Peer PrEP Referral + HIV Self-test Delivery for PrEP Initiation Among Young Kenyan Women: Pilot Study & Randomized Trial
Phase: NA
Conditions: HIV Prevention
Sponsor: Fred Hutchinson Cancer Center

Peer PrEP referral + HIV self-test delivery for PrEP initiation 
among young Kenyan women: Pilot study & randomized 
implementation trial 
NCT04982250 
Protocol 
Approved: June 2nd, 2025

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Peer PrEP referral + HIV self-test delivery for PrEP initiation 
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among young Kenyan women: 
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Pilot study & randomized implementation trial
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Version 1.11
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May 22, 2025
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Funding:
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United States National Institute of Mental Health (NIMH)
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Fred Hutch IRB
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PROTOCOL TEAM
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Fred Hutchinson Cancer Research Center, Seattle, USA
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Katrina Ortblad, ScD, MPH (PI)
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Rachel Malen, MPH (Project Manager) 
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Stephanie Roche, PhD (Co-Investigator)
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Adriana Reedy, MS (Project Coordinator)
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Carlos Culquichicon, MSPH, MD (Research Assistant)
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University of Washington, Seattle, USA
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Jared Baeten, MD, PhD (Co-investigator)
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Kenneth Sherr, PhD, MPH (Co-investigator)
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Ruanne Barnabas, DPhil, MBChB, MSc (Co-investigator)
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Jane Simoni, PhD (Co-investigator)
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Jomo Kenyatta University of Agriculture and Technology Nairobi, Kenya
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Kenneth Ngure, PhD, MPH, MSc (Site Principal Investigator)
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Kenya Medical Research Institute, Nairobi, Kenya
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Nelly R. Mugo, MBChB, MMed, MPH (Co-investigator)
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National AIDS & STI Control Programme, Nairobi, Kenya
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Mary Mugambi, BA (Consultant)
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Heidelberg University
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Maureen McGowan, MS (Research Assistant) 
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Partners in Health and Research Development, Thika, Kenya 
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Njeri Wairimu, B.A. (Project Coordinator)
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Catherine Kiptinness BPharm, MPH (Site Coordinator)
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Nairobi County Health Management Services 
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Antony Kiplagat, MSc (Co-investigator) 
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TABLE OF CONTENTS
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ABREVIATIONS ...................................................................................................................................5
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PROTOCOL SUMMARY.......................................................................................................................6
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LAY SUMMARY....................................................................................................................................7
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ABSTRACT...........................................................................................................................................7
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BACKGROUND ....................................................................................................................................8
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Study Objectives ...........................................................................................................................................12
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Research Questions.....................................................................................................................................12
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Overview- Study Design ..............................................................................................................................13
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Setting.............................................................................................................................................................13
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Aim 1: Pilot study procedures .....................................................................................................................13
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HIV Self-Testing Kit ......................................................................................................................................17
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Data Collection..............................................................................................................................................17
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Data Analysis & Outcomes..........................................................................................................................18
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Participant retention and withdrawal ..........................................................................................................18
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Limitations......................................................................................................................................................19
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Aim 2: Randomization Trial Procedures....................................................................................................19
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Study Population...........................................................................................................................................19
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HIV Self-Testing Kit ......................................................................................................................................30
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Randomization ..............................................................................................................................................21
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SAFETY ..............................................................................................................................................30
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PrEP................................................................................................................................................................30
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Pregnancy......................................................................................................................................................30
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Social harm considerations .........................................................................................................................30
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HUMAN SUBJECTS CONSIDERATIONS .........................................................................................31
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Study oversight..............................................................................................................................................31
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Risks ...............................................................................................................................................................31
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Protection against risk..................................................................................................................................32
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Benefits...........................................................................................................................................................32
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Care for persons identified as HIV infected ..............................................................................................32
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Benefits to the community ...........................................................................................................................32
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Importance of the knowledge to be gained ...............................................................................................33
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Treatment for injury.......................................................................................................................................33
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Study records ................................................................................................................................................33
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Confidentiality................................................................................................................................................33
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Dissemination Plan.......................................................................................................................................33
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TIMELINE............................................................................................................................................35
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REFERENCES ....................................................................................................................................36
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ABBREVIATIONS
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3TC
Lamivudine
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AE
Adverse Event
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AGYW
Adolescent girls and young women
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ART
Antiretroviral Therapy
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DAIDS
Division of AIDS (NIH)
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DBS
Dried Blood Spots
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EC
Ethics Committee
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FDA
Food and Drug Administration (US)
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FGD 
Focus Group Discussion
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FSW
Female sex worker
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FTC
Emtricitabine
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FTC-TP
Emtricitabine-triphosphate 
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HCW
Healthcare worker
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HIVST
HIV Self-testing
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IEC
Information, communication, education 
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IRB
Institutional Review Board
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KEMRI
Kenya Medical Research Institute
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MoH
Ministry of Health
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MSM
Men who have sex with men
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NGT
Nominal group technique 
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NIH
National Institutes of Health (US)
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PHRD
Partners in Health & Research Development
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PrEP
Pre-exposure prophylaxis
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RA
Research assistant 
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SAE
Serious adverse event
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TDF
Tenofovir
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TFV-DP
Tenofovir diphosphate
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UNAIDS
Joint United Nations Program on HIV/AIDS
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WHO
World Health Organization
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NASCOP
National AIDS and STIs Control Programme
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PROTOCOL SUMMARY
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Pre-exposure prophylaxis (PrEP) for HIV prevention is highly effective. In Kenya, a country with the 4th 
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largest HIV epidemic worldwide, the government began delivering PrEP on a national scale in 2017. One 
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of the target groups for HIV incidence reduction is young women (16-24 years), who account for 33% of 
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the total of new HIV infections in Kenya yet comprise only 10% of the population. To date, PrEP initiation 
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rates are low among young women. Barriers to PrEP initiation are multi-faceted and include institutional 
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(e.g., stigma associated with use), and intra-personal (e.g., lack of PrEP knowledge or self-efficacy) 
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barriers. Thus, innovative PrEP delivery models that can help overcome these barriers – and that are 
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affordable to young women and health systems – are needed.
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The opinion of peers often influences the behaviors and preferences of young women, globally and in 
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Kenya, including opinions related to health and health care. Peer referrals or peer-delivered interventions 
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have been commonly used among key populations with tight social connectivity to increase identification 
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of new individuals living with HIV and facilitate linkage to treatment but have not yet been used to increase 
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identification of individuals eligible for HIV prevention and facilitate linkage to interventions like PrEP. We 
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hypothesize that a formalized peer PrEP referral + HIVST delivery model can amplify screening for HIV 
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and PrEP initiation among young Kenyan women at HIV risk. Specifically, this study aims to: 
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Aim 1: Pilot and refine a peer PrEP referral + HIVST delivery model 
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Approach: Pilot the aim 1 delivery model among 16 young female PrEP users in Thika, Kenya, who will 
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deliver formalized peer PrEP referral + HIVSTs to ~4 peers each (=64 peers total). One month later, we 
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aim to measure model adoption (e.g., peer referral, HIVST use, and PrEP initiation) through quantitative 
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measures. We also aim to understand model acceptability and model weak points for refinement through 
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qualitative data collection using CFIR-informed focus group discussions (FGDs) with those delivering and 
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receiving the intervention (4-5 FGDs, 3-6 participant/FGD).
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Hypothesis: The proposed model will be adopted and accepted by PrEP users and peers, feasible, and 
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easily refined to address identified weak points. 
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Aim 2: Conduct a hybrid effectiveness-implementation randomized trial to test the effect of the 
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refined peer PrEP referral + HIVST delivery model on PrEP initiation among young Kenyan women 
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Approach: Conduct a 2-arm trial in Thika, Kenya where ~80 young female PrEP users are randomized 
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to: (1) “formal peer PrEP referral + HIVST delivery”, where they are encouraged to refer 4 peers using 
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PrEP materials (developed in Aim 1) and distribute HIVST kits (2/peer, = 8 total), vs. (2) “informal peer 
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PrEP referral”, where they are encouraged to refer 4 peers to PrEP services by word-of-mouth, as is 
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ongoing in Kenya. All outcomes will be measured among peers and PrEP users three months later. 
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Outcomes will include adoption (e.g., PrEP referral, PrEP retention, HIVST use), fidelity, cost, and safety. 
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The effectiveness outcome will be PrEP initiation (primary), confirmed using dried blood spots. 
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Hypothesis: The formal referral model will result in higher PrEP adoption (e.g., initiation and retention) 
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among peers compared to the informal referral model and will have low cost and high fidelity. 
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This study will provide important information on how to increase PrEP initiation among young Kenyan 
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women at high HIV risk and will inform a future proposal for a community-randomized trial that tests the 
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peer PrEP referral + HIVST delivery model at scale.
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LAY SUMMARY 
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Few young women at risk of HIV infection are initiating pre-exposure prophylaxis (PrEP) for HIV 
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prevention in Kenya, thus we propose developing, refining, and testing a new model to increase PrEP 
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initiation among young women at high HIV risk that has not yet been explored: peer PrEP referral + HIV 
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self-testing (HIVST) delivery. Through a pilot based on qualitative formative research and stakeholder 
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engagement, we will develop and refine an acceptable and feasible model where young (≥16 to 24 years) 
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female PrEP users refer their peers to PrEP using materials we determine to be appropriate (e.g., 
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pamphlets) and HIVSTs. We hypothesize that relative to informal word-of-mouth peer PrEP referral 
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(ongoing in Kenya), formalized peer PrEP referral + HIVST delivery will increase PrEP adoption (i.e., 
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initiation, retention, and adherence) among peers, and be low cost and have high fidelity in Kenya. 
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ABSTRACT
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PrEP for HIV prevention is highly effective. However, in Kenya, where the government offers PrEP free 
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of charge, few young women (16-24 years old) at high HIV risk are initiating PrEP. We propose piloting 
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and testing an innovative model that might overcome barriers to PrEP initiation among young Kenyan 
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women: peer PrEP referral + HIVST delivery. The specific aims of the proposed research are to: 1) pilot 
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a delivery model based on formative research and refine the model using focus group discussions 
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informed by implementation frameworks (Year 1 and 2) test the effect and implementation of the refined 
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delivery model on PrEP initiation and other outcomes (including PrEP adoption, model fidelity, and costs) 
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using a hybrid-randomized implementation trial (Years 2-3). This proposed research addresses one of 
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the greatest challenges to PrEP scale-up today and will inform a National Institutes of Health (NIH) R01 
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proposal for a community-randomized trial and budget impact analysis.  
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BACKGROUND
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Importance of the problem  
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More than two million persons become newly infected with HIV each year, the majority in Africa.1 In 
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Kenya, more than 1.5 million people are living with HIV2 making it the country with the 4th largest 
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epidemic. The past five years have witnessed major strides in the development of highly effective HIV 
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prevention interventions, particularly using antiretroviral medications: antiretroviral therapy (ART) to 
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decrease infectiousness and pre-exposure prophylaxis (PrEP) to prevent acquisition. Novel models to 
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deliver these strategies successfully and efficiently, at scale, are needed to achieve maximum HIV 
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prevention impact. 
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Young Kenyan women are at high risk of HIV 
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Kenyan adolescent girls and young women (AGYW) remain at particularly high risk of HIV infection. 
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AGYW ages 16-24 years accounted for 33% (n= 23,312) of total new HIV infections in 2015, thereby 
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being nearly twice as likely to acquire HIV compared to their male counterparts.3 This discrepancy is 
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associated in part with perceptions of HIV risk, lack of knowledge and/or access to effective HIV 
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prevention interventions, and high prevalence of experienced sexual violence4,5 – it is estimated that 33% 
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of young women in Kenya have been raped before the age of 18 years.6  
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PrEP is an effective, recommended, and impactful strategy for HIV prevention 
