PrEPARE: PrEP in Pregnancy, Accelerating Reach and Efficiency
Phase: NA
Conditions: Pre-Exposure Prophylaxis, HIV Infections, Pregnancy Related
Sponsor: University of Washington

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PrEPARE: PrEP in pregnancy, accelerating reach and efficiency 
 
 
Study Protocol: 
Principal Investigators: Grace John-Stewart, Pamela Kohler, Anjuli Wagner, John Kinuthia 
Proposal Identification Number: R01 HD094630 Supplement, K01MH121124 
ClinicalTrials.gov Identification Number: NCT04712994 
Study Dates: 
Version 1.61 
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Table of Contents 
1) 
TITLE: ........................................................................................................................................................ 4 
2) 
INVESTIGATORS (Roles and responsibilities): ...................................................................................... 4 
3) COLLABORATING INSTITUTIONS ............................................................................................................. 6 
4) FUNDING AGENCY ...................................................................................................................................... 6 
5) SIGNATURES: .............................................................................................................................................. 7 
6) Executive Summary .................................................................................................................................... 8 
7) BACKGROUND ............................................................................................................................................ 9 
8) LITERATURE REVIEW ............................................................................................................................... 10 
9) GUIDING FRAMEWORKS .......................................................................................................................... 12 
10) RATIONALE ............................................................................................................................................. 15 
11) HYPOTHESIS, OBJECTIVES, & STUDY QUESTIONS:........................................................................... 15 
12) STUDY DESIGN AND METHODOLOGY .................................................................................................. 15 
12.1) STUDY AREA DESCRIPTION: .......................................................................................................... 15 
12.2) AIM 1: ................................................................................................................................................. 17 
12.2.1)    STUDY DESIGN ........................................................................................................................ 17 
12.2.2)    STUDY POPULATIONS ............................................................................................................ 17 
12.2.3)    SAMPLE SIZE DETERMINATION AND FORMULAS USED .................................................... 18 
12.2.4)    RECRUITMENT PROCEDURES ............................................................................................... 18 
12.2.5)    ENROLLMENT & STUDY PROCEDURES ............................................................................... 19 
12.2.6)     LABORATORY METHODS ...................................................................................................... 20 
12.2.7)    DATA COLLECTION INSTRUMENTS ...................................................................................... 20 
12.2.8)    VARIABLES: Outcomes, indicators, and source documents ............................................... 20 
12.2.9)  TRAINING PROCEDURES ......................................................................................................... 20 
12.3 AIM 2: .................................................................................................................................................. 21 
12.3.1)    STUDY DESIGN ........................................................................................................................ 21 
12.3.2)    INTERVENTION DETAILS ........................................................................................................ 21 
12.3.3)    STUDY POPULATIONS ............................................................................................................ 22 
12.3.4)    SAMPLE SIZE DETERMINATION AND FORMULAS USED .................................................... 22 
12.3.5)    RECRUITMENT PROCEDURES ............................................................................................... 23 
12.3.7)     LABORATORY METHODS ...................................................................................................... 24 
12.3.8)    DATA COLLECTION INSTRUMENTS ...................................................................................... 24 
12.3.9)    VARIABLES: Outcomes, indicators, and source documents ............................................... 24 
12.3.10)    TRAINING PROCEDURES ..................................................................................................... 25 
12.4 AIM 3: .................................................................................................................................................. 26 
12.4.1)    STUDY DESIGN ........................................................................................................................ 26 

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12.4.2)    STUDY POPULATIONS ............................................................................................................ 26 
12.4.3)    SAMPLE SIZE DETERMINATION AND FORMULAS USED .................................................... 26 
12.4.4)    RECRUITMENT PROCEDURES ............................................................................................... 27 
12.4.5)    ENROLLMENT & STUDY PROCEDURES ............................................................................... 27 
12.4.6)     LABORATORY METHODS ...................................................................................................... 28 
12.4.7)    DATA COLLECTION INSTRUMENTS ...................................................................................... 28 
12.4.8)    TRAINING PROCEDURES ....................................................................................................... 28 
12.4.9)     STUDY MATERIALS: ..................................................................................................................... 28 
13) QUALITY ASSURANCE PROCEDURES ................................................................................................. 28 
14) ETHICAL CONSIDERATIONS .................................................................................................................. 29 
14.1 ASSESSMENT OF RISKS AND BENEFITS ........................................................................................ 29 
15) DATA MANAGEMENT AND STATISTICAL ANALYSIS PLANS ............................................................. 29 
16) STUDY LIMITATIONS AND HOW TO MINIMIZE THEM: ......................................................................... 30 
17) TIMELINE/ TIME FRAME: ........................................................................................................................ 31 
18) HUMAN SUBJECTS ................................................................................................................................. 32 
19) BUDGET (total budget period) ................................................................................................................ 33 
20) LIST OF ABBREVIATIONS ...................................................................................................................... 33 
21) LIST OF APPENDICES/ATTACHMENTS ................................................................................................. 33 
22)  REFERENCES ......................................................................................................................................... 36 
 
 

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1)  TITLE:   
 
PrEPARE: PrEP in pregnancy, accelerating reach and efficiency 
 
2)  INVESTIGATORS (Roles and responsibilities): 
 
Grace John-Stewart, MD, PhD (MULTIPLE PRINCIPAL INVESTIGATOR, Mentor K01) 
(Responsible for overseeing all aspects of the project, including study design, administration (overseeing budget 
management and assuring regulatory requirements are met), leadership of staff, conduct of the study, analyses 
and interpretation of results.) 
Professor 
Departments of Global Health, Medicine, Epidemiology and Pediatrics, University of Washington 
Harborview Medical Center, 325 Ninth Ave., Box 359909, Seattle, WA 98104 
Tel:  +1-206-543-4278 
Fax: +1-206-543-4818 
Email:  gjohn@uw.edu 
  
Pamela Kohler, BSN, MPH, PhD (MULTIPLE PRINCIPAL INVESTIGATOR) 
(Responsible for overseeing all aspects of the project, including study design, administration (overseeing budget 
management and assuring regulatory requirements are met), leadership of staff, conduct of the study, analyses 
and interpretation of results.) 
Associate Professor 
Department of Psychosocial & Community Health, University of Washington 
Harborview Medical Center, 325 Ninth Ave., Box 359932, Seattle, WA 98104 
Tel:  +1-206-616-7962 
Email: pkohler2@uw.edu 
 
Anjuli Wagner, PhD, MPH (MULTIPLE PRINCIPAL INVESTIGATOR) 
(Responsible for overseeing all aspects of the project, including study design, administration (overseeing budget 
management and assuring regulatory requirements are met), leadership of staff, conduct of the study, analyses 
and interpretation of results.) 
Acting Assistant Professor 
Department of Global Health, University of Washington 
Harborview Medical Center, 325 Ninth Ave., Box 359909, Seattle, WA 98104 
Tel:  +1-978-460-2331 
Email: anjuliw@uw.edu 
 
John Kinuthia, MBChB, MMed, MPH (SITE PRINCIPAL INVESTIGATOR) 
(Responsible for providing leadership on the study design and analyses and will oversee the study team in 
Kenya.) 
Head, Department of Research & Programs, Kenyatta National Hospital 
PO Box 20723-00202, Nairobi, Kenya 
Tel: +254 0722 799-052 
Email: kinuthia@uw.edu 
  
Jared Baeten, MD, PhD (Mentor K01) 
(Responsible for oversight and science for PrEP components) 
Professor, Vice Chair 
Departments of Global Health, Medicine, and Epidemiology, University of Washington 
Harborview Medical Center, 325 Ninth Ave., Box 359927, Seattle, WA 98104 
Tel:  +1-206-520-3808 
Fax: +1-206-520-3831 
Email: jbaeten@uw.edu 

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Bryan Weiner, PhD (Mentor K01) 
(Responsible for providing methodologic leadership on implementation science) 
Professor 
Departments of Health Services and Global Health 
University of Washington, Box 357965, Seattle WA, 98104 
Tel: +1 206-282-7882 
Email: bjweiner@uw.edu  
 
Kristin Beima-Sofie, PhD (Co-Investigator) 
(Responsible for providing methodologic leadership in qualitative methods) 
Acting Assistant Professor 
Department of Global Health 
Department of Global Health, University of Washington 
Harborview Medical Center, 325 Ninth Ave., Box 359909, Seattle, WA 98104 
Tel:  +1-206-221-4970 
Email: beimak@uw.edu 
 
Ruanne Barnabas, DPhil, MD (Mentor K01) 
(Responsible for providing methodologic leadership in budget impact analysis) 
Associate Professor 
Departments of Global Health, Allergy and Infectious Diseases, University of Washington 
Harborview Medical Center, 325 Ninth Ave., Box 359927, Seattle, WA 98104 
Tel:  +1-206-520-3813 
Fax: +1-206-520-3831 
Email: rbarnaba@uw.edu  
 
Kenny Sherr, PhD, MPH (Mentor K01) 
(Responsible for methodologic guidance on implementation science and quasi-experimental designs) 
Professor 
Departments of Global Health, Industrial Engineering, and Epidemiology 
1107 NE 45th Street, Suite 350, Seattle, WA 98105 
Tel: +1 206-221-7635 
Email: ksherr@uw.edu  
 
Peter Cherutich, PhD, MBChB, MPH (Mentor K01) 
(Responsible for guidance in engaging policymakers in best practices development and implementation science 
research) 
Senior Deputy Director of Medical Services 
Ministry of Health 
Tel: +254721924030 
Email: pcheru2013@gmail.com  
 
Jillian Pintye, PhD (Co-Investigator) 
(Responsible for providing guidance on PrEP optimization strategy development and implementation) 
Acting Assistant Professor 
Departments of Global Health, University of Washington 
Harborview Medical Center, 325 Ninth Ave., Box 359927, Seattle, WA 98104 
Tel:  +1-206-520-3808 
Fax: +1-206-520-3831 
Email: jpintye@uw.edu 
 

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Julia Dettinger, MPH (RESEARCH SCIENTIST) 
(Responsible for overseeing study coordination, ERC/IRB communication, protocol development and analysis) 
Department of Global Health and Nursing, University of Washington 
Harborview Medical Center, 325 Ninth Ave., Box 359931, Seattle, WA 98104 
Tel:  +1-206-221-1041 
Fax: +1-206-744-3693 
Email: jcdettin@uw.edu 
  
Laurén Gómez (STUDY COORDINATOR) 
(Responsible for study coordination, ERC/IRB communication, protocol development and analysis) 
Department of Global Health and Nursing, University of Washington 
Harborview Medical Center, 325 Ninth Ave., Box 359931, Seattle, WA 98104 
Tel:  +1-206-685-5044 
Fax: +1-206-744-3693 
Email: gomezl4@uw.edu 
 
