Connecting Youth and Young Adults to Optimize ART Adherence: Testing the Efficacy of the Youth Thrive Intervention
Phase: NA
Conditions: HIV Infections
Sponsor: University of Minnesota

ATN 138 – YouTHrive  
 
Version 4.7_02-March-2021 
 
Version 4.7 
March 8, 2021 
ATN 138 - Connecting Youth and Young Adults to Optimize ART Adherence: Testing the Efficacy 
of the YouTHrive Intervention 
Funded by: 
The Eunice Kennedy Shriver 
National Institute of Child Health and Human Development (NICHD) 
with co-funding from: 
The National Institute on Drug Abuse (NIDA) 
The National Institute of Mental Health (NIMH) 
Protocol Chair: 
Keith J. Horvath, PhD 
San Diego State University 
San Diego, CA 
Protocol Co-Chair: 
K. Rivet Amico, PhD 
University of Michigan  
Ann Arbor, MI 
Page  of 
 
1
45

ATN 138 – YouTHrive  
 
Version 4.7_02-March-2021 
 
ATN 138 - Connecting Youth and Young Adults to Optimize ART Adherence: Testing the Efficacy 
of the YouTHrive Intervention 
SIGNATURE PAGE 
I will conduct the study in accordance with the provisions of this protocol and all applicable 
protocol-related documents. I agree to conduct this study in compliance with United States (US) 
Health and Human Service regulations (45 CFR 46); applicable U.S. Food and Drug 
Administration regulations; standards of the International Conference on Harmonization 
Guideline for Good Clinical Practice (E6); Institutional Review Board/Ethics Committee 
determinations; all applicable in-country, state, and local laws and regulations; and other 
applicable requirements (e.g., US National Institutes of Health, Division of AIDS) and 
institutional policies. 
Investigator of Record: _______________________________________________ 
Print/Type 
Signed: ___________________________________ Date: ____________________ 
Role: SRV Site Principal Investigator 
SRV Site: ___________________________________________________________ 
Page  of 
 
2
45

ATN 138 – YouTHrive  
 
Version 4.7_02-March-2021 
 
Page  of 
 
3
45

Table of Contents 
1.1  Background 
 
......................................................................................................................10
1.2  Rationale 
 
..........................................................................................................................10
STUDY OBJECTIVES 
 
.................................................................................................................11
STUDY DESIGN 
 
.........................................................................................................................12
3.1  Study Phases/Aims 
 
..........................................................................................................12
3.2  Study Population 
 
..............................................................................................................13
3.3 Study Randomization, Stratification, or Description of Non-Random Assignment 
Procedures 
 
..............................................................................................................................13
SELECTION AND ENROLLMENT OF STUDY PARTICIPANTS 
 
................................................14
4.1  Inclusion Criteria 
 
...............................................................................................................14
4.2  Exclusion Criteria 
 
..............................................................................................................14
4.3 Recruitment 
 
.......................................................................................................................15
4.4 Informed Consent 
 
..............................................................................................................17
4.5 Screening 
 
..........................................................................................................................18
STUDY PROCEDURES 
 
..............................................................................................................18
5.1 Enrollment Procedures 
 
......................................................................................................18
5.2 Locator/Contact Information 
 
..............................................................................................19
5.3 Randomization Procedures 
 
...............................................................................................19
5.4 Intervention/Investigation Procedures 
 
...............................................................................20
EVALUATIONS AND MEASURES 
 
..............................................................................................21
6.1 Screening 
 
..........................................................................................................................21
6.2 Enrollment 
 
.........................................................................................................................22
6.3 5-month Assessment (Immediate Post-Intervention) 
 
.........................................................22
DATA COLLECTION AND SITE MONITORING 
 
..........................................................................23
7.1 Development of Protocol and Case Report Forms 
 
............................................................23
7.2 Data Records 
 
.....................................................................................................................24
7.3  Data Collection 
 
.................................................................................................................24
7.4 Data Submission 
 
...............................................................................................................26
7.5 Data Quality Assurance 
 
.....................................................................................................29
7.6 Role of Data Management 
 
.................................................................................................29
7.7 Study Site Monitoring and Record Availability 
 
...................................................................29
PARTICIPANT MANAGEMENT 
 
..................................................................................................29
8.1 Tracking Participants / Follow-up 
 
.......................................................................................29
8.2 Compensation 
 
...................................................................................................................29
8.3 Intervening on “Social Harms" 
 
...........................................................................................30
8.4 Criteria for Premature Study Discontinuation 
 
....................................................................32
Page  of 
 
4
45

MONITORING UNTOWARD EFFECTS ASSOICATED WITH OR RESULTING FROM STUDY ...
 
32
STATISTICAL/ANALYTIC CONSIDERATIONS 
 
...........................................................................33
10.1 Introduction 
 
......................................................................................................................33
10.2 Power Estimates 
 
..............................................................................................................34
10.3 Statistical Analysis Plan 
 
...................................................................................................35
10.4 Missing Data 
 
....................................................................................................................36
HUMAN SUBJECTS 
 
...................................................................................................................37
11.1 Participants’ Confidentiality 
 
..............................................................................................37
11.2 Certificate of Confidentiality 
 
.............................................................................................37
11.3 Risks and Benefits 
 
...........................................................................................................38
11.4 Institutional Review Board (IRB) Review and Informed Consent 
 
.....................................40
11.5 Waiver of the Requirement for Parental Permission for Special Circumstances 
 
.............40
11.6 Waiver of the Requirement for Signed Consent Form 
 
.....................................................40
11.7 Prisoner Participation 
 
.......................................................................................................41
11.8 45 CFR Parts 160 and 164 Standards for Privacy of Individually Identifiable Health 
Information ("Privacy Rule" Pursuant to the Health Insurance Portability and Accountability Act 
- HIPAA) 
 
...................................................................................................................................41
11.9 Study Discontinuation 
 
......................................................................................................41
PUBLICATION OF RESEARCH FINDINGS 
 
...............................................................................41
REFERENCES ............................................................................................................................43
 
545

PROTOCOL TEAM ROSTER 
Keith J Horvath, PhD 
Chair 
San Diego State University 
San Diego, CA 
khorvath@sdsu.edu 
K. Rivet Amico, PhD 
Co-Chair 
University of Michigan 
Ann Arbor, MI 
ramico@umich.edu 
  
Richard MacLehose, PhD 
Co-Investigator 
University of Minnesota 
Minneapolis, MN 
macl0029@umn.edu 
  
Lisa Hightow-Weidman, MD, MPH 
Co-Investigator 
University of North Carolina at Chapel Hill 
Chapel Hill, NC 
lisa_hightow@med.unc.edu 
  
Patrick Sullivan, DVM, PhD 
Co-Investigator 
Emory University 
Atlanta, United States 
pssulli@emory.edu  
  
