Feasibility, Acceptability and Appropriateness of MedViewer: A Novel Hair-Based Antiretroviral Real-Time Clinical Monitoring Tool Providing Adherence Feedback to Patients and Their Providers.

Antiretroviral therapy (ART) adherence is key to achieving viral load suppression and ending the HIV epidemic but monitoring and supporting adherence using current interventions is challenging. We assessed the feasibility, acceptability and appropriateness of MedViewer (MV), a novel intervention that provides real-time adherence feedback for patients and providers using infra-red matrix-assisted laser desorption electrospray ionization (IR-MALDESI) for mass spectrometry imaging of daily ART concentrations in patients' hair. We used mixed methods to feasibility test MV at a busy Infectious Diseases (ID) clinic, enrolling 16 providers and 36 patients. Providers underwent standardized training; patients and providers watched an 8-min informational video about MV. We collected patient and provider data at baseline and within 24 h of clinic visits and, with patients, approximately 1 month after clinic visits. MedViewer was feasible, liked by patients and providers, and perceived to help facilitate adherence conversations and motivate patients to improve adherence. Trial Registration: NCT04232540.

Establishing Novel Antiretroviral Imaging for Hair to Elucidate Nonadherence: Protocol for a Single-Arm Cross-sectional Study.

BACKGROUND: Adherence to antiretroviral (ARV) therapy is critical for achieving HIV RNA suppression in people living with HIV and for preventing HIV infection in uninfected individuals using preexposure prophylaxis. However, a high level of adherence can be challenging to achieve for people living with HIV on lifelong ARVs and for HIV-negative individuals using daily preexposure prophylaxis who are not at daily risk for HIV infection. Current biological measures of adherence are invasive and use bioanalytical methods that do not allow for real-time feedback during a clinic visit. This study was designed to test the feasibility and acceptability of using MedViewer, a novel, minimally invasive, hair-based assay that measures longitudinal ARV drug adherence in real time and provides an output for provider-patient discussion. OBJECTIVE: The primary objectives were to investigate the feasibility of delivering the MedViewer results as planned, the acceptability of participation in a discussion of the MedViewer results, and the appropriateness of using MedViewer for adherence counseling. The secondary objectives were to investigate additional dimensions of feasibility, acceptability, and appropriateness of using the MedViewer test during a routine clinic visit for people with HIV. METHODS: The proposed study was a single-arm cross-sectional study among patients receiving HIV care and providers of HIV care in a southeastern infectious disease clinic. The study originally planned to implement the MedViewer test with 50 eligible patients who were living with HIV across 2 viral load strata (undetectable or detectable plasma HIV RNA over the previous 2 years), administer brief visit-specific questionnaires to all patient and provider participants, and conduct qualitative in-depth interviews and quantitative end-line questionnaires with a subsample of patient participants (n=30) and all provider participants. RESULTS: The Establishing Novel Antiretroviral Imaging for Hair to Elucidate Nonadherence study was funded by the National Institute of Allergy and Infectious Diseases and approved by the local institutional review board on November 4, 2019. Provider participant enrollment began on January 17, 2020, and patient participant enrollment began on January 22, 2020. Participant enrollment was halted on March 16, 2020, because of the COVID-19 pandemic (16 providers and 10 patients on study). Study activities resumed on February 2, 2021, with COVID-19 modifications approved by the local institutional review board. Participant enrollment closed on October 8, 2021, and data collection closed on November 15, 2021. In total, 36 unique patient participants, representing 37 samples, and 20 provider participants were enrolled. Data analysis and manuscript writing will take place throughout 2023. CONCLUSIONS: We anticipate that the data collected through this study will provide important insights regarding the feasibility, acceptability, and appropriateness of incorporating new real-time longitudinal, minimally invasive adherence tests into routine clinical care and identify potential barriers to medication adherence among patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04232540; https://clinicaltrials.gov/ct2/show/NCT04232540. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/41188.

A Novel Algorithm to Improve PrEP Adherence Monitoring Using Dried Blood Spots.