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PrEP has been demonstrated to be efficacious and safe for reducing HIV risk among men who have sex 
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with men (MSM),7 heterosexual men and women,8,9 and injection drug users10 in diverse geographic 
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settings. In 2012, the U.S. Food and Drug Administration (FDA) approved combination tenofovir 
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disoproxil fumarate/emtricitabine (TDF/FTC) as the first medication with a label indication for HIV 
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prevention in adults11. In 2015, the World Health Organization (WHO) issued guidance recommending 
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TDF-containing PrEP as an additional prevention option for all persons at high risk for acquiring HIV 12 
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and in 2017, Kenya added PrEP to its national HIV prevention portfolio and began distributing free 
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government-issued PrEP to all individuals at HIV risk at select public clinics.13,14
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Adherence is essential for PrEP efficacy. PrEP clinical trials had a wide range of results for estimates of 
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PrEP’s efficacy for HIV protection – explained by the degree to which the trial populations were adherent 
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to PrEP15. Secondary analyses from clinical trials and demonstration studies have shown that PrEP is 
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highly efficacious and safe when taken as prescribed: at the individual level, HIV protection is on the 
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order of 90-100% in both MSM and heterosexual populations when PrEP adherence was high, as 
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measured by the presence and quantity of PrEP in blood samples.8,16,17 PrEP adherence and HIV 
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prevention effectiveness have been higher than in prior clinical trials, in many cases very high, in open-
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label demonstration projects among HIV sero-discordant couples, MSM, and young women at HIV risk,18–
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20 which has been hypothesized to be a result of offering a strategy with demonstrated safety and 
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effectiveness and without a placebo. In those PrEP demonstration studies, HIV incidence has been very 
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low, and visits were generally quarterly and brief, suggesting that many who initiate PrEP in the context 
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of known safety and efficacy may not need intensive follow-up to achieve high adherence. In some high 
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income settings (e.g., San Francisco), delivery of PrEP at scale, layered onto high coverage of HIV testing 
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and ART delivery, has resulted in substantial reductions in new HIV infections in the past five years.21–23
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HIV self-testing (HIVST) is an effective and recommended strategy to increase HIV testing
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In 2016, the WHO released a guideline which strongly recommended the implementation of HIVST as an 
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HIV testing strategy. HIVST was recommended to support the so called “first 90” of the Joint United 
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Nations Program on HIV/AIDS (UNAIDS) 90-90-90 targets (e.g., 90% of all people living with HIV will 
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know their status by 2020). HIVST has found to be appropriate at increasing HIV testing uptake and 
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frequency among diverse populations (e.g., key populations, sero-discordant couples, men, and women) 
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in a range of countries, including Kenya.24 Additionally, HIVST may increase self-efficacy (e.g., knowing 
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one’s HIV status), knowledge of partner’s HIV status (one’s personal risk), and awareness of one’s PrEP 
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eligibility (when HIV-negative). 
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Diverse models for PrEP referral + HIVST are needed 
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In 2017, Kenya added PrEP to its national HIV prevention portfolio and began distributing free 
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government-issued PrEP to all individuals at HIV risk at select public clinics.13,14 While PrEP scale up in 
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Kenya has been relatively easy to implement among key populations (e.g., men who have sex with men 
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[MSM] and female sex workers [FSWs]) it has been difficult to scale up among AGYW at HIV risk. A study 
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conducted in Kenya among young women (16-20 years) which screened HIV risk and offered PrEP, 
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found that only 5% (9/168) eligible for PrEP initiated it.25 Barriers to PrEP use among AGYW included 
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lack of PrEP knowledge, mistrust about PrEP efficacy and safety, low HIV risk perception, and 
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community-level barriers (e.g., stigma associated with PrEP use).26 
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In Kenya, young women have tight social networks that often influence health behavior  
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Peer-delivered HIV prevention interventions have been found to be effective and feasible among key 
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populations with high social connectivity (e.g., MSM27,28 and FSWs29,30,31,32,33). Similarly, young women 
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have tight peer networks and are often influenced by one another in terms of healthcare behavior. In a 
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HPTN-082 study conducted among AGYW in South Africa and Zimbabwe, 62% (254/409) of participants 
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reported being encouraged to uptake PrEP by peers.14 Similarly, in Kenya, informal peer PrEP referral 
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(e.g., word-of-mouth referral) was a major facilitator to PrEP uptake among AGYW.
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Peer PrEP referral + HIVST delivery is a novel approach that could reach AGYW at risk of HIV 
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This pilot study and subsequent hybrid-randomized implementation trial for peer PrEP referral + HIVST 
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delivery will be the first model of its kind in sub-Saharan Africa. This approach is novel in its aim to build 
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upon existing informal (word-of-mouth) referral systems and its aim to function within existing peer 
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networks. This pilot study will be unique in its: 1) utilization of PrEP and HIVST- two innovations that have 
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been recently introduced by the Kenyan Ministry of Health (MoH), 2) training of PrEP users as “PrEP 
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champions”, 3) implementation of HIVST to facilitate peer PrEP referral, and 4) implementation of a 
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hybrid-effectiveness randomization trial. The perceived acceptability and feasibility of this study are 
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supported by the formative stage of this research study (e.g., in-depth interviews and stakeholder 
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meetings) developed through a K99 grant. 
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Findings from formative research on peer PrEP referral + HIVST
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As formative research for this project, in the first half of 2021, we conducted in-depth interviews with 
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AGYW using (n=15) and not using (n=15) PrEP to understand their perspectives and attitudes towards 
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HIV, HIVST, PrEP, and COVID-19. We additionally asked about their acceptability towards a peer PrEP 
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referral + HIVST delivery intervention. The median age of participants was 20 years (IQR: 20-22). Most 
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participants were in a relationship but unmarried (n=22; 73%) and nearly half (n=14; 47%) had one or 
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more children. 24 participants (80%) had tested for HIV within the last 3 months. 
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The main findings included that AGYW were often aware of HIVST although many had not used HIVST. 
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While some AGYW reported interest in HIVST for reasons including learning one’s HIV status privately 
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and mitigating structural barriers associated with facility-based HIV testing (e.g., transportation costs, 
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long waiting times); other AGYW described reluctance accepting HIVST due to perceived lack of 
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knowledge and skills to perform the test accurately.  Second, many AGYW were aware of PrEP although 
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rampant misinformation was evident. AGYW described that they (or their communities) often mistook 
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PrEP for post-exposure prophylaxis (PEP) or ARTs. Thereby stigmatizing PrEP use as it was associated 
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with persons engaging in risk behaviors or being HIV-positive. Third, we found that peer-delivered HIV 
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prevention interventions may be of increased relevance following the COVID-19 pandemic as some 
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AGYW reported changing partners during lockdowns while others described PrEP attrition during COVID-
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19 due to less frequent sexual activity and thereby lower perceived risk of HIV infection. Most importantly 
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however, we found that most AGYW believed peer PrEP referral and HIVST delivery to be largely 
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acceptable among Kenyan AGYW. Many participants expressed willingness to educate peers about 
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PrEP use and side effects, to assist peers with HIVST and results interpretation, and to support peers 
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with linkage to PrEP care and adherence. However, it should be noted that some participants mistrusted 
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being approached by peers during a peer PrEP referral + HIVST model due to fear of involuntary HIV 
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status or PrEP disclosure and its associated stigmatization. Example quotes highlighting findings above 
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are presented in Table 1. 
Table 1. Example quotes from AGYW during formative in-depth interviews
Perceptions about HIVST
“I think (HIVST) it’s good since you become aware of your (HIV) status. It’s not a must you go to the 
hospital if you’re afraid. If you have sex with someone and you fear going to the hospital, you need 
to test yourself” (PrEP user, age 21) 
Perceptions about PrEP
They (my peers) feel like they’ll be stigmatized (for using PrEP), you know, mostly it is said that 
PrEP is majorly used by infected people. They haven’t realized the difference between PrEP and 
HIV drugs” (PrEP user, age 20)
Peer PrEP referral + HIVST model
“I told them (peers) about PrEP…I tell them it doesn’t have side effects, it is just like any other 
drug. When we meet, we just talk about it, I don’t fear” (PrEP user, age 22) 
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Findings from stakeholder meeting peer referral to PrEP + HIVST
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On May 28, 2021 we convened a stakeholders’ meeting with 34 participants from regulatory agencies 
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and suppliers (e.g., Ministry of Health-, Pharmacy and Poisons Board, National AIDS & STI Control 
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Programme, National AIDS Control Council), PrEP implementing partners (JHPIEGO, Clinton Health 
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Access Initiative, Elton John AIDS Foundation), non-governmental organizations (e.g., LVCT Health, Bar 
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Hostess Empowerment & Support Programme), health care providers (e.g., Kenyatta National Hospital, 
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Ruiru Hospital), research institutions (e.g., Partners in Health & Research Development, Kenya Medical 
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Research Institute, Jomo Kenyatta University of Agriculture and Technology), and young Kenyan women. 
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At this meeting, we first presented formative research findings on the acceptability and feasibility of the 
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peer PrEP referral + HIVST delivery model among young Kenyan women to stakeholders. We then used 
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the nominal group technique (NGT) to build consensus among stakeholders on the implementation 
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strategies for the core components of this model to be including for pilot testing. The core components 
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for which implementation strategies were developed included: 1) recruitment of PrEP users, 2) training 
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of PrEP users for intervention delivery, 3) identification of peers at HIV risk, 4) delivery of HIVST and 
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PrEP referral, 5) linkage to PrEP or HIV care support, and 6) PrEP adherence support (see Fig. 1). For 
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the NGT, meeting participants first individually brainstormed implementation strategies for each core 
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component that they then refined in small and large group discussions. Once the top implementation 
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strategies for each component identified, individuals voted on the efficacy and feasibility of each strategy 
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using 5-point Likert scale. 
Fig. 1. Core components of the peer PrEP referral + HIVST delivery model for PrEP initiation among young Kenyan women
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Overall, stakeholders were supportive of the peer PrEP referral + HIVST delivery model and felt that it 
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would be acceptable and feasible among young Kenyan women. The highest scored strategies (by 
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efficacy and feasibility ratings) were reviewed by stakeholders in the follow-up meeting (July 9th, 2021) 
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and incorporated into care pathway for pilot testing, summarized in Fig. 2. 
Fig. 2. Collaboratively developed care pathway for peer PrEP referral + HIVST delivery for young Kenyan women
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METHODS
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Taking PrEP to scale will require simplifying and diversifying models for delivery to achieve options that 
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are affordable, accessible, and meet the needs of AGYW and health systems. We have assembled a 
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multidisciplinary team to test peer PrEP referral + HIVST delivery. We hypothesize that a formalized 
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peer referral model to PrEP will result in higher PrEP adoption (e.g., initiation and retention) 
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among AGYW compared to on-going informal referral models. 
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Study objectives
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1.
To test and refine a peer PrEP referral + HIVST delivery model (Aim 1 pilot)  
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2.
To determine adoption and feasibility of a peer PrEP referral + HIVST delivery model (Aim 1 pilot)
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3.
To identify weak points for peer a PrEP referral + HIVST delivery model (Aim 1 pilot)
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4.
To test a model of PrEP initiation through an implementation randomized trial and to analyze 
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study PrEP adoption, fidelity, cost, and safety (Aim 2 randomized trial)
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Hypothesis. AGYW will be interested in a model of peer PrEP referral + HIVST. Understanding the 
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potential weak points for peer PrEP referral will permit refinement of the intervention. Peer PrEP referral 
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+ HIVST will result in higher PrEP adoption (e.g., initiation and retention) compared to ongoing informal 
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referral models. 
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Research questions
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1.
Will a peer PrEP referral + HIVST delivery model be adopted by and feasible among Kenyan 
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AGYW?
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2.
What are the weak points in a peer PrEP referral + HIVST delivery model for PrEP initiation?
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3.
How can these weak points be mitigated for a future peer PrEP referral + HIVST delivery 
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community-randomization trial?
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4.
How will a peer PrEP referral + HIVST delivery model compare in outcomes of PrEP adoption, 
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fidelity, cost, and safety compared to ongoing informal peer PrEP referrals (the current standard 
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of care)?
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Study design
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For Aim 1 (Objectives 1-3), we will conduct a one-arm 
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intervention trial, or pilot study. There is no comparison arm in 
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this pilot. The intervention we are testing was developed from 
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extensive formative research, including analysis of data from 
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in-depth qualitative interviews with young female PrEP users 
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and non-users and a meeting with stakeholders. 
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For Aim 2 (Objective 4), we will subsequently conduct a two-
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arm hybrid type 3 randomized trial, in which young female 
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PrEP users are randomized to: 1) “formal peer PrEP referral 
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+ HIVST delivery model” – where after training, participants 
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are encouraged to refer 4 peers using PrEP educational 
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materials and HIVST (2 HIVST kits/peer = 8 HIVST kits total) 
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vs. 2) “informal peer PrEP referral”- where participants are 
396
encouraged to refer 4 peers to PrEP through word-of-mouth 
397
(Fig. 3).  
398
Setting
399
400
We will conduct the research for this study in Thika, Kenya (Fig. 4). 
401
Thika is an urban center, ~40 km outside of Nairobi in Central 
402
Kenya, which has a large peri-urban and rural surrounding 
403
population. HIV prevalence in Thika is 6%.3 
404
We selected Thika, Kenya to conduct this research because the 
405
research team implementing the project here has extensive 
406
experience with the provision of PrEP to diverse populations. They 
407
were involved in the Partners PrEP Study clinical trial,8 then the 
408
open-label Partners Demonstration Project,34 and are currently 
409
leading the Partners Scale-Up Project, MPYA study, POWER 
410
project, and pharmacy PrEP scale-up project. The site has technical 
411
expertise related to PrEP, community engagement with diverse 
412
populations (with high recruitment and retention >90%), and 
413
collaborative experience working with health providers outside of 
414
their own research clinics – precisely the components necessary for 
415
this work. The Thika research team also has extensive experience 
416
with the development of PrEP delivery models in Kenya – members 
417
of our study teams were deeply involved in the Kenya PrEP guideline process, including guidelines for 
418
clinical delivery.35
419
Aim 1: Pilot study procedures
420
We have chosen a single-arm trial for the pilot study (i.e., no comparison to an informal peer PrEP referral 
421
arm) because this study is focused on testing the adoption and feasibility of a formal peer PrEP referral 
422
+ HIVST delivery intervention and refining care pathways for this delivery model. Ongoing informal PrEP 
423
referral can still be observed and can serve as a general comparison in terms of demographics, PrEP 
424
uptake, and adherence.  
425
Participant eligibility & recruitment
426
We will recruit 16 AGYW using PrEP for the pilot study.  PrEP users will be identified from prior Partners 
Fig. 4.  Study setting
Fig. 3: Randomized trial design (2-arms) to test 
peer PrEP referral + HIVST delivery.
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in Health and Research Development (PHRD) studies targeting AGYW and from public HIV clinics 
428
providing PrEP in Kiambu County. This will be a rolling recruitment and will end when all 16 participants 
429
have been identified. PrEP user participants will then be encouraged to refer 4 peers to PrEP, for a total 
430
of 64 peer study participants. The PrEP users will be trained on the importance of recruiting peers that 
431
are emancipated/mature minors only likely to benefit from using PrEP. This study sample size is deemed 
432
appropriate to measure the outcomes of interest and to refine the intervention care pathway prior to the 
433
randomized trial. This sample size is also similar in size to other PrEP implementation pilots led by the 
434
PHRD (Table 2). We will use the same recruitment strategies for both emancipated minors 16-17 years 
435
and women ≥18 years.36
436
Table 2. Eligibility and recruitment strategies- pilot study
            Eligibility                                    Ineligibility                                  Recruitment Strategies
PrEP users
(n=16)
>16- to 24 years old36
Female
Adherent to PrEP (i.e., self-
report taking PrEP all the time)
Can identify 4 peers at HIV risk 
who would be
interested in PrEP
Able & willing to provide written 
informed consent

