mL lower limit of quantitation (LLOQ) for both tenofovir (TFV) and FTC. Noncompartmental analysis was carried out with Phoenix® WinNonlin® for maximum concentrations (Cmax), area under the concentration-time curve from time 0 to the last measured time point (AUClast) and AUC extrapolated to infinity (AUCinf). Geometric mean ratios were calculated for each parameter and bioequivalence was defined as the 90% confidence interval (CI) of each ratio being within 80%-125%. Twenty-four participants (11 males; 19 white, 3 African American, and 2 Hispanic) completed both visits. Mean ± SD age was 28 ± 4 years and weight was 74 ± 14 kg. The 90% CIs for TFV Cmax, AUClast, and AUCinf were 89%-119%, 94%-111%, and 96%-111%, respectively. The 90% CIs for FTC Cmax, AUClast, and AUCinf were 96%-120%, 96%-108%, and 96%-108%, respectively. Bioequivalence was observed for the coencapsulation of TDF/FTC with the Proteus ingestible sensor, as assessed by a rigorously conducted pharmacokinetic study. Future studies will evaluate the utility and effectiveness of the sensor system as a tool to monitor PrEP adherence in clinical settings.

Keywords: PrEP; adherence; bioequivalence; digital medicine; pharmacokinetics.

Conflict of interest statement

Study drug was donated by Gilead and the sensor was provided by Proteus. P.L.A. receives grant and contract funding from Gilead Sciences, paid to his institution. No competing financial interests exist.

Figures

FIG. 1.

Geometric mean concentration vs time plots of coencapsulated (●) and unencapsulated (□) TFV (left) and FTC (right). FTC, emtricitabine; TFV, tenofovir.