3) COLLABORATING INSTITUTIONS 
Kenyatta National Hospital, Nairobi, Kenya  
 
4) FUNDING AGENCY 
  
Funding type: Grant 
Name of Funding agency: National Institutes of Allergy and Infectious Disease (NIAID), National Institutes of 
Health (NIH) 
Principal Investigator on Proposal: Grace John-Stewart, Jared Baeten 
Proposal Identification Number: 1 R01 AI25498-01 
Title of Proposal:  Delivering PrEP in Pregnancy 
Dates: 05/01/2016-04/30/2021 
   
Funding type: Grant 
Name of Funding agency: The Eunice Kennedy Shriver National Institute of Child Health and Human 
Development (NICHD), National Institutes of Health (NIH) 
Principal Investigator on Proposal: Grace John-Stewart, Pamela Kohler 
Proposal Identification Number: R01 HD094630 
Title of Proposal: PrEP Adherence Among AGYW: A Multidimensional Evaluation 
Dates: 07/01/2017 - 06/30/2020 
 
Funding type: Grant 
Name of Funding agency: The Eunice Kennedy Shriver National Institute of Child Health and Human 
Development (NICHD), National Institutes of Health (NIH) 
Principal Investigator on Proposal: Grace John-Stewart, Pamela Kohler 
Proposal Identification Number: R01 HD094630-03S1 
Title of Proposal: PrEP optimized for mothers (PrOM): efficient PrEP integration in MCH clinics 
Dates: 07/01/2017 09/25/2019 – 06/30/2020 
 
Funding type: Grant 
Name of Funding agency: National Institutes of Mental Health (NIMH), National Institutes of Health (NIH) 
Principal Investigator on Proposal: Anjuli Wagner 
Proposal Identification Number: K01MH121124 
Title of Proposal: Testing implementation strategies to improve delivery f PrEP for pregnant and postpartum 
women in Kenya 
Dates: 08/06/2019 – 07/31/2024 
 

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5) SIGNATURES: 
 
Grace John-Stewart, MD, PhD  
 
 
__
__________ 
Email:  gjohn@uw.edu 
  
 
Pamela Kohler, BSN, MPH, PhD  
 
 
__________________________ 
Email: pkohler2@uw.edu 
 
Anjuli Wagner, PhD, MPH  
 
 
 
_
_____________ 
Email: anjuliw@uw.edu 
 
John Kinuthia, MBChB, MMed, MPH  
 
__________________________ 
Email: kinuthia@uw.edu 
  
Jared Baeten, MD, PhD  
 
 
 
__________________________ 
Email: jbaeten@uw.edu 
  
 
Bryan Weiner, PhD   
 
 
 
__________________________ 
Email: bjweiner@uw.edu  
 
Kristin Beima-Sofie, PhD  
 
 
 
__
_____ 
Email: beimak@uw.edu 
 
 
Ruanne Barnabas, DPhil, MD  
 
 
__________________________ 
Email: rbarnaba@uw.edu  
 
Kenny Sherr, PhD, MPH  
 
 
 
__
__________ 
Email: ksherr@uw.edu  
 
 
 
Peter Cherutich, PhD, MBChB, MPH  
 
__________________________ 
Email: pcheru2013@gmail.com  
 
 
Jillian Pintye, PhD 
 
 
 
 
__________________________ 
Email: jpintye@uw.edu 
 
 
Julia Dettinger, MPH   
 
 
 
__________________________ 
Email: jcdettin@uw.edu 
  
 
Laurén Gómez  
 
 
 
 
__________________________ 
Email: gomezl4@uw.edu 
 

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6) Executive Summary 
 
Title:  
PrEPARE: PrEP in pregnancy, accelerating reach and efficiency 
 
Objective:  
Improve integrated delivery of PrEP to women seeking health services in maternal and 
child health and family planning clinics and translate implementation improvements into 
useful tools for policymakers and stakeholders 
 
Aims:  
1: To identify determinants of PrEP implementation and identify innovative and promising 
implementation strategies to increase fidelity (accuracy), penetration (screening), and 
integration of PrEP into MCH and FP clinics using a mixed methods approach. 
 
2:  To pilot and evaluate four strategies or bundles of strategies for optimized PrEP 
delivery for impact on penetration (screening), fidelity (accuracy), timeliness, efficiency, 
client and HCW satisfaction (including time), client PrEP knowledge, PrEP continuation, 
and PrEP adherence. We will test three strategies identified by stakeholders and 1 pre-
developed package of strategies (video counseling, HIVST, and optimized delivery). 
 
3: To review evidence, and understanding of study findings by stakeholders through 
stakeholder workshops, IDIs and surveys. 
 
Methods  
1:  Qualitative focus group discussions and in-depth interviews, quantitative surveys 
2:  Interrupted time series quasi-experimental tests with surveys, record abstraction, 
and direct observation 
3:  Qualitative in-depth interviews and facilitated workshops 
 
Population:  
1: Health care workers, facility in-charges, PrEP users, PrEP policymakers and 
implementers 
2: Health care workers, women seeking health services at family planning, maternal 
and child health, or PrEP care 
3: PrEP policymakers, implementers, frontline HCW, PrEP ambassadors, community 
advisory board members 
 
Sites:  
Clinics in Kisumu County, Siaya County, and Homa Bay County, Kenya   
  
Study Duration:  
5 years  
 
  
 
 

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7) BACKGROUND 
 
Women have persistent risk for acquiring HIV during pregnancy and the postpartum period. In settings 
with high HIV prevalence, HIV-uninfected women continue to be at risk for HIV acquisition during pregnancy and 
the postpartum period. In a systematic review, pooled HIV incidence during pregnancy was 4.7 per 100 person-
years, comparable to incidence in ‘high risk’ groups [1]. 
Importantly, HIV incidence estimates in pregnant cohorts 
were derived from the general pregnant population, 
suggesting that the subset of pregnant women with partners 
who are HIV-infected or of unknown HIV status may have 
even higher HIV incidence. Both biologic and behavioral 
factors likely contribute to increased incidence during 
pregnancy and postpartum [2]. A recent analysis among 
HIV-uninfected women in serodiscordant partnerships 
demonstrated a 2.82-fold increased risk of HIV per-coital 
event during late pregnancy and a 3.97-fold increased risk 
during 
the 
postpartum 
period 
compared 
to 
non-
pregnant/non-postpartum periods [2] (Figure 1).  
 
To reach EMTCT targets, primary maternal HIV prevention is necessary. Prevention of mother-to-child HIV 
transmission (PMTCT) programs have yielded remarkable success in decreasing infant infections. Globally, 
WHO 2017 estimated 81% ART coverage among pregnant women in Africa [3]. Over the past decade, as 
population HIV testing has increased, the majority of HIV-infected women presenting to antenatal care (ANC) 
already know their HIV status—others are newly diagnosed at their first ANC visit.  In well-functioning PMTCT 
programs, prompt maternal HIV diagnosis and ART can decrease 
MTCT risk to <1% [4]. As women with chronic HIV infection are 
effectively treated in PMTCT programs, new maternal HIV infections 
acquired during pregnancy and postpartum contribute an increasing 
proportion of infant HIV infections [5–7] (Figure 2). PrEP 
implementation for at-risk HIV-uninfected women in MCH clinics is 
necessary to protect women and to achieve elimination of mother-
to-child HIV transmission (EMTCT) targets.  
   
Oral pre-exposure prophylaxis (PrEP) is a female-controlled, 
acceptable, 
effective 
HIV 
prevention 
evidence-based 
intervention [8–10] and is recommended during pregnancy in 
high incidence settings. WHO recommendations note that current 
safety data [11–14] support the provision of PrEP for individuals at substantial risk [15]. Kenyan national 
guidelines support provision of PrEP during pregnancy [16]. Pregnant women report finding PrEP acceptable 
and desirable for HIV prevention [17]. PrEP can protect pregnant women who do not know their partner’s HIV 
status and cannot negotiate condom use. While condoms and partner antiretroviral treatment (ART) are effective 
HIV prevention methods, they are not feasible for many women [18]. Pregnant women are often unaware of their 
male partner’s HIV status and fear broaching the discussion, particularly in relationships with intimate partner 
violence [19]. In a study from Western Kenya, only 33.6% of pregnant women reported knowing their partner’s 
HIV status [20]. While couples testing is encouraged in antenatal care, uptake remains low [21,22]. Women in 
regions with high HIV prevalence with partners who are HIV-infected or who have unknown HIV status are at 
risk for HIV. In addition, women whose partners are HIV-uninfected may suspect or know that their partners have 
external partnerships, or women may be in polygamous marriages, and may fear that a currently HIV-uninfected 
partner will acquire HIV. Women are often unable to negotiate condom use, particularly in married or 
longstanding partnerships [20], and this inability is exacerbated during pregnancy.  
  
Two large projects in Kenya have implemented PrEP for peripartum women: an ongoing cluster randomized 
trial, PrEP Implementation for Mothers in Antenatal Care (PrIMA) (NIAID R01: MPI John-Stewart, Baeten) and 
Figure 1. HIV risk in women increased in pregnancy 
and postpartum Thomson, J Infect Dis Infect Dis 
Figure 2. Percentage of MTCT from mothers 
infected after their first ANC visit Johnson, 
JAIDS 2012 

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a recently completed implementation project, PrEP Implementation for 
Young Women and Adolescents (PrIYA) (PEPFAR: MPI John-Stewart, 
Baeten). The PrIMA and PrIYA projects have integrated PrEP delivery into 
routine antenatal care (ANC) clinics in the Kenyan public health sector. 
The PrIYA project took place in 16 facilities and screened >10,000 women 
and initiated ~4,100 on PrEP and is the first and largest implementation 
project for PrEP delivery during pregnancy in the world. The ongoing PrIMA 
trial takes place in 20 facilities and will enroll and offer PrEP to ~4,000 
pregnant women. This study will leverage the research infrastructure, political 
will, and unique implementation experience from the ongoing PrIMA and past 
PrIYA projects.  
 
Delivering PrEP in MCH clinics is a ‘one-stop’ approach to protect pregnant and postpartum women. We 
recently demonstrated that it is feasible to deliver PrEP in MCH clinics in a program supported by a DREAMS-
Innovation Challenge. The PrIYA program incorporated PrEP provision in MCH clinics piloted by a full-time extra 
nurse in 16 facilities in Kisumu County, Kenya and additionally trained personnel at 21 ‘mentored’ clinics to 
implement PrEP within MCH or FP services [23]. Importantly, women and health care workers (HCW) felt it was 
critical to provide PrEP at the MCH or FP clinic rather than refer women to HIV treatment Comprehensive Care 
Centers (CCC) to minimize stigma and decrease time spent by women as they shuttled between programs. 
  