 
645

LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
AC 
 
 
Analytic Core 
AIDS  
 
Acquired Immunodeficiency Syndrome 
ART                            Antiretoviral Therapy  
ATN 
 
 
Adolescent Medicine Trials Network for HIV/AIDS Interventions 
CASI  
 
Computer Assisted Self-Interview 
CFR 
 
 
Code of Federal Regulations 
CRF 
 
 
Case Report Form 
DHHS  
 
U.S. Department of Health and Human Services 
EC 
 
 
Ethics Committee 
GCP 
 
 
Good Clinical Practices 
HIPAA  
 
Health Insurance Portability and Accountability Act 
HIV 
 
 
Human Immunodeficiency Virus 
ICH 
 
 
International Conference on Harmonization 
IRB 
 
 
Institutional Review Board 
MC 
 
 
Management Core 
MSM                           Men who have Sex with Men 
NICHD  
 
National Institute of Child Health and Development 
NIDA  
 
National Institute on Drug Abuse  
NIH 
 
 
National Institutes of Health 
PI 
 
 
Principal Investigator 
OHRP  
 
Office for Human Research Protections 
QNS 
 
 
Query and Notification System 
RCG                           Radiant Creative Group 
RCT                            Randomized Controlled Trial 
RDC 
 
 
Remote Data Capture 
SID 
 
 
Study Identification Number 
SRV 
 
 
Subject Recruitment Venue 
SSL                             Secure Sockets Layer 
TC 
 
 
Technology Core 
TWM                           Thrive With Me 
UMN                            University of Minnesota 
VL                                Viral Load 
YLWH                          Youth Living With HIV 
YO                               Years Old 
YT                                YouTHrive 
 
745

STUDY ABSTRACT 
DESIGN: 
YouTHrive (YT) is a two-arm randomized controlled trial 
(RCT) to test the efficacy of an adapted version of the 
Thrive With Me intervention for youth living with HIV 
(YLWH). 
DURATION:
YLWH are enrolled for 5 months.
SAMPLE SIZE:
Total study sample is 368 of which the following will be 
enrolled for each aim: 1) 48 participants for focus groups 
to inform intervention adaption; 2) 12-20 participants for 
usability testing to finalize intervention components; 3) 300 
participants for a randomized controlled trial of YT, with 
participants randomized to either YT (n=150) or control 
(n=150).
 
POPULATION: 
Participants for all aims of the study will include YLWH 
inclusive of all genders and all races/ethnicities. Focus 
group participants will be recruited from SRVs in Bronx, 
Chicago, and Houston. Usability participants will be 
recruited from SRVs in Bronx, Chicago, Houston, 
Philadelphia, Tampa, and Atlanta. RCT participants will be 
recruited from SRVs in Bronx, Chicago, Houston, 
Philadelphia, Tampa, Atlanta, Raleigh/Durham/Chapel Hill 
and Charlotte area.  Usability participants must have had a 
detectable VL in the past 12 months. RCT participants will 
be required to meet eligibility criteria.
STRATIFICATION: 
Focus group discussions will be stratified by age (50% 
15-19 yo; 50% 20-24 yo). We will stratify by SRV (i.e., city) 
site for the RCT.
DATA 
COLLECTION:
Focus group discussions will be conducted in-person, 
digitally recorded, and professionally transcribed. There 
will be three data collection (screening, baseline, and 5-
month) time points for the RCT. Visits are conducted in-
person at the SRV or remotely. Surveys will be completed 
using online survey tools (Alchemer and Qualtrics). VL 
measure collection will occur in-person at the participant’s 
SRV or remotely. Urine screen will happen at in-person 
visits only. Process data of participant activity on YT and 
control interventions will include log-in activity, tasks 
completed on the website, and number of written posts. 
 
845

OBJECTIVES:
1) In a 2-arm RCT (n=300), assess the efficacy 
of YouTHrive (YT) to sustain suppressed viral load (VL) 
among YLWH, compared to an HIV information-only 
control condition. 
2) Assess whether YT is more beneficial for substance-
using than non-substance-using YLWH.  
 
945

 INTRODUCTION 
1.1  
Background 
Fifty thousand persons are estimated to be infected with HIV in the United States each year,1 of 
whom one-quarter were youth between the ages of 13 and 24 years in 2010.2 Young gay and 
bisexual men accounted for 72% of all new HIV infections in the same year, with the majority of 
those being black youth.2 Despite elevated risk for HIV infection, it is estimated that only 6-16% 
of youth/young adults living with HIV (YLWH) are virally suppressed.3-5 Sufficient and sustained 
adherence to antiretroviral therapy (ART) reduces excess morbidity and mortality among people 
living with HIV (PLWH)6 and lowers the probability of forward transmission to sexual partners.7 
Advancing targeted and innovative ART adherence interventions for YLWH is an urgent priority.3  
Technology-supported ART adherence interventions have proliferated in recent years8-10 due to 
the widespread adoption of technology across sociodemographic groups,11 their ability to reach 
a broad audience, rapid scalability, and low implementation costs.12,13 In the US, nearly all teens 
(between 12-17 years of age) use the Internet14 and 78% own a cell phone.15 Smartphone 
ownership among 18-29 year olds is high (86%).16 ART adherence interventions that leverage 
software on PCs or through the internet10 capitalize on consistency in delivery of content and 
long-term cost savings; however, to date the peer-to-peer interactivity that has come to 
symbolize Web 2.017 remains underutilized in technology-based ART adherence approaches. 
Peer-to-peer support is a recommended strategy to improve ART adherence,18 is widely used 
by PLWH,19 and has an evidence-base for in-person approaches (especially with adults20). 
However, youth in the US are increasingly accustomed to technology-mediated peer-to-peer 
interactions, suggesting that intervention approaches that specifically leverage high-use 
channels of interpersonal communication and support are needed. 
The “Thrive with Me” (TWM) intervention leverages enhanced peer-to-peer interaction, ART 
adherence reminders and self-monitoring, and ART and HIV informational content21 to improve 
ART adherence. In a pilot study of 123 adult MSM (average age = 43 years), those randomized 
to the TWM intervention showed improvements across all ART adherence outcomes compared 
to control participants, with greatest benefits for current drug-using MSM. Currently, our 
research team is funded to conduct an efficacy trial of an extended (5-month intervention 
period) and enhanced (tailored informational content; multi-dimensional self-monitoring; and 
gamification components, such as leveling and badges) version of the TWM intervention for 
adult MSM. Given youth’s broad acceptance and adoption of many of the components of the 
TWM intervention, and the critical need for novel and scalable ART adherence interventions for 
this population, the next logical step is to adapt the TWM intervention for YLWH.  
As part of the UNC/Emory Center for Innovative Technology (iTech), we propose to test the 
efficacy of an adapted version of the TWM intervention, called YouTHrive (YT), for YLWH. In this 
4-year study, 300 YLWH between the ages of 15-24 with detectable viral load (VL) will be 
randomized to the YT or an HIV information-only control intervention for a 5-month period. A 
target of 50% of YLWH participants with self-reported alcohol and/or illicit drug use will be 
enrolled. The primary endpoint is VL post-intervention. 
1.2  
Rationale 
There is a clear need to develop effective ART adherence interventions that meet the needs of 
YLWH. Although young MSM – especially racial and ethnic minorities – are at high risk for 
acquiring HIV and, if HIV-positive, having poor ART adherence, relatively few ART adherence 
interventions exist that are tailored to the needs of this population. For this reason, The TWM 
online peer-to-peer support intervention will be adapted for YLWH and assessed for 
effectiveness in a 2-arm randomized controlled trial (RCT) called YouTHrive (YT).  
 
