Data-informed Stepped Care (DiSC) to Improve Adolescent HIV Outcomes (UH3)
Phase: NA
Conditions: Adolescent Behavior, Hiv
Sponsor: University of Washington

 
 
 
Data-informed Stepped Care (DiSC) to Improve Adolescent HIV Outcomes (UH3):  
A cluster randomized trial on a Data Informed Stepped Care intervention to improve 
retention among adolescents living with HIV 
 
Protocol Number: STUDY00011096 
 
National Clinical Trial (NCT) Identified Number:  NCT05007717 
Principal Investigator*: Pamela Kohler, PhD, RN and Grace John-Stewart, MD, MPH, PhD 
 
 
Sponsor: National Institutes of Health 
Grant Title: Data-informed Stepped Care (DiSC) to Improve Adolescent HIV Outcomes 
Grant Number*: UH3 HD096906 
Funded by: National Institute for Child Health and Human Development (NICHD) 
Version Number:  v 9.0 
20 March, 2023 
 
 
 
 
 
 
 
 
 
 
 
 

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Summary of Changes from Previous Version: 
 
Affected 
Section(s) 
Summary of Revisions Made 
Rationale 
Section 5.5 
Change frequency of Caregiver 
Surveys from every 6 months to every 
12 months 
This data does not need to be 
collected as frequently; there was 
an instance of this language that 
was not corrected previously on pg. 
26  
Section 10.6.1 
Reduce frequency of DSMB meetings 
The frequency of DSMB meetings 
has been incorrectly stated as 
being semiannual; however, these 
meetings have occurred annually 
(in line with standards of NIH and 
the study’s DSMB members) 
 
 
 

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CONFIDENTIALITY STATEMENT 
This document is confidential communication. Acceptance of this document constitutes 
agreement by the recipient that no unpublished information contained herein will be published or 
disclosed without prior approval of the Principal Investigator or other participating study leadership 
and as consistent with the NIH terms of award.  
 

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Table of Contents 
STATEMENT OF COMPLIANCE ................................................................................................. 1 
INVESTIGATOR’S SIGNATURE .................................................................................................. 4 
1 
PROTOCOL SUMMARY .................................................................................................... 5 
1.1 
Synopsis .................................................................................................................... 5 
1.2 
Schema ...................................................................................................................... 6 
1.3 
Schedule of Activities ................................................................................................. 8 
2 
INTRODUCTION ................................................................................................................ 9 
2.1 
Study Rationale ......................................................................................................... 9 
2.2 
Background ................................................................................................................ 9 
2.3 
Risk/Benefit Assessment ......................................................................................... 12 
2.3.1 
Known Potential Risks ............................................................................. 12 
2.3.2 
Known Potential Benefits ......................................................................... 13 
2.3.3 
Assessment of Potential Risks and Benefits ........................................... 13 
3 
OBJECTIVES AND ENDPOINTS ..................................................................................... 15 
4 
STUDY DESIGN ............................................................................................................... 16 
4.1 
Overall Design ......................................................................................................... 16 
4.2 
Scientific Rationale for Study Design ....................................................................... 18 
4.3 
Justification for Intervention ..................................................................................... 18 
4.4 
End-of-Study Definition ............................................................................................ 18 
5 
STUDY POPULATION ..................................................................................................... 18 
5.1 
Inclusion Criteria ...................................................................................................... 19 
5.2 
Exclusion Criteria ..................................................................................................... 19 
5.3 
Lifestyle Considerations ........................................................................................... 20 
5.4 
Screen Failures ........................................................................................................ 20 
5.5 
Strategies for Recruitment and Retention ................................................................ 20 
6 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) ......................... 21 
6.1 
Study Intervention(s) or Experimental Manipulation(s) Administration .................... 21 
6.1.1 
Study Intervention or Experimental Manipulation Description ................. 21 
6.1.2 
Administration and/or Dosing ................................................................... 22 
6.2 
Fidelity ..................................................................................................................... 22 
6.2.1 
Interventionist Training and Tracking ....................................................... 22 
6.3 
Measures to Minimize Bias: Randomization and Blinding ....................................... 23 
6.4 
Study Intervention/Experimental Manipulation Adherence ...................................... 23 
6.5 
Concomitant Therapy............................................................................................... 23 
6.5.1 
Rescue Therapy ...................................................................................... 23 
7 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION DISCONTINUATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL ................................................................ 23 
7.1 
Discontinuation of Study Intervention/Experimental Manipulation ........................... 23 
7.2 
Participant Discontinuation/Withdrawal from the Study ........................................... 23 
7.3 
Lost to Follow-Up ..................................................................................................... 24 
8 
STUDY ASSESSMENTS AND PROCEDURES ............................................................... 24 
8.1 
Endpoint and Other Non-Safety Assessments ........................................................ 24 
8.2 
Safety Assessments ................................................................................................ 29 
8.3 
Adverse Events and Serious Adverse Events ......................................................... 29 
8.3.1 
Definition of Adverse Events .................................................................... 29 
8.3.2 
Definition of Serious Adverse Events ...................................................... 29 
8.3.3 
Classification of an Adverse Event .......................................................... 29 
8.3.4 
Time Period and Frequency for Event Assessment and Follow-Up ........ 30 
8.3.5 
Adverse Event Reporting ......................................................................... 30 

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8.3.6 
Serious Adverse Event Reporting ............................................................ 30 
8.3.7 
Reporting Events to Participants ............................................................. 31 
8.3.8 
Events of Special Interest ........................................................................ 31 
8.3.9 
Reporting of Pregnancy ........................................................................... 31 
8.4 
Unanticipated Problems ........................................................................................... 31 
8.4.1 
Definition of Unanticipated Problems ....................................................... 31 
8.4.2 
Unanticipated Problems Reporting .......................................................... 31 
8.4.3 
Reporting Unanticipated Problems to Participants .................................. 32 
9 
STATISTICAL CONSIDERATIONS .................................................................................. 32 
9.1 
Statistical Hypotheses ............................................................................................. 32 
9.2 
Sample Size Determination ..................................................................................... 32 
9.3 
Populations for Analyses ......................................................................................... 34 
9.4 
Statistical Analyses .................................................................................................. 34 
9.4.1 
General Approach.................................................................................... 34 
9.4.2 
Analysis of the Primary Endpoint(s) ......................................................... 34 
9.4.3 
Analysis of the Secondary Endpoint(s) .................................................... 35 
9.4.4 
Safety Analyses ....................................................................................... 35 
9.4.5 
Baseline Descriptive Statistics ................................................................. 35 
9.4.6 
Planned Interim Analyses ........................................................................ 35 
9.4.7 
Sub-Group Analyses................................................................................ 35 
9.4.8 
Tabulation of Individual Participant Data ................................................. 36 
9.4.9 
Exploratory Analyses ............................................................................... 36 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ............. 36 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ....................................... 36 
10.1.1 
Informed Consent Process ...................................................................... 36 
10.1.2 
Study Discontinuation and Closure .......................................................... 37 
10.1.3 
Confidentiality and Privacy ...................................................................... 38 
10.1.4 
Future Use of Stored Specimens and Data ............................................. 39 
10.1.5 
Key Roles and Study Governance ........................................................... 39 
10.1.6 
Safety Oversight ...................................................................................... 40 
10.1.7 
Clinical Monitoring ................................................................................... 40 
10.1.8 
Quality Assurance and Quality Control .................................................... 41 
10.1.9 
Data Handling and Record Keeping ........................................................ 41 
10.1.10 
Protocol Deviations .................................................................................. 42 
10.1.11 
Publication and Data Sharing Policy ........................................................ 42 
10.1.12 
Conflict of Interest Policy ......................................................................... 43 
10.2 
Additional Considerations ........................................................................................ 43 
10.3 
Abbreviations and Special Terms ............................................................................ 43 
10.4 
Protocol Amendment History ................................................................................... 46 
11 
REFERENCES ................................................................................................................. 47 
 

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STATEMENT OF COMPLIANCE 
 
The trial will be carried out in accordance with International Council on Harmonization 
Good Clinical Practice (ICH GCP) and the following: 
 
• 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies 
(45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR 
Part 812). 
 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials 
will be submitted to the IRB for review and approval. Approval of both the protocol and the 
consent form(s) must be obtained before any participant is consented. Any amendment to 
the protocol will require review and approval by the IRB before the changes are 
implemented to the study. All changes to the consent form(s) will be IRB approved; a 
determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form. 
 
 

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INVESTIGATORS  
Principal 
Investigators 
Pamela Kohler 
Associate Professor, Nursing, Global Health 
University of Washington 
Harborview Medical Center 
325 9th Avenue, Box 359932 
Seattle WA 98104  USA 
Tel:  +1-206-616-7962 
Email: pkohler2@uw.edu 
 
Grace John-Stewart 
Professor, Medicine, Epidemiology, Pediatrics, Global Health 
University of Washington 
Harborview Medical Center 
325 9th Avenue, Box 359932 
Seattle WA 98104  USA 
Tel:  +1-206-543-4278 
Email: gjohn@uw.edu 
 
Site-Principal 
Investigator 
KawangoAgot 
Director and CEO 
Impact Research and Development Organization (IRDO) 
Email:kawango@impact-rdo.org 
 
Co-
Investigators  
 
Kristin Beima-Sofie 
Research Scientist, Global Health 
University of Washington 
Email: beimak@uw.edu 
 
Irene Inwani 
Head of Department,Paediatrics and Child Health 
Kenyatta National Hospital  
Email: iinwani@yahoo.com 
 
Barbra Richardson 
Research Professor, Global Health, Biostatistics 
University of Washington 
barbrar@uw.edu 
 
Seema Shah 
Associate Professor, Associate Director of Bioethics 
Lurie Children’s Hospital / Northwestern University 
Email: cmashah@gmail.com 
 
 

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Collaborating 
Institutions 
University of Washington 
4333 Brooklyn Avenue NE 
Box 359472 
Seattle WA 98195 USA 
 
Tuungane Hospital, Tom Mboya Estate 
Mito Jura Road, off Kisumu- Kakamega Highway 
P.O. Box 9171-40141 
Kisumu, Kenya 
 
 
 
 

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INVESTIGATOR’S SIGNATURE 
The signature below constitutes the approval of this protocol and provides the necessary 
assurances that this study will be conducted according to all stipulations of the protocol, 
including all statements regarding confidentiality, and according to local legal and regulatory 
requirements and applicable US federal regulations and ICH guidelines. 
 
