ABSTRACT
BACKGROUND: QUANTI-TAF aimed to establish tenofovir-diphosphate/emtricitabine-triphosphate (TFV-DP/FTC-TP) adherence benchmarks in dried blood spots (DBS) for persons with HIV (PWH) receiving tenofovir alafenamide/emtricitabine (TAF/FTC)-based antiretroviral therapy (ART). METHODS: During a 16-week pharmacokinetic study, PWH received TAF/FTC-based ART co-encapsulated with an ingestible sensor to directly measure cumulative (enrollment to final visit) and 10-day adherence. At monthly visits, intraerythrocytic concentrations of TAF/FTC anabolites (TFV-DP/FTC-TP) in DBS were quantified by LC-MS/MS and summarized at steady-state (week 12 or 16) as median (IQR). Linear mixed-effects models evaluated factors associated with TFV-DP/FTC-TP. RESULTS: 84 participants (86% male, 11% female, and 4% transgender), predominantly receiving bictegravir/TAF/FTC (73%) enrolled. 92% completed week 12 or 16 (94% receiving unboosted ART). TFV-DP for <85% (7/72), ≥85%-<95% (9/72), and ≥95% (56/72) cumulative adherence was 2696 (2039-4108), 3117 (2332-3339), and 3344 (2605-4293) fmol/punches. All participants with ≥85% cumulative adherence had TFV-DP ≥1800 fmol/punches. Adjusting for cumulative adherence, TFV-DP was higher with boosted ART, lower BMI, and in non-Blacks. FTC-TP for <85% (14/77), ≥85%-<95% (6/77), and ≥95% (57/77) 10-day adherence was 3.52 (2.64-4.48), 4.58 (4.39-5.06), and 4.96 (4.21-6.26) pmol/punches. All participants with ≥85% 10-day adherence had FTC-TP ≥2.5 pmol/punches. Low-level viremia (HIV-1 RNA ≥20-<200 copies/mL) occurred at 60/335 (18%) visits in 33/84 (39%) participants (range: 20-149 copies/mL), with similar TFV-DP (3177 [2494-4149] fmol/punches) compared with HIV-1 RNA <20 copies/mL visits (3279 [2580-4407] fmol/punches). CONCLUSIONS: We propose PK-based TFV-DP (≥1800 fmol/punches)/FTC-TP (≥2.5 pmol/punches) benchmarks in DBS for PWH receiving unboosted TAF/FTC-based ART with ≥85% adherence. In the setting of high adherence, low-level viremia was common.
ABSTRACT
BACKGROUND: Medication nonadherence is a costly problem that is common in clinical use and clinical trials alike, with significant adverse consequences. Digital pill systems have proved to be effective and safe solutions to the challenges of nonadherence, with documented success in improving adherence and health outcomes. OBJECTIVE: The aim of this human factors validation study is to evaluate a novel digital pill system, the ID-Cap System from etectRx, for usability among patient users in a simulated real-world use environment. METHODS: A total of 17 patients with diverse backgrounds who regularly take oral prescription medications were recruited. After training and a period of training decay, the participants were asked to complete 12 patient-use scenarios during which errors or difficulties were logged. The participants were also interviewed about their experiences with the ID-Cap System. RESULTS: The participants ranged in age from 27 to 74 years (mean 51 years, SD 13.8 years), and they were heterogeneous in other demographic factors as well, such as education level, handedness, and sex. In this human factors validation study, the patient users completed 97.5% (196/201) of the total use scenarios successfully; 75.1% (151/201) were completed without any failures or errors. The participants found the ID-Cap System easy to use, and they were able to accurately and proficiently record ingestion events using the device. CONCLUSIONS: The participants demonstrated the ability to safely and effectively use the ID-Cap System for its intended use. The ID-Cap System has great potential as a useful tool for encouraging medication adherence and can be easily implemented by patient users.
ABSTRACT
Background: Nonadherence to prescribed medications is an important consideration in the clinical management of patients and in clinical research and drug development. The ID-Cap System is a novel technology that provides an objective measure of medication ingestion and enables real-time reporting of verified medication adherence data at the dose level. The ID-Cap System consists of an ingestible microsensor that is embedded in an oral dosage form and, once activated by stomach fluid, communicates digital messages to an external wearable reader to confirm ingestion. Objective: The objective of this exploratory study was to evaluate the performance, reliability, usability, and safety of the ID-Cap System for remote monitoring of 20 ingestion events over four weeks in 20 healthy volunteers. Design: This study was an open-label, single-arm, exploratory study of the ID-Cap System. The study design included the following three phases: 1) screening phase, 2) treatment phase consisting of 20 daily capsule ingestion events over a four-week period, and 3) follow-up phase consisting of a follow-up study visit that included an abdominal X-ray and a follow-up phone call. The initial use of the ID-Cap Reader and ingestion of the first study capsule were directly observed by the investigator during the first study visit. Subsequent study capsule ingestions were completed outside the research facility at the study participant's home or other location of his or her choice with ingestion assessed using the ID-Cap System. Setting: The study was conducted at a single clinical research site in Gainesville, Florida. Participants: Twenty healthy volunteers were enrolled in this four-week pilot study that was conducted between September and November 2014. Measurements: Study measurements included ID-Tag detection indicating capsule ingestion, utilization of the ID-Cap System consistent with instructions for use, adverse event reports, discontinuations of the System during the study, and safety assessments related to excretion of the ID-Tags through abdominal X-ray evaluations. Results: Positive detection accuracy was 100 percent for the 20 directly observed ingestions of study capsules that occurred during the initial study visits. Of the 384 ingestion events that were self-administered by the study participants without direct observation, 371 were accurately detected using the ID-Cap System. Overall adherence to the prescribed study capsules as measured by the ID-Cap System was 97.75 percent (391 detections/400 expected ingestion events). Significant intra-individual and inter-individual variability in the timing of self-administered doses was observed in this study. No adverse events were reported, and no study participants discontinued use of the ID-Cap System for any reason during the study. There was no evidence indicating retention of ID-Tags based on abdominal X-ray evaluations. Conclusion: The ID-Cap System enables accurate measurement of medication adherence for oral drug therapy at the dose level. This study supports the clinical validation of the technology and feasibility in using the system for the collection and real-time reporting of medication adherence in the clinical management of patients and in clinical research and drug development.