1045

1.2.1 Focus groups with youth (ages 15-19 years old) and young adults (20-24 years old) 
Focus groups will provide insights into what features and functions of the current TWM study 
youth like and dislike to assist intervention adaptation. Focus groups will be conducted at 3 
SRVs (Bronx, Chicago, and Houston), and stratified by age (15-19 years old & 20-24 years old), 
to ensure that a geographically and demographically diverse sample of youth and young adults 
provide input to guide intervention adaptation. In addition, age stratification is intended to help 
younger participants (15-19 years old) to feel more comfortable sharing their opinions and 
feedback.  
1.2.2 Usability Testing 
The purpose of usability testing is to gain feedback about the intervention once a functional 
version of the intervention is available and to give SRV staff experience in implementing all 
procedures associated with intervention arm participation. It is primarily intended to get 
feedback from the target population about any technical issues they encountered, as well as to 
obtain any feedback about the look and feel of YT. As we have done in prior technology-based 
studies, we will recruit up to 12-20 youth total across the 6 SRVs where the RCT will occur: 
Houston, Bronx, Chicago, Tampa, Atlanta, and Philadelphia to use the YT intervention for a 2-
week period. In order to ensure diversity in the sample, each SRV site will recruit two total 
participants, one male and one female from the younger (15-19 years old) and older (20-24 
years old) age categories. We also will recruit at least one perinatally infected female, one 
perinatally infected male, and at least one behaviorally infected gay or bisexual male (these 
targets will be across all sites, not per site). SRV research staff will briefly introduce participants 
to the intervention and provide instruction on how to log their impressions and feedback about 
the intervention. After the 2-week period, participants will participate in an online interview using 
VSee to interact with YT research staff to provide their feedback about YT. The information will 
be placed in summary form, and provided to our technology development partner to guide any 
final changes to the YT intervention.  
1.2.3 RCT of YT 
A 2-arm RCT of YT will be conducted, comparing the full version of the YT intervention to a 
control group. The control group will consist of weekly e-mails with a link to a webpage 
containing information about topics of interest to YLWH, but not addressing ART adherence. A 
RCT was chosen since it is the gold standard for assessing the effectiveness of an intervention 
under tightly controlled conditions. The intervention and control group will have access to 
intervention content for 5 months, with CASI performed at baseline and 5-month (i.e., immediate 
post intervention). VL will be assessed at baseline and 5- month time points to assess primary 
hypotheses (i.e., more participants in the YT group will have undetectable VL at the 5-month 
and assessment and, among those in YT, a greater proportion of substance-using participants 
will demonstrate sustained virally suppression than non-substance-using participants). Up to 
twenty purposively selected participants from the intervention group will also take part in a short, 
semi-structured interview over VSee or Zoom about their experiences on the site with study staff 
at their 5-month follow-up.  
STUDY OBJECTIVES 
2.1  
Primary Objective: In a 2-arm RCT (n=300), assess the efficacy of YouTHrive (YT) to 
sustain suppressed viral load (VL) among YLWH, compared to an HIV information-only 
control condition. 
 
1145

2.2  
Secondary Objective: Assess whether YT is more beneficial for substance-using than 
non-substance-using YLWH.  
2.3  
Study Hypotheses/Research Questions   
•
H1: A higher proportion of participants in the YT intervention arm than in the 
information-only control arm will have undetectable VL at the 5-month follow-up time 
point. 
•
H2: Among YLWH in the YT intervention arm, a higher proportion of substance-
using YLWH will demonstrate VL suppression at the 5-month follow-up time point 
compared to non-substance-using YLWH. 
STUDY DESIGN 
3.1  
Study Phases/Aims 
We will evaluate the YT intervention in a randomized controlled efficacy trial (see YT Schema) 
YLWH will be recruited from the 8 SRVs (Bronx, Houston, Chicago, Philadelphia, Tampa, 
Atlanta, Raleigh/Durham/Chapel Hill, and Charlotte), screened, and randomized to receive 
either the YT intervention or HIV-information only control condition. VL will be collected at the 
enrollment visit and 5-month follow-up assessment time point.  
Phase/Aim 1: YT Intervention Adaptation 
We will conduct six focus groups with approximately 8 youth (15-19 years old) and young adults 
(20-24 years old) each at 3 SRVs to obtain:  1) feedback from YLWH about the “look and feel” 
and content of the original TWM intervention; 2) suggestions for adapting the intervention for 
YLWH similar to themselves; 3) information about barriers to ART adherence and other 
challenges of living with HIV. Focus groups will be transcribed verbatim and a content analysis 
will be assisted by the Analytic Core (AC).  
Phase/Aim 2: YT Adaptation and Build 
Information and feedback gathered from the focus groups will inform the adaptation of the TWM 
intervention for YLWH. The ADAPT-ITT model will be used to guide the adaptation process. 
Briefly, the ADAPT-ITT model follows 8 steps- each contributing to the acronym; Assessment of 
target population needs and local resources; Decision making on components to leverage and 
adapt from TWM; Adaptation of components to target group and pre-testing; Production of 
intervention draft; Topical experts review adaptations; Integration of feedback leading to second 
draft; Training for implementation; and Testing. 
Dr. Horvath and the research team will partner with Radiant Creative Group (RCG) in order to 
update the TWM intervention to include those features and functionality that arise during the 
aforementioned adaptation process. Usability testing with 12-20 participants at 6 SRVs (Bronx, 
Chicago, Houston, Philadelphia, Tampa, and Atlanta) will be conducted to finalize all features 
and components of the intervention (i.e., ensure that all features are working properly and 
function in a way that users can easily navigate). 
Phase/Aim 3: Randomized Controlled Trial to Test Efficacy of YT 
YLWH will be recruited from 8 SRVs (Bronx, Houston, Chicago, Philadelphia, Tampa, Atlanta, 
Raleigh/Durham/Chapel Hill, and Charlotte). Persons interested in the study will be screened to 
determine if they meet the eligibility criteria. Prospective participants can screen remotely or in 
person, and can be recruited within the SRV clinic or in the community, as long as they meet 
inclusion criteria. YLWH who meet all inclusion criteria will be invited for either an in-person or 
virtual enrollment visit. Screening and enrollment may also happen during one visit, when 
possible.   
 
