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Mass Spectrometry Imaging of Hair Identifies Daily Maraviroc Adherence in HPTN 069/ACTG A5305

View ORCID ProfileElias P. Rosen, Nicole White, William M. Gilliland Jr, Roy R. Gerona, Monica Gandhi, K. Rivet Amico, Kenneth H. Mayer, Roy M. Gulick, View ORCID ProfileAngela DM Kashuba
doi: https://doi.org/10.1101/2023.01.30.526384
Elias P. Rosen
aEshelman School of Pharmacy, University of North Carolina at Chapel Hill at Chapel Hill; Chapel Hill, North Carolina, United States
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  • For correspondence: eli@unc.edu
Nicole White
aEshelman School of Pharmacy, University of North Carolina at Chapel Hill at Chapel Hill; Chapel Hill, North Carolina, United States
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William M. Gilliland Jr
bDepartment of Chemistry, Furman University; Greenville, South Carolina, United States
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Roy R. Gerona
cDepartment of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco; San Francisco, CA, United States
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Monica Gandhi
dDepartment of Medicine, University of California San Francisco; San Francisco, California, United States
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K. Rivet Amico
eSchool of Public Health, University of Michigan; Ann Arbor, Michigan, United States
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Kenneth H. Mayer
fFenway Health, Department of Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School; Boston, Massachusetts, United States
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Roy M. Gulick
gWeill Cornell Medicine; New York, New York, United States
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Angela DM Kashuba
aEshelman School of Pharmacy, University of North Carolina at Chapel Hill at Chapel Hill; Chapel Hill, North Carolina, United States
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  • ORCID record for Angela DM Kashuba
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Abstract

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). 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 49-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.

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Posted February 02, 2023.
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Mass Spectrometry Imaging of Hair Identifies Daily Maraviroc Adherence in HPTN 069/ACTG A5305
Elias P. Rosen, Nicole White, William M. Gilliland Jr, Roy R. Gerona, Monica Gandhi, K. Rivet Amico, Kenneth H. Mayer, Roy M. Gulick, Angela DM Kashuba
bioRxiv 2023.01.30.526384; doi: https://doi.org/10.1101/2023.01.30.526384
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Mass Spectrometry Imaging of Hair Identifies Daily Maraviroc Adherence in HPTN 069/ACTG A5305
Elias P. Rosen, Nicole White, William M. Gilliland Jr, Roy R. Gerona, Monica Gandhi, K. Rivet Amico, Kenneth H. Mayer, Roy M. Gulick, Angela DM Kashuba
bioRxiv 2023.01.30.526384; doi: https://doi.org/10.1101/2023.01.30.526384

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