# Novel Mass Spectrometry Imaging Methods to Quantify Antiretroviral Adherence

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $749,632

## Abstract

Adherence to antiretroviral (ARV) therapy is critical for achieving HIV RNA suppression in HIV- infected
patients and for preventing HIV acquisition in uninfected individuals using pre-exposure prophylaxis (PrEP).
Yet a high level of adherence is challenging for HIV-infected individuals on life-long ARVs, and for
HIVnegative individuals using daily PrEP who are not at daily risk for HIV acquisition. Poor adherence was
primarily responsible for a lack of drug effectiveness in multiple recent double-blind, placebo-controlled PrEP
studies. These studies found that counting product returns and using patient self-report significantly over
predicted adherence as measured by ARV concentrations in blood plasma or cells. Since the consequences
of poor or intermittent adherence are significant, valid measures of adherence are critical for optimizing the
effectiveness of both HIV treatment and prevention, in both the clinic and research settings. Blood plasma or
intracellular concentration monitoring have been considered the “gold standard” for determining if an ARV
has been ingested, and is a common marker for therapeutic drug monitoring or clinical trial adherence
monitoring. However, this approach has its own set of limitations, including being invasive, requiring
advanced processing or storage (e.g. intracellular measures), being a short-term measure of drug taking
behavior (depending on the half-life of the analyte), and requiring long turn-around times or substantial
sample processing prior to analysis. We propose the use of infra-red (IR) matrix-assisted laser desorption
electrospray ionization (MALDESI) technology for mass spectrometry imaging (MSI) to visualize and quantify
ARV concentrations in hair. Our hypothesis is that IR-MALDESI MSI can rapidly quantify ARV concentrations,
provide evidence of drug ingestion non-invasively and longitudinally, and allow for clinician/researcher and
patient/study participant feedback on adherence performance. Three specific aims are proposed: 1) Develop
IR-MALDESI MSI hair protocols for high sensitivity and accuracy to quantify 11 ARVs in 5 therapeutic drug
classes, 2) Conduct 3 structured dose proportionality studies to develop mathematical benchmarks for real-
time IR-MALDESI hair adherence monitoring in both PrEP and HIV treatment applications, and validate the
benchmarks with a Phase 2 PrEP study, and 3) In the setting of REAL TIME clinical monitoring, investigate
the acceptability, appropriateness, and feasibility of using hair IRMALDESI MSI to provide HIV+ patients with
feedback regarding longitudinal patterns of medication adherence. The goal of this work is to develop a
simple, noninvasive, longitudinal depiction of ARV adherence that will provide high clarity feedback for both
clinicians and patients.
RELEVANCE (See instructions):
It is important to identify if someone is taking a medication regularly and as prescribed to optimize their health
and wellbeing, but sometimes patients have trouble rememberi...

## Key facts

- **NIH application ID:** 10260722
- **Project number:** 4R01AI122319-06
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Angela D Kashuba
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $749,632
- **Award type:** 4C
- **Project period:** 2016-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10260722

## Citation

> US National Institutes of Health, RePORTER application 10260722, Novel Mass Spectrometry Imaging Methods to Quantify Antiretroviral Adherence (4R01AI122319-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10260722. Licensed CC0.

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