Principal Investigator: 
Signed: 
 
Date: 
 
 
Name*: Pamela Kohler 
 
Title*: Principal Investigator  
 
Investigator Contact Information 
Affiliation*: Associate Professor, Nursing, Global Health, University of Washington 
Address: Harborview Medical Center, 325 9th Avenue, Box 359932, Seattle WA 98104 USA 
Telephone: +1-206-616-7962 
Email: pkohler2@uw.edu 
 
Principal Investigator: 
Signed: 
 
Date: 
 
 
Name*: Grace John-Stewart  
 
Title*: Principal Investigator  
Investigator Contact Information 
Affiliation*: Professor, Medicine, Epidemiology, Pediatrics, Global Health 
Address: Harborview Medical Center, 325 9th Avenue, Box 359932, Seattle WA 98104 USA 
Telephone: +1-206-543-4278 
Email: gjohn@uw.edu 
 
Site Principal Investigator  
Signed: 
 
Date: 
 
 
Name: Kawango Agot  
 
Title: 
Professor, Director and CEO 
 
Affiliation: Impact Research and Development Organization  
 
 

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PROTOCOL SUMMARY 
1.1 SYNOPSIS 
 
Title: 
Data-informed Stepped Care (DiSC) to Improve Adolescent HIV 
Outcomes (UH3): A cluster randomized trial on a Data Informed 
Stepped 
Care 
intervention 
to 
improve 
retention 
among 
adolescents living with HIV 
Grant Number: 
UH3 HD096906 
Study Description: 
The goal of this study is to develop, pilot and test a Data informed 
Stepped Care (DiSC) Intervention in a cluster randomized 
controlled trial (cRCT). The intervention is comprised of a system 
to assign adolescents living with HIV (ALHIV) to different levels of 
care, depending on their current and anticipated health care needs. 
 
Objectives*: 
 
Primary objective  
Aim 1:To develop, adapt, pilot, and optimize implementation of  
a data-informed stepped care (DiSC) intervention for ALHIV  
HIV treatment management. 
 
Aim 2:To evaluate effectiveness of the DiSC intervention on  
ALHIV retention in up to 24 high-volume HIV clinics in  
Homabay, Kisumu and Migori counties in Western Kenya. 
 
Secondary objectives  
Aim 1: To determine acceptability, feasibility, adaptability and 
fidelity of the DiSC intervention 
 
Aim 2: To evaluate the effectiveness of the DiSC intervention on 
ALHIV cascade outcomes (adherence, viral suppression) and 
adolescent self-efficacy, health service outcomes, implementation 
outcomes in high volume HIV clinics in Homabay, Kisumu and 
Migori counties.  

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Endpoints*: 
Primary Endpoint:% retained at 6 and 12 months  
 
Secondary Endpoints:% virally suppressed at 6 and 12  
months after ART initiation, proportion with >80% adherence 
since last refill, % retained at 18 and 24 months, adolescent 
self-efficacy and correlates of retention and viral suppression.  
 
Secondary implementation outcomes: intervention reach, 
adoption, fidelity, acceptability, feasibility, implementation and 
maintenance.  
Study Population: 
Up to 40 Health care workers (HCW), youth, policy makers and 
stakeholders in adolescent HIV care (aim 1 intervention 
development), HCW in 2 clinics in Kenya (aim 1 pilot) 
 
6000medical records of adolescents and young adults ages 10-24 
years enrolled in HIV care, and HCW in participating facilities, 
Approximately 3000 HIV positive adolescents and young 
adults,900 caregivers of HIV positive adolescents and young 
adults and a 200 HCWs. (Aim 2). 
Phase* or Stage: 
Phase III Clinical Trial 
Description of 
Sites/Facilities Enrolling 
Participants: 
Aim 1: 2 HIV clinics in Homa-bay, Migori or Kisumu.  
Aim 2: up to 24 HIV clinics in Homa-bay, Migori or Kisumu.  
Description of Study 
Intervention/Experimental 
Manipulation: 
Data-informed Stepped Care (DiSC) intervention is comprised of 
a system to assign ALHIV to different levels of care depending on 
their current and anticipated health care needs. The intervention 
will be delivered at the individual level by HCW providing routine 
care during routine HIV clinic visits.   
Study Duration*: 
24 months  
Participant Duration: 
24 months 
1.2 SCHEMA 
 

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1.3 SCHEDULE OF ACTIVITIES 
 
 
 
 
 
Outcome 
assessed  
Pre-screening 
(Pre-consent) 
 
Enrollment  
Enrollment  
Month 0±2 
 
Month 6 
Month 6±2 
 
Month 12 
Month 12±2 
 
 
Unscheduled 
Visits 
Clinic Eligibility 
 
X 
 
 
 
 
 
Aim 2  
 
 
 
 
 
 
 
EMR data abstractions 
Retention, viral 
non suppression 
 
X 
X 
X 
X 
 
Informed Consent 
(surveys)  
 
NA 
 
X 
 
 
 
 
Caregiver/adolescent 
surveys   
Secondary 
outcomes 
 
X 
 
X 
X 
 
HCW surveys  
Health service & 
Implementation 
outcomes 
 
X 
 
 
X 
 
HCW implementation 
logs/surveys 
Implementation 
outcomes 
 
 
 
 
 
X 
HCW implementation 
surveys, IDI /FGD 
(intervention sites only)  
Implementation 
outcomes 
 
 
 
X 
 
 
Facility surveys  
Implementation 
outcomes 
 
X 
 
 
X 
 
Adolescent/caregiver 
satisfaction surveys 
(intervention only)  
Implementation 
outcomes 
 
 
 
 
X 
 
 
Adolescent FGDs  
Implementation 
outcomes  
 
 
 
 
 
 
Randomization 
NA 
X 
 
 
 
 
 

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2 
 
INTRODUCTION 
 
2.1 STUDY RATIONALE 
UNAIDS ‘95-95-95’ targets cannot be achieved without additional support for adolescents living 
with HIV (ALHIV) to increase retention in care and to support viral suppression. Risk prediction 
tools as well as a stepped care approach to care can support differentiation of ALHIV to different 
risk groups, and tailor care based on risk.  
Our team has conducted formative work with ALHIV, caregivers, HCW and policy makers and 
has developed and validated a clinical prediction tool to identify ALHIV at highest risk of not being 
retained in care and poor viral suppression that could be adapted to identify adolescents who may 
need more support in their care. Understanding how best to use the risk prediction tool as well as 
how to tailor services based on risk may ultimately result in more efficient HIV care services, as 
well as adequate support for ALHIV at highest risk of poor outcomes. 
This study aims to test a data informed stepped care approach to improve retention and viral 
suppression among ALHIV. We will also study implementation and service delivery outcomes.  
2.2 BACKGROUND 
B1. Adolescents are disproportionally affected by HIV 
Adolescents represent an estimated 40% of new 
infections worldwide,[2] and 84% of HIV-infected 
adolescents live in sub-Saharan Africa (sSA).[3] In 
Kenya, HIV incidence among adolescents has 
increased by 17% since 2013, while incidence has 
reduced by 19% in adults and 49% in children.[4]The 
majority (91%) of AIDS-related deaths among 
adolescents in the region have not declined (Figure 
1).[5] A growing number of perinatally infected 
adolescents will need lifelong antiretroviral therapy 
(ART).[6, 7]‘90-90-90’ targets cannot be achieved without substantially increasing 
engagement in care and viral suppression among adolescents. 
B2. Adolescent HIV care cascade outcomes are poor 
Adolescents in African countries have lower retention, adherence to ART [8] and viral suppression 
compared to adults.[8-14] Loss to follow-up (LTFU) among adolescents within the first 12 months 
of treatment ranges from 15% to 83%.[12, 15, 16] Poor ART adherence is common and increases 
risk of HIV transmission and disease progression.[17, 18] The greatest gap in the adolescent care 
cascade is viral load, [19, 20] with >30% experiencing virologic non-suppression or failure after 
12 months on ART.[7, 21-24]Lack of viral suppression among adolescents undermines progress 
in retention and adherence. 
Figure 1: Static mortality among 10-19 year 

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B3. Reasons for poor adolescent engagement in care are unclear and varied   
Cofactors of viral suppression may be distinct in this age group. Male gender, poor mental 
health,[25] stigma, substance use,[25] fear of provider judgement, [26] lack of support,[27, 28] 
and school barriers [29] are risk factors for poor adherence and retention among adolescents, 
though data are limited.[30] Lack of age-disaggregated data in research and programs in high-
burden settings remains a major barrier to responding effectively to the adolescent HIV 
epidemic.[31, 32]Systematic cohort data on social, behavior, and clinical factors affecting 
retention and treatment outcomes are necessary to inform new HIV care interventions for 
adolescents. 
B4. Adolescence is a unique period of life, with specific challenges for HIV-infected adolescents 
Adolescence is a time of rapid physical, cognitive, sexual, and social transition, characterized by 
increased autonomy, experimentation, growing peer influence, and identity formation.[33] These 
contexts and behaviors affect health outcomes in adulthood and next generations.[34, 35] 
Adolescents with HIV face unique challenges transitioning successfully to adulthood and 
achieving optimal health.[11, 36] Younger adolescents (10-14) are more likely to be perinatally 
infected, live at home, and have parental supervision. Many do not know their status or have been 
recently disclosed to.[37, 38] Older adolescents want more autonomy to make choices about 
relationships and health, but have decision-making challenges.[34, 39, 40] Adolescent females 
have added risk of poor adherence due to relationship violence[41] while gender norms and lack 
of targeted services are linked to lower male engagement in care.[42] New interventions to 
optimize retention and clinical outcomes must be tailored to adolescents’ developmental, 
health, and social needs.  
B5. Caregivers influence clinical outcomes in adolescents, but need support  
Parents or non-parent caregivers are the primary sources of support, social norms, and 
supervision in early adolescence.[43] Caregivers have the potential to improve adolescent 
disclosure, treatment adherence, and retention, but feel ill-prepared for this role.[37, 38, 44] A trial 
conducted in Zimbabwe found that a community health worker-led intervention to train and 
support caregivers resulted in a significant reduction in viral non-suppression or mortality in their 
HIV-infected children.[45]Caregiver perspectives are necessary to inform adolescent 
services and to improve clinical outcomes in adolescents. 
B6. ‘Test and Start’ will burden health systems in resource-constrained settings 
Adoption of Test and Start models, where all persons living with HIV are rapidly initiated on 
treatment, addresses loss to follow-up in the pre-ART period as part of initiatives to reach 90-90-
90 goals, with early evidence of success.[46]However, there are fears that increasing caseloads 
and HCW burden in already strained healthcare systems will result in difficulty accessing or poor 
quality of care.[47]Differentiated models of service delivery have been proposed as a client-
centered approach that simplifies and adapts HIV services across the cascade to better serve 
those in care and to reduce unnecessary burdens on the health system.[48]Due to poor retention 
outcomes, Kenyan guidelines currently classify all adolescents as “unstable”,[49] thus not able to 
access differentiated approaches, like community models or longer refill durations, which may 
benefit for this population. 