PrEP integration in MCH clinics needs to avoid overburdening the health system and HCW. The PrIYA 
program aimed to provide proof of concept that PrEP delivery in MCH was acceptable to pregnant women and 
feasible operationally. We designed the program to circumvent known health systems challenges by providing 
full-time nurses to work with each clinic to build a PrEP delivery system within the MCH clinic. While the PrIYA 
implementation project added staff to clinics, scaling up PrEP delivery through MCH clinics will require health 
systems innovations that do not require increases in human resources. MCH clinics provide routine antenatal 
care (ANC) to pregnant women and postnatal care (PNC) to mothers and children. The primary mandate for 
MCH services is to provide high quality maternal and child health care and to improve maternal and child survival. 
Thus, the MCH clinic is tasked with monitoring pregnancy, syphilis and hemoglobin testing, malaria prophylaxis, 
and PMTCT interventions. Nurses need to have multi-faceted training to be vigilant for pregnancy complications 
and child morbidity, while providing routinized services such as PMTCT.  
 
Systems to decrease workload for nurses, including task-shifting for PMTCT and PrEP, are important to decrease 
HCW burden on MCH care [24–26]. Regional evaluations of MCH clinics have noted uneven quality of care, 
need for improved training to systematically recognize pregnancy danger signals, and monitor children [27,28]. 
In addition, PMTCT programs need persistent oversight to maintain gains or to address recent declines in 
performance. Within PTMCT programs, HIV testing coverage, ART provision, retention and early infant diagnosis 
all have room for improvement and innovation. Adding PrEP to MCH clinics must not detract from vital routine 
MCH services. A streamlined approach that integrates with PMTCT services and minimizes HCW workload and 
optimizes client experience is needed. 
  
8) LITERATURE REVIEW 
 
Implementation science to accelerate scale up of scientific discoveries: While discovery science was crucial in 
determining PrEP efficacy and effectiveness, scaling up PrEP for pregnant women will require implementation 
science [29]. Implementation science is the systematic approach of identifying strategies to scale up evidence-
based interventions and promote their widespread application in routine practice. Implementation science 
includes the identification of determinants of poor or strong implementation and then tests implementation 
strategies to overcome specific barriers and improve implementation outcomes. Implementation strategies can 
address individual, collective, or structural-level changes [30]; a review of implementation strategies has been 
compiled, ranging from altering incentive structures, to using audit and feedback, to modifying job responsibilities 
[31]. Implementation strategies can be introduced individually or packaged to address a series of determinants. 

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There have been no implementation strategies tested to improve PrEP delivery during the peripartum period in 
resource-limited settings. 
 
Models of integrating PrEP delivery into antenatal care: Between June 2017 and December 2018, women of 
reproductive age seeking MCH and FP services at 16 clinics were screened for behavioral risk factors and 
offered PrEP in accordance with Kenyan national PrEP guidelines (developed in May 2017). Time-and-motion 
data were collected to estimate 
time 
required 
during 
PrEP 
integration into MCH and FP 
clinics [23]. Nurses worked with 
MCH and FP clinic teams to 
develop 
optimal 
systems 
for 
incorporating PrEP into existing 
clinical 
flow 
and 
procedures.  
These discussions led to two 
models, the integrated (or “co-
delivery”) 
approach 
and 
the 
sequential 
approach, 
which 
depended on clinic configuration, staffing and flow [23] (Figure 3). We found that implementing PrEP in MCH 
required a median of 18 additional minutes per client that initiated PrEP, and 13 additional minutes per client that 
did not initiate PrEP [23].  While the time-cost was modest for a single client, this one-on-one approach 
cumulatively increases MCH workload; 20 clients at ~10-15 minutes per client would add 5 hours of HCW labor 
per day. 
 
Screening and uptake are heterogeneous: Barriers to 
integrating PrEP delivery into ANC are not well 
characterized due to limited implementation experience 
globally. Integrating PrEP services into ANC includes 
adding steps to a typical ANC visit, including repeat HIV 
testing, behavioral risk assessment, creatinine testing, 
PrEP counseling, and PrEP dispensing. These steps add 
additional workload with fixed numbers of health workers, 
increasing both waiting and service delivery time. There 
was substantial heterogeneity between clinics in the 
penetration of PrEP screening (the proportion of women 
who are screened for PrEP / total women receiving 
antenatal or postnatal services), limiting uptake of 
subsequent steps (Figure 4). The large number of health 
workers and heterogeneous clinics who have implemented 
PrEP during the peripartum period provides an excellent 
learning opportunity to identify further determinants of poor 
and of successful implementation. Effective implementation 
strategies are needed to increase coverage of PrEP 
provision in ANC, while addressing systems-level and organizational barriers.  
 
Video based counselling approaches: 
Table 1: Benefits and drawbacks of video 
 
Barriers overcome by video  
Data available 
Heterogeneous PrEP coverage due to high patient volumes  
- Saves HCW time or enables education without HCW time [35] 
Unavailability of counselors after hours [32] 
    - Allows for all hours counseling 
Language barrier   
    - Can be translated into different languages [32,35–37] 
Figure 3: Models of PrEP integration in ANC  
Figure 4: A) PrEP screening and B) PrEP uptake rates in 
PrIYA sites  
Screening: 
33-93%

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There are many potential implementation strategies that may improve PrEP delivery in MCH and FP clinics. 
Video-based education provides standardized messages, can be engaging, and saves time for women and 
HCW. Integrating PrEP into MCH clinics requires that women receive education regarding PrEP, confirmation of 
HIV-uninfected status and medical eligibility, and advice regarding PrEP adherence. Video-based education has 
been used in HIV pre-test and post-test counseling to achieve both high testing coverage and high HIV-related 
knowledge, allowing for standardized messaging in multiple languages, available at all hours [32–37]. Compared 
to counselor-delivered education, video-based education is easier to update, scale, and standardize. Video-
based education could provide standardized messaging regarding HIV risk in pregnancy/postpartum, 
benefits/risks of PrEP, and importance of adherence and serial HIV testing. Women could listen to video-based 
educational content while waiting for their routine MCH appointment (typically a 90-minute wait). This process 
would decrease nurse time with women and allow women to request PrEP based on the video and ask further 
questions, if needed. Video-based education has been shown to be as effective as in-person counseling 
[32,34,37–40]. 
 
Other strategies for PrEP optimization 
Serial HIV testing for PrEP can be expedited by HIV self-testing in clinics. HIV retesting is required for all clients 
on PrEP, but the high volume of testing may overburden fixed numbers of HCW, or may shift HCW away from 
other tasks. Rapid oral HIV self-testing (HIVST), which is saliva-based, has excellent diagnostic performance, 
with high sensitivity and specificity when compared to standard rapid blood HIV testing [43,44]. HIVST has been 
used in varied settings and recently been expanded by the Kenya Ministry of Health as an option to increase 
HIV testing in Kenya. A recent cluster randomized trial in Malawi demonstrated that facility-based HIVST in 
outpatient waiting areas significantly increased number and proportion of clients tested [45,46]. HIVST for 
retesting for PrEP users is being tested among serodiscordant couples in Kenya, and is anticipated to increase 
fidelity (accuracy in adherence) to retesting guidelines, save HCW time, and be more cost-effective. 
 
Policy Implications 
Policymakers may consider affordability data, in addition to effectiveness data, to make relevant, local PrEP 
policy decisions. Cost-effectiveness analyses are useful for comparing interventions against one another; 
however, interventions considered “cost-effective” by standard Gross Domestic Product thresholds may not be 
affordable, particularly in resource-limited settings [47,48]. A recent review of PrEP cost-effectiveness called for 
budget impact analyses to assess affordability [49]. Budget impact analyses quantify total cost when 
implemented on a large scale, which helps policymakers determine whether a specific intervention is affordable 
given budget constraints. As Kenya moves towards adopting universal health care this year, this type of analysis 
will be particularly needed. PrEP is a relatively expensive evidence-based intervention; the Ministry of Health 
has outlined a series of PrEP cost research questions, including drivers of total cost and cost of delivery through 
varied service delivery platforms, to direct their roll out of PrEP nationally. Gaps exist in understanding how 
policymakers use research to make decisions. Systematic reviews have revealed a weak understanding in how 
policymakers consider scientific evidence in making policy decisions [50]. This study will explicitly address this 
gap, providing innovative data to promote more rapid translation of research findings into policy. 
  
 
9) GUIDING FRAMEWORKS 
 
Overview: This study uses a series of 3 frameworks to inform the study design and data collection elements. 
Traditional psychosocial or behavioral theory models are widely used to inform public health research, reflecting 
Inconsistent information given by counselors 
- Consistent messages result in higher knowledge scores [34–36,38,39,41] 
Client fear of asking sensitive questions  
- Opportunity to learn and review sections with no embarrassment [42] 
Pending  
questions 
Unclear whether benefits shown in high resource settings translate to resource-limited settings  
Unclear whether nuanced decision-making information inherent in PrEP counseling lends itself well to standardized video 
format 

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mechanisms at the individual, group, and societal levels. These theories are essential in selecting appropriate 
interventions, elucidating mechanisms of action, and understanding barriers at multiple levels. However, 
investigating implementation requires that these traditional theories be adapted or modified to reflect distinct 
needs of implementation science. The three frameworks or theories described below have been derived from 
traditional psychosocial or behavioral models and specifically modified to reflect such implementation science 
needs. They have been applied to this study to select study outcomes, inform data collection tools, and integrate 
information from different aims.  
  
Aim 1: In-Depth Interviews and Focus Group 
Discussions 
CFIR Model: We will utilize the Consolidated 
Framework for Implementation Research (CFIR) to 
inform Aim 1 (Figure 5). The CFIR is an original 
framework for implementation science that synthesizes 
20 unique frameworks into a single consolidated 
framework that describes determinants in terms of 5 
major domains (intervention characteristics, outer 
setting, inner setting, characteristics of individuals, and 
process) and 39 constructs within those domains [53]. 
CFIR is flexible and can serve both as an explanatory 
and predictive framework. We will use CFIR first as an 
explanatory framework in Aim 1 to identify factors that 
served as positive and negative determinants (barriers 
and facilitators) to PrEP integration into ANC, and to understand why the wide range of implementation strategies 
tried in PrIYA and PrIMA had different implementation success. Subsequently, we will use CFIR as a predictive 
framework to hypothesize which implementation strategies might overcome specific barriers to inform Aim 2. 
During the interviews with policymakers, we will use the CFIR to create question guides; the goal of these 
interviews will be to understand which of the CFIR constructs are considered by policymakers, and to understand 
how they consider cost data in decision-making.  
 
