Pharmacokinetics of Coencapsulated Antiretrovirals with Ingestible Sensors

Honghu Liu, Eric Daar, Yan Wang, Lisa Siqueiros, Kayla Campbell, Jie Shen, Mario Guerrero, Meng Wei Ko, Di Xiong, John Dao, Todd Young, Marc Rosen, Courtney V. Fletcher

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

We investigated the use of a system with an ingestible sensor (Proteus Digital Health Feedback system) coencapsulated with antiretrovirals (ARVs) to measure real-Time adherence. To assess the safety and impact, if any, coencapsulation might have on ARV concentrations, we evaluated the pharmacokinetics of ARVs coencapsulated 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 concentration-Time curve (AUC) were determined from plasma concentrations measured at predose, 1, 2, 4, and 6 h postdose, 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 significantly 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 coencapsulated and the unencapsulated formulations for FTC/TDF were the following: FTC, 84.6% (90% confidence interval [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 coencapsulated ARVs for future HIV treatment-Adherence research.

Original languageEnglish (US)
Pages (from-to)65-74
Number of pages10
JournalAIDS Research and Human Retroviruses
Volume36
Issue number1
DOIs
StatePublished - Jan 2020

Keywords

  • adherence
  • antiretroviral medication
  • bioavailability
  • coencapsulated ARV
  • ingestible sensor
  • pharmacokinetics

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Pharmacokinetics of Coencapsulated Antiretrovirals with Ingestible Sensors'. Together they form a unique fingerprint.

Cite this