< 16 years old, > 24 years old

Male

Not adherent to PrEP

Cannot identify 4 peers who would 
be at HIV risk and/or interested in 
PrEP

Is not able or willing to provide 
written informed consent

Recruit participants from prior AGYW 
studies 

Recruit participants from HIV clinics where 
PrEP is available using PHRD recruitment 
strategies (e.g., workshops for HCWs) 

Strategies developed from the formative 
research and stakeholder meetings 
Peers (n=64)
Age ≥16 to 24 years*
Female
Referred by peer (i.e., a 
PrEP users) to initiate PrEP
Able & willing to provide 
informed consent

Age <16 or >24 years

Male

Not referred by peer (i.e., a 
PrEP users) to initiate PrEP

Not able and willing to provide 
informed consent

Peer referral from PrEP users
437
Pilot procedures
438
All participants will be enrolled in the 
439
pilot study and followed for 1 month, 
440
as outlined in Fig. 5. 
441
442
PrEP users. Once all PrEP users 
443
have been recruited and identified, 
444
they will complete a 1-day in-person 
445
group 
training 
(with 
appropriate 
446
COVID precautions in place) on the 
447
peer PrEP referral + delivery model 
448
(Month 0). This training will include 
449
education on HIV risk screening, HIV 
450
prevention, HIVST use (including 
451
results 
interpretation), 
PrEP 
452
adherence and safety, and the 
453
importance of confidentiality. With reference to the Rapid Assessment Screening Tool for PrEP (RAST), 
454
PrEP users will be taken through the eligibility criteria or risk factors that would warrant individual peers 
455
qualify to be initiated on PrEP. All PrEP users will be given educational resources on PrEP and HIVST 
456
(approved by the trial IRB) that they can share with their peers, including a list of locations in Thika where 
457
PrEP is provided for free (by Kenyan Ministry of Health [MoH]). Additionally, all PrEP users will receive 8 
458
HIVST kits and be encouraged to use these (2 HIVST kits per peer) to refer 4 peers to PrEP. We will 
459
complete all enrollment procedures with PrEP users at the beginning of the group training, and all PrEP 
460
users will complete the quantitative baseline survey before training and complete a short post-training 
Fig. 5. Timeline of pilot enrollment and follow-up
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questionnaire to assess understanding of key components of HIVST and PrEP at the end of the group 
462
training. We will follow-up with all PrEP users in-person or remotely 1 month following this training to 
463
complete a structured questionnaire and collect self-reported outcomes, including the number of peers 
464
referred and PrEP initiation among peers (see Data analysis & outcomes section). During the COVID-19 
465
pandemic, the Kenyan research team has successfully completed a number of remote questionnaires 
466
and in-depth interviews for other PrEP implementation and COVID-19 studies. 
467
468
Peers. PrEP users will refer peers to the study using a recruitment script given to them at the training. 
469
The peers that are interested in HIVST, PrEP for HIV prevention, and study participation will call study 
470
staff (study team number specified in the recruitment script) before receiving the intervention from PrEP 
471
users so the study team has their contact information and can reach them 1 month later to complete a 
472
follow-up questionnaire. PrEP users will then deliver PrEP promotional materials and HIV self-tests to 
473
interested peers. The information of study staff and locations where peers can go to access free PrEP 
474
and HIV treatment services will be included in the promotional materials so peers can contact the study 
475
staff if they have any questions about PrEP, HIVST, or linkage to care. For peer follow up, research 
476
assistants will call peers 1 month following when they received the intervention from PrEP users (and 
477
gave their contact information to study staff) to complete a formal consent process and a structured 
478
quantitative questionnaire either remotely or in-person (at the research site or at their home). 
479
480
All participants will receive transportation reimbursement and an additional 300 KES (~$2.70 USD) to 
481
compensate for their time and effort and for completion of a structured questionnaire at baseline (PrEP 
482
users) or follow-up (PrEP users and peers). PrEP users will also receive an additional small incentive for 
483
participation in training and peer recruitment activities. For participants that have to complete 
484
questionnaires remotely, we will send mobile money to reimburse participants. 
485
Intervention core components
486
Throughout the duration of the study, participants will support the implementation of the peer PrEP 
487
referral + HIVST model through core components identified in the stakeholder meetings (Fig. 1).
488
1.
Recruit young female PrEP users – through health facilities and institutions. Specifically, study 
489
counsellors and healthcare workers (HCWs) will identify young women who can serve as “PrEP 
490
champions” (i.e., display knowledge about PrEP, engage in PrEP adherence, and have the ability to 
491
recruit/train peers). 
492
2.
Train young female PrEP users – through a 1-day in-person group or individualized training using 
493
a targeted curriculum. It is vital that training is appropriate to the AGYW age group (e.g., information 
494
is comprehensible, engaging). Further, this approach may be combined with elements of peer 
495
education, an approach which had similar ratings in terms of effectiveness and feasibility. Peer 
496
education is deemed appropriate to educate AGYW in terms of HIVST use and interpretation as well 
497
as PrEP use, efficacy, and side effects. 
498
3.
Identify peers at HIV risk – through peer networks. Participants will identify peers through 
499
snowballing methods and will approach the topic of PrEP by demonstrating emotional support to peers 
500
(e.g., sharing personal experiences using PrEP). 
501
4.
HIVST use and support – through the in-person or online provision of information, education, and 
502
communication (IEC) materials. These materials may include posters, graphics, package inserts 
503
(HIVST kits) or pamphlets to aid researchers and healthcare workers teaching AGYW about HIVST 
504
and PrEP. 
505
5.
Support linkage to PrEP or HIV care – through information provided in the PrEP pamphlet shared 
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with them by PrEP users, which includes the contact information of study staff that can help support 
507
linkage to care and the information for nearby health facilities that provide free PrEP services. 
508
Additionally, PrEP users will be trained on how to guide peers on linkage to nearby free PrEP services 
509
and may escort peers to these services if peers request this and they feel comfortable doing so.  PrEP 
510
users who support their peers via escorted referrals will be asked to encourage peers to return for 
511
PrEP refills without escorted referrals to mitigate peer dependency. 
512
6.
Support continued PrEP use – through the implementation of peer support groups and drug-
513
buddies. Drug-buddies refer to peers who are paired and can hold one another accountable to daily 
514
PrEP use. PrEP adherence will also be combined with a formalized PrEP reminder and tracking 
515
system (e.g., USHAURI phone application). Further, continued PrEP use will be supported through 
516
the implementation of capacity building activities among healthcare workers to provide youth friendly 
517
PrEP services. 
518
The PrEP medication will be provided for free from the public health clinics via the Kenyan MoH and HIV 
519
self-tests for this pilot study will be provided for free via ChemBio Diagnostics Systems. 
520
This pilot study will be conducted during the ongoing COVID-19 pandemic. As such, the pilot study will 
521
be conducted in accordance with the Kenyan COVID-19 prevention measures in place at the time of the 
522
study. Participants will be asked/screened about symptoms of COVID-19 (including temperature) prior to 
523
entering the PHRD study site for a follow-up appointment, all in-person data collection will be conducted 
524
with appropriate distance, ventilation, and participants will be asked to wear a face mask to reduce the 
525
risk of COVID-19 infection. As necessary, we will explore options to complete surveys over the phone.
526
Condoms will be available through the PHRD research site but are not included in the package of PrEP 
527
services provided in this study. 
528
PrEP medication
529
Tenofovir disoproxil fumarate (or TDF, 9-[(R)-2-[[bis [[(isopropoxycarbonyl) oxy] methoxy] phosphinyl] 
530
methoxy] propyl] adenine fumarate), emtricitabine (or FTC, 5-fluoro-1-(2R,5S)-[2-(hydroxymethyl)-1,3-
531
oxatholan-5-yl]cytosine), and lamivudine (or 3TC, 2',3'-dideoxy-3'-thiacytidine 4-Amino- 1-[(2R,5S)- 2-
532
(hydroxymethyl)- 1,3-oxathiolan-5-yl]- 1,2-dihydropyrimidin- 2-one) are reverse transcriptase inhibitors 
533
that have been approved for the treatment of HIV infection in humans in Kenya and the United States. 
534
A fixed-dose, oral co-formulation of FTC/TDF (Truvada®) has also been approved for HIV prevention 
535
in Kenya and the United States. The WHO recommends TDF-containing medications as PrEP, which 
536
includes TDF combined with FTC as well as potentially TDF alone and TDF combined with lamivudine 
537
(or 3TC, a medication closely related to FTC). Any TDF-containing medications that align with WHO 
538
and Kenyan national guidelines for PrEP will be used in this study. PrEP will be prescribed for once-daily 
539
oral use.  Study medication will be provided by the Kenyan MoH and stored in accordance with the drug 
540
manufacturer’s recommendations.
541
542
PrEP discontinuation
543
PrEP initiation and continuation will be in accordance with the Kenyan PrEP guidelines. Use of PrEP 
544
may be interrupted by the site investigators or Kenyan clinicians due to safety concerns for the participant 
545
or use of concomitant medications that could interfere with PrEP or present a safety concern. All 
546
treatment interruptions will be documented.  
547
548
Referral to continued PrEP care
549
For participants that wish to continue PrEP use following the pilot study (1-month trial duration); 
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participants will remain enrolled in PrEP at the healthcare facility at which they had enrolled/initiated in 
551
PrEP use. PrEP will then be prescribed and administered via this physician who will provide 3-month 
552
supplies of PrEP. 
553
HIV Self-Testing Kit 
554
ChemBio (who has committed to providing HIVST kits to the 
555
pilot study) manufactures the SURE CHECK® HIV 1/2 Assay 
556
(Fig. 6), a blood-based HIVST that has 99.7% sensitivity, 
557
99.9% specificity, presents results in 15 minutes, and is 
558
