LAUSR

We investigated the use of a system with an ingestible sensor (Proteus Digital Health Feedback system) co-encapsulated with antiretrovirals (ARVs) to measure real-time adherence. To assess the safety and impact, if any, co-encapsulation might have on ARV concentrations, we evaluated the pharmacokinetics of ARVs co-encapsulated with an ingestible sensor for eight commonly used fixed-dose combination ARVs: emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF); FTC/tenofovir alafenamide (TAF); efavirenz (EFV)/FTC/TDF; abacavir (ABC)/lamivudine (3TC); dolutegravir (DTG)/ABC/3TC; rilpivirine (RPV)/TAF/FTC; elvitegravir (EVG)/cobicistat (COBI)/FTC/TAF; and bictegravir (BIC)/FTC/TAF. The steady-state apparent peak plasma concentration (Cmax) and area under the curve (AUC) were determined from plasma concentrations measured at pre-dose, 1, 2, 4 and 6 hours post dose, and compared with literature values. A total of 49 unique patients on stable regimens for at least 12 weeks with undetectable viral loads were recruited. Cmax and AUC values were not statistically significant different from literature values for all of the formulations except the Cmax of FTC/TDF, Cmax of BIC, and the Cmax of RPV. In a subsequent evaluation of FTC/TDF and BIC/FTC/TAF using a crossover design, the geometric mean ratio (GMR) between the co-encapsulated and the un-encapsulated formulations for FTC/TDF were: FTC, 84.6% (90% CI 66.6%-107.4%) for AUC and 77.5% (60.1%-99.9%) for Cmax. For tenofovir (TFV) the GMR was 96.2% (90% CI 89.2%-103.8%) for AUC and 87.3% (64.2%-118.7%) for Cmax. The GMR for BIC (from the BIC/FTC/TAF formulation) was 98.0% (90% CI 84.5%-113.5%) for AUC and 89.9% (84.5%-95.7%) for Cmax. The observed deviation in FTC/TDF (Truvada) may be due to participant characteristics, fasted/fed conditions, and/or random variation and may warrant further investigations with a larger sample size. These findings provide assurance for use of co-encapsulated ARVs for future HIV treatment-adherence research.