Protocol No: ECCT/19/11/05 Date of Protocol: 23-09-2019

Study Title:

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

Pilot trial to examine the feasibility, acceptability and impact on longer-term adherence of an intervention using a new urine-based tenofovir adherence assay

 

N/A

Study Objectives:

Aim #1:           To perform a pilot randomized controlled trial (RCT) in Kenya to establish the impact of real-time adherence monitoring/feedback via the urine POC TFV immunoassay on increasing PrEP adherence over time (as established by a long-term metric of adherence using hair levels).

Aim #2:           To assess acceptability of the urine-based test to participants and feasibility administering the test for research healthcare providers.  Specifically, we seek to understand user and provider experiences, preferences, barriers, and facilitators related to POC urine tenofovir adherence testing among women receiving PrEP and providers after the pilot trial.

 

1 To perform a pilot randomized controlled trial (RCT) in Kenya to assess the acceptability of the urine POC TFV assay to participants, the feasibility of administering the test for providers, and the impact of real-time adherence monitoring/feedback via the POC test on increasing PrEP adherence over time (as established by a long-term metric of adherence using hair levels).
Laymans Summary:

Pre-exposure prophylaxis (PrEP) with oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) prevents HIV infection if taken every day. However, previous PrEP trials demonstrated that many women in Africa at risk for HIV who are not in couples (with an HIV-positive partner) need help remembering to take the pill every day.  Also, patients on PrEP may not always report their adherence to the pill accurately and “objective” measures of adherence (where PrEP drug levels were measured) are far superior to self-report. We also know that telling a patient his/her PrEP drug levels can be motivating for better adherence in the future. The usual ways to measure PrEP drug levels are very complicated and require expensive equipment and trained laboratory staff. However, our group has now developed a new and innovative way to measure adherence to PrEP using a drug level (specifically tenofovir, TFV) via an antibody-based test (“immunoassay”) in urine that can be performed cheaply at the point-of-care (POC) by any healthcare worker (like a urine pregnancy test). A few drops of the patient’s urine is dropped into the test and tells the provider “yes” or “no” if the patient has been taking PrEP recently. This protocol is for a pilot trial where we randomize women on PrEP (who are not in serodiscordant couples) at Thika Clinic to having information from the urine assay delivered to them (or not delivered to them in the control group) in order to provide feedback on adherence from this test in a supportive, motivating manner and enhance adherence counseling. The pilot trial will assess if the urine tool is acceptable to participants, feasible for the clinic to perform, and if providing feedback on adherence from the urine tool to the participant increases future adherence to PrEP (measured by a longer-term adherence metric with hair levels). Good adherence to PrEP will eventually lead to fewer HIV infections worldwide.

 

1 Pre-exposure prophylaxis (PrEP) with oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) prevents HIV infection if taken every day. However, previous PrEP trials demonstrated that many women in Africa at risk for HIV who are not in couples (with an HIV-positive partner) need help remembering to take the pill every day. Also, patients on PrEP may not always report their adherence to the pill accurately and “objective” measures of adherence (where PrEP drug levels were measured) are far superior to self-report. We have reason to believe that telling a patient his/her PrEP drug levels, and subsequent counseling on adherence, can motivate better adherence in the future. The usual ways to measure PrEP drug levels are very complicated and require expensive equipment and trained laboratory staff. However, our group has now developed a new and innovative way to measure adherence to PrEP (specifically tenofovir, TFV) via an antibody-based test (“immunoassay”) in urine that can be performed cheaply at the point-of-care (POC) by any healthcare worker (like a urine pregnancy test). A few drops of the patient’s urine is dropped into the test and tells the provider “yes” or “no” if the patient has been taking PrEP recently. This protocol is for a pilot trial where we randomize women on PrEP (who are not in serodiscordant couples) at Thika Clinic to having information from the urine assay delivered to them (or not delivered to them in the control group) in order to provide feedback on adherence from this test in a supportive, motivating manner and enhance adherence counseling. The pilot trial will assess if the urine tool is acceptable to participants, feasible for the clinic to perform, and if providing feedback on adherence from the urine tool to the participant increases future adherence to PrEP (measured by a longer-term adherence metric with hair levels). Good adherence to PrEP will eventually lead to fewer HIV infections worldwide.
Abstract of Study:

Study Summary

Worldwide expansion of pre-exposure prophylaxis (PrEP) will be critical to ending the HIV epidemic. The original PrEP clinical trials showed us that 1) adherence is critical to effectiveness; 2) daily PrEP adherence was difficult to maintain, especially among women not in serodiscordant relationships; 3) objective adherence measures (e.g. measuring PrEP drug levels) are more reliable than self-reported adherence; and 4) real-time monitoring of PrEP drug levels with feedback to the patient could improve subsequent adherence. Objective measures of PrEP adherence, especially point-of-care measures that enable real-time assessment, intervention and feedback, will be important for both interpreting and optimizing effectiveness during PrEP implementation. Our group has developed a novel point of care urine-based measure of PrEP adherence which has been validated among HIV-uninfected volunteers who were administered TDF/FTC.1-4The test has now been developed into a lateral flow assay (LFA), allowing real-time monitoring.4This test is cheap, easy to perform and can be done at the point-of-care. However, this tool has not yet been tested among participants on PrEP in a trial to see if real-time monitoring of adherence using the urine assay is feasible, acceptable and motivates better adherence in the future.  