approved by the US FDA.37  Results are easy to read (1 line: 
559
HIV-negative, 2 lines: HIV-positive, no lines: invalid result). 
560
HIVST serves as a preliminary test result and must be 
561
followed-up with confirmatory facility-based HIV testing to 
562
indicate a diagnosis. 
563
Data Collection
564
Quantitative data will be collected through surveys at baseline (Month 0) and follow-up (Month 1) and 
565
focus group discussions (FGDs) will be completed near the end of the pilot (Month 3).
566
Quantitative surveys. Trained research assistants (RAs) stationed at healthcare facilities delivering PrEP 
567
will approach eligible individuals and invite them to 
568
participate in the study. They will review the informed 
569
consent form with these individuals and answer any 
570
questions they may have regarding participation. Once 
571
written informed consent is obtained, RAs will conduct a 
572
structured quantitative survey with the participant. Table 
573
3. outlines the data collection activities which will be 
574
conducted among the participant (PrEP user) and the 
575
recruited peers at baseline (Month 0) and follow-up (Month 
576
1). All quantitative data will be collected on a tablet using 
577
CommCare (Dimagi, Cambridge, USA), an electronic data 
578
collection platform.
579
FGDs. We will conduct FGDs with about 12 PrEP users who delivered and about 12 peers who received 
580
the peer PrEP referral + HIVST delivery model. We will conduct 4-5 FGDs in total (3-6 participant/FGD); 
581
of these 2-3 FGDs will be conducted among PrEP users (recruiters) and 2-3 FGDs will be conducted 
582
among peers (those recruited to the study). We hereby aim to explore their experiences with this new 
583
PrEP delivery model and understand the acceptability of a peer PrEP referral + HIVST model. FGDs will 
584
utilize the Consolidated Framework for Implementation Research (CFIR)41 to understand model 
585
acceptability, measure model weak points (barriers) and to assess model facilitators in order to inform 
586
the subsequent randomization trial. Topics discussed in the FGDs are summarized in Table 4. All 
587
participants that participate in these focus group 
588
discussions will sign documents of informed consent. 
589
Additionally, all participants will be reimbursed for 
590
transportation and an additional 300 KES (~$2.70 USD) 
591
for participation in FGDs.
592
All qualitative FGDs will be conducted in the participant’s 
593
preferred language (English or Kiswahili) by trained 
Table 3. Data collection activities 
PrEP user
   Peer
Variables
M0
M1
M1
Demographics
X
X
HIV risk 
X
X
Depression38,39 
X
X
Sexual health/HPV 
X
X
Self-efficacy40 
X
X
Peer support 
X
X
HIVST distribute/use
X
X
PrEP initiation/use
X
X
X
PrEP/HIV stigma
X
X
X
Table 4. FGD themes, informed by CFIR domains: constructs
Intervention: complexity Clarity of instructions/logistics
Outer: peer pressure
Peer influence on HIVST use, PrEP 
initiation
Individual: self-efficacy
Confidence to initiate PrEP, use HIVST
Individual: knowledge
Understanding of PrEP benefits, HIV risk
Process; Executing
Experiences delivering model/materials
Process: Reflecting 
Attitudes towards the model, identify 
weak points 
Fig. 6. Sure Check HIV 1 / 2 assay
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594
qualitative research assistants using pre-piloted, semi-structured interview guides. Each FGD will be 
595
audio recorded, transcribed, and translated into English by study team members who will also routinely 
596
complete debriefing reports42 to accelerate real time learning. Dr. Ngure, an experienced behavioral 
597
scientist who has led our qualitative research in Thika for the past decade, will supervise these 
598
discussions. 
599
Data analysis & outcomes
600
601
Quantitative surveys. Table 5 shows the study outcomes that will be obtained from the quantitative 
602
surveys. For Aim 1 (Objective 1), we will calculate the number and proportion of participants who initiated 
603
PrEP at healthcare facilities, peers referred to PrEP, and peers that used HIVST. These outcomes will 
604
be measured along outcomes of “acceptability,” “appropriateness,” and “feasibility” (Objective 2). 
605
606
FGDs.  Transcripts will be reviewed separately by two or more qualitative researchers, who will ensure 
607
completeness. These researchers will immerse themselves in the data through repeated readings of the 
608
transcripts and create a preliminary codebook of inductive43,44 and deductive45–47 codes to capture the 
609
experiences of AGYW regarding a peer PrEP referral + HIVST model including barriers and facilitators 
610
(Objective 3). A sample of transcripts will be double coded independently by two or more researchers, 
611
with coding discrepancies identified and resolved via consensus. During this process, the codebook will 
612
be refined, with existing codes combined, separated, or eliminated and new codes added as needed to 
613
capture emerging themes.48,49 Thereafter, remaining transcripts will be coded in Dedoose (Los Angeles, 
614
California, USA) or Nvivo 12 (QSR International, Melbourne, Australia). We have extensive experience 
615
analyzing qualitative data to inform intervention development.50–72
616
Participant retention and withdrawal
617
The Thika research site will develop retention methods tailored to and most efficient for the local study 
618
settings. Retention activities may include explanation of the study schedule (i.e., return for follow-up after 
619
one month) and procedural requirements during the informed consent process. Further, peers referred 
620
to the study, will be contacted and directed to the PHRD study site for follow-up or will be visited (e.g., at 
621
home) by PHRD researchers. However, should the aimed sample size not be attained (e.g., < 75% 
622
referral rate), then alternative follow-up strategies may be implemented including 1) giving peers mobile 
623
money conditional on texting researchers their contact information or 2) having PrEP users report 
624
outcomes for their peers. 
625
Participants may voluntarily withdraw from the study for any reason at any time. The site investigators 
626
may also withdraw participants from the study in order to protect their safety and/or if they are unwilling 
627
or unable to comply with required study procedures. Reasons for withdrawal will be recorded. 
628
Limitations
629
630
This pilot study has some potential limitations that are important to note. First, some of the participants 
631
may be recruited for this study from prior or ongoing PHRD studies targeting AGYW. These participants 
632
may not accurately represent PrEP and HIVST knowledge among AGYW who have not been enrolled in 
633
prior PrEP and HIVST interventions. We aim to mitigate this challenge by recruiting other participants 
Table 5. Outcomes for the peer PrEP referral + HIVST delivery pilot and measured at Month 1. * primary 
Outcome:
Details:
Reported:
Metric of success: Allow seamless 
progression to trial
PrEP initiation*
Prop. of referred peers that initiated PrEP*
Peers and PrEP 
users
40% of those followed up (n≥19)
PrEP referral
No. of peers referred to PrEP
PrEP users
≥3 peers per PrEP user (n≥48)
HIVST use
Prop. of referred peers that used HIVST
Peers
75% of those followed up (n≥36)
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634
from public HIV clinics who have no prior PrEP and/or HIVST education. 
635
636
Additionally, the pilot study will encourage participants to recruit 4 peers to the study. The limitation of 4 
637
peers may inherently exclude some AGYW who maintain at high risk of HIV and would be interested in 
638
PrEP initiation through a peer PrEP referral+ HIVST model. Further, those recruited to the pilot study will 
639
be provided 2 HIVST kits to test themselves (independently or with the assistance from the PrEP user) 
640
or to test a primary sexual partner. Some AGYW may benefit from testing multiple sex partners (e.g., in 
641
sex worker relationships). Although a focus on partner testing is outside the scope of this study- future 
642
research should be considered in this area. 
643
644
Finally, in the pilot study, peers recruited to the study are supplied HIVST kits free of cost (from ChemBio). 
645
In settings outside of a research or intervention setting, AGYW may have to purchase HIVST kits at cost 
646
which may influence the appropriateness and feasibility of this model. The randomization trial will further 
647
research this factor through a cost analysis. 
648
649
Aim 2: Randomization trial procedures
650
651
Study population
652
Based on confusion with naming conventions from the pilot study, we have revised our description of 
653
PrEP users and peers to the following: “peer providers” and “peer clients.” From here on out, peer 
654
providers (formerly “PrEP users”) will be young women using PrEP who we will training on the peer PrEP 
655
referral + HIVST delivery in in the intervention arm or who will continue with informal models of peer PrEP 
656
referral in the standard-of-care control arm. Peer clients (formerly “peers”) will then be the young women 
657
that receive the peer PrEP referral + HIVST intervention delivered by the peer providers. For reporting 
658
purposes, we will also refer to peer providers as “index peers” and peer clients as “referred peers.”
659
We will recruit 80 young female peer providers from public healthcare clinics delivering PrEP in Kiambu 
660
County and neighboring Counties using established PHRD site techniques. These participants will further 
661
refer 4 peer clients each to PrEP for a maximum 320 potential peer clients.
662
Eligibility criteria. 
663
664
Peer providers. Eligible peer providers will be: i) female, ii) ≥16 to 24 years old (including emancipated 
665
minors ≥16 to 17 years36), iii) must have refilled or initiated PrEP (i.e., been dispensed PrEP), iv) are able 
666
to identify 4 peers at risk of HIV infection who may be interested in PrEP, v) not currently enrolled in 
667
another HIV study, and vi) are able and willing to be randomized to the intervention, complete research 
668
activities, and provide written consent (Table 6). Due to the nature of the training intervention which 
669
includes slides, quizzes, and other activities that involve reading and writing, peer providers will be 
670
considered ineligible if they do not have basic literacy skills. Due to some challenges recruiting young 
671
female peer providers in the Aim 1 pilot, we made some modifications to the inclusion criteria in this 
672
section, including reducing the duration of PrEP use and dropping the requirement for PrEP disclosure. 
673
674
Peer clients. Eligible peer clients will be: i) female, ii) ≥16 to 24 years old (including emancipated minors 
675
≥16 to 17 years36), iii) referred by a peer provider to initiate PrEP, and iv) are able and willing to provide 
676
informed consent. 
677
 