1245

At the enrollment visit, participants will complete an in-office or online baseline CASI, complete 
a viral load test if one was not performed in the past 60 days, a urine screen for recent drug use, 
and will be randomized at survey outset to either intervention or control. The randomization 
sequence will be stratified by city and use random permuted blocks of size 2 and 4. YLWH 
assigned to the YT intervention will be shown example webpages of the intervention, will be 
given basic training on how to navigate the intervention, and will be given the opportunity to ask 
questions they have about the website. Control condition assigned participants will be shown 
example webpages they will receive during the intervention period. 
The intervention period lasts five months. During this time, intervention participants will have 
continuous access to the YT website (mobile enhanced and available on all devices with 
internet connection). Participants in the control condition will receive an email with HIV-related 
information once per week.  
Follow-up assessments will be conducted at the 5-month (i.e., immediate post-intervention; 
follow-up 1 in the clinical setting or online via a teleconferencing platform such as VSee of 
Zoom) time point. The 5-month follow-up visit will include an in-office or online administered 
CASI, a blood draw or self-administered finger prick to test for detectable viral load, and a urine 
screen for drug use. At the 5-month follow-up visit, up to 20 intervention participants will be 
offered additional compensation (as specified in each SRV’s informed assent/consent form) to 
take part in an additional semi-structured interview with SRV staff or via Zoom with a member of 
the study team. 
3.2  
Study Population 
We propose to enroll 368 HIV-positive individuals for the purposes of this study. Approximately 
48 participants will be recruited for focus group discussions (with the goal of 8 per group), 12-20 
participants will be recruited to conduct usability testing of the YT intervention, and 300 
participants (n=150 YT and n=150 control) will be recruited to participate in the YT RCT. An 
enrollment target of 50% for illicit drug use and/or problematic alcohol use in the past 6 months 
is set for each SRV. Participants who are pregnant at the time of screening or who become 
pregnant during the study period will not be excluded from the study. 
3.3 
Study Randomization, Stratification, or Description of Non-Random Assignment 
Procedures 
3.3.1 Focus Groups 
Focus groups will be stratified by age such that 2 focus groups (1 consisting of youth 15-19 year 
olds and 1 consisting of young adults 20-24 years old) will be conducted at each of the 3 SRVs. 
Study staff at each SRV will oversee that approximately 8 participants (with a minimum of 5) are 
recruited for each of the 2 focus groups conducted at that site. SRV study staff will have at least 
weekly check-ins with the AC lead and the YT protocol chair to provide updates about 
recruitment successes and challenges, and to brainstorm recruitment strategies that may be 
used should recruitment goals not be met. 
3.3.2 Usability Testing 
Usability testing participants will be recruited from 6 SRVs (Bronx, Chicago, Houston, 
Philadelphia, Tampa, and Atlanta) without stratification or random assignment. However, 
participant demographics for this aim should be closely monitored to ensure that diversity in 
ages, genders, and race/ethnicity is achieved at each site.  Management Core will work with 
sites to recruit a diverse sample for usability testing. Each SRV will recruit two participants for 
 
1345

usability testing. One participant will be from the younger age group (15-19) and one from the 
older age group (20-24). SRV recruitment staff will be asked to recruit one male and one female 
at each site. In addition, across all SRV sites, we will recruit at least one perinatally infected 
female and at least one perinatally infected male to ensure that YouTHrive is relevant for youth 
infected through different transmission routes. 
3.3.3 RCT 
At outset of the survey, participants will be randomized 1:1 to YT intervention or control group, 
based on a randomization sequence developed by the AC lead statistician and loaded into 
DFexplore via SAS. The randomization sequence will be stratified by city and use random 
permuted blocks of size 2 and 4.  
SELECTION AND ENROLLMENT OF STUDY PARTICIPANTS 
4.1  
Inclusion Criteria 
Inclusion Criteria for Aim 2 Usability Testing 
•
15-24 years of age at the enrollment visit 
•
HIV-positive status (medical chart-verified) 
•
In HIV clinical care in the Chicago, Houston, Bronx (NYC), Philadelphia, Atlanta, 
or Tampa area 
•
Currently prescribed ART (medical chart verified) 
•
Medical chart-verified detectable VL (above the lower limit of detection for the 
clinical assay) within 52 weeks of enrollment date and an ART prescription for at 
least 90 days prior to this VL test date 
•
English-speaking (since the intervention will be in English) 
•
Internet and SMS messaging access for the usability testing period 
(approximately two weeks) 
•
Available to meet with SRV staff in person for the first research appointment 
•
Availability to meet with UMN research staff for a remote (i.e., telephone or video-
conference) feedback interview 
Inclusion Criteria for Aim 3 Randomized Control Trial 
•
15-24 years of age at the enrollment visit; 
•
HIV-positive status; 
•
Residing in Chicago, Houston, NYC, Philadelphia, Atlanta, Tampa, Raleigh/
Durham/Chapel Hill, or Charlotte areas and available to meet with SRV staff for 
visits at baseline and 5-month follow-up assessment. Participants who are 
unable to attend in-person session will be given the option to complete 
assessments online; 
•
English-speaking (since the intervention will be in English); 
•
Anticipated continuous internet access and SMS messaging for the intervention 
period (approximately 5 months); 
•
Not enrolled in another ART adherence intervention research study at the time of 
screening; 
•
Has or is willing to create an e-mail address to use during the study period; 
•
Did not attend an iTech YAB (Youth Advisory Board)/YAC (Youth Advisory 
Council) meeting where the YouTHrive study was presented or YouTHrive study 
materials were discussed; 
4.2  
Exclusion Criteria 
 