Aim 2: Interrupted Time Series Intervention testing 
Proctor Model: A review in 2000 noted that it took, on average, 17 years for just 14% of effective evidence-based 
interventions to become part of routine clinical practice [51]. While discovery science has tended to dominate 
HIV research historically, there is a growing recognition of the need for implementation science to bring promising 
evidence-based interventions to scale to realize their full impact. Implementation science is a new scientific field; 
while terminology and definitions are evolving, this application will use NIH terminology and define terminology 
Figure 5: Consolidated Framework for Implementation Research 
Figure 6: Adapted Proctor model of taxonomy of outcomes in health research 

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that is unique to implementation science. The Proctor model characterizes 1) implementation outcomes, 2) 
service, and 3) client outcomes, noting that implementation strategies are applied to improve implementation of 
interventions from discovery science [52] (Figure 6). This study will measure: 1) implementation outcomes, 
including fidelity (proportion of women who receive all PrEP specific steps in a visit: HIV testing, HIV risk 
screening, PrEP counseling), penetration (proportion of women who are screened for PrEP / total women 
receiving antenatal or postnatal services), acceptability, uptake, and costs; 2) service outcomes, including 
efficiency, effectiveness, and timeliness, and 3) client outcomes, including satisfaction. Operational definitions 
of each outcome are provided in Section 11.3.9 Variables. 
 
Summarizing study results across aims 
PRISM framework: We will use the PRISM (Practical, Robust Implementation and Sustainability Model) Model, 
which synthesizes the RE-AIM framework, Model for Improvement, and the Chronic Care model. This 
implementation science model is 
particularly well-suited to scaling 
up new interventions, optimizing 
performance, 
and 
considering 
sustainability [54]. It considers 
implementation science RE-AIM 
outcomes (reach, effectiveness, 
adoption, 
implementation, 
and 
maintenance) as a function of 
multiple levels of provider and 
patient 
perspectives 
of 
the 
intervention, characteristics of the 
recipient 
organization 
and 
patients, 
and 
infrastructure 
available for implementation and 
sustainability, as well as the 
external environment (Figure 7). 
Aim 1 will provide qualitative 
information about key stakeholder 
perspectives of MCH-PrEP and 
FP-PrEP integration, guided by 
the multiple levels of the social-
ecological framework [55,56]. Aim 
1 will further provide quantitative 
data about the organizational and 
health systems issues and factors 
related 
to 
environment, 
infrastructure, 
and 
facility 
organization. Aim 2 will pilot the 
optimized delivery model and 
measure 
implementation 
outcomes.  
  
 
 
  
 
 
Figure 7: PRISM model with study aims mapped to components 

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10) RATIONALE 
  
It is critical to optimize the delivery and integration of PrEP into existing health services for women in resource-
limited settings. Applying robust implementation science methods to define barriers, test strategies, and engage 
with stakeholders to support dissemination are critical.  
 
11) HYPOTHESIS, OBJECTIVES, & STUDY QUESTIONS: 
 
AIM 1: To identify determinants of PrEP implementation and identify innovative and promising implementation 
strategies to increase fidelity, penetration, and integration of PrEP into MCH and FP clinics using a mixed 
methods approach. 
Hypothesis 1: We predict that determinants will include overburdened staff, inefficient patient flow, insufficient 
provider knowledge in counselling techniques, and paperwork burden. We predict that promising implementation 
strategies may include HIV self testing, task shifting PrEP risk assessment, video-based PrEP counseling, and 
streamlining data collection registers. 
 
AIM 2:  To pilot and evaluate four strategies or bundles of strategies for optimized PrEP delivery for impact on 
penetration, fidelity, timeliness, efficiency, client and HCW satisfaction (including time), client PrEP knowledge, 
PrEP continuation, and PrEP adherence. We will test three strategies identified by stakeholders and 1 pre-
developed package of strategies (video counseling, HIVST, and optimized delivery). 
Hypothesis 2: We predict that several implementation strategies will be effective in improving implementation 
and service outcomes.  
 
AIM 3: To review evidence, findings, and understanding of study findings through two stakeholder workshops 
and to evaluate these workshops through IDIs and surveys. 
Hypothesis 3: We predict that meaningful stakeholder engagement will ensure that tested implementation 
strategy findings are more widely disseminatable.  
 
 
12) STUDY DESIGN AND METHODOLOGY 
12.1) STUDY AREA DESCRIPTION: 
The proposed study will be conducted in twenty health care facilities in Kisumu, Siaya, and Homa Bay counties. 
Facilities will be selected for inclusion if they have ongoing PrEP delivery through maternal and child health 
(MCH) clinics and if they have ongoing PrIMA or PrIYA-SP activities.  At least ten of the facilities selected for 
inclusion should have PrEP delivery occurring in Family Planning (FP) clinics in addition to MCH clinics.  
  
Table 2: Summary of study aims, population, design, data collection, sample size, outcomes and inclusion 
 
Aim 1 
Aim 2 
Aim 3 
 
Implementation determinants, 
implementation strategies, and 
service availability 
Implementation strategy tests 
Stakeholder views on research 
findings and best practices 
Population 
Health care workers (HCW), Facility 
in-charges, PrEP users, PrEP 
policymakers  
HCW, clients attending study clinics 
PrEP policymakers, implementers, 
frontline HCW, PrEP ambassadors, 
community advisory board 
members 
Design 
Qualitative and quantitative cross-
sectional design 
Interrupted time series (ITS) quasi-
experimental design 
Qualitative cross-sectional design 
Data 
collection 
In-depth interviews (IDI), Focus 
Group Discussions (FGD), and 
quantitative surveys 
Register abstraction of existing 
program data, client observation, 
quantitative surveys 
IDI, facilitated workshops 
Sample size 
HCW: up to 26 FGDs with 7-10 
participants each, and quantitative 
survey with 260 participants 
Facility in-charge: In-charges from 
Register abstraction of existing 
program data: unable to predict 
total number of records to be 
abstracted; expected abstraction of 
PrEP policymakers: up to 15 IDIs  
Workshop participants: up to 50 
participants  

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26 facilities 
PrEP users: up to 4 FGDs with 7-10 
participants each 
PrEP policymakers and 
implementers: up to 40 participants 
for in-depth interviews 
~200 clients per month per clinic  
Client observations: up to 200 
clients per clinic per interrupted time 
series experiment cycle 
Quantitative surveys: up to 240 
clients per clinic per interrupted time 
series experiment cycle; up to 20 
HCW per clinic per interrupted time 
series experiment cycle 
Outcome(s) 
of interest 
Implementation determinants, range 
of potential implementation 
strategies, prioritized 
implementation strategies, service 
availability and readiness 
PrEP penetration, fidelity, uptake, 
continuation, adherence, efficiency, 
timeliness, client and HCW 
satisfaction, client PrEP knowledge, 
service availability 
Decision-making process and 
understanding of budget impact 
analyses, consensus-determined 
best practices for PrEP delivery and 
integration 
Inclusion 
criteria 
HCW: work at a facility involved in 
study, involved in PrEP service 
delivery, >18 years 
Facility in-charge: work at a facility 
involved in study, >18 years 
PrEP users: female PrEP users at 
study facilities, >15 years (includes 
emancipated minors) 
PrEP policymakers and 
implementers: involved in making 
decisions related to PrEP at 
national or county level, >18 years 
HCW: work at a facility involved in 
study, involved in PrEP service 
delivery, >18 years 
Clients: female clients seeking 
health services at study facilities, 
>15 years (includes emancipated 
minors) 
PrEP policymakers and 
implementers: involved in making 
decisions related to PrEP at 
national or county level, >18 years 
Other stakeholders:  stakeholder in 
in PrEP delivery, >18 years; 
adolescent PrEP ambassadors, >15 
years 
Exclusion 
criteria 
N/A 
N/A 
N/A 
 
 
 

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12.2) AIM 1:  
To identify determinants of PrEP implementation and identify innovative and promising implementation strategies 
to increase fidelity, penetration, and integration of PrEP into MCH and FP clinics using a mixed methods 
approach. Operational definitions of each outcome are provided in Section 11.3.9 Variables. 
 
 
Aim 1 
 
Implementation determinants, implementation strategies, and service availability 
Population 
Health care workers (HCW), Facility in-charges, PrEP users, PrEP policymakers  
Design 
Qualitative and quantitative cross-sectional design 
Data 
collection 
In-depth interviews (IDI), Focus Group Discussions (FGD), and quantitative surveys 
Sample size 
HCW: up to 26 FGDs with 7-10 participants each, and quantitative survey with 260 participants 
Facility in-charge: In-charges from 26 facilities 
PrEP users: up to 4 FGDs with 7-10 participants each 
PrEP policymakers and implementers: up to 40 participants for in-depth interviews 
Outcome(s) 
of interest 
Implementation determinants, range of potential implementation strategies, prioritized implementation strategies, 
service availability and readiness 
Inclusion 
criteria 
HCW: work at a facility involved in study, involved in PrEP service delivery, >18 years 
Facility in-charge: work at a facility involved in study, >18 years 
PrEP users: female PrEP users at study facilities, >15 years (includes emancipated minors) 
PrEP policymakers and implementers: involved in making decisions related to PrEP at national or county level, >18 
years 
Exclusion 
criteria 
N/A 
 
12.2.1)    STUDY DESIGN 
Mixed methods including Focus Group Discussions (FGDs), In-Depth Interviews (IDI), Health Care Worker 
(HCW) surveys, and Service Availability and Readiness Assessment (SARA) with Facility In-Charges 
 
12.2.2)    STUDY POPULATIONS 
Health Care Workers: 
HCW working on 16 facilities will be approached for participation in 26 (16 MCH, 10 FP) clinic-based FGD and 
to complete a quantitative survey to understand their experience with PrEP delivery. Facility in-charges at all 
facilities from PrIMA and PrIYA will be identified and approached to conduct a health systems survey. 
 
HCW Inclusion Criteria: 
● HCW at a study facility in Kisumu, Homa Bay, or Siaya Counties. 
 
