Mass spectrometry imaging of hair identifies daily maraviroc adherence in HPTN 069/ACTG A5305.

Autor: Rosen EP; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill at Chapel Hill, Chapel Hill, North Carolina, United States of America., White N; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill at Chapel Hill, Chapel Hill, North Carolina, United States of America., Gilliland WM Jr; Department of Chemistry, Furman University, Greenville, South Carolina, United States of America., Gerona RR; Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, California, United States of America., Gandhi M; Department of Medicine, University of California San Francisco, San Francisco, California, United States of America., Amico KR; School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America., Mayer KH; Fenway Health, Department of Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts, United States of America., Gulick RM; Weill Cornell Medicine, New York, New York, United States of America., Kashuba ADM; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2023 Jun 23; Vol. 18 (6), pp. e0287449. Date of Electronic Publication: 2023 Jun 23 (Print Publication: 2023).
DOI: 10.1371/journal.pone.0287449
Abstrakt: Objective measures of adherence for antiretrovirals used as pre-exposure prophylaxis (PrEP) are critical for improving preventative efficacy in both clinical trials and real-world application. Current objective adherence measures either reflect only recent behavior (eg days for plasma or urine) or cumulative behavior (eg months for dried blood spots). Here, we measured the accumulation of the antiretroviral drug maraviroc (MVC) in hair strands by infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) mass spectrometry imaging (MSI) to evaluate adherence behavior longitudinally at high temporal resolution. An MSI threshold for classifying daily adherence was established using clinical samples from healthy volunteers following directly observed dosing of 1 to 7 doses MVC/week. We then used the benchmarked MSI assay to classify adherence to MVC-based PrEP regimens in hair samples collected throughout the 48-week HPTN069/ACTGA5305 study. We found that only ~32% of investigated hair samples collected during the study's active dosing period showed consistent daily PrEP adherence throughout a retrospective period of 30 days, and also found that profiles of daily individual adherence from MSI hair analysis could identify when patients were and were not taking study drug. The assessment of adherence from MSI hair strand analysis was 62% lower than adherence classified using paired plasma samples, the latter of which may be influenced by white-coat adherence. These findings demonstrate the ability of MSI hair analysis to examine daily variability of adherence behavior over a longer-term measurement and offer the potential for longitudinal comparison with risk behavior to target patient-specific adherence interventions and improve outcomes.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Rosen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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