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B7. “Stepped care” as an evidence-based model for differentiated care 
The stepped care model grounded in Stages 
of Change Theory,[50]has been used in 
mental health fields to organize provision of 
services; and to support clients, HCW, and 
caregivers to identify the most effective 
interventions (Figure 2).[51] Models typically 
start with a low-intensity, evidence-based 
treatment, and systematically progress to 
higher levels of care or intervention as 
clients fail to respond.[52] A key feature of 
stepped care is outcome monitoring, 
giving both clients and HCWs feedback 
to inform care options and service 
delivery. 
Early 
studies 
suggest 
improvements in access to care, client 
outcomes, 
and 
program 
efficiencies, 
including client volume.[53] A systematic 
review found effectiveness on 6-month depression outcomes,[54] and a randomized trial 
demonstrated reduced incidence of depression and anxiety among older adults.[55] 
B8. Clinical prediction tools identify high-risk individuals for interventional support 
Clinical prediction tools are useful to classify individuals into high and low risk groups, to identify 
those in need of intervention, and to deliver services more efficiently.[56-59] Studies among MSM 
in the United States [56, 59] and two studies in Kenya found that clinical characteristics were 
predictive of HIV risk.[58, 60]Tools validated in clinic cohorts of HIV-infected adults in the US [61] 
and in low resource settings [62] have shown to be predictive of virologic failure or mortality using 
minimal variables.[61-63]Prediction tools could enable HCWs to provide better support to 
adolescents at risk for poor outcomes rather than waiting until poor outcomes occur. 
B9. Health systems interventions may improve adolescents care cascade and clinical outcomes  
Despite nearly 15 years of research to improve retention outcomes in adults, there is lack of 
evidence of what works for HIV-infected adolescents.[64-66] Individual psychosocial interventions 
may improve ART adherence for adolescents at risk of treatment failure, [65] but alone are not 
sustainable in high-burden countries. Health systems interventions can empower HCWs to tailor 
services for their unique population needs and optimize limited resources.[48] A US study found 
that multidisciplinary care teams improve adolescent retention in care, [67] and the SAIA trial used 
a systems engineering approach to triple ART coverage for prevention of mother to child 
transmission in Africa.[68] It is plausible that a health systems approach, using a data-driven, 
provider-led intervention to optimize adolescent HIV services, may result in health services 
efficiencies and improved adolescent HIV care engagement and clinical outcomes. 
C. INNOVATION   
 
 
 
 
 
 
 
 

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• 
A clinical prediction tool can identify adolescents at risk for loss to care before negative clinical 
outcomes occur.  Simple, practical tools can be incorporated into routine data collection to 
identify adolescents at highest risk of disengagement before loss to care, providing an 
opportunity for health systems to intervene. 
• 
Stepped care models paired with accurate risk identification can reach priority adolescents 
without increasing burden on the health system. There are great concerns about the capacity 
of health systems to manage care in the ‘Test and Start’ era. Stepped care models use 
programmatic data to target services to those most in need. This framework is highly aligned 
with international movements for differentiated care. 
• 
Current Kenyan guidelines for differentiated care do not include adolescents. All HIV-infected 
adolescents are considered “unstable” and thus not eligible for differentiated HIV services 
under current Kenyan guidelines.[49] This approach masks heterogeneity and diverse needs. 
Carefully and systematically assessing individual risk can identify those who need heightened 
services, as well as those at lower risk, who may benefit from less intensive or frequent clinic 
visits according to differentiated care models. 
• 
A health systems intervention can be widely applied across different settings. Despite national 
roll out of the Adolescent Package of Care (APoC) guidelines, large scale and local programs 
targeting adolescents with HIV are not uniform. A health systems approach can be applied 
across clinical facilities to enhance diverse interventions by matching them to client 
characteristics and specific health system compositions. 
• 
Client-centered interventions that involve providers, families, and youth in design and 
implementation can maximize uptake and impact. Youth perspectives are critical to 
engagement in HIV research and programs and to determine what additional support might 
be needed.[69] Addressing legal and ethical considerations can maximize representative 
participation and better inform design and delivery. 
• 
Effectiveness research is necessary to develop sustainable models for adolescent HIV care: 
We will evaluate the DiSC intervention by leveraging routine electronic medical record 
(EMR)data and clinic populations and engaging community stakeholders throughout the study 
lifecycle. By approximating real-world conditions, we maximize generalizability and 
sustainability of this modelin resource-limited settings.[70] 
• 
Using an implementation-effectiveness hybrid design improves translation to practice: Our 
study is structured a priori to address both clinical intervention and implementation outcomes. 
Use of hybrid study designs may improve policy relevance and public health impact of new 
interventions.[71] 
IMPACT: A data-driven, provider-led, health systems intervention can identify adolescents most 
at risk for loss to care, sub-optimal adherence, and viral failure. Our stepped care approach, 
combined with a clinical prediction tool, is a timely and flexible intervention in the context of 
differentiated care and numerous ongoing care initiatives. By improving adolescent engagement 
in care and optimizing provision of limited resources, this intervention can ultimately improve 
health and decrease HIV transmission risk among adolescents in Kenya. 
2.3 RISK/BENEFIT ASSESSMENT 
 
2.3.1 KNOWNPOTENTIAL RISKS 

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There are no medical interventions associated with the study, therefore we anticipate no risk of 
serious physical harm to participating HCWs, adolescents or caregivers. In all HIV research 
studies there is a non-negligible risk of loss of confidentiality of HIV status or other medical 
information. There is also risk of emotional discomfort when responding to sensitive personal 
questions. HCWs who are trained in the DiSC intervention may have concerns about job loss if 
they perform poorly in implementing the stepped care approach. There is a possibility for social 
harm (depression, violence after disclosure, abandonment) related to routine HIV treatment and 
management during clinical encounters with routine providers during the course of the study. 
However, the possibility of this social harm would exist if this intervention were not conducted. 
There is a possibility that during a clinical encounter with the more intensive care steps, an ALHIV 
may be more comfortable disclosing that they are suffering from previously undiagnosed mental 
health problems such as depression. Any patients with potential mental health problems will be 
referred for psychosocial support at the facility or nearest referral hospital, according to standard 
HIV care and treatment guidelines for adolescents at that clinic. 
2.3.2 KNOWN POTENTIAL BENEFITS 
 
Direct benefits:  
Participants may benefit from enhanced HIV treatment services tailored to adolescents. This 
could result in better retention, adherence, and viral suppression. Clinics and HCWs may benefit 
from increased time and resources efficiencies from the stepped care approach.  
Indirect benefits:  
The study may produce data that will lead to improved interventions for treatment and care of 
adolescents with HIV, thus a benefit to society. 
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS 
All adult study participants will have the study and relevant study procedures explained to them, 
their questions answered, and provide written consent for their enrollment.  
Together, the UW, Nairobi, and Kisumu Study Team has more than 10 years’ experience 
managing HIV-infected children and adolescents and in clinical trials and observational research 
and will take every precaution to protect participants’ and their caregivers’ confidentiality. All study 
staff will have been trained in the Protection of Human Subjects and new staff will receive similar 
training. 
Procedures to minimize physical risks: There are no medical interventions associated with the 
study, therefore we anticipate no risk of serious harm to study participants. 
Procedures to minimize confidentiality risks: All key personnel will be trained in the Protection of 
Human Subjects. The field team will take every precaution to protect participants’ confidentiality. 
We will only collect personal identifiers for the purposes of identifying and contacting participants 
about the study. This information will include the names, telephone numbers and emails for those 
identified as interested in participating in the study. Personal identifiers will be used to contact 
stakeholders in aim 1 and HCWs to remind them of their scheduled study activities. This 
information will also be used to contact them again to verify the accuracy of the information 

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collected or to elaborate or clarify certain information provided during study procedures if they 
select the option to be re-contacted on the consent form.  
All participants will be assigned a study identification number (ID). Participant identifiers will be 
linked to their study ID in a link-log document that will be stored separately from all other study 
data. Only necessary study staff will have access to this document and will not share this 
information with other study staff or with others outside of this study. 
 
Procedures to minimize psychological risks: All participants will be assured that their participation 
is voluntary and that they may withdraw from the study at any time. Kenyan study personnel 
experienced in research with adolescents will be available for questions when participants take 
the surveys. While there is a risk of discomfort related to answering sensitive questions about 
sexual behavior, mental health, and stigma on the surveys, these questions are similar to what 
would be asked as part of routine HIV care for adolescents. Survey participants will be informed 
that they can skip any question or stop the interview at any time. Any participant who reports 
emotional distress, exposure to violence, or other threat will be offered support or referral to 
additional services, as appropriate, according to standard operating procedures. Some younger 
adolescents receiving HIV care and taking ART (which may be called ‘medicine’ and not HIV 
medicine) may not yet know their HIV status, because the caregiver is not ready for the child to 
learn this information. The ALHIV surveys will not include specific mention of HIV or ART unless 
a participant reports knowledge of their own HIV status on a screening question. This approach 
will minimize the possibility of involuntary disclosure to an ALHIV and maximize representative 
enrollment.  
Procedures to minimize other risks: Study staff will be trained to take all precautions to ensure 
confidentiality of participation and data collected and will have standardized operating procedures 
(SOPs) to follow to minimize the risks of a participant’s loss of confidentially. Risk of breach of 
confidentiality of study data is low, as all patient data collected will not include names and will be 
located on a password protected secure study server. ALHIV participants will be assured that 
their sensitive information will not be shared with anyone outside the study team, including a 
parent, caregiver, or partner who may be present. Study staff will be trained in the importance of 
confidentiality during training prior to study implementation. The community-driven process of 
adaption and optimization of the intervention to local context will ensure that the intervention is 
culturally sensitive before implementation in the pilot and RCT. All HCW participants will be 
assured that their participation will not affect their employment status.  
Procedures to minimize unexpected events, including social harms, including violence: We will 
minimize social harms by training study staff on how to counsel participants on ways to avoid 
harm as per national guidelines, including not disclosing their HIV status to anyone who may harm 
them. We will also inform participants that they can contact study staff using the number provided 
on the consent form if they experience social harms. We will refer participants to the appropriate 
clinic staff, as needed.  
There are no mandatory reporting requirements in Kenya for studies that ask about gender-based 
violence. If a participant reports directly to a study staff that they are experiencing violence or 
other threat, we will follow study SOPs to refer that person to a clinic staff person for appropriate 
follow-up services. If they report violence or other threat on the self-administered survey, a 

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message will appear that recommends a referral and that our study staff could help with that 
referral if they choose. As part of routine practice, HIV care clinicians are expected to ask 
adolescent clients about exposure to violence and are mandated to perform the relevant tests 
and offer care and referrals to legal and medical resources. There will be no mention of HIV on 
adolescent recruitment talking points or consent and assent forms for surveys. Adolescent 
surveys will not include specific mention of HIV or ART unless a participant reports knowledge of 
their own HIV status on a standardized set of screening questions. If we learn of social harms 
related to routine HIV care (and not this study), we will follow our standard operating procedures 
and clinic guidelines to offer referrals to the appropriate counseling or services. 
 