PrEP users 
Up to 40 PrEP users will be identified from participating facilities and invited to participate in FGDs to explore 
their experience with PrEP use.  Ten participants from each of the following groups will be invited to an FGD.  
● FP-based PrEP user, 15-24 years old 
● FP-based PrEP user, 25 or older 
● MCH-based PrEP user, 15-24 years old 
● MCH-based PrEP user, 25 or older 
 
PrEP user inclusion criteria: 
● Female gender 

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● Receiving care in an MCH or FP clinics at a facility 
● ≥15 years old 
● Able and willing to provide informed consent for participation 
● Currently using PrEP for any duration 
 
PrEP Policy Makers and Implementers 
Up to 40 policy makers and representatives from PrEP implementing partners will be identified and invited to 
participate in in depth interviews. 
 
PrEP Policy Maker and Implementer Inclusion Criteria: 
● Has a role at the National or County level in PrEP policy making or implementation 
● Able and willing to provide informed consent 
 
12.2.3)    SAMPLE SIZE DETERMINATION AND FORMULAS USED 
FGD sample size: We will conduct 26 FGDs with HCW and 4 FGDs with PrEP users. Each FGD will consist of 
7-10 participants, sufficient to generate conversation without being too large to become intimidating [57,58]. We 
will aim to recruit health workers from varying cadres, including those involved in antenatal and postnatal care, 
HIV testing services, and laboratory. Based on previous studies in this region with health workers and PrEP 
users, we predict that our sample size will be sufficient to reach theoretical saturation, that no new themes are 
identified with each additional FGD [59].  
 
IDI sample size. We will conduct 26 IDIs with facility in-charges and 40 IDIs with policymakers and implementers. 
Based on previous experience conducting qualitative research, we believe our sample size will be enough to 
reach sufficient diversity and data saturation [60,61].  
 
Quantitative prioritization of strategies: We will aim to enroll up to 260 individuals. Given that these data are for 
prioritization purposes, rather than to identify determinants associated with high and low performance, formal 
power calculations were not appropriate. Instead, analysis will involve calculating mean frequency, strength of 
influence, and likelihood of success scores, accounting for unequal numbers per cluster by weighting 
observations. 
 
12.2.4)    RECRUITMENT PROCEDURES 
Health Care Workers: 
Study staff will communicate with county-level health officials of Kisumu, Homa Bay and Siaya Counties to 
compile a list of facilities that meet our eligibility criteria. Study staff will communicate the study purpose and 
objectives to in-charges of the facilities identified. Facility in-charges will be asked to introduce the facility’s 
HCWs. A member of the study team will randomly select HCWs at each facility and contact each of them either 
in-person or by phone to invite them to participate in the FGD or survey. The study background and procedures 
will be explained to potential HCW participants to inform the HCWs’ decision to participate. The HCWs will also 
be assured that participation in the FGD or survey will not impact their employment.  
 
FGDs: All FGDs with HCWs will be conducted by qualitative study staff at the 16 K-PrOM facilities. Up to ten 
HCWs at each facility will be invited to participate in the FGD. A member of the study team will then schedule 
the FGD for HCWs willing to participate at a time convenient for the majority of the potential participants. 
 
Facility In-Charge: 
In addition to participating in the HCW FGDs, facility in-charges will be approached to complete a health systems 
survey.  
 
PrEP Users: 
During antenatal, early postnatal, and family planning care visits, study staff will approach women, request to 
review their health records card to determine whether they are currently taking PrEP, and will describe the 

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purpose of the FGDs and invite interested women to participate. Study staff will track the age of interested 
participants to ensure that no more than 10 AGYW and 10 older women participate in the FGDs at each facility.  
 
PrEP Policy Makers and Implementers: 
PrEP Policy Makers and Implementers will be identified through consultation with NASCOP and the PrEP 
Technical Working Group at NASCOP. We will invite identified policy makers to participate in the IDI.   
 
12.2.5)    ENROLLMENT & STUDY PROCEDURES 
General procedures for all IDIs/FGDs 
Consent will be obtained from participants to take notes and audio record all focus group discussions (FGDs). 
Trained study staff will be responsible for conducting informed consent procedures and enrolling participants. 
During enrollment, participants will be informed of the facilitation procedure, including the length (30-120 minutes 
each) and that the FGDs/IDIs will be audio recorded and transcribed. Participants scheduled to return at a later 
date for an IDI or FGD will provide contact information and names upon consent, for the purpose of reminding 
them of the interview date. Participants will meet a trained interviewer or moderator who will ask questions and 
take notes. All FGDs will be performed in a private areas by trained study staff members and in local languages, 
as needed.  
 
The interviewer/moderator will describe procedures and norms for discussion and participation. Participants will 
be given a chance to ask questions regarding procedures prior to the discussion. The socio-demographic 
information will be documented on separate forms. After IDI/FGD completion, participants may re-contacted to 
verify the accuracy of the data collected. To compensate for time and travel costs, each participant will be offered 
1000 Kenyan Shillings (KES) following completion of the IDI/FGD. Once the IDI/FGD is completed, transcripts 
of recordings will be stored without links to patient identifiers, except for those needed to link with consent forms, 
for up to six years. 
 
We have included draft IDI and FGD guides in Appendix 2. Although the content of the interview and focus group 
guides will remain the same throughout the study, the phrasing and order of the questions are subject to change 
after pilot testing of these tools. If the content areas covered in the guides change, they will be resubmitted for 
IRB approval. 
 
PrEP user FGDs: 
Socio-demographic information for the PrEP user FGDs will include: age, marital status, education level, 
employment, number of children, and partner HIV status as shown in the participant survey portion of the in-
depth interview guide. FGDs with women will explore experiences with initiating and continuing PrEP with a 
focus on factors and actions impeding and/or contributing to optimal PrEP integration and implementation 
strategies that have been or could be employed to improve efficiency, synergy, and access. 
 
HCW FGDs: 
For HCW FGDs, sociodemographic information will include age, education level, duration of employment, and 
experience providing PrEP. The HCW FGD will use discussion guides based on Consolidated Framework for 
Implementation Research (CFIR) to elicit information about health worker experiences with specific 
implementation strategies and opinions on modifications to these strategies to further improve implementation 
outcomes of fidelity and penetration.  
 
HCW Surveys: 
HCW will be asked to complete a survey that captures the frequency and perceived strength of influence of each 
PrEP delivery determinant and the perceived likelihood of success of a variety of possible PrEP optimization 
strategies, all using 3 point Likert scales with semantic anchors (e.g. never, sometimes, frequently). HCWs will 
be asked about transitioning PrEP delivery from research (PrIMA & PrIYA-SP) staff to clinic staff. HCWs will also 
be asked about the impact of COVID-19 on PrEP delivery and clinic duties. The survey will include questions 
about their daily experiences, sociodemographic information such as age, education level, duration of 

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employment, and experience providing PrEP.  Surveys will be administered in-person, over telephone or 
electronically via a computer-assisted self-interview. Participants will receive a reimbursement of 600 KES 
following completion of the survey. Mobile money transfer will be used for individuals participating remotely. 
 
PrEP Policy Maker and Implementer IDI 
For PrEP policy maker and implementer IDIs, sociodemographic information will include age, education level, 
duration of employment, and experience providing PrEP. PrEP policy maker and implementer IDI guides will 
also include knowledge, attitudes, and beliefs about PrEP delivery strategies, preferred and essential attributes 
for PrEP delivery best practices, and experiences with PrEP delivery at national, county, or partner organization 
level. 
 
Planned Analyses: 
PrEP user FGDs: We will use qualitative methods to explore women’s experiences with initiating and continuing 
PrEP with a focus on factors and actions impeding and/or contributing to optimal PrEP integration. 
 
HCW FGDs and Surveys: Survey data collected from HCWs will be analysed descriptively with mean frequency, 
strength of influence, and likelihood of success scores, accounting for unequal numbers per cluster by weighting 
observations, to identify HCW preferences in PrEP optimization strategies.  
 
The HCW FGD will use the Consolidated Framework for Implementation Research (CFIR) to elicit information 
about health worker experiences with specific implementation strategies and opinions on modifications to these 
strategies to further improve implementation outcomes of fidelity and penetration.  
 
PrEP Policy Maker and Implementer IDI: We will use qualitative methods to explore knowledge, attitudes, and 
beliefs about PrEP delivery strategies, preferred and essential attributes for PrEP delivery best practices, and 
experiences with PrEP delivery at national, county, or partner organization level. 
 
12.2.6)     LABORATORY METHODS 
Not applicable 
 
12.2.7)    DATA COLLECTION INSTRUMENTS 
● PrEP user focus group guide 
● PrEP user demographic information 
● HCW Survey 
● HCW FGD guide 
● Service Availability and Readiness Assessment Tool 
● PrEP policy maker and implementer interview guide 
 
12.2.8)    VARIABLES: Outcomes, indicators, and source documents 
Not applicable 
 
12.2.9)  TRAINING PROCEDURES 
Drs. Beima-Sofie and Wagner will supervise training of facilitators for the qualitative components of the study.  
 
Study Materials 
• 
HCW FGD Consent Form 
• 
HCW Survey Consent Form 
• 
Policy Maker IDI Consent Form 
• 
PrEP User FGD Consent Form 
 
 

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12.3 AIM 2:   
To pilot and evaluate four strategies or bundles of strategies for optimized PrEP delivery for impact on 
penetration, fidelity, timeliness, efficiency, client and HCW satisfaction (including time), client PrEP knowledge, 
PrEP continuation, and PrEP adherence. We will test three strategies identified by stakeholders (based on 
qualitative information from Aim 1) and 1 pre-developed package of strategies (video counseling, HIVST, and 
optimized delivery). Operational definitions of each outcome are provided in Section 11.3.9 Variables. 
  
Aim 2 
 
Implementation strategy tests 
Population 
HCW, clients attending study clinics 
Design 
Interrupted time series (ITS) quasi-experimental design 
Data 
collection 
Register abstraction of existing program data, client observation, quantitative surveys 
Sample size 
Register abstraction of existing program data: unable to predict total number of records to be abstracted; expected 
abstraction of ~200 clients per month per clinic 
Client observations: up to 200 clients per clinic per interrupted time series experiment cycle 
Quantitative surveys: up to 240 clients per clinic per interrupted time series experiment cycle; up to 20 HCW per 
clinic per interrupted time series experiment cycle 
Outcome(s) 
of interest 
PrEP penetration, fidelity, uptake, continuation, adherence, efficiency, timeliness, client and HCW satisfaction, client 
PrEP knowledge, service availability 
Inclusion 
criteria 
HCW: work at a facility involved in study, involved in PrEP service delivery, >18 years 
Clients: female clients seeking health services at study facilities, >15 years  (includes emancipated minors) 
Exclusion 
criteria 
N/A 
 
12.3.1)    STUDY DESIGN  
We will utilize interrupted-time series design; this is a quasi-experimental design that compares data before an 
intervention is introduced to data after the intervention is introduced, and controls for time trends (Figure 8). Four 
rounds of interrupted-time series evaluations to evaluate four PrEP optimization interventions, three identified by 
stakeholders based on qualitative information in Aim 1, and one pre-developed package of interventions (video-
based PrEP counselling, HIV Self-Testing 
[HIVST], and optimized PrEP delivery). Each 
of the four rounds of interrupted-time series 
evaluations will include 4 facilities receiving the 
intervention and 4 facilities serving as an 
ongoing concurrent comparator group; these 4 
facilities will not receive any of the packages of 
interventions, but will undergo the same data 
collection procedures. There will be three 
months of baseline data collection and a three 
month intervention period for each of the 4 
intervention facilities, and six months of data 
collection during the same calendar period for 
each of the 4 comparator clinics for each of the 
4 interrupted-time series interventions.  
 