1445

Exclusion Criteria for Aim 2 Usability Testing 
•
Aged younger than 15 years or older than 24 years 
•
HIV-negative 
•
Is not in HIV care in the Chicago, Houston, Bronx (NYC), Philadelphia, Atlanta, or 
Tampa area 
•
Not currently on ART medication (does not have an active ART prescription by a 
health provider) 
•
Does not have medical chart-verified detectable VL (above the lower limit of 
detection for the clinical assay) within 52 weeks of enrollment date and an ART 
prescription for at least 90 days prior to this VL test date 
•
Non-English speaking (since the intervention will be in English) 
•
Anticipate not having access to the internet or SMS messaging during the 
usability period (approximately two weeks) 
•
Not available to meet with SRV staff in person for first research appointment 
•
Not available to meet with UMN research staff for a remote (i.e., telephone or 
video-conference) feedback interview 
Exclusion Criteria for Aim 3 Randomized Control Trial 
•
Aged younger than 15 years or older than 24 years 
•
HIV-negative 
•
Does not reside in Chicago, Houston, NYC, Philadelphia, Atlanta, Tampa, 
Raleigh/Durham/Chapel Hill, or Charlotte areas or is not available to meet with 
SRV staff for visits at baseline, and 5-month and follow-up assessment 
•
Non-English speaking (since the intervention will be in English) 
•
Anticipate not having access to the internet or SMS messaging for the 
intervention period (approximately 5 months) 
•
Enrolled in another ART adherence intervention research study at the time of 
screening 
•
Planning to move out of study area during the study period and unwilling to 
participate in virtual visits 
•
Unwilling or unable to comply with protocol requirements 
•
Participated in Aim 2 of the study (Aim 1 participants may be included if they 
meet other criteria) 
•
Does not have or is not willing to create an e-mail address 
•
Attended an iTech YAB (Youth Advisory Board)/YAC (Youth Advisory Council) 
meeting where the YouTHrive study was presented or YouTHrive study materials 
were discussed 
All genders may participate in the study. Women who are pregnant at study onset or become 
pregnant during the study period are eligible and can be included as participants. 
4.3 
Recruitment  
Participants for all aims of this study may be approached and recruited in one of three ways:  1) 
in the clinic, 2) in the community; and 3) online. Recruitment procedures may vary slightly 
depending on the SRV and study aim, which will be negotiated prior to the beginning of each 
aim of the study. In order to enroll approximately 8 participants per focus groups (minimum of 5 
and no more than 10), SRVs where focus group recruitment will occur should over-recruit 
(12-15 potential participants) for each focus group to account for persons who express interest 
in the study but fail to show for the focus group. Over enrollment is not required for usability 
 
1545

testing (Aim 2) or the RCT (Aim 3), as enrollment will continue until the target recruitment goals 
are met. 
For the Aim 3 RCT, we will follow respondent-driven sampling (RDS) methods and use a long-
chain referral method to supplement recruitment, especially with the adolescents (15-17) who 
may be harder to reach than young adults (18-24). 
Clinic Recruitment:  Individuals in care at the clinic may be screened and enrolled in one of two 
ways. First, those who have had their medical chart reviewed to assess potential eligibility (e.g., 
age, HIV status, on ART, clinic appointment attendance) and who are referred to the study by a 
provider will be approached for recruitment either in the clinic before or after a medical visit or 
remotely (e.g., telephone or email). Potential participants will be informed of the nature of the 
study, the information to be collected, and the evaluations and assessments that are involved. 
Those who express interest in the study will be required to be screened electronically to 
determine if they meet all inclusion criteria. If the individual meets all eligibility requirements, 
research staff will inform them of their eligibility and will initiate the enrollment visit immediately 
or schedule the enrollment visit if the potential participant cannot complete the procedures at 
that time. Second, any individual in care may be screened for eligibility without reviewing their 
medical chart to assess for potential eligibility, as they may be eligible for the study based on 
self-reported criteria. These individuals may be approached for recruitment either in the clinic 
before or after a medical visit or remotely (e.g., telephone or email).  If the prospective 
participant screens eligible remotely, research staff will initiate a follow-up call, text, or email that 
will inform them that they are preliminarily eligible and to schedule the enrollment visit. If the 
prospective participant screens in the clinic and meets all eligibility requirements, research staff 
will inform them of their eligibility and will initiate the enrollment visit immediately or schedule the 
enrollment visit if the potential participant cannot complete the procedures at that time. 
Individuals who do not consent to participate will be asked if they are willing to provide their 
reason for declining participation; responses will be recorded. Individuals assessed as ineligible 
for enrollment will have the reason(s) for ineligibility recorded.   
The Protocol Team may request tabulated information on individuals who participated in the 
recruitment process, but did not provide informed consent and the reasons these individuals 
refused to participate. These data will be de-identified and will not include PHI. These data will 
provide general information on the population that is recruited at the study sites into the study. 
Community and Online Recruitment: SRV staff will identify YLWH in the surrounding community. 
This may be accomplished through RDS, the use of outreach workers to community venues 
where YLWH not in care spend time, through targeted ads on widely used websites and social 
media channels (such as but not limited to Facebook; Grindr), or by posting flyers in high traffic 
areas where these youth may frequent. These individuals may be approached for recruitment 
either in the community or contacted remotely (e.g., telephone or email), and asked to complete 
the online screener.  If the prospective participant screens eligible remotely, research staff will 
initiate a follow-up call, text, or email that will inform them that they are preliminarily eligible and 
to schedule the enrollment visit. If the prospective participant screens in person in the 
community and meets all eligibility requirements, research staff will inform them of their eligibility 
and schedule a time for the enrollment visit. The receipt of outside community or clinic services 
will not depend on expressing interest or enrolling in the YT study (i.e., the receipt of services 
will be based on usual clinic requirements). Other processes described above under Clinic 
Recruitment, where appropriate, will apply to participants who are recruited from the community 
or online.  
Those recruited online will be directed to a website to complete an online screener to determine 
eligibility. The self-administered screener will also include a brief online consent to screen. 
 
1645

Screeners will only be conducted via a secure online platform. Personal contact information will 
be obtained from potential participants who meet eligibility criteria. This includes screener’s 
name, email address, and phone number. 
4.4 
Informed Consent  
Informed consent/assent. For Aim 3 – RCT, those recruited online and/or who will complete 
the enrollment virtually will be shown an abbreviated consent/assent form to screen and to 
obtain a VL measure. Those who consent/assent to these procedures will be screened and, if 
eligible, potential participants will complete a VL test. This test will be performed by drawing 
potential participant’s blood during an in-person visit to a lab (such as but not limited to Quest or 
LabCorp) or during an in-person visit at the SRV site, or by using a self-collection VL kit mailed 
to the potential participant’s home. Potential participants may also log into their online health 
portal and show SRV staff the viral load test results in person or over a secure, HIPAA-
compliant, videoconferencing platform. SRV staff may also obtain the VL test result from the 
participant’s medical record if one has been performed within 60 days prior to the study visit. 
Participants will be asked to sign a HIPAA release form at the SRV site. SRV site staff will 
virtually consent participants to the study using complete consent/assent forms and procedures.  
For individuals who are able to meet in person, the informed consent process will occur on the 
day the enrollment visit is held. Interested persons will be guided through the informed assent/
consent process by SRV study staff, who will explain all study procedures, answer questions 
concerning the study and assent/consent process, and offer a copy of the informed consent/
assent form. The research staff member will give the participant as much time as needed and 
will address any questions or concerns they may have. The participant will be allowed to take 
the consent/assent form home or have an electronic body emailed to them to review it before 
enrolling in the study if the participant needs more time to review the form. The research staff 
member will ask the participant questions to gauge comprehension. The consent/assent form 
describes all study procedures, including confidentiality and privacy, information about potential 
risks, discomforts, benefits of participation, and information regarding who they can contact with 
further questions. It also states that participation is voluntary, that participants may decide not to 
take part or to withdraw from the study at any time without penalty or loss of any benefit to 
which they might otherwise be entitled, and that study participation is in no way related to being 
able to access or continue getting care or services at any participating study site. Participants 
can refuse to answer any question, and can withdraw from the study at any time. The PIs, Co-
PIs, or designee at each SRV site will review all informed consents and assents.    
Assessing for decisional capacity. For all participants, the research assistant (RA) reviews 
the informed consent/assent to make an assessment of the youth’s decisional capacity and 
ability to provide consent/assent prior to signing, using a 2-step process. First, the RA 
determines if the person understands the study goals by asking a question such as “Can you tell 
me what this study is about?” In step 2, potential participants will be asked questions designed 
to assess their capacity to understand, appreciate, reason with, and express a choice about 
participation in our specific protocol. Participants will be asked to: name things they will be 
expected to do during the study; explain what they would do if they no longer wished to 
participate in the study; explain what they would do if they experienced distress during the 
study; and identify potential risks for participating in the study. For youth who cannot answer 
these questions, the RA will go back and review the relevant elements of assent/consent with 
 