Tenofovir diphosphate (TFVdp; an active metabolite of oral HIV pre-exposure prophylaxis (PrEP)) is measured in dried blood spots (DBS) to estimate adherence. However, TFVdp's long half-life in whole blood may lead to misclassification following a recent change in adherence. PrEP's other metabolite, emtricitabine triphosphate (FTCtp), has a shorter half-life in whole blood but adherence thresholds are undefined. We characterized DBS TFVdp and FTCtp concentrations across many dosing scenarios. Population pharmacokinetic models were fit to TFVdp and FTCtp DBS concentrations from a directly observed therapy study (NCT03218592). Concentrations were simulated for 90 days of daily dosing followed by 90 days of 1 to 7 doses/week and for event-driven PrEP (edPrEP) scenarios. Thresholds of 1,000 and 200 fmol/punch, for TFVdp and FTCtp, respectively, were reflective of taking 4 doses/week (a minimum target for effective PrEP in men). TFVdp was < 1,000 fmol/punch for 17 days after initiating daily PrEP and > 1,000 fmol/punch for 62 days after decreasing to 3 doses/week. Respectively, FTCtp was < 200 fmol/punch for 4 days and > 200 fmol/punch for 6 days. Accuracy of edPrEP adherence classification depended on duration between last sex act and DBS sampling for both measures with misclassification ranging from 9-100%. These data demonstrate adherence misclassification by DBS TFVdp for 2 months following a decline in adherence, elucidating the need for FTCtp to estimate recent adherence. We provide proof of principle that individualized interpretation is needed to support edPrEP adherence monitoring. Our collective approach facilitates clinicians' ability to interpret DBS results and administer patient-centric interventions.

Mass Spectroscopy Imaging of Hair Strands Captures Short-Term and Long-Term Changes in Emtricitabine Adherence.

Most measures of adherence to antiretroviral therapy require a blood sample, and none capture longitudinal daily adherence. A new noninvasive method for measuring daily adherence to antiretroviral regimens containing emtricitabine (FTC) was developed for intact hair strands using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) mass spectrometry imaging (MSI). A directly observed therapy study of daily and intermittent (3, 1, and 0 doses/week) FTC dosing (n = 12) benchmarked adherence in hair, revealing distinct accumulation patterns and median FTC signal abundance (1,702, 495, 352, and 0, respectively) with each dosing frequency. A threshold value of FTCsignal abundance of 500 differentiated daily dosing from 3 or fewer doses/week (specificity, 100%; sensitivity, 100% over 30 days and 80% over 60 days). Using these criteria, daily FTC hair adherence was classified in young men (n = 8) who have sex with men (YMSM) engaged in or initiating preexposure prophylaxis (PrEP). Four types of adherence profiles were observed in sequential 30-day periods: consistently high, occasional missed doses, improvement following study initiation, and intermittent. Discrete days of nonadherence were identified across the 60-day window, with the average number of consecutive days classified as nonadherent increasing across the four profile types (1, 2, 19, and 58 days, respectively). Additionally, cumulative FTC response in hair (60-day average) significantly correlated with dried blood spot tenofovir diphosphate concentrations collected simultaneously (rs = 0.79, P = 0.03). Based on these data, IR-MALDESI FTC adherence classification in hair strands can better delineate short-term changes in adherence behaviors over a long retrospective window, offering great potential for noninvasive adherence monitoring and quick supportive interventions.

Infrared Matrix-Assisted Laser Desorption Electrospray Ionization Mass Spectrometry Imaging of Human Hair to Characterize Longitudinal Profiles of the Antiretroviral Maraviroc for Adherence Monitoring.

Here, we assess infrared matrix assisted laser desorption electrospray ionization (IR-MALDESI) mass spectrometry imaging (MSI) analysis of hair as a clinical tool for monitoring patient adherence to the antiretroviral maraviroc (MVC). A custom MATLAB-based algorithm has been developed to streamline data analysis and generate longitudinal profiles of drug incorporation along the length of hair strands. Hair strands from volunteers enrolled in a directly observed therapy study were analyzed by IR-MALDESI MSI and processed using this tool to characterize the profiles of single doses and a daily dose regimen of MVC. Single dose responses were 1.7 [1.1, 2.5] mm (median [range]) wide along the length of the hair and were detected in 8 out of 12 volunteers. Daily dose profiles capturing 28 days of continuous dosing were approximately 5 times the intensity of single dose profiles and 10.5 [7.0, 13] mm wide, corresponding to 1 month of hair growth. MVC ion abundance was observed in all 12 volunteers for the daily dosing period. Daily dosing profiles were consistent with a model of MVC accumulation in hair based on linear superposition of a single dose response, indicating the potential for prediction of daily drug-taking behavior based on deconvolution of a complex longitudinal profile in hair.

Decreased Tenofovir Diphosphate Concentrations in a Transgender Female Cohort: Implications for Human Immunodeficiency Virus Preexposure Prophylaxis.

Feminizing hormone therapy (FHT) may interact with human immunodeficiency virus preexposure prophylaxis (PrEP). We found that transgender women who took FHT exhibited a 7-fold lower rectal tissue ratio of PrEP's active metabolites vs competing deoxynucleotides compared to cisgender women and men (P = .03) that inversely correlated with estradiol (ρ = -0.79; P < .05). Thus, FHT may negatively impact PrEP efficacy. Clinical Trials Registration . NCT02983110.