Establishing Novel Antiretroviral Imaging for Hair to Elucidate Non-Adherence (ENLIGHTEN)

This study is part of a larger research program that is investigating a novel non-invasive approach to rapidly quantify ARV concentrations and provide evidence of drug ingestion. The ultimate goal is to provide clinicians and patients feedback on ARV adherence. Infra-red (IR) matrix-assisted laser desorption electrospray ionization (MALDESI) technology for mass spectrometry imaging (MSI) is used to visualize and quantify ARV concentrations in hair. The IR-MALDESI MSI has been labeled the "MedViewer".

Patient participants will be scheduled for the sampling visit to correspond with their next appointment at the University of North Carolina (UNC) Infectious Disease (ID) clinic. Patient participants will be asked to arrive to their clinic appointment at least two hours prior to the scheduled time to be consented and enrolled. If eligible and enrolled in the study, patient participants will have a small hair sample (5 strands) plucked from a discrete location on the back of their head. Patient participants will also have a small blood sample collected. The results from the MedViewer test will be provided to both the patient and their provider, in order to facilitate a discussion around medication adherence. After receiving the results, all participants will complete a brief questionnaire about their experience with the MedViewer.

As this is a feasibility study, results from the Medviewer test will not be used to make clinical decisions related to care.

Major changes after the start of enrollment:

• Removed the term "real-time" throughout the document-Pertinent feasibility endpoints now use "delivery of the report to the designated research staff member within 2 hours of initiation of hair processing" rather than "…within 2 hours of hair sample collection"
• Removed mitra sampling for the remaining 15 participants in cohort A. Now stated as "blood sample will be collected for 10 participants in Group A and a subset of participants in Group B." After Mitra is analyzed for the first 10 participants in Group B, we will reevaluate to determine if additional samples are needed to validate hair samples.
• V1 and V2 study activities will be conducted virtually (except hair collection and in-person patient provider clinic visits) to minimize in-person contact. Consent and screening will be conducted virtually using videoconferencing via zoom on computer, tablet or phone. All questionnaires (patient baseline, patient post-visit, patient endline, provider baseline, provider post-visit, and provider endline) will be conducted virtually through REDCap (emailed to participant or verbally administered via phone or videoconferencing). Hair collection will be conducted by research staff at remote locations to limit time in clinic. Implementation of the intervention will now be allowed in the setting of telehealth clinical visits between patient and provider in addition to in-person clinical visits. MedViewer reports will be sent to providers via secure email. All remaining V2s will be conducted virtually. Hair and blood samples will not be collected.
• Consenting will take place up to 3 days before scheduled clinic appointment with provider. Hair sample will be collected by research staff at a remote location in the 3 days between consent and the scheduled provider visit. MedViewer report will be discussed between patient and provider (or patient and pharmacist, if needed) within 4 weeks of hair sample collection.
• Interviewer-administered portions of the baseline questionnaire have been modified. Health Literacy measure (Newest Vital Sign) removed. ART adherence Visual Analog Scale modified to allow for remote self-administration.
• Maximum duration on study extended by 6 months for providers (increased from 10 to 16 months). Provider sample size range reduced (from 20-30 to 16-30)

These changes were implemented on November 5, 2020 in a Letter of Amendment (LOA) to ENLIGHTEN Protocol Version 2. The LOA detailed changes made to the protocol due to the COVID-19 Pandemic.

Inclusion criteria

Patient participants:

• Documentation of HIV-1 infection by means of any one of the following:

• Documentation of HIV diagnosis in the medical record by a licensed health care provider;
• OR HIV-1 RNA detection by a licensed HIV-1 RNA test demonstrating >1000 RNA copies/mL;
• OR any licensed HIV screening antibody and/or HIV antibody/antigen combination test confirmed by a second licensed HIV test such as a HIV-1 Western blot confirmation or HIV rapid Multispot antibody differentiation test.
• At least 18 years of age on the day of consent.
• Documentation of HIV viral loads over 2-year period prior to screening.
• Has been a patient at the UNC ID clinic for at least 90 consecutive days prior to the date of enrollment in the study (i.e. attended first appointment at the UNC ID Clinic at least 90 days prior to the date of enrollment in the study).
• Has attended at least one HIV appointment at the UNC ID clinic within the 365 days prior to the date of enrollment in the study.
• Has been prescribed one of the ARV medications eligible in this study (Dolutegravir, Emtricitabine) by a UNC provider for at least 90 days prior to the date of enrollment in the study.
• Has an HIV appointment scheduled at the UNC ID clinic during the enrollment period of the study with a medical provider enrolled in the study.
• Evidence of a personally signed and dated informed consent form indicating that the participant has been informed of all pertinent aspects of the study.
• Has stated willingness and availability to comply with all study procedures for the duration of the study.
• Literate in English.
• Has at least 1.0 cm of natural caput hair.
• As enrollment will occur in a stratified manner based on 2 viral load strata, (n = 25 for patients with undetectable viral loads, n = 25 for those with detectable viral loads), once a stratum quota is reached, patients whose viral loads fall within that stratum will not be eligible to participate in the study.

Provider participants:

• Medical provider (including, but not limited to: attending physician, ID fellow, nurse practitioner, physician assistant, or a designated HIV Care pharmacist) for UNC ID clinic patients living with HIV.
• Provides medical care for patients at the UNC ID clinic at least one half-day per week (i.e. 4 hours per week).
• Evidence of a personally signed and dated informed consent form indicating that the participant has been informed of all pertinent aspects of the study.
• Has stated willingness and availability to comply with all study procedures for the duration of the study.

Exclusion criteria

Patient participants:

• Previous participation in the study UNC 11530- Formative Sub-Study for Novel Mass Spectrometry Imaging Methods to Quantify Antiretroviral Adherence.
• Deemed, by medical provider in UNC ID clinic, too ill, or other relevant reason, to participate in the study.
• Prior history of clinically significant alteration of the gastrointestinal system or drug absorption capability, including but not limited to: gastrectomy, total colectomy
• Any chemical hair treatment with dye, bleach, or relaxers within the past 4 weeks prior to sampling

Provider participants:

• Not willing or able to participate in any of the provider training sessions for this study or any form of make-up training session with research team.