1745

the participant again and repeat the process. Youth who appear not to understand after 
repeated review will not be enrolled in the study. 
Waiver of parental consent. We will request that the UNC-CH IRB as the single IRB (IRB of 
Record) grant a waiver of parental consent to participate in this research study for youth 
participants who are 15 to 17 years of age. The research team has been granted waivers of 
parental permission for prior studies with sexual minority youth. Under 45 CFR 46.408 (c), an 
IRB has the authority to waive parental permission if it determines that “a research protocol is 
designed for conditions or a subject population for which parental or guardian permission is not 
a reasonable requirement to protect the subjects” and “an appropriate mechanism for protecting 
the children who will participate as research subjects is substituted” and “that the waiver is not 
inconsistent with Federal, State, or local law.” A waiver of signed consent and parental/legal 
guardian permission will be sought given that minor individuals can often seek sexually 
transmitted infection (STI) and HIV testing without parental/legal guardian permission, 
depending on each site’s state laws, and given that many of the youth in our study are likely to 
be gender and/or sexually fluid or have an attraction to persons of the same gender, but may 
not be out to their parents; requiring parental permission may place participants at risk for outing 
themselves as part of the LGBT community or being at risk for HIV infection. A waiver of 
parental permission for studies with LGBT youth that do not involve greater than minimal risk is 
a common practice among researchers working in the area of gay and lesbian health/mental 
health. This is done to avoid the selection biases operating in only recruiting youth whose 
parents are both aware of and comfortable with their sexual orientation. Commonly, these youth 
have explored their sexual orientation without their parents’ knowledge as the youth struggle 
with issues of disclosure and its consequences within the social, religious, and economic 
context of their families. A requirement for parental permission in this type of study could not 
only affect a person’s willingness to participate, but could also potentially impact the ability of 
researchers to engage in this type of research with sexual minority youth. 
If the purpose of requiring parental permission as stated in CFR is to protect the minor subject, 
then requiring parental permission for youth in these circumstances is not a reasonable 
requirement.  Additional privacy protections are provided in that all assessments, notes, reports, 
and other records will be identified by only a coded number to maintain participant 
confidentiality. These records and any forms that do contain identifying information (e.g., 
consent/assent forms, contact information) will be kept in a locked, limited access area (such as 
a locked file cabinet) at the participating site. 
Consent/assent may be obtained up to 30 days prior to or on the day of enrollment, prior to 
implementing any study activities. If more than 30 days has elapsed, consent/assent must be 
reaffirmed on the day of enrollment.  
4.5 
Screening 
Once a potential participant has been identified online, through the community or clinic-based 
recruitment, they will be sent a link to the online screening survey or taken into a confidential 
room to complete the online screening survey on a computer or tablet. The online survey is 
hosted on Alchemer, which will include the eligibility script, consent/assent to be screened, and 
questions. For those who meet eligibility criteria, the survey will record the name, e-mail, and 
phone number of the participant. We use SSL encryption for transfers of information online and 
data will be stored in the secure, HIPAA-compliant servers of Alchemer. The Emory AC team 
maintains a business partner HIPAA agreement with Alchemer.  
STUDY PROCEDURES 
5.1 
Enrollment Procedures 
 
1845

Screening procedures are explained above in section 4.5. YLWH who meet all inclusion criteria 
will be invited for an enrollment visit within 60 days after screening. If a participant is eligible for 
the study and interested in participating, they will complete an enrollment visit. Screening and 
enrollment may happen during one visit if possible. The enrollment visit may be conducted in 
person or online. Online enrollment visits will be conducted via a HIPAA-compliant 
videoconferencing software, such as but not limited to Zoom.  
Participants who elect to complete their enrollment visit virtually will be asked to complete a VL 
test. This test will be performed by drawing potential participant’s blood during an in-person visit 
to a lab (such as but not limited to Quest or LabCorp) or during an in-person visit at our site, or 
by using a self-collection VL kit mailed to the potential participant’s home. Participants may also 
log into their online health portal and show SRV staff the viral load test results in person or over 
a videoconferencing platform. SRV staff may also obtain the a VL test result from the 
participants medical record if one has been performed within 60 days prior to the study visit. 
Participants will be asked to sign a HIPAA release. SRV staff will contact potential participants 
and obtain their consent to mail the VL test either to the participant’s address or to an alternate 
address provided by the potential participant. SRV will virtually consent participants to the study 
and email participant a secure link to complete the computer-assisted baseline survey, created 
by AC staff and hosted on Alchemer, a secure, HIPAA-compliant platform. Once the assessment 
is complete, SRV staff will contact the participant to schedule a virtual enrollment visit. 
During the enrollment visit for Aims 2 and 3, SRV staff will confirm the participants’ eligibility. 
YLWH who are eligible for the study will be guided through an informed consent process by 
research staff. Next, participants completing will complete a computer-assisted baseline survey, 
created by AC staff and hosted on Alchemer, a secure, HIPAA-compliant platform. During the 
RCT, participants will then be randomized 1:1 to YT intervention or control group, based on a 
randomization sequence developed by the AC lead statistician and loaded into DFexplore via 
SAS. The randomization sequence will be stratified by city and use random permuted blocks of 
size 2 and 4. The time between screening to enrollment must not exceed 60 days. If more than 
60 days lapses between the screening and enrollment visit, then a person must be re-screened 
(see section 4.5). Participants will be considered enrolled upon signing the enrollment RCT 
consent form, completing the CASI, completing either an in-person or virtual enrollment visit, 
and being randomized to YT intervention or control.  
5.2 
Locator/Contact Information  
Once consented and enrolled, designated site study staff will complete a Locator/Contact 
Information Worksheet with participants and/or enter the participant’s contact information directly 
into SMART Web during the enrollment visit. Participants will be asked to provide a working 
phone number or valid email address through which they can be reached. Participants will also 
be asked to provide social media contact information, if the participant is willing. Participants will 
also be asked to provide valid contact information for a family member and/or friend who can be 
called in the event the participant cannot be reached by phone or email. Participants will be 
asked if messages can be left at the numbers provided. Study staff will not leave messages 
unless expressly permitted to do so by the participant which also will be documented on this 
form. If permission is given to leave messages, site staff will assure participants that messages 
left with a family member or friend will only ask the participant to contact study staff and will not 
include any protected health information or information related to study participation.  
 