Study justification 
UNAIDS ‘95-95-95’ targets cannot be achieved without additional support for ALHIV to increase 
retention in care and to support viral suppression. Risk prediction tools as well as a stepped care 
approach to care can support differentiation of ALHIV to different risk groups, and tailor care 
based on risk.  
Our team has conducted formative work with ALHIV, caregivers, HCW and policy makers and 
has developed and validated a clinical prediction tool to identify ALHIV at highest risk of not being 
retained in care and poor viral suppression that could be adapted to identify adolescents who may 
need more support in their care. Understanding how best to use the risk prediction tool as well as 
how to tailor services based on risk may ultimately result in more efficient HIV care services, as 
well as adequate support for ALHIV at highest risk of poor outcomes. 
A data-driven, provider-led, health systems intervention can identify adolescents most at risk for 
loss to care, sub-optimal adherence, and viral failure. Our stepped care approach, combined with 
a clinical prediction tool, is a timely and flexible intervention in the context of differentiated care 
and numerous ongoing care initiatives. By improving adolescent engagement in care and 
optimizing provision of limited resources, this intervention can ultimately improve health and 
decrease HIV transmission risk among adolescents in Kenya. Improved models of data-informed, 
client-centered care are urgently needed for this population and may translate to other programs 
in Kenya, and more generally in sub-Saharan Africa. 
 
3 
OBJECTIVES AND ENDPOINTS 
 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
Primary 
 
 
Aim 1: To develop, adapt, pilot, and optimize 
implementation of a data-informed stepped care 
(DiSC) intervention for ALHIV treatment 
management. 
DiSC intervention  
To provide intervention 
for the trial    

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OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
Aim 2: To evaluate effectiveness of the DiSC 
intervention on ALHIV retention in care in up to 
24 high-volume HIV clinics in Kenya. 
Retention in care  
Marker of successful 
HIV care  
Secondary 
 
 
Aim 1: To determine acceptability, feasibility, 
adaptability and fidelity of the DiSC intervention  
 
Pilot acceptability, 
feasibility, 
adaptability and 
fidelity  
Pilot data to inform 
intervention 
adaptations    
Aim 2: To evaluate effectiveness of the DiSC  
intervention on ALHIV cascade outcomes 
(adherence and viral suppression) and 
adolescent self-efficacy and correlates of 
outcomes in up to 24 high-volume HIV clinics in 
Kenya 
ART adherence  
Viral suppression  
 
ALHIV self-efficacy  
Markers of successful 
HIV care 
 
Covariate, mediator 
data  
Aim 2: To evaluate effectiveness of the DiSC  
intervention on health service outcomes in care  
in up to 24 high-volume HIV clinics in Kenya 
Client wait time  
Costs  
Impact of intervention 
on service delivery  
Aim 2: To evaluate effectiveness of the DiSC  
intervention on implementation outcomes in care 
in up to 24 high-volume HIV clinics in Kenya 
Feasibility, 
acceptability, 
adaptation, fidelity, 
adoption, reach, 
maintenance  
Intervention delivery 
data to support 
effectiveness data  
Mediator data  
 
4 
STUDY DESIGN 
 
4.1 OVERALL DESIGN 
In aim 1, with relevant stakeholders in adolescent HIV, we will collaboratively develop the DiSC 
intervention, then adapt and pilot test the intervention.  
 
In aim 2, we will conduct a cluster randomized trial (cRCT) in up to 24 sites in western Kenya (12 
randomized to intervention and 12 to control) (Figure 1). 
Figure 1: Study design, main activities, and outcomes  

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We do not plan for interim analysis. Subgroup analysis (age and gender) are planned as described 
in the statistical analysis section. 
 
4.2 SCIENTIFIC RATIONALE FOR STUDY DESIGN 
 
A cRCT design is appropriate because the intervention will be administered at the clinic level.  
 
4.3 JUSTIFICATION FOR INTERVENTION 
 
The intervention will be delivered by HCW during routine clinical visits; and works at improving 
clinic level effectiveness in care management. We anticipate at least 50 adolescents per site will 
be exposed to the intervention during the course of the study period. The intervention will be 
offered during regular clinic visits that are typically scheduled 1-6 monthly.  
4.4 END-OF-STUDY DEFINITION 
 
The definition of the end of the study is: completion of the 12-month follow-up assessment shown 
in the Schedule of Activities (SoA), Section 1.3. 
 
5 
STUDY POPULATION 
Aim 1 
Intervention development: Policy makers at national, county and care partner levels, HCW, ALHIV 
and caregivers as well as other stakeholders in HIV care will be invited to participate in an 
intervention development workshop.  
HCWs in 2 facilities participating in the completed formative phase of the study will pilot the 
intervention in their clinics.  
Aim 2  
Cluster RCT: We will conduct this study at up to 24 HIV care and treatment facilities located in 
Kisumu, Homa-Bay, Migori County.  
The population of interest is ALHIV age 10-24 enrolled in participating clinics, caregivers of 
adolescents and young adults and HCW offering services. The intervention will be administered 
by existing HCW, who will also participate in implementation surveys, interviews, and focus 
groups to assess health service and implementation outcomes.  A cohort of ALHIV ages 10-24 
years will also be enrolled to participate in longitudinal surveys. A subset of ALHIV and caregivers 
of ALHIV will also complete satisfaction surveys at the end of the trial.  
 

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5.1 INCLUSION CRITERIA 
 
Aim 1  
HCW 
18 years or older 
Policymakers 
18 years or older 
Employed currently or in past at national/county or 
partner level  
Other stakeholders 18 years or older 
Relevant experience with adolescents  
All aims  
Clinics 
Approximately 150 adolescents in care  
Active EMR system 
Willing to participate in the study  
HCW 
18 years or older  
Working with ALHIV in participating clinics  
Provision of informed consent  
Willing and able to give informed consent  
Aim 1  
Stakeholders in 
adolescent care  
18 years or older  
Working in adolescent health 
Provision of informed consent  
Willing and able to give informed consent  
Aim 2  
Adolescents  
Ages 10-24 years 
HIV-positive 
Enrolled in HIV care 
Provision of informed consent (intervention/surveys and 
FGDs/IDIs)  
Willing and able to give informed consent 
(intervention/surveys and FGDs or IDIs) 
AYA15-17 years that are considered mature/emancipated 
minors will provide informed consent without caregiver 
consent; For 10-17 year old AYA, provision of caregiver 
informed consent  
Caregivers  
18 years or older 
Caregiver of 10-17 years ALHIV 
Provision of informed consent  
Willing and able to give informed consent  
5.2 EXCLUSION CRITERIA 
 
All aims  
Clinics  
Participating in other studies that could overlap 
procedures/clients  
Adolescents, 
HCW, caregivers, 
adolescent 
Not able or willing to give informed consent  

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stakeholders 
 
5.3 LIFESTYLE CONSIDERATIONS 
NA 
 
5.4 SCREEN FAILURES 
 
Screen failures are defined as clinics that are not included in the final list of clinics for 
randomization. After randomization, we do not anticipate to re-screen or include additional 
facilities.   
 
5.5 STRATEGIES FOR RECRUITMENT AND RETENTION 
 
Recruitment  
Intervention adaptation workshop 
Policy makers at national and county level, adolescent representatives, frontline HCW, adolescent 
caregivers and representatives from HIV care partners will be purposively selected by the study 
team to participate in an intervention development workshop. Recruitment will be consecutive 
until at least 40 participants are reached. A script outlining talking points, purpose and scope of 
work will be used for recruitment. Written informed consent for participation and audio-recording 
of sections of the proceedings will be obtained.   
Intervention optimization (pilot)  
Following adaptation of intervention materials, HCWs from 2 clinics will pilot the adapted 
intervention for up to3 months using a modified quality improvement approach. The 2 HIV clinics 
will be purposively selected by the study team to participate in the pilot activities from a pool of 
HIV clinics involved in the formativephase of the study. 
 
Cluster RCT 
The sampling frame will consist of all55 clinics in participating counties that were part of the earlier 
phase of the study or that have been identified as potential clinics. Among those, up to 24clinics 
that meet eligibility criteria, have the highest AYA enrollment and whose leadership is willing to 
participate will be selected and randomized to intervention or control.  
 
Adolescent and caregiver surveys  
A proportion of ALHIV in participating facilities (~150per site) and caregivers (~45per site) will be 
enrolled to participate in surveys to determine ALHIV behavior, self-efficacy and co-factors of 
retention and viral suppression. Clinic staff members will refer ALHIV currently in HIV care to our 
trained study team for eligibility screening for the ALHIV longitudinal cohort. A standard 
recruitment script with talking points will be used. Recruitment will be conducted during different 
days and times of the week, during at least 2 school breaks and ‘youth friendly days’ to maximize 
enrollment. ALHIV who meet eligibility criteria will be invited to enroll in the cohort and complete 

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behavioral surveys at enrollment and every 6 months thereafter. Clinic staff members will refer to 
the study team a purposeful sample of caregivers of adolescents coming in for routine clinic visits. 
A large number of adolescents come to clinic alone; the study will only recruit caregivers who 
accompany adolescents. Caregivers who meet eligibility criteria will be invited to enroll and 
complete caregiver surveys at enrollment and at 12 months. 
 
HCW surveys  
HCW in participating sites working in the ALHIV clinic will be invited to participate in health service 
and implementation surveys. A script outlining talking points, purpose and scope of work will be 
used for recruitment. Written informed consent for participation will be collected from all 
participants prior to study activities. 
 
Participant incentives  
The study will provide reimbursement for transportation costs, accommodation and meals during 
the workshop and provide a per-diem allowance equal to current rates used by organizations or 
facilities where the HCWs work. 
Adolescents and caregivers who participate in surveys will be reimbursed KSH 200 ($2.00 USD). 
HCW attending study related meetings and completing surveys will be reimbursed KSH 1000 
(~10USD).  
 