12.3.2)    INTERVENTION DETAILS  
There will be four strategies or bundles of strategies tested, one bundle in each of the four interrupted-time series 
evaluations. Three of the bundles of strategies will be determined based on the qualitative information gathered 
in Aim 1 by stakeholders and are unknown at this time. One bundle of strategies is pre-developed and includes 
3 components: video-based PrEP counselling, HIV Self-Testing [HIVST] for women undergoing repeat HIV 
Figure 8: Interrupted time series experiment design and timeline 

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testing, and optimized PrEP delivery 
and prescription processes (Figure 9). 
We will work with a videography 
company to develop the video-based 
PrEP counseling component. We will 
borrow processes from ongoing and 
recently completed studies in western 
Kenya related for optimizing PrEP 
dispensing and HIVST while clients 
wait. PrEP will be stored in MCH clinics. 
Once women ask for PrEP and have 
been confirmed eligible, women will 
receive PrEP at MCH clinic. In our prior 
work, we have arranged with pharmacy and CCC to maintain supplies of PrEP at MCH. HIVST will be provided 
as an option in private cubicle-style kiosks, which have been tested in western Kenya and found to be acceptable 
and feasible.  
 
12.3.3)    STUDY POPULATIONS 
The twenty (20) health care facilities that were included in Aim 1 surveys will be included in the implementation 
and evaluation of PrEP optimization strategies identified through Aim 1 activities. Of the 20 facilities, facilities will 
be assigned one of four intervention groups (4 facilities per group) or a comparator group (4 facilities) throughout 
the four interrupted-time series rounds. Up to twenty HCW will be approached at each facility per interrupted 
time series cycle to participate in a satisfaction survey to understand their experience with the PrEP optimization 
intervention. 
 
During each of the four interrupted-time series rounds, we will abstract all clinical records for HIV-negative 
patients receiving MCH services to assess penetration of PrEP screening and PrEP uptake.  We anticipate 
abstracting records for up to 200 clients per month per clinic (1,200 abstracted records per facility per interrupted-
time series). Additionally, to assess intervention fidelity and client satisfaction through exit surveys with up to 40 
clients per month per facility (240 exit surveys per facility per ITS). We will assess client time using client 
observation with up to 200 clients per clinic per interrupted-time series cycle.  
 
12.3.4)    SAMPLE SIZE DETERMINATION AND FORMULAS USED 
 
To maintain the greatest amount of power, outcome estimates will be based on individual count data, not 
aggregated to summaries. We utilized Stata 14 for sample size calculations.  
 
• 
Time period: Each experiment will include 3 months of data before each strategy is introduced and 3 
months after each strategy is introduced 
• 
Sample size (facilities): There will be 4 experiments, each will include 4 intervention facilities (16 facilities) 
and the same 4 comparator facilities; for a total of 20 facilities.  
• 
Sample size (participants): We will observe 200 clients per clinic per experiment. We will collect survey 
data from 240 clients and 20 HCW per clinic per experiment. We will abstract register data during each 
experiment; while we are unable to predict total number of records to be abstracted, we expect 
abstraction of ~200 clients per month per clinic. 
• 
Assumptions: α=0.05, two-sided tests, a conservative harmonic mean of 100 women presenting to ANC 
per month (~600 women over 6 months) per cluster (mean in PrIYA sites was ~163 per month), and a 
conservative estimate of the coefficient of variation of 0.5. We assume that penetration of PrEP screening 
and counselling is 68% (SD: 18%), time spent by HCW on PrEP services is 18 minutes (SD: 8 minutes) 
per PrEP initiator and 13 minutes (SD: 6 minutes) per PrEP-non-initiator, uptake is 10.5% (SD: 5%), and 
that knowledge and satisfaction scores are on a 100-point scale and have an SD of 20. 
Figure 9: Pre-determined bundle of implementation strategies  

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• 
Detectable effect size: We will be able to detect an absolute change of +/-4.8% for outcomes of 
penetration of PrEP screening, an absolute change of +/- 2 minutes in time, an absolute change of +/1% 
in PrEP uptake, and an absolute difference of 4 points in knowledge and satisfaction scores. 
• 
Power: We will have at least 80% power  
 
12.3.5)    RECRUITMENT PROCEDURES 
Register abstraction: We will not actively recruit individual participants for register abstraction.  
 
Client observation: Women receiving MCH services will be approached as they enter the facility and asked to 
carry a time card. Each time card will collect the time that each service starts and ends and will be filled by 
providers, but will not collect any identifying information. Study staff will be posted at  each facility until the sample 
size is reached. 
 
Surveys with clients: Women receiving MCH services will be approached as they exit the facility and asked to 
participate in a brief survey. Study staff will be posted at each facility until the sample size is reached. 
 
Surveys with HCW: HCW providing services will be approached by study staff in person, by phone or email and 
invited to complete a survey. 
 
12.3.6    ENROLLMENT & STUDY PROCEDURES 
Register abstraction 
Consent: Individual patients will not be asked to provide consent as abstracted data are anonymous and 
it would not be feasible to contact clients to seek consent.  
 
Procedures: We will abstract anonymous patient level count data from health registers at all of the 
intervention and comparator facilities. We will abstract the following count data from registers: women 
screened for PrEP interest (penetration), women offered HIV testing and PrEP (fidelity), women who 
initiate PrEP (uptake), women who adhere to PrEP (adherence determined via pill count), and women 
who refill PrEP (continuation).   
 
Client observation 
Consent: Individual patients will be given the opportunity to verbally accept or decline to carry cards; data 
are anonymous. 
 
Procedures: A trained research assistant will conduct flow mapping (physical walk throughs to graphically 
represent patient flow pathways in a facility) and conduct time-and-motion data collection (counting 
minutes spent waiting and receiving various services) to describe the flow of women within health facilities 
and between providers as they receive services. Individual patients will be given the opportunity to carry 
a single sheet of paper with a study identification number to each service delivery point. Health care 
workers or research assistants will note the time that services begin and end. We will characterize the 
following outcomes: efficiency and time spent by HCW and clients.  
 
Surveys with clients 
Consent: Women will be given the opportunity to provide oral informed consent for participation or to 
decline participation; these surveys are anonymous.  
 
Procedures: Women will complete a survey following service delivery completion. The following data will 
be collected via survey: client satisfaction with services, client PrEP knowledge, client perception of being 
offered PrEP services.  
 
SARA Surveys with HCW 
Consent: HCW will be given the opportunity to provide oral informed consent for participation or to decline 
participation; these surveys are anonymous.  

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Procedures: HCW will complete a survey. The following data will be collected via survey: HCW 
satisfaction with training and service delivery modifications. 
 
Planned Analyses: We will use interrupted time series methodology to compare changes in penetration (PrEP 
screening), uptake (PrEP initiation), adherence, and continuation (PrEP refills) between the baseline and 
intervention periods for intervention facilities and with the comparison facilities.  
 
12.3.7)     LABORATORY METHODS 
Not applicable 
 
12.3.8)    DATA COLLECTION INSTRUMENTS 
● Exit Survey 
● Record abstraction form 
 
12.3.9)    VARIABLES: Outcomes, indicators, and source documents 
 
Outcome 
Indicator 
Source documents 
PrEP penetration 
Proportion of women who are screened for 
PrEP / total women receiving antenatal or 
postnatal services 
Routine program data; PrEP register, antenatal register, 
postnatal register, family planning register 
PrEP fidelity 
Proportion of women who receive all PrEP 
specific steps in a visit: HIV testing, HIV risk 
screening, PrEP counseling 
Primary data of anonymous exit survey assessing 
services received 
 
Direct observation of client-provider interactions 
 
Routine program data: HIV testing register, PrEP 
register, antenatal register, postnatal register, family 
planning register 
PrEP uptake 
Proportion of women who accept PrEP 
among those offered 
Routine program data: PrEP register 
PrEP continuation 
Proportion of women who present for a refill 
among those initially prescribed PrEP 
Routine program data: PrEP register, pharmacy records 
PrEP adherence 
Proportion of women who have >80% 
adherence to PrEP by pill count among 
those initially prescribed PrEP 
Routine program data: PrEP register, pharmacy records 
PrEP efficiency 
Patient flow mapping to identify more 
efficient client flows with fewer transitions 
between physical spaces and providers 
Primary data collection through direct observation of 
patient flow 
Timeliness 
Time and motion data to assess wait times, 
service delivery times, and HCW burden 
Primary data collection through direct observation and 
time collection 
Client satisfaction 
Satisfaction on a scale of 1-10 adapted 
from Training Satisfaction Survey 
Primary data collection through anonymous surveys 
HCW satisfaction 
Satisfaction on a scale of 1-10 adapted 
from Training Satisfaction Survey 
Primary data collection through anonymous surveys 
Client PrEP knowledge 
10 questions based on content covered in 
counseling sessions 
Primary data collection through anonymous surveys 
 
 

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12.3.10)    TRAINING PROCEDURES 
Dr. John Kinuthia will oversee training of study staff on PrEP optimization procedures, exit surveys, and record 
abstraction. Trained study staff will work with facility staff at all facilities to ensure appropriate implementation of 
ITS-specific PrEP optimization procedures. 
 
12.3.11)    STUDY MATERIALS 
• 
Oral consent guide 
 
 

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12.4 AIM 3:  
To review evidence, findings, and understanding of study findings through two stakeholder workshops and to 
evaluate these workshops through IDIs and surveys. 
  