 
5.3 
Randomization Procedures  
Participants in the RCT will complete a computer-assisted baseline survey at or before the 
enrollment visit, created by AC staff and hosted on Alchemer, a secure, HIPAA-compliant 
platform. After completion of the survey, participants will be randomized 1:1 to YT intervention or 
control group, based on a randomization sequence developed by the AC lead statistician and 
 
1945

loaded into DFexplore via SAS. The randomization sequence will be stratified by city and use 
random permuted blocks of size 2 and 4.  
5.4 
Intervention/Investigation Procedures 
5.4.1 Focus Groups 
Focus groups will be conducted in person and at 3 SRVs (Bronx, Chicago, and Houston). Two 
focus groups will be conducted at each of the 3 SRVs, and focus groups should not be 
scheduled more than 3 days apart (so that they can be conducted in one visit by the Protocol 
Chair). Focus groups are anticipated to last approximately 90 minutes, and light refreshments 
and food will be served at each group (Focus Group Discussion Guide). The Protocol Chair and 
potentially 1 additional research staff member will conduct the focus groups. All focus groups 
will be audio recorded (equipment provided by the Protocol Chair). The Protocol Chair will 
coordinate with SRV staff to have cash/gift cards available (as determined by each SRV) to 
disperse at the end of each focus group. 
5.4.2 Usability Testing  
Twelve to twenty (2-3 per SRV) YLWH will be recruited at 6 SRVs (Bronx, Chicago, Houston, 
Philadelphia, Tampa, and Atlanta) to participate in usability testing (Usability Testing Checklist 
for site study staff). Usability testing will involve identifying potential participants at the SRV 
clinic/site, briefly describing the study, and screening for eligibility using an online survey 
accessible on a clinic/site computer or tablet in a confidential room. Once determined eligible, 
participants take the baseline CASI and then will be taken through a brief tutorial of the YT 
intervention (Usability Testing Script), and asked to use the intervention daily for the following 2 
weeks. Participants will be scheduled to return for the follow-up visit in approximately 2 weeks. 
During the follow-up visit, the participant will be given access to software on the clinic/site 
computer to conduct a secure video session with the project coordinator from the University of 
Minnesota remotely. Participants will be asked to provide feedback about all aspects of the YT 
intervention (Usability Debriefing Interview Guide). The interview is anticipated to take 30-45 
minutes. Clinic/site research staff will provide participants $25 at the first study visit and $25 at 
the conclusion of the debriefing interview at the second study visit ($50 total).  
5.4.3 RCT 
Recruitment for the RCT will occur via community and online outreach and at all eight SRVs. 
Once enrolled (i.e., eligibility is confirmed and the participant provides consent, completes the 
baseline survey, is randomized, and completes a urine screen [as described in the Baseline 
Checklist for Research Assistants]) they will be walked through a brief description of their 
respective study arm (Control Group Script and YT Intervention Group Script). To end the 
enrollment visit, participants will be compensated as specified in Section 8.2 and as outlined in 
each SRV’s informed assent/consent form, and reminded that they will be asked to complete a 
study visit in 5 months. Participants who are unable to attend the in-person 5 month visit will be 
able to complete a virtual visit. 
In order for the earliest participants to have peer interaction on the site as intended, 5 YLWH will 
receive compensation for being active on the site until 15-20 participants have been enrolled. 
Once the target of 15-20 has been reached the study team will re-evaluate the need for these 
peer advocates. 
The YT site and control pages (although there are no interactive features on the control pages) 
will be monitored by research staff at the San Diego State University to ensure that participants 
are following established community guidelines (YT Intervention Community Guidelines). 
 
2045

Therefore, any concerns (e.g., hostile interactions, suicidal ideation) or comments that are 
evident on the YT site will be addressed by San Diego State University research staff and, if 
relevant, will activate the YT Clinical Protocol for User Postings.   
At the follow-up assessment (5-month) time point, SRV staff will contact participants to either 
schedule a follow-up appointment or to complete an online survey at a confidential place of their 
choice. Follow-up appointments may be scheduled 30 days prior to or as late as the date of 
enrollment. Participants who do not have a confidential space to complete the survey will be 
encouraged to complete the survey at a computer or tablet located at the clinic. Participants will 
receive compensation once they have completed a follow-up survey.  
In addition to the assessments undergone by all study participants, up to 20 intervention 
participants will be offered additional compensation to take part in an additional optional semi-
structured interview remotely via Zoom or a comparable HIPAA-compliant videoconferencing 
platform with study staff at their 5-month follow-up visit. Participants that were particularly active 
on the site based on activity reports tracked by study staff will be offered the opportunity to 
interview. 
5.4.4 Research and Training Staff 
Research staff at individual SRVs who interact with YT participants at assessments do not need 
to be clinicians. A research assistant (RA) level position should be sufficient to obtain informed 
consent, be available for questions during the CASI, collect the urine sample for drug testing, 
and explain the YT intervention or control websites. A certified phlebotomist will be required to 
collect blood samples. RAs will also receive training on the use of self-administered VL testing 
to assist participants who may have questions about the specimen collection. The YT 
intervention is delivered online and will be accessible on multiple devices (computer, tablet, or 
smartphone). Research staff at SRVs will be trained via videoconferencing on the intervention 
components and will be given a script and checklist to review with participants. Along with 
reviewing components of the website, research staff will also explain community guidelines/
rules of site use and explain when researchers may intervene. If a participant asks a question 
that the RA does not feel equipped to answer, the RA will contact research staff at the San 
Diego State University and then follow-up with the participant. Research staff at the San Diego 
State University will monitor the site daily. Since this is a social networking site, users may post 
information (such as suicidal ideation) which would require involvement from the clinical team at 
the SRV, as described in the Clinical Protocol for User Postings. 
5.4.5 Intervention Monitoring/Quality Control 
Because the YT intervention and the Control webpages are fully online and available on 
computers, tablets, and smartphones, intervention fidelity is assured (i.e., all participants will 
receive the intervention in the same way and have access to all of the same resources).  Study 
visit checklists will be used during study visits to ensure that study procedures are followed in 
the same steps for each participant. 
EVALUATIONS AND MEASURES  
Overviews of the administration of clinical and behavioral measures are shown in the Schedule 
of Evaluations. Presented below is additional information on visit-specific measure 
administration and procedures.  
6.1 
Screening 
 