678
Recruitment strategies.  Peer providers. Peer providers will be recruited through a multipronged approach 
679
that will include recruitment through other ongoing PrEP research projects, and from nearby public health 
680
facilities implementing PrEP programs, such as, workshops for healthcare workers, use of IEC materials, 
681
and working with community health workers to identify potential participants. Peer providers will be 
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compensated 300 KES (~$2.70 USD) and be reimbursed for travel at their baseline appointment and 
683
again at their 3-month follow-up appointment. No travel reimbursement at follow-up will be provided if 
684
follow-up questionnaires are conducted via phone. All peer providers will be encouraged to disclose PrEP 
685
use to peers, although this is not required. Study counselors will conduct follow-up calls with peer 
686
providers to check in and see how the referral process is going and answer any questions or concerns 
687
regarding the intervention. Recruitment of peer providers will be on a rolling basis, so it is possible that 
688
peer providers and peer clients may not be mutually exclusive (as future peer providers could be previous 
689
peer clients). 
690
Peer clients. Peer providers will recruit peer clients. Peer clients will contact study counselors (via phone), 
691
to provide RAs with contact information to schedule a follow-up visit (Month 3) at the PHRD study site 
692
(transport refunded) or via phone interview. Clients won’t be engaged in study activities at Month 3 until 
693
they have provided informed consent. To help prompt peer providers to remind peer clients to call 
694
research staff at the point of recruitment (a challenge during the pilot study), we will compensate peer 
695
providers and their peer clients a small amount (150 KES each, ~$1.40 USD each) each time a peer 
696
client pings the study phone line to enroll in the study. For any peer clients who do not ping the study 
697
phone, study staff will attempt to collect contact information for the peer clients from the peer providers 
698
during a follow-up visit/call. The peer client can still decline enrollment when contacted by study staff. 
699
Peer clients will be compensated 300 KES (~$2.70 USD) and reimbursed for travel for attending the 3-
700
month follow-up appointment. No travel reimbursement will be provided if the questionnaires are 
701
conducted over the phone. To facilitate the delivery of this compensation, we will use a secure mobile 
702
money platform (M-Pesa) that we have used successfully for other research projects. Research staff will 
703
call these individuals twice (one week apart) and stop trying to contact these potential participants if these 
704
phone calls do not go through. Additionally, they will do their best to confirm the identity of the potential 
705
peer client before describing any details of the research study (and their potential participation in this 
706
study). 
707
708
Consenting procedures. Peer providers. All peer providers that meet eligibility requirements will provide 
709
written informed consent at the point of recruitment and prior to randomization with a trained research 
710
assistant. This signed consent form will be stored as confirmation of informed consent and a copy will be 
711
made available to the participant. 
712
Peer clients. All peer clients that have contacted the study team directly, expressed interest in the study, 
713
and have met eligibility requirements will complete informed consent at the Month 3 follow-up visit, before 
714
completing any questionnaires assessing their experience with the peer PrEP referral + HIVST 
715
intervention or informal peer PrEP referral process. Those unable or unwilling to come to the PHRD site 
716
to sign a consent form will have the option to provide verbal consent over the phone. If verbal consent 
717
was provided, the trained research assistant will note the date that verbal consent was obtained on a 
718
copy of the consent script. The signed consent form and scripts will be stored as confirmation of informed 
719
consent. A subset of peer clients who sign the written consent form will also be asked to provide a DBS 
720
sample collected from a finger prick or venous blood. No peer client providing verbal consent will be 
721
asked to provide a DBS sample. 
722
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21
723
Table 6. Eligibility and recruitment strategies- randomized trial
            Eligibility                                                 Ineligibility                                 Recruitment Strategies
Peer 
providers 
(formerly 
“PrEP users”)
(n=80)
>16- 24 years old36
Female
Must have refilled or initiated 
PrEP (i.e., been dispensed 
PrEP)
Not currently enrolled in an HIV 
study
Can identify 4 peers at HIV risk 
who could benefit from PrEP
Able & willing to be randomized 
to the intervention, participate 
in research activities, and/or 
provide written informed 
consent

Not between 16-24 years old

Male

Have not used PrEP

Cannot identify 4 peers who would 
benefit from PrEP

Is not able or willing to be 
randomized to the intervention, 
participate in research activities, 
and/or provide written informed 
consent

Currently enrolled in an HIV study

Illiterate

Recruit participants from HIV 
clinics where PrEP is available 
using PHRD recruitment 
strategies (e.g., workshops for 
healthcare workers)

Strategies developed and 
refined during the pilot study 
Peer clients 
(formerly 
“peers”)
(n=320)
Age ≥16 to 24 years
Female
Referred by peer provider (i.e., 
a “PrEP user”) to initiate PrEP
Able & willing to provide 
informed consent

Age <16 or >24 years

Male

Not referred by peer provider (i.e., 
a PrEP users) to initiate PrEP

Not able and willing to provide 
informed consent

Peer providers will recruit peer 
clients. At point the of 
recruitment, peer clients will call 
research staff to provide contact 
info for follow-up

At follow-up, peer providers 
share the contact information of 
peer clients so they can be 
reached for follow-up.

If peer client calls the study 
staff, both the peer client and 
provider will be compensated 
150 KES via mobile money.
724
725
Randomization
726
Shortly after trial enrollment, peer providers will open in the presence of a study RA an opaque sealed 
727
envelope sequentially distributed to them that has their randomization arm specified inside (e.g., formal 
728
peer PrEP referral + HIVST arm; informal peer PrEP referral arm).       
729
730
Study procedures & intervention 
731
Depending on the arm peer providers are randomized to, the following procedures will apply (Table 7, 
732
and Figure 7): 
733
[Intervention arm]: Formal peer PrEP referral + HIVST delivery (n=40 peer providers). Peer providers 
734
randomized to this intervention arm will receive a training on PrEP referral and HIVST delivery. We will 
735
train peer providers in groups of around 4-8 peer providers. The training materials will be based on 
736
Kenya’s national PrEP guidelines and delivered in a 1-day session led by experienced research staff. 
737
The training will cover HIV prevention methods, how to use and interpret HIVST kits, how to initiate 
738
conversation with peers about PrEP, practice scenarios, pre-training and post-training quizzes, and other 
739
related activities. Based on feedback from the Objective 2 FGDs, we modified the pilot training materials 
Table 7. Interventions/materials received by peer providers and peer clients in the intervention and control arms
Intervention arm
Control arm
Intervention/material
Peer provider
Peer client
Peer provider
Peer client
Formal 1-day training on PrEP & HVIST
X
Formalized conversation about PrEP, HIVST & referral
X
X
PrEP educational brochure  
X
X
HIVST kits for distribution/self-testing
X
X
WhatsApp group for questions
X
PrEP referral card
X
X
X
X
Informal conversation about PrEP & referral
X
X
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to also include more training on HIVST interpretation, common PrEP misconceptions, issues surrounding 
741
PrEP stigma, reminders for consistent PrEP use, and the importance of delivering the intervention 
742
package to peers privately.  
743
Following the training, peer providers will be asked to identify 4 peer clients they perceive as at HIV risk 
744
and think might be interested in daily oral PrEP and deliver the intervention to these individuals. This 
745
intervention arm will include a formalized conversation about PrEP with peers, delivery of HIVST kits, 
746
sharing a PrEP & HIVST educational brochure, delivery of a PrEP referral card, and access to a 
747
(monitored) WhatsApp group to ask questions and for support (Table 7 and Figure 7): 
748

Formalized PrEP conversation. Peer provider in this intervention arm will be trained on techniques 
749
they can use to start conversations with their peer clients about PrEP and provide correct information 
750
about PrEP effectiveness, use, and safety (and answer any questions related to these). Additionally, 
751
they will deliver a study-developed PrEP and HIVST informational brochure to peer clients that covers 
752
the talking points about PrEP use and safety and can be used by as a reference in the future. 
753

HIVST kit delivery.  The intervention will include the distribution of 2 HIVST kits by peer providers to 
754
each peer client. With delivery of the HIVST kits, peer providers will be trained to share information 
755
on how to use the HIVST kits with peer clients and direct them to the information and pictorial brochure 
756
that comes with the HIVST kits for more information as needed. Referred peer clients can use the 
757
HIVST kits to test themselves for HIV, test for HIV with a peer, or test a main sexual partner (if they 
758
feel comfortable) which may increase feelings of self-efficacy and knowledge of PrEP eligibility or 
759
need – potentially facilitating PrEP initiation.
760

PrEP educational brochure: This informational brochure will reinforce key points of the training 
761
session provided to peer providers. It will be delivered by peer providers to peer clients during the 
762
formalized PrEP conversation.
763
764

PrEP referral card. The intervention will also include the delivery of a PrEP referral card by peer 
765
provider to peer clients with training on how to help peers link to PrEP services if needed. On this 
766
card will be listed information on the location of nearby public clinics and in neighboring counties with 
767
free PrEP services and that peer client can ask for when they arrive for assistance with PrEP services. 
768
This referral card will also contain the study phone number to support peer clients that wish to go to 
769
another facility for PrEP support.
770
771