Population justification   
This study will be conducted in ALHIV age 10-24 years old, who have a high risk of mortality, 
and require innovative client-centered strategies to improve retention, adherence, and viral 
suppression. The study will be conducted in Kenya, where 140,000 adolescents (ages 10-
19) have HIV, and HIV is among the leading causes of mortality in this age group. 
6 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) 
6.1 
STUDY 
INTERVENTION(S) 
OR 
EXPERIMENTAL 
MANIPULATION(S)ADMINISTRATION 
6.1.1 STUDY INTERVENTIONOR EXPERIMENTAL MANIPULATIONDESCRIPTION 
The Data-informed Stepped Care (DiSC) intervention is comprised of a system to assign ALHIV 
to different levels of care, or “steps”, depending on their current and anticipated health care needs. 
Stepped care is a model grounded in Stages of Change Theory and has been used in mental 
health fields to organize provision of services, and to support clients, HCWs, and caregivers to 
identify interventions tailored to individual need. HCWs at participating sites will assign ALHIV to 
different levels or intensity of HIV services. The trajectory of services moves from a relative 
position of ALHIV autonomy to more intensive service provision. Intervention steps could start 
with multi-month refills or community treatment delivery, then social support activities (support 
groups, life skills activities), progress to individualized services (text messaging, ‘big 
brother/sister’ older peer support, motivational interviewing), and ultimately a case management 
approach involving referrals to specialized care like mental health or gender-based violence 
services, individualized counseling, and active tracking of individual participation in support and 
care services. The stepped care framework is designed to be flexible, to accommodate variable 

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will work with HCWs to improve their ability to use the DiSC intervention during initial 
implementation period (about 3-6 months) during which an implementation/adaptation log will be 
used to track changes in implementation and HCWs will participate in twice-monthly planning and 
feedback meetings.  
Surveys and tracking tools will be used to track implementation (see section 8).  
 
6.3 MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
 
Randomization procedures are described in section 4.1.Blinding is not possible as the intervention 
will be delivered at the clinic level.  
 
6.4 STUDY INTERVENTION/EXPERIMENTAL MANIPULATIONADHERENCE 
 
The study team will track ALHIV to determine if they received care as per assignment in the 
intervention sites using intervention adherence logs. These logs will be adapted based on the 
final intervention steps. 
 
6.5 CONCOMITANT THERAPY 
NA 
 
6.5.1 RESCUE THERAPY 
NA 
 
7 
STUDY INTERVENTION/EXPERIMENTAL 
MANIPULATIONDISCONTINUATIONAND 
PARTICIPANTDISCONTINUATION/WITHDRAWAL 
 
7.1 DISCONTINUATION 
OF 
STUDY 
INTERVENTION/EXPERIMENTAL 
MANIPULATION 
We do not anticipate that clinics will discontinue participation or withdraw from the study after 
randomization. However, if this occurs, the study team will get permission from the clinic to use 
study data up until the time of discontinuation.  
 
7.2 PARTICIPANTDISCONTINUATION/WITHDRAWAL FROM THE STUDY 
 
Participants are free to withdraw from participation in surveys or individual data collection 
procedures at any time upon request. Participants may also be discontinued if there is:  
• 
Lostto Follow-up; unable to contact subject (see Section 7.3, Lost to Follow-Up) 

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• 
Any event or medical condition or situation occurs such that continued collection of follow-
up study data would not be in the best interest of the participant  
• 
The participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation 
 
The reason for participant discontinuation or withdrawal from the study will be recorded. Subjects 
who sign the informed consent form and withdraw or discontinue may be replaced.   
 
7.3 LOST TO FOLLOW-UP 
 
Since the study primary outcome is retention, study staff will not contact caregivers or ALHIV who 
miss their appointments for longitudinal survey data collection. However, we will contact 
stakeholders and HCW as needed to schedule study related activities.  
8 
STUDY ASSESSMENTS AND PROCEDURES 
 
8.1 ENDPOINT AND OTHER NON-SAFETY ASSESSMENTS 
 
Intervention development workshop  
The intervention development workshop will be led by study team members. Workshop material 
will be summarized and sent to participants prior to the workshop. Materials will include literature 
on the use of risk assessment tools, information on the risk tool from the formative phase of the 
study, proposed core elements of the risk tool, differentiated care services, best practices for 
adolescent care, national guidelines on HIV care, flow maps of existing services in clinics in the 
catchment area and proposed framework for stepped care levels including sample intervention 
tables. The workshop will begin with a review of all material shared before the workshop. Next, 
the risk prediction tool will be introduced and discussed in detail in small groups including 
performance, strengths, weaknesses, and proposed categories. HCWs will be encouraged to 
think about how the tool would work in their work setting, while incorporating the views of 
stakeholders. A framework of proposed intervention steps with different levels of care with 
increasing intensity will be presented. HCWs will discuss what interventions would work at the 
different levels of care, keeping in mind current practices in the facilities. HCWs will be 
encouraged to be participatory and as practical as possible, and to develop the most inclusive 
and simplest interventions that would work in the largest number of facilities in Kenya. Small 
working groups will present their discussions to the larger group, and the large group will work to 
come to consensus on a draft tool. The tool will continue to be refined after the workshop, 
incorporating the views and feedback of all stakeholders present.  Selected workshop members 
will be contacted to review the refined tool after the workshop. The study will provide 
reimbursement for transportation costs, accommodation and meals during the workshop and 
provide a per-diem allowance equal to current rates used by organizations or facilities where the 
HCWs work.  
Data Collection Procedures: 

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Small and large group discussions during the workshop will be audio recorded. Notes will be taken 
during discussions, and audio recordings will be transcribed as needed for team review. Prior to 
the intervention development workshop, HCWs will complete a short demographic form to collect 
socio-demographic information. Neither the transcribed notes from the workshop or transcripts 
will include any personal identifiers other than the participant’s first name. Collected transcript 
data will be de-identified. The audio recordings of discussions will be destroyed after study 
participation and data analysis has been completed and no later than 6 years after the workshop 
took place. Audio files and English transcripts will be uploaded to a password protected secure 
website for back-up. A qualitative software program (ex: ATLAS.ti or Dedoose) will be used for 
data management and analysis.  
 
Listed below are all the required procedures for the intervention development workshop  
1) Invitation to participate in workshop  
2) Collect locator information (phone number) and schedule meeting dates 
3) Provide a copy of the materials to review prior to the meeting  
4) Complete demographic surveys  
5) Present results of qualitative work 
6) Present the risk prediction tool  
7) Discussion on how to use the risk tool  
8) Present outline for proposed DiSC intervention  
9) Group discussion on DiSC intervention components  
10) Small group discussions to develop and refine steps in care   
11) Whole group presentations with iterative refinement  
12) Presentation of refined tool and risk categories  
13) Post workshop review of refined tool  
Intervention optimization (pilot)  
HCWs and AYA in participating sites will consent to participate in the pilot phase which includes 
intervention administration, twice-monthly intervention adaptation meetings, as well as 
implementation surveys. At the start of the pilot, HCWs will complete a short demographic form 
to collect socio-demographic information. HCWs will be introduced to the adapted intervention 
materials, trained on how to use them, and encouraged to make small adaptations and changes 
to the way they implement the intervention throughout the pilot period. If a new HCW enters the 
facility during the pilot, they will also be trained on the intervention materials and have socio-
demographic information collected. An implementation/adaptation log will be used to track 
changes in implementation and HCWs will participate in twice-monthly planning and feedback 
meetings. Meetings will be audio recorded and transcribed when necessary. Transcripts will not 
include HCW names. Routinely collected data at the facility, such as the number of adolescents 
attending and the number of adolescents exposed to the intervention, will be collected to monitor 
implementation outcomes of adoption and reach. Following the pilot period, HCWs from clinics 
who participated in the pilot will take part in individual in-depth interviews (IDIs) or focus group 
discussions (FGDs) to share their suggestions for optimizing the intervention based on their pilot 
experience. IDIs and FGDs will be audio recorded and will be transcribed verbatim. Transcripts 
and notes from twice-monthly meetings will be analyzed to identify themes related to how to revise 
intervention materials and implementation. After the pilot phase, the tool will be further refined 
with input from selected members who participated in the intervention development workshops 
prior to use in the RCT phase.  

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Cluster RCT 
Intervention details, administration and assessments are described in the sections above (see 
section 6.1 and 6.2).  
 
Program records: We will abstract ALHIV medical record data at baseline and regular intervals 
throughout the study. Data from all adolescents with at least 1 clinic record within the 12-month 
period prior to the first data abstraction date will be included. Data will be abstracted at the facility 
or at the office of the technical partner that supports the EMR system at the facility. The EMR 
system captures data on client anthropometric measures, demographics, HIV testing history, 
family members, clinical history, ART adherence data, laboratory data, CD4 count, transfers, and 
discontinuations. Routine viral load testing (done 6 months after ART initiation, then annually) will 
be abstracted from the EMR, if available, or NASCOP’s laboratory database. If EMR data is 
unavailable, paper medical records will be abstracted using mobile REDCap which enables 
automatic upload of data to a secure, password-protected study server.  
Adolescent behavioral surveys: Adolescent surveys will include questions on socio-
demographics, health care use, stigma, sexual behavior, psychosocial support, mental health, 
personal health knowledge, HIV disclosure and medication adherence. Surveys will be 
administered every 6 months either in-person or over phone by a trained study staff. Survey visits 
will coincide with clinic visits as much as possible. 
Caregiver behavioral surveys: Caregiver surveys will include questions on socio-demographics 
and family, caregiver roles, HIV disclosure, HIV care experience, disclosure, social support, 
mental health, HIV testing and awareness, personal health and HIV experience, HIV stigma, ART 
knowledge and adherence. Surveys will be administered every 12 months either in-person or over 
phone by a trained study staff. Survey visits will coincide with clinic visits as much as possible.  
Data on health services and implementation outcomes will be collected as previously described 
(see section 6.2). 
To track implementation, the following surveys will be conducted:  
Facility surveys: Facility managers will complete baseline and annual facility surveys to 
understand baseline resource capacity to implement future interventions and modifiable and non-
modifiable health system factors. Variables will include availability of youth-friendly services, 
management and referral systems, and differentiated care services available.  
HCW surveys and FGDs/IDIs: Surveys with all HCWs at intervention and control sites who are 
willing to participate will be conducted at baseline and annually on demographic information, 
including training history and experience providing HIV care. HCWs at intervention sites will also 
complete an organizational readiness for change survey after training on the intervention, but 
prior to implementation at their clinic, and will participate in twice-monthly planning and feedback 
meetings during the first 6 months of implementation. We will conduct surveys, FGDs, and IDIs 
with HCWs in intervention sites at 6 months post-intervention implementation and at the end of 
the trial to evaluate barriers and facilitators of intervention implementation, overall implementation 
outcome measures using the Reach, Effectiveness, Adoption, Implementation and Maintenance 
(RE-AIM) framework as well as costs. Cost data will be collected from HCW or policy makers in 
adolescent health, published literature and government data. FGDs and IDIs with HCWs will 