Aim 3 
 
Stakeholder views on research findings and best practices 
Population 
PrEP policymakers, implementers, frontline HCW, PrEP ambassadors, community advisory board members 
Design 
Qualitative cross-sectional design 
Data 
collection 
IDI, facilitated workshops 
Sample size 
PrEP policymakers: up to 15 IDIs 
Workshop participants: up to 50 participants  
Outcome(s) 
of interest 
Decision-making process and understanding of budget impact analyses, consensus-determined best practices for 
PrEP delivery and integration 
Inclusion 
criteria 
PrEP policymakers and implementers: involved in making decisions related to PrEP at national or county level, >18 
years 
Other stakeholders:  stakeholder in in PrEP delivery, >18 years; adolescent PrEP ambassadors, >15 years 
Exclusion 
criteria 
N/A 
 
12.4.1)    STUDY DESIGN  
PrEP policy makers, implementers, and other stakeholders will be invited to participate in a series of workshops 
aimed at identifying priority interventions to test for PrEP optimization, review findings of the interrupted time 
series intervention testing, draft a document of best practices for PrEP implementation, and review budget impact 
analyses. At the final workshop, cognitive interviews will be conducted with stakeholders to understand how they 
interpret and understand the budget impact analysis.  
 
12.4.2)    STUDY POPULATIONS 
Stakeholder meeting to develop best practices 
PrEP policy makers, implementers, and other stakeholders will be identified through consultation with national 
and county level ministry of health officials.  We will ensure that each workshop includes up to 50 participants 
representing a range of stakeholder perspectives and experiences, at least: 
• 
5 national level policy makers 
• 
5 county level policy makers 
• 
5 facility level policy makers 
In aligning with core principles of community engagement and ensuring voices of all key stakeholders are 
represented, including potential end users and those within the community of practice [62], we will purposively 
invite adolescent PrEP ambassadors, frontline HCWs, implementing partner organizations, representatives from 
the National AIDS and STD Control Program (NASCOP), and County health officials to participate in the Best 
Practices Development Workshop. Representatives from stakeholder groups will be identified through informal 
discussions with MOH and County Health officials, Community Advisory Board members, PrEP implementers 
and peer-reviewed published articles or presentations from local, regional or international conferences.  
 
12.4.3)    SAMPLE SIZE DETERMINATION AND FORMULAS USED 
Stakeholder meetings to develop best practices: 
We will conduct 1 workshop with up to 50 participants representing a range of stakeholder perspectives and 
experiences. Based on a previous workshop conducted in this region with diverse stakeholders from various 
cadres who engaged with formative research materials, this number of participants is sufficient to reflect a range 
of experiences and priorities, but small enough to facilitate crucial interactive activities; we predict that this 
sample size will additionally be sufficient to reach theoretical saturation, that no new themes are identified with 
each additional individual. 
 

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Budget impact analysis review: 
We will conduct a series of 15 semi-structured, in-depth interviews with policymakers. Based on previous studies 
in this region, we predict that 15 IDIs will be sufficient to reach theoretical saturation, that no new themes are 
identified with each additional IDI [59].  
 
12.4.4)    RECRUITMENT PROCEDURES 
We will conduct a working meeting with an estimated 50 selected HCWs and policy makers from throughout 
Kenya with expertise PrEP delivery and MCH services. HCWs with significant experience in assisting PrEP 
delivery and/or MCH services will be purposively recruited from high performing clinics from Aims 1 and 2. We 
will also recruit healthcare workers known for their work in PrEP and MCH through reviewing peer-reviewed 
published articles or presentations at scientific meetings.  
 
HCWs and policy makers participating in the working group will be purposively selected and contacted by phone, 
email or in person by study staff. They will be told the details of the working group, including its purpose and 
scope of work.  A script outlining talking points used for recruitment is attached as an appendix. Those willing 
and eligible to participate will be asked to give written consent to be part of the working group and have the 
discussions audio recorded and information about the process written up into a publishable manuscript. It will be 
emphasized that participation is completely voluntary and opting not to participate will have no repercussions on 
the HCWs employment. They will read through the consent form on their own. One of the study personnel will 
then go through it with them verbally and answer any questions they might have. Those who consent will 
participate in the workshop with study staff to refine and adapt the transition tools. All participants will provide 
their contact information (phone, name, email if necessary) for follow-up until the working group meeting is 
conducted.  
 
12.4.5)    ENROLLMENT & STUDY PROCEDURES 
 
Stakeholder meeting to develop best practices: 
Consent: Stakeholders will be invited to provide written informed consent for participation in this 
workshop.  
 
Procedures: A best practices document will be developed and refined during a 2-day workshop. The 
workshop will be aligned with community-based participatory research and community engagement 
practices [63], including developing a shared vision, collaboratively identifying goals, and meeting the 
objective of developing trusting and sustainable relationships between all stakeholders to ensure long-
lasting impact and improved health outcomes.  
 
Data from Aims 1 and 2, as well as past learning from the PrIMA and PrIYA projects, will be compiled into 
brief reports synthesizing key elements of PrEP provision through MCH and FP clinics in Kenya. Reports 
will include information on client demographics, PrEP uptake and access experiences, challenges in 
PrEP delivery across ecological levels, and employed implementation strategies and identified 
implementation strategy domains.  
  
The Best Practices Development Workshop will be conducted over 2 days. Aligning with previously 
conducted best practices and intervention development processes [64–66], the workshop will include 
small and large group deliberative processes designed to maximize opportunities to hear all stakeholder 
views. To ensure accurate portrayal of stakeholder input, all large and small group sessions will be audio 
recorded and reviewed during final best practices development processes. Final workshop sessions will 
focus on implementation planning, addressing key steps towards implementation found in the Guideline 
Implementation Planning Checklist [67]. We will also conduct an evaluation of the best practices 
development process using post-development workshop questionnaires, focusing on 3 key process 
outcomes: recruitment, context, and satisfaction [64].  
 
Budget impact analysis review: 

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Consent: Policymakers will be invited to provide written informed consent for participation in semi-
structured in-depth interviews.  
 
Procedures: During the interviews, policymakers will be asked to narrate their thoughts aloud, borrowing 
methodological approaches from cognitive interviewing, a technique used in psychology to assess 
comprehension [68].  
 
Question guides will cover the following topic flow: 1) factors that influence policymaker’s current 
approach to making a decision about whether or not to adopt a new intervention into their 
clinic/county/national program, 2) current approach to considering cost data, budget impact, and cost-
effectiveness data in their decision-making. Midway through the interview, a hypothetical vignette will be 
introduced, in which the policymaker is asked to consider adopting PrEP delivery integrated into ANC, 
either with or without additional implementation strategies from Aim 2, into their clinic/county/national 
program. Initially, information will only be provided about effectiveness in terms of penetration of PrEP 
screening. The interviewer will then assess: 3) factors that influence the policymaker’s initial decision 
about whether or not to adopt the intervention. Then the results from the budget impact analysis will be 
shared in printed form, supplemented by standardized explanatory scripts, and the interviewer will 
assess: 4) policymaker’s understanding of the results, 5) any changes to policymaker’s initial decision 
regarding adoption of PrEP provision integrated into ANC. 
 
Planned Analyses: 
Stakeholder workshop: We will use a facilitated workshop in order to identify best practices for PrEP 
implementation in MCH and FP settings. Key themes from the workshop with be documented and summarized 
into a PrEP implementation best practices report.  
 
Budget impact analysis: We will use qualitative methods to explore policymaker approaches to decision making 
with limited resources.  
 
12.4.6)     LABORATORY METHODS 
N/A 
 
12.4.7)    DATA COLLECTION INSTRUMENTS 
- Workshop Evaluation Survey 
• 
Workshop participant demographic survey 
 
12.4.8)    TRAINING PROCEDURES 
Drs. Beima-Sofie and Wagner will oversee the training of study staff on workshop procedures and oversee the 
workshop.  
 
12.4.9)     STUDY MATERIALS: 
Workshop consent 
• 
Recruitment Script 
• 
Workshop topic domains overview 
 
13) QUALITY ASSURANCE PROCEDURES 
Adherence to protocol: Weekly reporting of enrollment, IDIs/FGDs transcript completion, and data collection will 
enable us to monitor that the study is running according to approved protocols. Frequent reporting will also 
enable us to respond quickly to any problems that arise during the study. 
 
Data Quality: A dedicated data team will be responsible for data collection using an electronic data collection 
platform, RedCAP.  The data team will communicate weekly with the operations team and leadership including 
reporting on data cleaning, study monitoring, and interim analyses. 
 

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14) ETHICAL CONSIDERATIONS 
14.1 ASSESSMENT OF RISKS AND BENEFITS 
i) 
ADEQUACY OF PROTECTION AGAINST RISKS 
Participants may feel discomfort in the questions they are asked during the FGDs, IDIs, and surveys.  All 
participants will be informed that they do not have to answer any questions they do not want to answer.  
Additionally, there may be a breach in confidentiality of participants.  We are taking all necessary precautions to 
prevent a breach in confidentiality, including storing materials that could identify participants in locked files, and 
storing all participant information in encrypted locations.  
 
ii) 
POTENTIAL BENEFITS OF PROPOSED RESEARCH TO THE SUBJECTS AND OTHERS 
Health care workers and women clients will not directly benefit from the proposed research.  PrEP policy makers 
and implementers may benefit from the best practices and budget impact analysis activities as it will provide 
information that can inform their jobs.  
 
iii) 
IMPORTANCE OF THE KNOWLEDGE GAINED 
Information gained through this study will result in improved PrEP delivery to women receiving MCH services, 
while also optimizing health care worker resources.  
 
15) DATA MANAGEMENT AND STATISTICAL ANALYSIS PLANS 
All data for this project will be managed at the Kisumu study office and the University of Washington in Seattle. 
Participants will be identified according to unique identification numbers—no identifying information will be 
captured or stored in this study, except the information needed for scheduling purposes or re-contacting to verify 
data accuracy. All qualitative data collected through interviews and focus groups to address Aim 1 and Aim 3 
will be stored on a secure server. All recording devices will be wiped clean after recordings are uploaded to the 
secure server. 
  
