Point-of-care Urine Monitoring of Adherence (PUMA): Testing a Real-Time Urine Assay of Tenofovir in PrEP

Study Overview
=================
Brief Summary
-----------------
Worldwide expansion of pre-exposure prophylaxis (PrEP) with oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) will be critical to ending the HIV epidemic. However, maintaining daily adherence to PrEP can be difficult and the accuracy of self-reported adherence is often limited by social desirability bias. Pharmacologic adherence monitoring (measuring drug levels in a biomatrix) has been critical to the interpretation of the PrEP trials, but testing usually requires expensive equipment and skilled personnel. We have recently developed a point-of-care (POC) immunoassay to measure tenofovir in urine, allowing real-time adherence monitoring for the first time. We now want to test the acceptability, feasibility and preliminary impact of monitoring adherence in real-time using this novel POC assay with adherence feedback provided to the patient with supportive messaging (versus standard of care adherence counseling).

Detailed Description
-----------------
The study is a pilot randomized trial to test the acceptability to participants, feasibility for providers, and impact on long-term metric of adherence among participants (assessed via tenofovir hair levels) of implementing a POC urine tenofovir test to provide real-time adherence feedback and enhanced adherence counseling among women on PrEP in Thika, Kenya. Eligible women (n=100) will be HIV-negative, ≥18 years old, and on PrEP. Participants will be randomized 1:1 to the intervention of providing real-time feedback via the urine assay versus standard-of-care adherence counseling. Acceptability will be assessed by a quantitative survey of participants at the end of the study, as well as by qualitative data collected via in-depth interviews (n=20) and focus group discussions (n=4 groups of 5-10 women each). Feasibility will be assessed by the proportion of women retained in the study, the mean number of missed visits, the proportion of planned urine assessments completed and messages delivered, while in-depth interviews with providers will explore the ease of administering the urine test. Tenofovir levels in hair serve as the long-term metric of adherence. Feasibility outcome: The investigators will assess the feasibility of the intervention by interviewing health care providers, who will be administering this test at the clinical point of care in the future. The investigators will examine provider perceptions of the assay using in-depth interviews. These key informant interviews will be performed at the end of this study with the healthcare providers (up to 8) who delivered the counseling messages to intervention arm participants after performing the POC urine TFV test. The semi-structured interview guide will draw from the Unified Theory of Acceptance and Use of Technology (UTAUT) model.200 This model incorporates factors that influence technology acceptance (in this case, of the POC immunoassay): perceived usefulness (performance expectancy), complexity to use (effort expectancy), stigma/social harm (social influence), and benefits (facilitating PrEP adherence among patients). These interviews will also elicit barriers and facilitators to delivering the TFV assay-informed counseling messages. Acceptability outcome: The investigators will conduct a mixed-methods assessment of the intervention arm participants' experiences with real-time monitoring and feedback at the end of the study. A quantitative survey and a qualitative interview guide for in-depth interviews of participants will draw from the Information-Motivation-Behavioral skills (IMB) model.205-212 Quantitative data collection will occur via standardized interviewer-administered questionnaires. Items to be assessed include the following: 1) Feelings about receiving their PrEP adherence results in real time; 2) Likelihood of participating in other studies using a similar design; 3) Likelihood of wanting to receive results of urine testing outside of a study while they are on PrEP; 4) Concern about the privacy and security of the data regarding their urine results; 5) Grading of the potential impact of knowing their urine TFV results on subsequent medication adherence; 6) Advantages and disadvantages of being told about their adherence in real time; 7) Likelihood of taking PrEP just before later study visits because they knew the urine test was being conducted; 8) Preferences regarding a yes/no assay versus an assay that provides information on high, moderate or low adherence. A 5-point Likert item format will be used to assess graded items (such as the likelihood of wanting continued urine testing in the context of PrEP; feelings about the urine testing, ranging from negative to positive; concerns about privacy, ranging from low to high; the potential impact of real-time feedback on subsequent adherence, ranging from low to high). Other items (advantages and disadvantages of being told about adherence results) will provide pre-specified options with one other option for open-ended text fields. Adherence outcome: A linear mixed effects linear regression model will estimate the effect of the intervention versus standard-of-care on logarithmically transformed levels of tenofovir in hair.

Official Title
-----------------
Pilot Trial to Examine the Feasibility, Acceptability and Impact of an Intervention Using a New Urine-based Tenofovir Adherence Assay

Conditions
-----------------
Risk Reduction

Intervention / Treatment
-----------------
* Behavioral: PUMA


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female Adult, age ≥18 years old HIV-1 uninfected based on a negative HIV-1 rapid test Not currently enrolled in an HIV-1 prevention clinical trial Not currently in a sero-discordant relationship Already taking PrEP and will be enrolled at the 3-month follow-up visit following PrEP initiation Willing to be randomized to point-of-care tenofovir drug testing Willing/able to provide informed consent to participate in the study No contraindication to use of TDF or FTC Note: Women who are pregnant or breast feeding at screening/enrollment are still eligible Exclusion Criteria: HIV positive women under 18 years old

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Pilot Randomized Trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention Arm<br>POC adherence testing by a urine TFV assay with feedback | Behavioral: PUMA<br>* Collect urine on intervention participants and screen for presence of TFV. Feedback will be provided to the participant based on the results on their adherence with provision of standard adherence counseling.<br>|
| No Intervention: Standard of Care<br>Follow Kenya's PrEP guidelines on standard adherence counselling | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acceptability of POC urine tenofovir testing among participants | Quantitative surveys and qualitative interviews of participants | 12 months | 
| Feasibility among healthcare providers of providing test feedback to participants | Interviews of health care providers | 12 months | 
| Long-term adherence metrics via hair concentrations of TFV and FTC | Measure TFV and FTC levels in hair samples | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
PrEP, women, Kenya, adherence, POC monitoring, urine test,TDF, immunoassay