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include a purposeful sample of those exposed to the intervention, stratified by clinic performance 
level during intervention implementation, cadre of HCW, and involvement in implementation. Exit 
surveys with HCWs at implementation sites will be conducted to determine experience with the 
DiSC intervention and barriers and facilitators for intervention utilization. Example validated tools 
that may be used to inform the surveys and measure each of the implementation outcomes 
include: 
• 
Determinants of DiSC intervention feasibility and acceptability classified using the 
Consolidated Framework for Implementation Research (CFIR) 
• 
Intervention adaptation classified according to the framework for reporting adaptations 
and modifications to evidence-based interventions (FRAME)  
• 
Reach, Acceptability and Feasibility, measured by the Applied Mental Health 
Research (AMHR) validated implementation science measure[72] 
• 
Adoption, measured using a 17-item validated survey to characterize intervention 
characteristics and likelihood of adoption[73] 
• 
Implementation, measured using surveys to assess enthusiasm, self-efficacy and 
preparedness[74] 
• 
Maintenance, measured using the Program Sustainability Assessment Tool (PSAT) 
HCW implementation logs: These will be collected weekly and combined with information 
collected in annual HCW surveys to understand intervention and implementation processes in 
real time and service efficiency outcomes. We will specifically evaluate the percent of HCWs using 
the intervention, percent of adolescents in each step, percent of adolescents assigned to correct 
step, and percent of adolescents ‘adherent’ to services in each step. We will also collect basic 
information on numbers of adolescents attending clinic each week, and the number exposed to 
the intervention. In control sites, we will collect information on classification of adolescents as 
stable/unstable and offer for differentiated services.  
ALHIV and caregiver satisfaction surveys: Surveys will be given to a random sample of 
adolescents and caregivers in intervention sites at the end of the study to evaluate satisfaction 
with their care.  
ALHIV FGDs/IDIs: We will conduct FGDs/IDIs with adolescents in intervention sites at the end of 
the intervention period to determine acceptability, feasibility ad satisfaction with the intervention. 
FGD/IDI participants will be purposively selected from adolescents in intervention clinics. We will 
conduct FGDs/IDIs with up to 50 people per facility.  
The table below summarizes study outcomes and definitions 
 
Summary of outcomes and definitions  
Aims 
Outcome type  
Outcome  
Definition  
Aim 1  
Primary  
Final optimized DiSC 
intervention  
Modified DiSC intervention with input 
from workshop and pilot phase  
Secondary  
DiSC intervention feasibility  
Suitability for everyday use and 
practicality  

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DiSC intervention 
acceptability   
HCW satisfaction with the intervention 
DiSC intervention adaptation 
and fidelity  
The degree with which the intervention 
is modified and implemented as 
planned 
Aim 2  
Primary  
Retention in care  
>30 days late for a scheduled visit at 6-
month intervals  
Secondary  
ART adherence 
Proportion of days on ART based on last 
dispense date 
Viral suppression 
<50 copies per milliliter and a second 
analysis using greater than lower limit of 
detection 
Co-factors of retention and 
viral suppression 
School drop-out, relationships, 
depressive symptoms, substance use, 
social support, and satisfaction with 
care 
ALHIV self-efficacy  
Self-efficacy 
scales 
from 
standard 
questionnaires  
Health 
service 
efficiency  
Client wait time  
Average ALHIV waiting time in clinic 
Costs  
Direct 
and 
indirect 
costs 
of 
the 
intervention  
Differentiated care process  
% of ALHIV correctly identified as stable 
or unstable  
Implementation 
outcomes  
Intervention feasibility   
Suitability for everyday use and 
practicality  
Intervention acceptability  
HCW and ALHIV satisfaction with the 
intervention 
Intervention adaptation and 
fidelity  
The degree with which the intervention is 
modified and implemented as planned 
Intervention adoption   
The initial decision to take up a new 
intervention 
Intervention reach   
The integration of the practice within 
the clinic 

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Intervention maintenance  
The longer-term ability to sustain or 
maintain intervention implementation 
 
 
 
 
8.2 SAFETY ASSESSMENTS 
 
We do not anticipate adverse events associated with the intervention, and therefore we will not 
actively monitor for adverse events. However, if any adverse events occur among participants 
enrolled in the study, we will report them as required by the regulatory bodies.  
8.3 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
 
8.3.1 DEFINITION OF ADVERSE EVENTS 
 
This protocol uses the definition of adverse event from 21 CFR 312.32 (a): any untoward medical 
occurrence associated with the use of an intervention in humans, whether or not considered 
intervention-related. 
 
8.3.2 DEFINITION OF SERIOUS ADVERSE EVENTS 
 
Serious adverse events will be defined as per the Division of AIDS (DAIDS) Table for grading the 
severity of adult and pediatric adverse events (grade 3-5 events).  
 
8.3.3 CLASSIFICATION OF AN ADVERSE EVENT 
8.3.3.1 SEVERITY OF EVENT 
We do not anticipate any significant adverse events to occur throughout this study. However, in 
the event that an adverse event occurs, participants will be given contact information for study 
team members and will contact study staff. Severity will be classified based on the DAIDS grading.  
8.3.3.2 RELATIONSHIP TO STUDY INTERVENTION/EXPERIMENTAL MANIPULATION 
 
We do not expect that adverse events will be related to the study intervention. However, all 
adverse events (AEs) will have their relationship to study procedures, including the intervention, 
assessed by an appropriately-trained clinician based on temporal relationship and his/her clinical 
judgment. The degree of certainty about causality will be graded using the categories below.  
 

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• 
Related – The AE is known to occur with the study procedures, there is a reasonable 
possibility that the study procedures caused the AE, or there is a temporal relationship 
between the study procedures and the event. Reasonable possibility means that there is 
evidence to suggest a causal relationship between the study procedures and the AE. 
• 
Not Related – There is not a reasonable possibility that the study procedures caused the 
event, there is no temporal relationship between the study procedures and event onset, 
or an alternate etiology has been established. 
 
8.3.3.3 EXPECTEDNESS  
 
A clinician with appropriate expertise in HIV management will be responsible for determining 
whether an adverse event (AE) is expected or unexpected. An AE will be considered unexpected 
if the nature, severity, or frequency of the event is not consistent with the risk information 
previously described for the study procedures. 
 
8.3.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-
UP 
NA 
 
8.3.5 ADVERSE EVENT REPORTING 
 
All unanticipated problems, including adverse events, will be reported to the study sponsor, PIs, 
and ethics committee according to UW and Maseno University Ethics Review Committee 
guidelines. 
 
8.3.6 SERIOUS ADVERSE EVENT REPORTING 
 
In consultation with the PI, a trained member of the study team will be responsible for conducting 
an evaluation of a serious adverse event.  
 
Reporting to Maseno University Ethics Review Committee (MUERC) 
The investigator shall notify the secretariat by telephone (+ 254 57 351 622) within twelve (12) 
hours of the event. In addition, the adverse event(s) noted during the conduct of a study or project 
must be reported to the MUERC via email (muerc-secretariate@maseno.ac.ke) within twenty-four 
(24) hours after the applicant becomes aware of the event.The investigator must submit a 
completed adverse event form alongside a summary of the event. The hard copies of the report 
must be forwarded to the MUERC Secretariat within three (3) working days of the initial 
notification. 
 
Reporting to University of Washington IRB:  
Adverse events that meet the following criteria must be reported to the UW Human subjects 
division  

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a) AEs that were related to research procedures, serious, and unexpected (report 
immediately and within 10 business days)  
b) AEs that were related to research procedures and expected, but more severe or occurred 
at a greater frequency than expected (report immediately and within 10 business days)  
c) AEs that were related, non-serious, but unexpected (report annually)  
 
Reporting to Study sponsor (NIH):  
According to sponsor guidelines. 
 
8.3.7 REPORTING EVENTS TO PARTICIPANTS 
NA 
 
8.3.8 EVENTS OF SPECIAL INTEREST 
NA 
 
8.3.9 REPORTING OF PREGNANCY 
NA 
 
8.4 UNANTICIPATED PROBLEMS. 
 
8.4.1 DEFINITION OF UNANTICIPATED PROBLEMS 
 
This protocol uses the definition of Unanticipated Problems as defined by the Office for Human 
Research Protections (OHRP).  OHRP considers unanticipated problems involving risks to 
participants or others to include, in general, any incident, experience, or outcome that meets all 
of the following criteria: 
 
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures 
that are described in the protocol-related documents, such as the Institutional Review 
Board (IRB)-approved research protocol and informed consent document; and (b) the 
characteristics of the participant population being studied; 
• 
Related or possibly related to participation in the research (“possibly related” means there 
is a reasonable possibility that the incident, experience, or outcome may have been 
caused by the procedures involved in the research); and 
• 
Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized. 
 
8.4.2 UNANTICIPATED PROBLEMS REPORTING 
 

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The investigator will report unanticipated problems (UPs) to the reviewing Institutional Review 
Board (IRB) and to the lead principal investigators (PIs). The UP report will include the following 
information: 
 
• 
Protocol identifying information: protocol title and version, PI’s name, and the IRB project 
number 
• 
A detailed description of the event, incident, experience, or outcome 
• 
An explanation of the basis for determining that the event, incident, experience, or 
outcome represents an UP 
• 
A description of any changes to the protocol or other corrective actions that have been 
taken or are proposed in response to the UP 
 
To satisfy the requirement for prompt reporting, UPs will be reported using the following timeline:   
 
• 
UPs that are serious adverse events (SAEs) will be reported to MUERC and UW HSD. 
The investigator shall notify the MUERC secretariat by telephone (+ 254 57 351 622) 
within twelve (12) hours of the event. In addition, the adverse event(s) noted during the 
conduct of a study or project must be reported to the MUERC via email (muerc-
secretariate@maseno.ac.ke) within twenty-four (24) hours after the applicant becomes 
aware of the event. UW HSD will also be notified within 10 business days.   
 
8.4.3 REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS 
NA 
 
9 
STATISTICAL CONSIDERATIONS 
 
A formal statistical analysis plan (SAP) will be developed and completed prior to database lock. 
The SAP will be posted at the clinical trials.gov site. The section below summarizes key aspects 
of the SAP.   
9.1 STATISTICAL HYPOTHESES 
 
Statistical hypothesis are described in section 4.1  
 
9.2 SAMPLE SIZE DETERMINATION 
 
Sample Size and Power for primary outcome 
In our sample of HIV care facilities with >1,000 clients enrolled overall, we anticipate at least 10% 
will be eligible adolescents and young adults or about 100-200 AYA per clinic on average. Based 
on our UG3 data, we assume that 75% will be in care (not LTFU) and viral suppression of 64% 
(85% suppressed x 75% actively in care). Given a minimum of 20 facilities in the trial (minimum 
10 per arm), we estimated the minimum average number of AYA per facility to detect a 15-20% 
change in retention using EMR data. We assumed 80% power, an a=0.05 and coefficient of 

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variation of 0.15. In table 3a below, we can detect a 17% percentage point different (75% to 93%) 
with an average of 100 AYA per facility and 20 facilities. The same estimates hold for as few as 
50 AYA per arm and up to 170 per arm. Detecting less than a 17% percentage point difference 
would require more facilities per arm or at least 180 AYA per facility.  
 
