Background The worldwide expansion of preexposure prophylaxis (PrEP) with oral tenofovir-disoproxil-fumarate/emtricitabine 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 interpreting 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. Objective The goal of this study is to examine a point-of-care adherence metric in PrEP to support and increase adherence via a randomized controlled trial. Methods The paper describes the protocol for a pilot randomized controlled trial to test the acceptability, feasibility, and impact on long-term adherence of implementing a POC urine test to provide real-time adherence feedback among women on PrEP. Eligible women (n=100) will be HIV-negative, ≥18 years old, and recruited from a clinic in Kenya that provides PrEP. Participants will be randomized 1:1 to the intervention of providing real-time feedback via the assay versus standard of care adherence counseling. Acceptability by participants will be assessed by a quantitative survey, as well as by qualitative data collected via in-depth interviews (n=20) and focus group discussions (n=4 groups, 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 (n=8) will explore the ease of administering the urine test. Tenofovir levels in hair will serve as long-term adherence metrics. A linear mixed-effects model will estimate the effect of the intervention versus standard of care on logarithmically transformed levels of tenofovir in hair. Results This study has been funded by the National Institute of Health, approved by the Kenya Medical Research Institute Institutional Review Board, and will commence in June 2020. Conclusions A novel urine assay to measure and deliver information on adherence to PrEP in real-time will be tested for the first time in this trial planned among women on PrEP in Kenya. Study findings will inform a larger-scale trial assessing the impact of real-time adherence monitoring/feedback on HIV prevention. Improving adherence to PrEP will have long-term implications for efforts to end the HIV epidemic worldwide. Trial Registration ClinicalTrials.gov NCT03935464; https://clinicaltrials.gov/ct2/show/NCT03935464 International Registered Report Identifier (IRRID) PRR1-10.2196/15029

BackgroundMental disorders are a leading cause of global disability, driven primarily by depression and anxiety. Most of the disease burden is in Low and Middle Income Countries (LMICs), where 75% of adults with mental disorders have no service access. Our research team has worked in western Kenya for nearly ten years. Primary care populations in Kenya have high prevalence of Major Depressive Disorder (MDD) and Posttraumatic Stress Disorder (PTSD). To address these treatment needs with a sustainable, scalable mental health care strategy, we are partnering with local and national mental health stakeholders in Kenya and Uganda to identify 1) evidence-based strategies for first-line and second-line treatment delivered by non-specialists integrated with primary care, 2) investigate presumed mediators of treatment outcome and 3) determine patient-level moderators of treatment effect to inform personalized, resource-efficient, non-specialist treatments and sequencing, with costing analyses. Our implementation approach is guided by the Exploration, Preparation, Implementation, Sustainment (EPIS) framework.Methods/designWe will use a Sequential, Multiple Assignment Randomized Trial (SMART) to randomize 2710 patients from the outpatient clinics at Kisumu County Hospital (KCH) who have MDD, PTSD or both to either 12 weekly sessions of non-specialist-delivered Interpersonal Psychotherapy (IPT) or to 6 months of fluoxetine prescribed by a nurse or clinical officer. Participants who are not in remission at the conclusion of treatment will be re-randomized to receive the other treatment (IPT receives fluoxetine and vice versa) or to combination treatment (IPT and fluoxetine). The SMART-DAPPER Implementation Resource Team, (IRT) will drive the application of the EPIS model and adaptations during the course of the study to optimize the relevance of the data for generalizability and scale –up.DiscussionThe results of this research will be significant in three ways: 1) they will determine the effectiveness of non-specialist delivered first- and second-line treatment for MDD and/or PTSD, 2) they will investigate key mechanisms of action for each treatment and 3) they will produce tailored adaptive treatment strategies essential for optimal sequencing of treatment for MDD and/or PTSD in low resource settings with associated cost information – a critical gap for addressing a leading global cause of disability.Trial registrationClinicalTrials.gov NCT03466346, registered March 15, 2018.

BACKGROUND 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. OBJECTIVE To study a point-of-care adherence metric in PrEP to support and increase adherence via an RCT METHODS The paper describes the protocol for a pilot randomized trial to test the acceptability, feasibility, and impact on long-term adherence of implementing a POC urine tenofovir test to provide real-time adherence feedback among women on PrEP in Kenya. Eligible women (n=100) will be HIV-negative, ≥18 years old, and recruited from a clinic in Kenya providing 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. 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. RESULTS We expect to see increases in adherence via a long-term measure using a novel point-of-care method to monitor and deliver feedback on adherence. CONCLUSIONS A novel urine assay to measure and deliver information on adherence to PrEP in real-time will be tested for the first time in this trial planned among women on PrEP in Kenya. Study findings will inform a larger-scale PrEP trial assessing the impact of real-time monitoring/feedback via the urine tenofovir assay on HIV prevention. Improving adherence to PrEP will have long-term implications for the efforts to end the HIV epidemic worldwide. CLINICALTRIAL Clinicaltrials.gov NCT03935464