WhatsApp Group. The study team will answer questions, provide additional information, and promote 
772
discussion between peer providers through a monitored WhatsApp group (participation is optional). 
773
This forum has been used in other studies at PHRD and we plan to implement several measures to 
774
make these groups as confidential as possible. First, individual WhatsApp groups will be created for 
775
each peer provider training session. That way, peer providers that participate in this option will only 
776
be conversing with individuals they met during their training session.  Second, during the training 
777
session, peer providers will be instructed to not disclose any identifying information about peer clients 
778
in the WhatsApp group.  Third, a study team member will be assigned to monitor the group 24/7. If 
779
necessary, study staff will delete any messages that contain personal information about participants 
780
immediately. The study staff monitoring the group will also periodically delete older messages, so 
781
they are not stored long-term. Finally, the WhatsApp groups will only be available during the 3 month 
782
intervention time period and then all remaining messages from that group will be permanently deleted.
783
784
Peer providers randomized to this arm will be encouraged to disclose PrEP use to peers, although this 
785
is not required.
786
[Control arm]: Informal peer PrEP referral (n=40 peer providers). Peer providers randomized to this 
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23
787
control arm will be encouraged to refer 4 peers that they perceive to be at HIV risk and would be interested 
788
in daily oral PrEP through free public PrEP services. This control arm will include informal conversations 
789
about PrEP with peers (as per the standard of care) and delivery of a PrEP referral card (Table 7 and 
790
Figure 7):
791

Informal PrEP conversations. Peer providers in this arm will not receive any formalized training on 
792
PrEP or HIVST and will not receive any HIVST kits for distribution to peers. They will be encouraged 
793
to talk with their peers about PrEP in the way that feels most comfortable to them and in way they 
794
would typically have conversations about new products (e.g., lipstick) or things that interest them. 
795

PrEP referral card. This control arm will also include the delivery of a PrEP referral card by peer 
796
providers to peer clients. This will be the same referral card as that delivered to peer clients in the 
797
intervention arm, with information of nearby public clinics with free PrEP services. This referral card 
798
will also contain the study phone number so peer clients remember to ping the study counselor when 
799
these informal conversations occur and to support peer clients that wish to go to another facility for 
800
PrEP support.
801
Like in the intervention arm, peer providers randomized to this arm will be encouraged to disclose PrEP 
802
use to peers, although this is not required. No WhatsApp group will be available in this arm.
803
804
Fig. 7. Study procedures for intervention, and standard of care groups. 
805
806
807
808
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May 22, 2025
24
809
Data Collection 
810
811
Overview. Fig. 8 highlights a timeline of study visits and 
812
data collection activities for this trial. There are two data 
813
collection time points in this study: Month 0 (peer 
814
provider baseline questionnaire) and at Month 3 (peer 
815
provider follow-up questionnaire and peer client follow-
816
up questionnaire). After providing informed consent, all 
817
peer providers enrolled in the trial will complete a 
818
baseline (Month 0) and follow-up (Month 3) survey. 
819
Additionally, all peer clients who voluntarily provide their 
820
contact information directly to the study team and request to be enrolled in the study will be contacted to 
821
schedule an interview at Month 3. The peer client will be screened for eligibility and consented prior to 
822
completing a follow-up survey at Month 3. This timeline will provide recruited peer clients with the 
823
opportunity to enroll in PrEP (approx. 1 month following the baseline survey) and return to healthcare 
824
facilities for one PrEP refill (approx. 3 months following the baseline survey). Sociodemographic 
825
information will be collected at baseline among peer providers and follow-up among peer clients (i.e., 
826
their first research visit). At all follow-up visits, we will measure both self-reported outcomes related to 
827
adoption of PrEP services, as well as process-level outcomes (e.g., number of HIVST kits received in the 
828
intervention arm, PrEP referral cards received in both arms), and implementation outcomes (e.g., 
829
intervention acceptability, appropriateness, fidelity, satisfaction). 
830
831
Setting. Experienced quantitative researchers will collect electronic data using CommCare (Dimagi, 
832
Cambridge, USA), an electronic data collection tool, in questionnaires at baseline (Month 0) and follow-
833
up (Month 3). While we will encourage all enrolled peer clients to come to the PHRD research site to 
834
complete the questionnaires in person, we will additionally allow for the option of questionnaire 
835
participation/completion over the phone to allow for easier engagement in follow-up activities (in 
836
particular, peer clients that might have been recruited outside of Kiambu County). Peer providers will 
837
need to come in-person to the clinic during baseline to receive the intervention they are randomized to. 
838
All participants will receive 300 KES (~$2.70 USD) for their time and effort completing each study 
839
visit/questionnaire. For participants completing questionnaires remotely via the phone, we will send this 
840
reimbursement via a secured mobile money platform (i.e., M-Pesa), as we have done routinely for other 
841
projects. For participants that come to the PHRD research site to complete these visits/questionnaires in 
842
person, we will additionally provide reimbursement for transportation. 
843
844
DBS samples. At follow-up (Month 3) DBS samples will be collected from peer clients to validate PrEP 
845
initiation. At a subset of in-person visits, a DBS collected from a finger prick or venous blood will be 
846
prepared at the site and stored at -20 degrees Celsius. Prior to storage, the DBS will be left to air-dry for 
847
at least 2 hours and thereafter placed in low gas-permeability Ziploc bags with a desiccant pack to reduce 
848
humidity thus maintaining integrity of the sample. The DBS samples will be labeled with the de-identified 
849
participant ID and will be shipped outside Kenya for temporary storage at Fred Hutchinson Cancer Center 
850
(Washington State, USA) and forwarded to Molecular Testing Labs (Washington State, USA) for TFV 
851
and FTC level testing. The shipped samples will be stored until the testing is completed and results 
852
confirmed. These outcomes are expanded on in the following section. It is possible that DBS samples 
853
will not be sent for testing if we do not achieve the target sample size of 23 peer clients per study arm.   
854
855
856
857
Fig. 8. Timeline for the Aim 3 randomized trial.
Peer Providers
with Peer Provider
Peer Clients
Peer providers 
refer peer clients 
to PrEP
(peer clients call 
researcher to share 
contact info)
Baseline 
survey
Peer client 
survey
Peer Provider 
follow-up 
survey
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859
Data Analysis
860
All outcomes will be measured at study follow-up (Month 3) (Table. 8). 
861
Primary adoption outcome. Our primary outcome is reported PrEP initiation among all referred peer 
862
clients, as reported by peer providers (Objective 4). We had originally planned to measure this as a self-
863
reported outcome among peer clients but had a challenge reaching peer clients that were referred in the 
864
pilot study; thus, have decided to link measurement of our primary outcome to peer providers delivering 
865
the intervention, as is typical in many studies assessing the impact of secondary distribution delivery 
866
models. To validate this, we will collect a DBS sample from a subset of willing peer clients that return in 
867
person at Month 3 (approximately 23/arm) to measure concentrations of tenofovir diphosphate (TFV-DP) 
868
and emtricitabine triphosphate (FTC-TP) using a validated liquid chromatography tandem mass 
869
spectrometry73,17. Any concentrations of TFV-DP in a DBS sample will confirm PrEP initiation and/or 
870
adherence.16 In sensitivity analyses, we will measure our primary outcome using self-report data from 
871
peer clients (not providers) on PrEP initiation. 
872
Secondary adoption outcomes. We will also measure secondary and process outcomes of peer clients 
873
as reported by peer providers, including number of peers referred, recent HIV testing, and PrEP 
874
continuation (e.g., peer clients that returned to the clinic and refilled PrEP drugs one month following 
875
initiation). As in the primary analysis, we will measure these outcomes using reported data from peer 
876
clients (not providers) in sensitivity analyses. We will also measure some secondary and process 
877
outcomes of peer clients as reported by themselves, including PrEP adherence (measured using a 
878
standard scale), HIVST use, and linkage to care.  Finally, we will also measure a secondary outcome of 
879
PrEP continuation among peer providers, as reported by themselves.
880
Implementation outcomes. Additionally, in all follow-up surveys among peer providers and clients we will 
881
measure a number of implementation outcomes including participants’ perceptions of the intervention’s 
Table 8. Outcomes for the peer PrEP referral + HIVST delivery trial, measured at 3 months. * = primary 
Outcome:
Details:
Outcome type: Reported:
Measures:
Metrics of success: for 
R01 progression 
PrEP initiation* Prop. of clients initiating PrEP 
Adoption 
(clients)
Provider
No. of new clients using 
PrEP / No. of referred 
clients
>20% increase 
PrEP referral
No.  of clients referred to PrEP
Adoption 
process 
(providers)
Provider
No. of clients referred to 
PrEP / No. of referred 
clients
>50 more peers 
PrEP 
continuation1
Prop. of clients refilling PrEP (any) since 
referral
Adoption 
secondary 
(clients)
Provider
No. of clients with >1 
PrEP clinic visits / No. of 
referred clients
>20% increase 
PrEP 
continuation1
Prop. of providers refilling PrEP (any) in 
the past 3 months
Adoption 
secondary 
(providers)
Provider
No. of providers with 1+ 
PrEP clinic visits in past 
three months / No. of 
providers
>20% increase
PrEP adherenceMedian of Wilson et al’s 0-100 point 
adherence score
Adoption 
secondary 
(clients)
Client
Median score
>20% increase 
HIVST use
Prop. of clients in the formal arm that 
used a HIVST.
Adoption 
process (clients)
Client
No. 
of 
clients 
self-
reporting use of HIVST 
/ No. of referred clients
>90% (n=144 – formal 
arm)
Client linkage to 
care
Prop. of clients that went to a clinic to 
access HIV services 
Adoption 
process (users)
Client
No. of clients reporting 
visiting a clinic / No. of 
referred clients
>20% increase 
Recent 
HIV 
testing
Prop. of clients who completed any HIV 
testing since referral
Adoption 
secondary 
(clients)
Provider
No. clients reporting 
testing for HIV since 
referral/ No. of referred 
clients
>20% increase
1Retention: >1 PrEP clinic visit (guidelines recommend first-time PrEP users return to a clinic after one month)
 