Secondary outcomes and assumptions: 
Viral suppression: An average of 50 AYA VL records per facility and a minimum of 10 facilities 
per arm would be sufficient to detect a change from 64% to 81%, assuming 80% power, an a=0.05 
and coefficient of variation of 0.15. 
 
Cohort analyses: Based on UG3 enrollment data in the AYA cohort, we assume that about 50% 
of the total AYA clinic population to enroll in the cohort and set 50 as the average enrollment 
target per facility. Separate power and sample size calculations will be performed based on the 
specific exposure and outcome. When the intervention is the exposure, we will assume to have 
adequate power to detect at least a 17% percentage point difference in proximate outcomes (e.g. 
implementation and client outcomes) 
Table 3a: Minimum Sample of AYA per Facility for the Primary ITT Analysis of Retention 
 
 
 
 
Retention % in the 
intervention arm 
n=100 AYA 
per facility 
Facilities 
per arm 
n=50 AYA 
per facility 
Facilities per 
arm 
75% 
90% 
100 
13 
50 
14 
75% 
92% 
100 
11 
50 
12 
75% 
93% 
100 
10 
50 
10 

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Mixed effects regression models will be used to compare the number of missed visits between 
arms, accounting for clustering by individual and clinic. LTFU will be compared using cox 
proportional hazards regression. Death or transfers will be censored. Sub-group analyses will be 
performed by gender and age-group. Facility factors, including concurrent adolescent-friendly 
services and high/low performance will be evaluated as moderators of intervention effectiveness. 
 
9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
Intervention effectiveness on secondary outcomes, including and the proportion virally 
suppressed at 6 and 12 months, proportion with >80% adherence since last refill, the proportion 
retained at 18 and 24 months, and proportion virally suppressed at 18 and 24 months, will be 
evaluated in separate regression models. Mediation analyses to understand mechanisms of 
intervention effectiveness will include whether intervention effectiveness is partially explained by 
ALHIV satisfaction and self-efficacy. 
Intervention impact on systems efficiencies will be evaluated in regression models comparing 
intervention and control clinics on service outcomes including median client wait time. We will 
include selected costing indicators at all sites in consultation with the UW CFAR Health Economic 
Impact Study Team for future cost-modeling, although a complete cost-effectiveness analysis is 
beyond the scope of this application.  
Implementation outcomes and health system outcomes will be evaluated using standard 
qualitative and quantitative analysis methods, corresponding to the type of data collected to 
measure each implementation outcome. The majority of implementation surveys will be evaluated 
using Likert scales, and data will be summarized using basic descriptive statistics. Qualitative 
data will be analyzed using thematic analysis approaches that account for the use of 
implementation frameworks (CFIR, FRAME). Themes will be organized based on selected 
frameworks. Adaptation of the intervention will include measuring micro-changes tested and 
evaluation of the results of these changes.  
 
9.4.4 SAFETY ANALYSES 
 
NA 
 
9.4.5 BASELINE DESCRIPTIVE STATISTICS 
 
NA 
 
9.4.6 PLANNED INTERIM ANALYSES 
 
NA 
9.4.7 SUB-GROUP ANALYSES 
 

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Subgroup analysis will be performed by gender and age group for primary and secondary 
outcomes. As with the primary analysis, sub-group analysis will be adjusted to account for 
clustering.   
 
9.4.8 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
 
Individual participant data will not be listed.  
 
9.4.9 EXPLORATORY ANALYSES 
NA 
 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
 
10.1.1 INFORMED CONSENT PROCESS 
 
10.1.1.1 
CONSENT/ASSENT 
AND 
OTHER 
INFORMATIONAL 
DOCUMENTS 
PROVIDED TO PARTICIPANTS 
 
 
Consent forms describing in detail the study intervention, study procedures, and risks will be given 
to the participant and written documentation of informed consent will be completed prior to starting 
the study intervention.  The following consent materials are submitted with this protocol  
Aim 1 
• 
Stakeholder consent to participate in workshop  
• 
HCW consent to participate in pilot study 
• 
Adolescent consent to participate in facility-based intervention 
• 
Consent for HCW post-pilot FGD  
Aim 2  
• 
Adolescent consent to participate in facility-based intervention 
• 
Adolescent consent to participate in surveys (age 18+) 
• 
Adolescent assent to participate in surveys (age under 18)  
• 
Caregiver consent for adolescent surveys (age under 18) 
• 
Caregiver consent for enrollment  
• 
HCW consent to participate in IS activities  
• 
HCW consent to participate in annual surveys  
• 
Facility survey consent  
• 
HCW consent for FGD and IDI (Intervention sites)  

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• 
Adolescent consent to participate in FGD and IDI (age 18+) 
• 
Adolescent assent to participate in FGD and IDI (age under 18) 
• 
Caregiver consent for adolescents to participate in FGD and IDI (age under 18) 
 
10.1.1.2 
CONSENT PROCEDURES AND DOCUMENTATION 
Prior to conducting consent, study staff will confirm eligibility. Adolescents and caregivers who are 
eligible will begin the consent/assent process. Study personnel will read through the consent or 
assent form with policy makers at national and county level, adolescent representatives, frontline 
HCW, adolescent caregivers and representatives from HIV care partners. During this process, 
potential participants will have the study and relevant study procedures explained to them, their 
questions answered, and provide written consent for their enrollment.  
If ALHIV participants <18 are brought to clinic by a caregiver, the caregiver will provide written 
informed consent and the ALHIV will assent to participate in the study. However, adolescents <18 
who meet the definition of emancipated minor (pregnant/has child, married/partnered, financially 
or otherwise independent of parents) or mature minor (age 15, living apart from parents, and 
managing own finances) under Kenyan law will be able to provide written consent as adults. We 
will request a waiver of parental permission for adolescents ages 15-17 who do not meet 
emancipated minor criteria and whose caregivers are not present. Caregivers will be informed 
that providing informed consent for their child does not permit them access to their child’s survey 
responses. Adolescents and caregivers will be told that participation in the study will not affect 
their child’s or their own personal care. Enrollment for adolescents less than 15 years of age will 
require caregiver consent.  
Assessment of consent/assent understanding: 
Comprehension will be assessed by asking the participant to repeat back what was explained 
and encourage them to ask questions. Study staff may ask the participant questions like the 
following to assess comprehension:  
a. "Just so that I'm sure you understand what is expected of you, would you please 
explain to me what you think we're asking you to do?" 
b. "Describe in your own words the purpose of the study." 
c. "What more would you like to know?" 
d. "What is the possible benefit to you of participating in this study? What are the 
possible risks?" 
If the participant is unable to answer these questions, study staff will go through the consent form 
with them again. If a participant continues to be unable to understand the study procedures and 
risks and benefits, the staff person will thank them for their time and let them go without enrolling 
them into the study. 
Children who become adults during the study (age 18) and whose caregivers had provide 
informed consent will be re-consented at their next visit.  
 
10.1.2 STUDY DISCONTINUATION AND CLOSURE 

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This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause. Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to participating clinics, 
investigator, funding agency, and regulatory authorities. If the study is prematurely terminated or 
suspended, the Principal Investigator (PI) will promptly inform study clinics and participants, the 
Institutional Review Board (IRB), and sponsor/funding agency and will provide the reason(s) for 
the termination or suspension. Study participants will be contacted, as applicable, and be 
informed of changes to study visit schedule. 
 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Insufficient compliance to protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
 
The study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the funding agency, sponsor, IRB, Food and Drug Administration (FDA), 
or other relevant regulatory or oversight bodies (OHRP, DSMB).] 
 
10.1.3 CONFIDENTIALITY AND PRIVACY 
 
Participant confidentiality and privacy is strictly held in trust by the participating investigators, their 
staff, the safety and oversight monitor(s), and the sponsor(s) and funding agency. This 
confidentiality is extended to the data being collected as part of this study. Data that could be 
used to identify a specific study participant will be held in strict confidence within the research 
team. No personally-identifiable information from the study will be released to any unauthorized 
third party without prior written approval of the sponsor/funding agency.  
 
All research activities will be conducted in a setting as private as possible. 
 
The study monitor, other authorized representatives of the sponsor or funding agency, 
representatives of the Institutional Review Board (IRB) or regulatory agencies may inspect all 
documents and records required to be maintained by the investigator, including but not limited to, 
medical records (office, clinic, or hospital) for the participants in this study. The clinical study site 
will permit access to such records. 
 
The study participant’s contact information will be securely stored at each clinical site for internal 
use during the study. At the end of the study, all records will continue to be kept in a secure 
location for as long a period as dictated by the reviewing IRB, Institutional policies, or 
sponsor/funding agency requirements. 
 
Study participant research data, which is for purposes of statistical analysis and scientific 
reporting, will be transmitted to and stored on a secure server hosted by the University of 
Washington, accessible by both Kenya and US based teams. The study data entry and study 
management systems used by clinical sites and by UW research staff will be secured and 

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password protected. At the end of the study, all study databases will be de-identified and archived 
at the UW.  
 
Measures Taken to Ensure Confidentiality of Data Shared per the NIH Data Sharing Policies  
It is NIH policy that the results and accomplishments of the activities that it funds should be made 
available to the public (see https://grants.nih.gov/policy/sharing.htm). The PI will ensure all 
mechanisms used to share data will include proper plans and safeguards for the protection of 
privacy, confidentiality, and security for data dissemination and reuse (e.g., all data will be 
thoroughly de-identified and will not be traceable to a specific study participant). Plans for 
archiving and long-term preservation of the data will be implemented, as appropriate.  
 
Data may also be shared across studies in the PATC3H program – composed of 8 research teams 
conducting clinical research to improve health outcomes among adolescents at risk for HIV. Data 
shared across the consortium members will not be considered public use.  
 
Certificate of Confidentiality  
To further protect the privacy of study participants, the Secretary, Health and Human Services 
(HHS), has issued a Certificate of Confidentiality (CoC) to all researchers engaged in biomedical, 
behavioral, clinical or other human subjects research funded wholly or in part by the federal 
government.  Recipients of NIH funding for human subjects research are required to protect 
identifiable research information from forced disclosure per the terms of the NIH Policy (see 
https://humansubjects.nih.gov/coc/index). As set forth in 45 CFR Part 75.303(a) and NIHGPS 
Chapter 8.3, recipients conducting NIH-supported research covered by this Policy are required to 
establish and maintain effective internal controls (e.g., policies and procedures) that provide 
reasonable assurance that the award is managed in compliance with Federal statutes, 
regulations, and the terms and conditions of award. It is the NIH policy that investigators and 
others who have access to research records will not disclose identifying information except when 
the participant consents or in certain instances when federal, state, or local law or regulation 
requires disclosure. NIH expects investigators to inform research participants of the protections 
and the limits to protections provided by a Certificate issued by this Policy. 
 