All quantitative data collected through surveys to address Aim 2 will also be stored on a secure server. 
Quantitative data collected during the course of this study will be collected electronically via REDCap data 
collection software. Data will be uploaded daily via REDCap Mobile App from tablets to the REDCap web server. 
Data will be transported via secure socket layer (SSL) and only accessible by authenticated users. Weekly 
reports will be generated to monitor study progress and troubleshoot problems. All computers, tablets (used for 
primary data collection), and individual study databases will be encrypted and password protected. Participants 
will be assigned a non-identifiable study code upon enrollment. Study analysts will receive only coded data. The 
links to patient identifiers will be retained in a password-protected file on an encrypted computer.  
 
a) Data Ownership 
The proposed project is a collaborative effort between investigators at the UW and KNH. The aforementioned 
institutions will jointly share ownership of the data.  Study investigators at the UW and KNH will have full access 
to the data.  Authorship on publications, conference presentations, abstracts and other materials generated from 
this study will reflect contribution to design, execution and analysis of the study. 
 
b) Data Release/Sharing Policy 
All quantitative data collected as part of this proposed research project will be made available to access or 
download files on a study related website (URL to be determined) following ERC approval for data sharing and 
agreement to the data sharing agreement. The data sharing agreement will ensure commitments to: 
1. Using the data only for research purposes and without attempting to identify study participants (if 
applicable); 
2.  Securing the data using appropriate computer technology; 
3.  Destroying or returning the data after analyses are completed; 
4. Restrictions on redistribution of the data to third parties; and 
5. Proper acknowledgement of the data resource. 
 

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c)  Data Monitoring Committee 
Prior to study initiation, we will convene a data monitoring committee (DMC) to review study aims, statistical 
analysis plan, and protocol. An annual DMC will be held during Aim 2 activities will be conducted to assess 
interim outcomes.  
 
16) STUDY LIMITATIONS AND HOW TO MINIMIZE THEM: 
Interrupted time series designs do not have as strong protection against confounding as randomized trials. 
Cluster randomized trials were not feasible or reasonable at this stage of scientific discovery. We considered 
alternative quasi-experimental designs (classical pre-post, difference in differences, regression discontinuity, 
stepped wedge), but none provided as strong control for temporal trends or heterogeneity between clinics. We 
considered adaptive designs, but wanted to isolate the individual, rather than additive or sub-group level, impact 
of the implementation strategies. 
 
We hope to gain insights on improving efficiencies for PrEP delivery in MCH and FP clinics based on views from 
a group of stakeholders with broad expertise. MCH and FP clinics in Kenya face unexpected events (specifically, 
health worker strikes and implementation of universal health care [UHC]) that may influence HCW and client 
views on PrEP implementation and may challenge the intervention pilot.  Our team has been able to work around 
these challenges in the past, liaising with private sector MCH/FP clinics (during public sector strikes) and overtly 
addressing new challenges such as UHC as part of process of stakeholder engagement. Stock-outs of self-tests 
or PrEP could challenge implementation of the pre-designed HIVST model; however, we have been assured 
that there is sufficient supply of PrEP and HIV self-tests in Kenya and that studies such as the one we propose 
are of high priority nationally and regionally in Kenya for use of these commodities.  
 
During direct observation, such as that employed for time-and-motion data collection, there is the possibility of 
the Hawthorne effect, in which individuals modify their behavior because they are observed. This is typically a 
concern with shorter data collection periods; these data will be collected over a series of approximately 2 weeks, 
so we anticipate a more limited or negligible Hawthorne effect. There is no potential benefit for the individuals 
being observed to modify their practices since the evaluation of is of the health system in general rather than a 
specific behavior.  
 

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17) TIMELINE/ TIME FRAME: 
 

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18) HUMAN SUBJECTS 
a) Ethical Approval 
We will obtain ethical approval from the University of Washington (UW) Human Subjects Division (IRB) and 
Kenyatta National Hospital-University of Nairobi (KNH-UoN) Ethics and Research Committee (ERC). There will 
be minimal risk to the participants taking part in this study.  Any changes to the protocol will be submitted to the 
UW IRB and KNH-UoN ERC.  
 
b) Collaborating sites 
The study will be conducted in collaboration with the UW, KNH, and NASCOP. The study will be reviewed by 
the KNH ERC and UW IRB and will not be started before approvals are obtained from all two organizational 
review boards. 
 
c) Informed Consent 
We will obtain electronic written informed consent for participation in all in-depth interviews, focus groups and 
HCW surveys that occur under Aim 1. The consent will explain to each potential participant the purpose, risks 
and benefits of the study. Participants will be informed that they can choose to withdraw from the study at any 
point and for any reason. They will also be informed that participation is completely voluntary. Participants will 
be offered a copy of the consent form to keep and will be informed that their role will end after they complete 
either the in-depth interview, focus group, or survey. Participants who agree to participate in study activities will 
sign the informed consent form using the electronic consent module through RedCap. This will allow for 
electronic collection of consent signatures, allowing for realtime consent quality monitoring, as well as secure, 
encrypted, storage of participant names and signatures.  Identifying information on participants will only be 
collected during the informed consent process.  
 
For exit interviews during Aim 2 activities, we are requesting a waiver of written consent. The purpose of these 
interviews is to assess knowledge and satisfaction for the PrEP optimization approaches.  Data collectors will 
approach women as they exit the facility, explain the purpose of the survey, and ask whether they are willing to 
answer a few questions. A waiver of written consent is requested as there will be no identifying information of 
the participants. The guide for obtaining oral consent is included in the consent material appendix.  
 
IDIs and surveys will be verbally administered to ensure participants who cannot read or write are still able to 
participate in this study.  
 
Comprehension: Participants who do not consent in the presence of study staff (for example, prior to self-
administered electronic surveys) will be given the phone number of study staff and will be encouraged to call if 
they have any questions about the consent or study. 
 
Study staff will review the informed consent information with each study participant when consenting is 
conducted in-person. Study staff will also ask participants a 2-3 questions to assess understanding.  Questions 
may include: 
 
1. What is the purpose of this study? 
2. When can you decide not to participate in this study? 
3. Will we record your voice during this study?  
4. Will we access your medical records during this study? 
 
Waiver of written consent for data extraction 
Register abstraction: For aims that involve register abstraction, we are not planning any direct contact with 
patients. We will exclusively abstract data from registers and medical records without abstracting any personally 
identifiable information or constellation of variables that could personally identify individuals. The study data clerk 
will review health registers and medical records and will abstract simple count data about the number of 
individuals who complete each step. While registers and medical records may contain personally identifiable 
data, study data clerks will not abstract any of these variables, nor any constellation of variables that could be 

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personally identifiable. We are requesting a waiver of informed consent to abstract medical records from this 
population.  
 
Waiver of parental permission for 15-17 year olds 
The age of majority in Kenya is 18 years. For adolescent girls, ages 15-17 years, we are requesting a waiver of 
parental consent for participation based on the following points: 
 
1. Adolescents are able to provide consent (parental consent can be waived) for HIV and STIs testing and 
treatment in Kenya). However, parental involvement is always desirable and adolescents would be able 
to choose whether they want to have parents involved in the decision of whether or not to provide consent, 
and participate in the study. 
2. If there are confidentiality issues regarding adolescents discussing personal HIV testing or sexual activity 
with their parents, requiring parent consent could breech confidentiality of the adolescent. 
3. Recent Kenya Demographic Health Surveys have allowed sexually active adolescents to participate in 
national surveys, which allows this marginalized population to be represented and their data used to help 
guide public health programs and policies. 
4. Excluding adolescents from the study would be denying them an opportunity to participate in research to 
improve PrEP delivery in FP and MCH clinics. Allowing adolescents the opportunity to provide their own 
consent is in alignment with the ethical principles of justice, beneficence, and autonomy. 
 
 
d) Handling Adverse events 
We do not anticipate any significant adverse events to occur throughout this study as the goal of this study is 
simply to understand barriers and facilitators to PrEP adherence. However, in the event that an adverse event 
occurs, participants will be given contact information for study team members. All unanticipated problems will be 
reported to the PIs and ethics committee according to UW, KNH, and KNH ERC guidelines. 
 
19) BUDGET (total budget period) 
20) LIST OF ABBREVIATIONS 
21) LIST OF APPENDICES/ATTACHMENTS  
 
Appendix A: Consent Forms 
• 
HCW Consent Form 
• 
Policy Maker IDI Consent Form 
• 
PrEP User FGD Consent Form 
• 
Exit Survey Oral Consent Guide 
• 
Workshop Consent form 
 
 
Appendix B: Summary of Key Themes from Data Collection Tools 
Aim 1:  
● PrEP user focus group guide 
○ Starting PrEP 
■ Factors that lead to the decision to start PrEP 
■ Experience at the facility 
■ Information received from clinic staff 
○ Using PrEP 
■ Duration of PrEP use 
■ How PrEP use has impacted the participant 
■ Plan for future PrEP use 
○ PrEP delivery 
■ What is their clinic doing well?  How can the clinic improve? 
■ Advantages of PrEP delivery through MCH/FP clinics 

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■ Advice for PrEP delivery through MCH/FP clinics 
● PrEP user demographic information 
○ Gender 
○ Age 
○ Education 
○ Employment 
○ Living situation 
○ Partner characteristics 
○ Children 
○ PrEP use and experience 
● HCW Survey 
○ Employment 
■ Location 
■ Title 
■ Experience 
○ Education 
○ Age 
○ Gender 
○ PrEP training 
○ PrEP experience 
○ PrEP delivery strategy preferences 
○ Impact of COVID-19 on PrEP delivery and clinic duties 
○ Transition of PrEP delivery from research to clinic staff 
○ HCW daily experiences 
● HCW FGD guide from CFIR Interview Guide, Themes include: 
○ Intervention Characteristics 
○ Outer/External Setting 
○ Inner Setting 
○ Characteristics of Individuals 
○ Process 
● Service Availability and Readiness Assessment Tool Survey 
○ Work health organization tool for measuring health system strength. Key themes: 
■ Service availability (facility density, health care worker density, service utilization) 
■ Service readiness (basic amenities, equipment and supplies, diagnostics, essential 
medicines, and commodities) 
■ Specific Service readiness in family planning, antenatal care, HIV, and PMTCT 
● PrEP policy maker and implementer interview guide 
○ Demographic information 
■ Age, gender, role, county, years of experience, experience with PrEP 
○ PrEP delivery 
■ What is working well for PrEP delivery? 
■ What are existing challenges? 
○ PrEP in MCH/FP 
■ Should PrEP be delivered in MCH/FP clinics? Advantages? Disadvantages? 
■ Strategies for improving efficiency 
■ Barriers to delivery 
 
Aim 2: 
• 
Exit Survey 
o Age 
o HIV Status 
o Assessment of risk behaviors and PrEP at clinic visit today 
o  Risk profile 

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 
Did you engage in any of the following in the last 6 months? Yes/No (Participant will not 
have to disclose WHICH risk behavior) 
o PrEP counselling 
o PrEP knowledge questions 
• 
Data Abstraction Tool 
o Collect data on PrEP screening, prescription, and discontinuation disaggregated by gender and 
age 
 
Aim 3: 
• 
Workshop Evaluation Survey 
o Satisfaction with workshop  
o Context of workshop  
 
 
 
 
 

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