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acceptability, feasibility, and appropriateness. To measure these outcomes, we will use validated scales 
883
and established theories/frameworks adapted to the Kenyan setting and to young women (e.g., the 
884
Theoretical Framework of Acceptability). Additionally, at follow-up, we will have peer clients complete a 
885
checklist of materials received from peer providers to measure “fidelity” of the intervention in both 
886
intervention arms.
887
Costs are another important implementation outcome we plan on measuring during this trial. To measure 
888
costs, we will micro-cost the formal delivery model and compare the incremental cost of this model with 
889
the existing informal referral strategy (Objective 4). Activity-based micro-costing will be conducted for 
890
costs incurred (e.g., HIVST kits) and costs averted (e.g., personnel). We will use time and motion studies 
891
to measure staff time spent training peer providers. Estimates of cost using the activity-based approach 
892
will be compared with the top-down approach (i.e., the budget divided by the number of peer providers 
893
and peer clients) 74 75 76 77 (Table 9). 
894
Safety. We will measure “safety” of the intervention by 
895
screening for PrEP side effects (i.e., nausea, vomiting, 
896
headache) among peer clients (and as reported by both peer 
897
provider and clients) and any reports of social harm (e.g., 
898
physical, verbal, emotional violence) related to our delivery 
899
model (Objective 4).
900
The findings from this trial (described above) will be used to inform a NIH R01 proposal for a peer PrEP 
901
referral + HIVST community-randomized trial and budget impact analysis. 
902
Statistical analysis 
903
We will measure effect size estimates using mixed effects multilevel regression models (primary 
904
predictor: study arm; standard errors adjusted for clustering by peer provider). All analyses comparing 
905
randomization arms will be intention-to-treat, complete case analyses conducted at the unit of the 
906
individual (either peer provider or peer client). The primary comparison will be formalized peer PrEP 
907
referral + HIVST delivery versus informal peer PrEP referral (the standard of care). For analyses 
908
conducted at the level of the peer client, we will adjust standard errors for clustering at the peer provider 
909
level. We will use mixed-effect logistic regression models to measure risk ratios. All statistical test with 2-
910
sided p-values <0.05 will be considered statistically significant. We will complete all analyses in R and 
911
STATA.
912
Sample size 
913
914
If we assume that peer providers refer 75% of the targeted peer clients, this leaves us with three clients 
915
per peer provider, or 240 peer clients in total. We performed power calculations for our primary outcome, 
916
the proportion of referred peer clients who initiated PrEP at three months, in Stata 16.1 using methods 
917
for cluster-randomized trials, where each cluster is a peer group of one peer provider and three peer 
918
clients (Figure 10). Table 10 shows the power we have to attain to detect various increases in the 
919
proportion of peer clients who initiated PrEP in the formal peer PrEP referral arm + HIVST (intervention 
920
group) vs. the informal peer PrEP referral arm (standard of care group). For our power calculations, we 
921
assumed 40 clusters (peer providers) per arm, 3 sampling units (peer clients) per cluster, and an intra-
922
cluster correlation coefficient (ICC) of 0.05, which is standard for cluster-randomized controlled trials.  
923
924
Table 9. Description of costing inputs 
Costs: Start-up: microplanning, training, mobilization; 
Recurrent: personnel, capital, supplies, overhead
Data: Project budget; time & motion; staff interviews; 
published literature; central price list & salaries
Unit cost: Cost/PrEP users trained, peer referred, peer 
initiated on PrEP, peer retained on PrEP.
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Fig. 10. Power calculation to detect increase in the percentage (%) of referred peer clients initiating PrEP in the intervention group.
926
927
Table 10. Increase in the % of referred peer clients initiating PrEP in the intervention group. ICC: 
0.05; clusters (providers) per arm: 40; units (clients) per cluster: 3 (75% of suggested clients referred)
Power (%)
Standard of care (%, p1)
Intervention (%, p2)
Increase (%, p2-p1)
70
30
46.3
16.3
40
56.8
16.8
50
66.5
16.5
60
75.7
15.7
70
84.1
14.1
80
91.7
11.7
80
30
48.4
18.4
40
58.9
18.9
50
68.5
18.5
60
77.5
17.5
70
85.7
15.7
80
92.9
12.9
90
30
51.4
21.4
40
61.7
21.7
50
71.2
21.2
60
79.9
19.9
70
87.8
17.8
 
80
94.5
14.5
928
929
930
Participant retention & withdrawal 
931
If we do not achieve our aim 1 pilot metrics of success (including our ability to follow-up with peers), we 
932
will revise the peer PrEP referral + HIVST delivery model with input from stakeholders before conducting 
933
the aim 2 trial. If necessary, we will try one of the alternative peer follow-up strategies outlined in aim 1, 
934
and in the worst-case scenario, we will have peer providers report peer client outcomes (an approach 
935
that has been used in other high-impact studies using peer-based health interventions78). In the aim 2 
936
trial, we will confirm self-reported PrEP initiation and adherence among a subset of peer clients with drug 
937
levels in DBS.
938
Participants may voluntarily withdraw from the study for any reason at any time. The site investigators 
939
may also withdraw participants from the study in order to protect their safety and/or if they are unwilling 
940
or unable to comply with required study procedures.  Reasons for withdrawal will be recorded. 
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PrEP discontinuation
942
PrEP initiation and continuation will be in accordance with Kenyan PrEP guidelines. Use of PrEP may 
943
be interrupted by the site investigators or Kenyan clinicians due to safety concerns for the participant or 
944
use of concomitant medications that could interfere with PrEP or present a safety concern. All treatment 
945
interruptions will be documented.  
946
947
Referral to continued PrEP care
948
For participants that wish to continue PrEP care following the randomization trial, participants will remain 
949
enrolled in PrEP at the healthcare facility at which they had enrolled in PrEP. PrEP will then be prescribed 
950
and administered via this physician who will provide a 3-month supply of PrEP. 
951
PrEP drugs
952
Tenofovir disoproxil fumarate (or TDF, 9-[(R)-2-[[bis [[(isopropoxycarbonyl) oxy] methoxy] phosphinyl] 
953
methoxy] propyl] adenine fumarate), emtricitabine (or FTC, 5-fluoro-1-(2R,5S)-[2-(hydroxymethyl)-1,3-
954
oxatholan-5-yl]cytosine), and lamivudine (or 3TC, 2',3'-dideoxy-3'-thiacytidine 4-Amino- 1-[(2R,5S)- 2-
955
(hydroxymethyl)- 1,3-oxathiolan-5-yl]- 1,2-dihydropyrimidin- 2-one) are reverse transcriptase inhibitors 
956
that have been approved for the treatment of HIV infection in humans in Kenya and the United States. 
957
A fixed-dose, oral co-formulation of FTC/TDF (Truvada®) has also been approved for HIV prevention 
958
in Kenya and the United States. The WHO recommends TDF-containing medications as PrEP, which 
959
includes TDF combined with FTC as well as potentially TDF alone and TDF combined with lamivudine 
960
(or 3TC, a medication closely related to FTC). Any TDF-containing medications that align with WHO 
961
and Kenya national guidelines for PrEP will be used in this study. PrEP will be prescribed for once-daily 
962
oral use. Study medication will be provided by the Kenyan MoH and stored in accordance with the drug 
963
manufacturer’s recommendations.
964
HIVST kits
965
ChemBio manufactures the SURE CHECK® HIV 1/2 Assay (Fig. 6), a blood-based HIVST that has 
966
99.7% sensitivity, 99.9% specificity, presents results in 15 minutes, and is approved by the US FDA 37.  
967
Results are easy to interpret (1 line to indicate HIV-negative, 2 lines to indicate HIV-positive, and no lines 
968
to indicate an invalid result). HIVST kits serve as a preliminary test result and must be followed-up with 
969
confirmatory facility-based HIV testing to indicate a diagnosis. Additionally, we will use other WHO-
970
approved blood-based HIVST kits to mitigate supply chain or any other challenges that may arise. 
971
Limitations 
972
This randomization trial has some potential limitations that are important to note. Foremost, the trial will 
973
encourage participants to recruit 4 peer clients to the study. The limitation of 4 peer clients may inherently 
974
exclude some AGYW who have a high risk of HIV infection and would be interested in PrEP initiation 
975
through a peer PrEP referral+ HIVST model. Further, peer clients recruited to the study and randomized 
976
to the “formal peer PrEP referral + HIVST” arm, will be provided 2 HIVST kits to test themselves 
977
(independently or with assistance from the participant) or to test a primary sexual partner. Some AGYW 
978
may benefit from testing multiple sex partners (e.g., in sex worker relationships). Although a focus on 
979
partner testing is outside the scope of this study, future research should be considered in this area. 
980
981
Additionally, the randomization of participants to either the “formal peer PrEP referral+ HIVST” arm or the 
982
“informal peer PrEP referral” arm may lead to feelings of frustration among participants who had hoped 
983
to be randomized to the formal intervention delivery arm which may lead to resentment towards the 
984
research team. Feelings of frustration are attempted to be mitigated by ongoing peer support (word-of-
985
mouth) to enroll in PrEP in the informal delivery arm. 
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29
986
987
Finally, in the randomized trial, peers recruited to the study will be supplied HIVST kits free of cost. In 
988
settings outside of a research or intervention setting, AGYW will have to purchase HIVST kits at cost 
989
which may influence the feasibility of this model. The randomization trial aims to address this challenge 
990
by conducting a cost analysis will which be used to inform the design and development of a future peer 
991
PrEP referral + HIVST community randomization trial. 
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30
992
SAFETY
993
994
PrEP 
995
Multinational studies demonstrated that PrEP (including FTC/TDF) was safe for use in women from 
996
Kenya and Uganda. 20 There were no statistically significant differences in the frequency of deaths, 
997
serious adverse events, adverse events overall, or key laboratory adverse events (specifically, creatinine 
998
elevation and phosphorus decrease) for those receiving PrEP compared to those receiving placebo in 
999
the Partners PrEP Study.  
1000
For the purposes of this study, only serious adverse events (SAEs) will be documented. SAEs felt to be 
1001
related to PrEP will result in temporary hold of PrEP. In the case of temporary holds, the hold will continue 
1002
until the event is stabilized or resolved. If the event resolves, PrEP may be reinitiated at the discretion of 
1003
the Data Monitoring Committee (see “Study oversight” below), resuming safety monitoring. The severity 
1004
of clinical symptoms will be scored using the Division of AIDS- NIH (DAIDS) Table (July 2017 Version) 
1005
for Grading the Severity of Adult and Pediatric Adverse Events (AEs). Reporting on adverse events to 
1006
relevant IRBs will be according to relevant regulations.  
1007
Pregnancy
1008
Animal and human data, including from the Partners PrEP Study and Partners Demonstration Project, 
1009
suggest safety of FTC/TDF when used by HIV infected women during pregnancy and breastfeeding.  
1010
Other studies are exploring detailed safety of PrEP use in pregnancy.  For this study, pregnant women 
1011
interested in PrEP will be referred to antenatal care clinics for PrEP initiation and refills, as caring for a 
1012
woman who is pregnant and on PrEP is outside of the scope of this study. 
1013
Social harm considerations
1014
We have extensively considered the risk of social harms related to both PrEP use and peer referral to 
1015
PrEP as well as peer HIVST delivery including risks of depression/anxiety and disclosure and stigma. 
1016
Our extensive experience with longitudinal follow-up of heterosexual HIV sero-discordant couples and 
1017
women at risk mitigates some of this risk, and we found very little risk of social harms or anxiety related 
1018
to HIV self-testing from our ongoing Pharmacy PrEP study. Analyses of social harm related to peer PrEP 
1019
referral + HIVST will be by relationship status and employment status/type, given the potential for 
1020
differential employment and relationship risks.  In the event of a clinical need (e.g., side effects, symptoms 
1021
of a sexually transmitted infection), participants will be referred to nearby HIV clinics for care.
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Approved 
6/2/2025

