DOT Diary Mobile App for Pre-Exposure Prophylaxis Adherence in Young Men

Study Overview
=================
Brief Summary
-----------------
The researchers are working with a technology company, AiCure, to develop a smartphone app, DOT Diary, which combines two drug adherence strategies. DOT Diary reminds people when it is time to take their medication, and uses motion-sensing technology to visually and automatically confirm the pill was swallowed. The goal of this study is to assess the impact of the app on adherence to HIV pre-exposure prophylaxis (PrEP) for the prevention of HIV.

Detailed Description
-----------------
In the DOT Diary research project, the AiCure automated directly observed therapy (aDOT) smartphone app has been adapted for use in monitoring and supporting HIV pre-exposure prophylaxis (PrEP) use among young men who have sex with men (YMSM). The aDOT app uses automated directly observed therapy (DOT) that use the smartphone camera and artificial intelligence software to confirm that the right person is taking the right medication at the right time. A sexual diary has been integrated into the aDOT app to assist YMSM in understanding whether they are receiving protection from PrEP for individual sexual episodes, and when it is particularly important to take PrEP (e.g. after a sexual episode). Specifically, the sexual diary allows participants to track sexual encounters, sexual behaviors that occurred in each encounter, and rating characteristics of partners. The app provides a calendar displaying all days in which PrEP medication was taken, and all days in which sexual activity occurred, allowing participants to see coverage of sexual encounters with PrEP. Based on pharmacokinetic and pharmacodynamic data from prior PrEP trials, the app will also indicate the estimated level of protection achieved from PrEP (e.g. low, medium, high), and also provide personalized messages on the additional numbers of doses needed to maximize protection. In the next stage of app development and assessment, the researchers will conduct the DOT Diary Longitudinal Pilot to assess the impact of the app on PrEP adherence as measured by pharmacokinetic measures of PrEP use (tenofovir diphosphate [TFV-DP] and emtricitabine triphosphate [FTC-TP] levels in dried blood spots [DBS]). The researchers will also assess the concordance of TFV-DP and FTC-TP in DBS with adherence measured by DOT Diary, and the acceptability and ease of use of the app over a longer (24-week) period. This pilot study will allow evaluation and further refinement of the app in preparation for testing in a larger efficacy trial among YMSM at risk for HIV acquisition. The researchers will conduct this pilot protocol among YMSM in Atlanta and San Francisco Bay Area, two metropolitan regions heavily impacted by HIV, yet differing in sociodemographics, as well as in the availability and uptake of HIV prevention services, including PrEP. These diverse research locations will allow collection of data to inform app development among a broad group of YMSM.

Official Title
-----------------
DOT Diary Longitudinal Pilot: A Mobile App for Pre-Exposure Prophylaxis Adherence in Young Men

Conditions
-----------------
Adherence, Medication, Risk Behavior, Pre-Exposure Prophylaxis, HIV Prevention

Intervention / Treatment
-----------------
* Drug: Emtricitabine / Tenofovir Disoproxil Oral Tablet
* Other: DOT Diary mobile app


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Self-identifies as a man Age 18-35 at enrollment Reports having insertive or receptive anal sex with a man or trans woman in the past 12 months and one or more of the following criteria in the last 12 months: Any condomless anal sex outside of a mutually monogamous relationship with an HIV-negative partner Two or more anal sex partners Self-reported sexually transmitted infection (STI; gonorrhea, chlamydia, syphilis) Having a known HIV-positive sexual partner HIV-negative as determined by a negative 4th generation HIV test at screening and negative rapid 4th generation test at enrollment Willing to initiate PrEP Eligible to take PrEP Creatinine clearance ≥60 ml/min as estimated by Cockcroft-Gault equation at screening Hepatitis B surface antigen (HBsAg) negative Willing and able to provide written informed consent Able to read and speak English Smartphone ownership compatible with DOT Diary app Meets local locator requirements Lives, works or plays in Atlanta Metropolitan Area, San Francisco, Alameda, Marin, Contra Costa, Santa Clara, or San Mateo Counties Exclusion Criteria: PrEP use within the past 4 months (PrEP naive participants will be prioritized) Any reactive HIV test at screening or enrollment Signs or symptoms of acute HIV infection at screening or enrollment History of pathological bone fracture not related to trauma Taking nephrotoxic medications History of participation in the active arm of an HIV vaccine trial In a mutually monogamous sexual relationship with an HIV-negative partner for the past 12 months Unable to commit to study participation for 24 weeks Any medical, psychiatric, or social condition or other responsibilities that, in the judgment of the investigator, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
-----------------
All

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

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

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, controlled study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DOT Diary Intervention<br>DOT Diary mobile app and Emtricitabine / Tenofovir Disoproxil Oral Tablet (once daily) | Drug: Emtricitabine / Tenofovir Disoproxil Oral Tablet<br>* Open label daily emtricitabine/tenofovir disoproxil oral tablet<br>* Other names: Truvada;Other: DOT Diary mobile app<br>* DOT Diary mobile application for tracking medication adherence and sexual activities.<br>|
| Other: DOT Diary Control<br>Standard of care for Emtricitabine / Tenofovir Disoproxil Oral Tablet (once daily) | Drug: Emtricitabine / Tenofovir Disoproxil Oral Tablet<br>* Open label daily emtricitabine/tenofovir disoproxil oral tablet<br>* Other names: Truvada;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of DOT Diary app on PrEP adherence | Measurement of PrEP Adherence as measured by TFV-DP in DBS among young MSM initiating PrEP | 24 weeks | 
| Concordance of TFV-DP and FTC-TP in DBS with adherence measured by DOT Diary app | Validation of DOT will focus on concordance between aDOT-based assessments of PrEP adherence by the DOT Diary app with DBS measurements | 24 weeks | 
| DOT Diary mobile app acceptability | Combined descriptive analysis of key attributes of acceptability of DOT Diary over 24 weeks by YMSM on PrEP, in order to identify potential improvements to the app to maximize acceptability | 24 weeks | 
| DOT Diary mobile app ease of use | Combined descriptive analysis of key attributes of ease of use of DOT Diary over 24 weeks by YMSM on PrEP | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PrEP coverage of sexual acts (prevention-effectiveness adherence) as measured by DOT Diary | Combined analysis of the probability of coverage of condomless receptive sexual acts in each period with sexual acts treated as trials, and coverage as success. | 24 weeks | 
| Evaluation of daily use of aDOT components of DOT Diary app | Estimation of the average use of aDOT components, as proportion of days on study | 24 weeks | 
| Evaluation of use of diary components of DOT Diary app | Estimation of the average use of diary component of DOT Diary app as proportions of weeks on study. | 24 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Adherence, PrEP, HIV Prevention, Truvada, HIV Risk Reduction, Mobile App