 

Pharmacologic measures of adherence to TDF/FTC-based PrEP, where tenofovir (TFV) drug levels are measured in a matrix such as plasma,5dried blood spots (DBS),6or hair (studied extensively as an adherence metric by our group)7-47capture drug ingestion and predict outcomes more accurately than self-reported adherence.12-14,16,18,19Pharmacologic adherence monitoring is especially important in PrEP, where a surrogate biomarker of response (e.g. HIV viral loads during HIV treatment) is not available. However, current methods to analyze PrEP drug levels in any matrix, including easily accessible urine,48require liquid chromatography-tandem mass spectrometry (LC-MS/MS), which cannot be performed in real-time because expensive equipment and trained laboratory staff are needed. Antibody-based tests allow for point-of-care testing.

 

The UCSF Hair Analytical Laboratory (directed by Dr. Monica Gandhi) has now developed a collaboration with Alere™ (recently bought by Abbott Rapid Diagnostics), a company with vast expertise in point-of-care (POC) diagnostics, to develop one of the first immunoassays that detects TFV in urine. The test is sensitive, specific, precise, and quantitates TFV levels in urine as accurately as LC-MS/MS,1,2,4allowing for low-cost (<$2.00 per test) POC adherence monitoring. The first iteration of the lateral flow immunoassay (LFA) has been developed4and allows for real-time testing, giving the provider qualitative yes/no information on recent adherence to PrEP. This novel POC adherence assay has the potential to address key knowledge gaps in PrEP implementation to both interpret and improve adherence.

 

1

Worldwide expansion of pre-exposure prophylaxis (PrEP) will be critical to ending the HIV epidemic. The original PrEP clinical trials showed us that 1) adherence is critical to effectiveness; 2) daily PrEP adherence was difficult to maintain, especially among women not in serodiscordant relationships; 3) objective adherence measures (e.g. measuring PrEP drug levels) are more reliable than self-reported adherence; and 4) real-time monitoring of PrEP drug levels with feedback to the patient could improve subsequent adherence. Objective measures of PrEP adherence, especially point-of-care measures that enable real-time assessment, intervention and feedback, will be important for both interpreting and optimizing effectiveness during PrEP implementation. Our group has developed a novel point of care urine-based measure of PrEP adherence which has been validated among HIV-uninfected volunteers who were administered TDF/FTC. 1-5The test has now been developed into a lateral flow assay (LFA), allowing real-time monitoring.4This test is cheap, easy to perform and can be done at the point-of-care. However, this tool has not yet been tested among participants on PrEP in a trial to see if real-time monitoring of adherence using the urine assay is feasible, acceptable and motivates better adherence in the future.  

 

Pharmacologic measures of adherence to TDF/FTC-based PrEP, where tenofovir (TFV) drug levels are measured in a matrix such as plasma, 6dried blood spots (DBS), 7or hair (studied extensively as an adherence metric by our group) 8-48capture drug ingestion and predict outcomes more accurately than self-reported adherence. 13-15,17,19,20 Pharmacologic adherence monitoring is especially important in PrEP, where a surrogate biomarker of response (e.g. HIV viral loads during HIV treatment) is not available. However, current methods to analyze PrEP drug levels in any matrix, including easily accessible urine,49require liquid chromatography-tandem mass spectrometry (LC-MS/MS), which cannot be performed in real-time because expensive equipment and trained laboratory staff are needed. Antibody-based tests allow for point-of-care testing.

 

The UCSF Hair Analytical Laboratory (directed by Dr. Monica Gandhi) has now developed a collaboration with Alere™ (recently bought by Abbott Rapid Diagnostics), a company with vast expertise in point-of-care (POC) diagnostics, to develop one of the first immunoassays that detects TFV in urine. The test is sensitive, specific, precise, and quantitates TFV levels in urine as accurately as LC-MS/MS,1,2,4or enzyme-linked immunoassay5allowing for low-cost POC adherence monitoring. The first iteration of the lateral flow immunoassay (LFA) has been developed4and allows for real-time testing, giving the provider qualitative yes/no information on recent adherence to PrEP. This novel POC adherence assay has the potential to address key knowledge gaps in PrEP implementation to both interpret and improve adherence.