Our data storage, transfer, and ownership will conform to Kenya's Data Protection Policy (2018).  
10.1.4 FUTURE USE OF STORED SPECIMENS AND DATA 
 
Data collected for this study will be analyzed and stored at the UW. After the study is completed, 
the de-identified, archived data will be transmitted to and stored at the UW, for use by other 
researchers including those outside of the study. Permission to use data will be included in the 
informed consent.  
 
When the study is completed, access to study data will be provided through the National Institute 
of Child Health and Human Development (NICHD) Data and Specimen Hub (DASH) 
https://dash.nichd.nih.gov. 
 
 
10.1.5 KEY ROLES AND STUDY GOVERNANCE 

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Principal Investigator 
Principal 
Investigator 
Site Principal 
Investigator 
 
Pamela Kohler 
Associate Professor, 
Nursing, Global Health  
Grace John-Stewart 
Professor, Medicine, 
Epidemiology, 
Pediatrics, Global 
Health 
Kawango Agot 
Founder, Director, 
Impact Research 
& 
Development 
Organization 
(IRDO) 
 
University of Washington  University 
of 
Washington   
IRDO 
 
Harborview 
Medical 
Center 
325 9th Avenue, Box 
359932 
Seattle WA 98104  USA 
Harborview 
Medical 
Center 
325 9th Avenue, Box 
359932 
Seattle 
WA 
98104  
USA 
Tuungane 
Hospital, Tom 
Mboya Estate 
Mito Jura Road, 
off Kisumu- 
Kakamega 
Highway 
P.O. Box 9171-
40141 
Kisumu, Kenya 
P.O Box 9171-
40141, Kisumu, 
Kenya 
 
+1-206-616-7962 
+1-206-543-4278 
+254-727-688550 
 
pkohler2@uw.edu 
gjohn@uw.edu 
kawango@impact-
rdo.org 
 
 
10.1.6 SAFETY OVERSIGHT 
 
Safety oversight will be under the direction of a Data and Safety Monitoring Board (DSMB) 
composed of individuals with the appropriate expertise, including adolescent HIV, epidemiology, 
biostatistics and implementation science. Members of the DSMB will be independent from the 
study conduct and free of conflict of interest. The DSMB will meet annually to assess safety and 
efficacy data from each arm of the study. The DSMB will operate under the rules of an approved 
charter that will be written and reviewed at the organizational meeting. At this time, each data 
element that the DSMB needs to assess will be clearly defined. The DSMB will provide its input 
to the study sponsor/National Institutes of Health and regulatory bodies.  
 
10.1.7 CLINICAL MONITORING 
 
Clinical site monitoring will be conducted to ensure that the rights and well-being of trial 
participants are protected, that the reported trial data are accurate, complete, and verifiable, 

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and that the conduct of the trial is in compliance with the currently approved 
protocol/amendment(s), with International Council on Harmonization Good Clinical Practice 
(ICH GCP), and with applicable regulatory requirement(s). Monitoring activities will be as 
follows: 
• 
Monitoring for this study will be performed by Westat 
 
10.1.8 QUALITY ASSURANCE AND QUALITY CONTROL 
 
Each clinical site will perform internal quality management of study conduct and collection, 
documentation and completion. All sites will follow a common quality management plan. 
 
Quality control (QC) procedures will be implemented as follows: 
 
Informed consent: Study staff will review both the documentation of the consenting process as 
well as 100% of the completed consent documents.  This review will evaluate compliance with 
GCP, accuracy, and completeness.  Feedback will be provided to the study team to ensure proper 
consenting procedures are followed.  
 
Source and the electronic documents data: Data will be directly entered into the study database 
(see Section10.1.9, Data Handling and Record Keeping). 
 
Intervention Fidelity: Consistent delivery of the study interventions will be monitored throughout 
the intervention phase of the study. Procedures for ensuring fidelity of intervention delivery are 
described in Section 6.2.1, Interventionist Training and Tracking. 
 
Protocol Deviations: The study team will review protocol deviations on an ongoing basis and will 
implement corrective actions when the quantity or nature of deviations are deemed to be at a level 
of concern. 
 
 
10.1.9 DATA HANDLINGAND RECORD KEEPING 
 
10.1.9.1 
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
 
Data collection will be the responsibility of the clinical trial staff at the site under the supervision 
of the site investigator. The investigator will be responsible for ensuring the accuracy, 
completeness, legibility, and timeliness of the data reported. 
 
All source documents will be completed in a neat, legible manner to ensure accurate interpretation 
of data.   
 
Hardcopies of the study visit worksheets will be provided for use as source document worksheets 
for recording data for each participant consented/enrolled in the study if needed.  Data recorded 

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in the electronic case report form (eCRF) derived from source documents will be consistent with 
the data recorded on the source documents.  
 
Survey data will be entered during client encounters into a REDCap database a 21 CFR Part 11-
compliant data capture system provided by the UW. The data system includes password 
protection and internal quality checks, such as automatic range checks, to identify data that 
appear inconsistent, incomplete, or inaccurate.  
 
 
10.1.9.2 
STUDY RECORDS RETENTION  
 
Records retention will follow required IRB/ERC and sponsor guidelines.  
 
10.1.10 
PROTOCOL DEVIATIONS 
 
This protocol defines a protocol deviation as any noncompliance with the clinical trial protocol, 
International Council on Harmonization, Good Clinical Practice (ICH GCP), or Manual of 
Procedures (MOP) requirements. The noncompliance may be either on the part of the participant, 
the investigator, or the study site staff. As a result of deviations, corrective actions will be 
developed by the site and implemented promptly.  
 
These practices are consistent with ICH GCP:  
• 
Section 4.5 Compliance with Protocol, subsections 4.5.1, 4.5.2, and 4.5.3  
• 
Section 5.1 Quality Assurance and Quality Control, subsection 5.1.1  
• 
Section 5.20 Noncompliance, subsections 5.20.1, and 5.20.2.  
 
It will be the responsibility of the site investigator to use continuous vigilance to identify and report 
deviations within 3 working days of identification of the protocol deviation. Protocol deviations will 
be sent to the reviewing IRB/ERC per their policies. The site investigator will be responsible for 
knowing and adhering to the reviewing IRB requirements. Further details about the handling of 
protocol deviations will be included in the MOP.  
10.1.11 
PUBLICATION AND DATA SHARING POLICY 
 
This study will be conducted in accordance with the following publication and data sharing policies 
and regulations: 
 
National Institutes of Health (NIH) Public Access Policy, which ensures that the public has access 
to the published results of NIH funded research. It requires scientists to submit final peer-reviewed 
journal manuscripts that arise from NIH funds to the digital archive PubMed Central upon 
acceptance for publication. 
 
This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-
Funded Clinical Trial Information and the Clinical Trials Registration and Results Information 

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Submission rule. As such, this trial will be registered at ClinicalTrials.gov, and results information 
from this trial will be submitted to ClinicalTrials.gov. In addition, every attempt will be made to 
publish results in peer-reviewed journals.  In accordance with the NIH Data Sharing Policy, de-
identified data will be stored in the National Institute of Child Health and Human Development 
(NICHD) Data and Specimen Hub (DASH) (https://dash.nichd.nih.gov) indefinitely. Data from this 
study may be requested from other researchers through DASH. Considerations for ensuring 
confidentiality of these shared data are described in Section 10.1.3. 
 
10.1.12 
CONFLICT OF INTEREST POLICY 
 
The independence of this study from any actual or perceived influence, such as by the 
pharmaceutical industry, is critical. Therefore, any actual conflict of interest of persons who have 
a role in the design, conduct, analysis, publication, or any aspect of this trial will be disclosed and 
managed. Furthermore, persons who have a perceived conflict of interest will be required to have 
such conflicts managed in a way that is appropriate to their participation in the design and conduct 
of this trial. The study leadership in conjunction with the NICHD has established policies and 
procedures for all study group members to disclose all conflicts of interest and will establish a 
mechanism for the management of all reported dualities of interest. 
 
10.2 ADDITIONAL CONSIDERATIONS 
 
NA 
 
10.3 ABBREVIATIONS AND SPECIAL TERMS 
 
AIDS  
Acquired Immune Deficiency Syndrome  
ALHIV 
Adolescents Living With HIV   
AMHR 
Applied Mental Health Research  
ART 
Antiretroviral Therapy 
CAB  
Community Advisory Board  
CEO  
Chief Executive Officer  
CFAR  
Center For AIDS Research 
CFIR  
Consolidated Framework for Implementation Research   
CRT  
Cluster Randomized Trial  
CCC 
Comprehensive care clinic 

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DiSC 
Data Informed Stepped Care  
DSMB 
Data Safety and Monitoring Board  
EMR 
Electronic Medical Records 
ERC 
Ethical Review Committee  
FGD  
Focus Group Discussion  
GEE 
Generalized Estimating Equations 
HCW 
Health Care Worker 
HIV 
Human Immunodeficiency Virus 
HS  
Health Systems 
HSD 
Human Subjects Division  
IDI  
In-Depth Interview  
IRB  
Institutional Review Board  
IRDO  
Impact Research and Development Organization  
IS  
Implementation Science  
KNH 
Kenyatta National Hospital 
LTFU  
Loss To Follow Up 
MoH 
Ministry of Health 
NICHD  
National Institutes of Child Health and Development  
NIH  
National Institutes of Health  
NASCOP 
National AIDS and STI Control Program 
RE-AIM  
Reach, Effectiveness, Adoption, Implementation and Maintenance  
RCT 
Randomized Controlled Trial  
sSA 
Sub-Saharan Africa 
UNAIDS  
Joint United Nations Programme on HIV/AIDS 
US 
United States 
UW 
University of Washington 

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VL  
Viral load  
WHO 
World Health Organization 
 
 
 

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10.4 PROTOCOL AMENDMENT HISTORY 
The table below is intended to capture changes of IRB-approved versions of the protocol, 
including a description of the change and rationale. A Summary of Changes table for the current 
amendment is located in the Protocol Title Page. 
 
Version 
Date 
Description of Change  
Brief Rationale 
2.0 
20-Dec-
2020 
Updated the protocol to address 
questions from MU ERC. These 
include updates to consent forms 
05, 06, & 07; updated ages for 
providing consent;  
To address comments from 
MU ERC. 
3.0 
13-May-
2021 
Asked for waiver of written consent 
for participation in intervention 
 
MUERC did not approve for 
waiver of written consent 
3.0 
3-Aug-
2021 
Submitted additional consents for 
participation in intervention 
MUERC approved additional 
consents for participation in 
intervention 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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