PROTOCOL: Peer PrEP Referral + HIVST    RG# 1121770           v1.11
May 22, 2025
31
1022
HUMAN SUBJECTS CONSIDERATIONS
1023
The protocol, informed consent forms (for pilot participation, for focus group discussions, and for the 
1024
randomization trial), and patient education and recruitment materials will be reviewed and approved by 
1025
the institutional review boards at the Fred Hutchinson Cancer Center and the Scientific Ethics Review 
1026
Unit (SERU) at the Kenya Medical Research Institute (KEMRI). All participants will provide informed 
1027
consent before participation in the pilot study and randomization trial. Participants will be informed of the 
1028
purpose of the study, the procedures to be followed and the risks and benefits of their participation. The 
1029
consents forms will be translated into Kiswahili. Specifically, the participants will be informed that this 
1030
novel study will answer critical questions on acceptability, feasibility, and facilitators/barriers to a model 
1031
of peer PrEP referral + HIVST among AGYW in Kenya. 
1032
Study oversight
1033
This study will be subject to oversight by an independent Data Safety Monitoring Committee that will 
1034
periodically review data from the study, including study execution, adherence, HIV incidence, PrEP side 
1035
effects, SAEs, and social harms by study arm. Adverse events (AEs) include any forms of verbal (e.g., 
1036
yelling, fighting), physical (e.g., hitting), emotional (e.g., depression) or economic (e.g., job loss) abuse.  
1037
While serious adverse events (SAEs) include hospitalization (for any condition, including those outside 
1038
the study) or death. During data collection and study follow-up, participants will be asked to report if 
1039
they’ve had any of these events and whether they are or are not study related. We have had a Data 
1040
Monitoring Committee for many of our other ongoing studies. The independent data monitoring 
1041
committee will provide recommendations to the study team as part of periodic reviews. Reports from all 
1042
reviews will be provided for submission to overseeing IRBs and Ethics Committees (ECs).
1043
Risks
1044
Participants may become embarrassed, worried, or anxious when completing their HIV risk assessment 
1045
and/or receiving HIV counseling at healthcare facilities for PrEP enrollment. They also may become 
1046
worried or anxious while waiting for their HIV test results following HIV self-testing. Participants who learn 
1047
that they have HIV may experience anxiety or depression related to their test results. Further, participants 
1048
may become embarrassed or worried when they approach peers about PrEP, encourage peers to 
1049
HIVST/assist peers to HIVST, or when they disclose their HIV status and/or PrEP use to peers (should 
1050
they choose to do so). At all study sites, individual counseling will be provided by researchers who have 
1051
been trained in specific issues related to HIV risk, HIV prevention, HIV acquisition, and HIV treatment. 
1052
Although study sites will make every effort to protect participant privacy and confidentiality, it is possible 
1053
that participants' involvement in the study could become known to others, particularly as this project will 
1054
utilize a peer-delivered model. There is a possibility that social harms may result (i.e., because 
1055
participants could become known as participating in studies involving HIV prevention). For example, 
1056
participants could be treated unfairly, stigmatized, or discriminated against, or could have problems being 
1057
accepted by their families and/or communities. Talking about HIV or PrEP and finding out HIV test results 
1058
could cause problems between a participant and their sexual partner(s), including the potential for 
1059
intimate partner violence (e.g., any physical, verbal, emotional, or economic harm). Understanding the 
1060
risk/benefit balance for confidential delivery of PrEP services in community settings is an explicit goal of 
1061
this project. Moreover, we have extensive experience with the strategies to minimize the potential for 
1062
social harms in populations participating in HIV prevention studies. 
1063
Risks and side effects related to PrEP include gastrointestinal intolerance and rarely more serious side 
1064
effects; these are detailed on the package insert and this project is not testing PrEP itself but its delivery.  
1065
The medical risks of HIV testing using blood collection are small. 
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Approved 
6/2/2025

PROTOCOL: Peer PrEP Referral + HIVST    RG# 1121770           v1.11
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32
1066
Protection against risk
1067
The study team has extensive experience with counseling about HIV risk, PrEP, HIVST, and strategies 
1068
for HIV prevention in general. Study procedures will include quantitative surveys (e.g., PrEP initiation, 
1069
peer PrEP referral) as well as qualitative interviews to understand acceptability of the model. PrEP will 
1070
be provided at specified healthcare facilities and will follow Kenyan clinical guidelines. Counseling about 
1071
antiretroviral-based HIV prevention will include messaging describing the benefits of all strategies, based 
1072
on evolving available data and national policies / national roll-out of antiretrovirals (including earlier 
1073
treatment and PrEP) for HIV prevention. 
1074
For data collection, standardized questionnaires will be used that will include questions on sensitive 
1075
topics, including sexual behavior, depression, alcohol use, and stigma. We have extensive experience 
1076
with these questionnaires from our prior studies and the expertise and counseling resources required to 
1077
attend to study participants (e.g., those with depression). We have published on very low rates of social 
1078
harm and intimate partner violence in our prospective studies of HIV sero-discordant couples, which likely 
1079
reflects the counseling available to couples; for women at risk, we have extensive experience with 
1080
management of potential social harms, through our prevention studies. 
1081
To minimize risks to minors, we will only enroll young women ≥16 to 17 years into the study if they are 
1082
emancipated minors and thus able to legally provide consent for participation in research. Kenyan law 
1083
acknowledges women ages 14 to 17 who have become pregnant as emancipated minors. We have 
1084
successfully enrolled emancipated minors into a number of prior studies, including PrEP clinical trials. In 
1085
addition, Kenya national policy guidelines explicitly permit PrEP use in this age group.
1086
The risks from the anticipated activities will be no greater than in our previous studies; in fact, given the 
1087
proven prevention benefits of PrEP and its national roll-out in Kenya, risks are anticipated to be less than 
1088
in some of our prior studies. We feel the risks associated with the study are small. The benefits are 
1089
consistent with clinical care benefits and cultural expectations, and they follow the established standard 
1090
with IRB approval in our other studies. We therefore believe the balance of benefit and risk is appropriate.
1091
Benefits
1092
All participants will have the benefit of using novel HIVST kits, which are being scaled-up by the Kenyan 
1093
Ministry of Health. Further, participants will have the added benefit of pioneering a combined peer PrEP 
1094
referral and HIVST model. HIV prevention practices, according to national guidelines, will be provided to 
1095
all participants enrolled in this study. This will include risk reduction counseling, addressing sexually 
1096
transmitted infections, and access to condoms. In addition, participants and others may also benefit in 
1097
the future from information learned from this study. There may be no other direct benefits to participants 
1098
in this study.  
1099
Care for persons identified as HIV infected
1100
This study may identify persons who are infected with HIV, either as part of the study screening process 
1101
(e.g., when peers utilize HIVST) or during follow-up of enrolled participants. Study staff will provide 
1102
participants with their HIV test results in the context of post-test counseling. Persons identified as HIV 
1103
infected during the study screening process, and who do not meet eligibility criteria will be referred to 
1104
nearby clinics where they can receive free HIV care and treatment services. For participants who are HIV 
1105
infected and who also become pregnant during follow-up, every effort will be made to facilitate access to 
1106
programs for preventing mother-to-child HIV transmission for appropriate antiretroviral treatment to 
1107
reduce the probability of HIV transmission from mother to child.  
1108
Benefits to the community
1109
An important goal of this study is to achieve the study objectives in a way that provides benefits to the 
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PROTOCOL: Peer PrEP Referral + HIVST    RG# 1121770           v1.11
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33
1110
community that endure beyond the proposed study lifetime regardless of the specific outcome of the 
1111
study. Some of these community benefits include development of optimized approaches to HIV 
1112
prevention care and community awareness of comprehensive HIV prevention. 
1113
Importance of the knowledge to be gained
1114
Knowledge gained from the studies proposed in this application will include information about optimal 
1115
delivery of PrEP for HIV prevention among a vulnerable group (e.g., AGYW), which may have substantial 
1116
impact on the global burden of HIV.
1117
Treatment for injury
1118
Participants will be asked to inform the clinic staff if they feel they have been injured because of taking 
1119
part in the study. Injuries may also be identified during laboratory testing, medical histories, and physical 
1120
examinations at the specified healthcare facilities where participants will have access to PrEP. Treatment 
1121
for adverse events related to study participation will be provided by the treatment clinic. If treatment is 
1122
required that is beyond the capacity of the clinic, the clinic staff will refer the participant to appropriate 
1123
services or organizations that can provide care for the injury. Participants will be financially responsible 
1124
for treatment for injuries.
1125
Study records
1126
Implementation investigators will maintain, and store in a secure manner, complete, accurate, and current 
1127
study records throughout the study. Study records include administrative documentation and regulatory 
1128
documentation as well as documentation related to each participant enrolled in the study, including 
1129
informed consent forms, data forms, notations of all contacts with the participant, and all other source 
1130
documents.  
1131
Confidentiality
1132
Every effort will be made to protect participant privacy and confidentiality to the extent possible. Personal 
1133
identifying information will be retained at the local study sites and not forwarded to Fred Hutch. The sites 
1134
will use their standard operating procedures for confidentiality protection that reflects the input of study 
1135
staff and community representatives to identify potential confidentiality issues and strategies to address 
1136
them.
1137
All study-related information will be stored securely at the study sites. All participant information will be 
1138
stored in areas with limited access. Data collection, administrative forms, and other reports will be 
1139
identified only by a coded number to maintain participant confidentiality. All records that contain names 
1140
or other personal identifiers, such as locator forms and informed consent forms, will be stored separately 
1141
from study records identified by code number. All local databases will be secured with password-
1142
protected access systems. Forms, lists, logbooks, appointment books, and any other listings that link 
1143
participant ID numbers to other identifying information will be stored in a separate, locked file in an area 
1144
with limited access. During FGDs, we will ask participants not to refer to each other by name.  During the 
1145
peer providers trainings, we will instruct peer providers to not enter any identifying information about peer 
1146
clients in the WhatsApp group messages. Any personal identifiers will he removed from the qualitative 
1147
data transcripts and immediately deleted from WhatsApp messages by the study team. Recordings will 
1148
be destroyed at the end of the study.  WhatsApp group messages will not be stored long term (they will 
1149
be periodically deleted), and the WhatsApp groups will be shut down at the end of the intervention period 
1150
for each group of peer providers in the intervention arm.
1151
Dissemination Plan
1152
The study team is committed to the public dissemination of results from the pilot study and the 
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6/2/2025

PROTOCOL: Peer PrEP Referral + HIVST    RG# 1121770           v1.11
May 22, 2025
34
1153
randomization trial to participants, local stakeholders in Kenya, the global scientific community, and U.S., 
1154
Kenyan, and global policymakers. Dissemination of study results will follow principles of good 
1155
participatory practice. Results will be published in conference abstracts and peer-reviewed journals. 
1156
Study results will be disseminated through presentations to local stakeholders and policymakers in 
1157
Kenya, including the Ministry of Health.  
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6/2/2025

PROTOCOL: Peer PrEP Referral + HIVST    RG# 1121770           v1.11
May 22, 2025
35
1158
TIMELINE 
1159
The findings from the pilot study and randomization trial will provide important information on how to 
1160
increase PrEP initiation and continuation among young women at HIV risk in Kenya, which can inform 
1161
Kenya MOH guidelines around PrEP delivery. Additionally, these findings will inform the development of 
1162
an R01 proposal for a community-randomized trial and budget impact analysis of peer PrEP referral + 
1163
HIVST delivery in Kenya, should aims 1 & 2 find the delivery model promising among young women 
1164
(Table 11).
1165
1166
1167
R00 phase:
Table 11. Timeline and outcomes 
      Y1
      Y2
      Y3
Protocol prep. & IRB submission
X
Pilot & refine Aim 1 delivery model 
X
Conduct & analyze FGDs
X
Aim 1: Pilot
Manuscript(s) preparation
X
Protocol prep. & IRB submission 
X
Enrollment, data collect, analysis 
X
X
X
Collect & analyze costing data 
X
X
Aim 2: 
Randomization 
Trial
Manuscript(s) preparation
X
Planned R01 submission (Community Randomization Trial)
X
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36
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