2145

See Section 4.5 for screening details. Enrollment is to be completed within 60 days of the 
screening. Below is a summary of screening procedures and laboratory screening tests used for 
in-person visits. 
6.1.1 Administrative and Behavioral Procedures 
•
Screening assessment using CASI 
•
HIPAA and/or medical record release authorization 
6.1.2 Clinical Procedures  
•
None 
6.1.3 Laboratory Procedures  
None 
6.2 
Enrollment 
The enrollment visit will only occur if potential participants meet the eligibility criteria. For those 
who are eligible, an appointment time will be scheduled for the enrollment visit that will include 
the following procedures listed below. Participants must be scheduled for an enrollment visit 
within 60 days of screening; otherwise they will need to be re-screened. Participants will be 
considered enrolled upon meeting all SMART eligibility criteria, signing the enrollment SMART 
consent/assent form, being randomized, completing the baseline CASI, and onboarding to their 
respective study arm. 
6.2.1 Administrative and Behavioral Procedures 
•
Consent to verify eligibility 
•
Eligibility verification using CRF 
•
Informed Consent 
•
HIPAA and/or medical record release authorization 
•
Baseline Assessment using CASI 
•
Randomization to intervention or control 
•
For intervention participants, training on the YT intervention/procedures 
•
For control participants, training on control intervention/procedures 
•
Collection of locator/contact information 
•
Medical record abstraction 
6.2.2 Clinical Procedures  
•
Urine collection (in-person visits only) 
•
Blood collection or self-administered VL test (if no VL test result in medical chart within 
60 days of enrollment date) 
6.2.3 Laboratory Procedures 
•
Urine test for presence of illicit drugs (if available in-person) 
•
Viral Load testing (if no VL test result in medical chart within 60 days of enrollment date) 
6.3 
5-month Assessment (Immediate Post-Intervention)  
 
2245

Participants will have access to intervention content (either the YT intervention or weekly control 
pages) for a total of 5 months. The 5-month assessment should occur as soon after their 5-
month enrollment period as possible. However, the assessment may occur 30 days prior to or 
up to 60 days after (inclusive of the 60th day) the ideal 5-month assessment time point. Remote 
5 month follow up will be offered to participants who reside outside of any participant who 
expresses an inability to make an in-person visit in an effort to reduce the number of participants 
who are lost to follow-up. In-person visits are the preferred method of follow-up. Participants will 
receive a phone call, e-mail, or text (as deemed appropriate for that site) from research staff at 
their respective SRV, and an appointment for this visit scheduled to complete the following 
procedures listed below. Blood collection should only be conducted if the participant does not 
have a measure of VL in their medical record or cannot provide proof of a VL test within the past 
60 days. If a VL test has been conducted in the past 60 days, the results of that test should be 
recorded and no blood drawn for VL. Participants whose 5 month follow-ups visit are conducted 
remotely will have a VL test conducted either in a SRV clinic, external laboratory, or a mailed 
self-administered test. 
At the 5 month visit, up to 20 participants randomized to the intervention arm will participate in a 
remote interview conducted by study staff over VSee or Zoom. The purpose of this interview is 
to elicit feedback on their experiences using the YT site, any technical difficulties encountered, 
and how the site could be further improved. Participants will be selected for interviews using 
purposive sampling based on level of engagement with the site (i.e., high engagement vs. low 
engagement relative to other users). All interviews will be audio recorded for transcription and 
analysis. Participants who are invited to interview and choose to do so will be provided an 
additional compensation payment. Study staff will track activity levels and select participants for 
the interview. 
In-person 5-month visit: 
6.3.1 Administrative and Behavioral Procedures 
•
5-month assessment using CASI 
•
Feedback interview for up to 20 youth in the YouTHrive intervention arm 
•
Medical record abstraction 
6.3.2 Clinical Procedures  
•
Blood collection (if no VL test result in the past 60 days is available in the participant’s 
medical record or electronic health record)  
•
Urine collection (in-person visits only) 
6.3.3 Laboratory Procedures 
•
Viral Load Testing (either from medical record, blood draw conducted in an SRV clinic, at 
an external laboratory, or self-administered VL test) 
•
Urine test for presence of illicit drugs (if available in-person) 
DATA COLLECTION AND SITE MONITORING 
7.1 
Development of Protocol and Case Report Forms 
 
2345

The Management Core, in collaboration with the Protocol Team, is responsible for the 
development of this protocol as well as the Case Report Forms (CRFs) needed to collect the 
information required to implement this protocol.  
7.2 
Data Records  
Participant-related study information will be identified through a study ID number (SID) and a 
participant code comprised of the first initial of the participant’s first name and their two digit day 
of the month born on all participant CRFs, audio and video files, transcripts, and CASI files. 
Participant names or other personally-identifying information will not be used on any study 
documents and should be redacted from focus group and usability interview transcripts. All 
study-related information will be kept in double-locked, limited access areas at each study site. 
Participant names and their SIDs and participant code will be stored separate from other study 
information in SMART, accessible only to designated study staff, iTech site monitors, and 
representatives from the NICHD.  Original source documents for individual participants will be 
maintained at the respective SRV and will be accessible only to the study staff. Data from 
original source documents will be transcribed on CRFs as applicable.    
7.3  
Data Collection  
7.3.1 CRFs 
Study monitoring data, including information about eligibility, demographic data, and monitoring 
untoward effects will be collected on CRFs. All CRFs for this study will be available for download 
from a secure Box or Microsoft OneDrive account.  
7.3.2 CASI Survey Data 
Self-administered surveys at the screener, usability testing first visit, enrollment and 5-month 
assessment time points will be completed by participants on a clinic computer or tablet. 
Participants completing the enrollment and 5-month assessment virtually will in a confidential 
setting of the participant’s choosing via a computer, tablet or smartphone. Surveys will be 
hosted on Alchemer. We use SSL encryption for transfers of information online and data will be 
stored in the secure, HIPAA-compliant servers of Alchemer. The Emory AC team maintains a 
business partner HIPAA agreement with Alchemer.  
All data collected using CASI will remain confidential; no personal identifying information will be 
collected during the computer session. The participant’s unique SID# will be used in order to link 
the interview responses to the participant’s CRF data.   
7.3.3 CASI Data Security 
CASI Data Security 
Only authorized users with a login name and password will be able to access and open the 
survey through the internet site. To ensure data privacy, as soon as data is entered (in real-
time), it will be encrypted during transmission to the AC using Secure Socket Layer technology. 
The data will then be immediately stored in a secure database on an AC server within the AC 
data center. 
7.3.4 VSee Platform Description  
For many of the interviews with participants, the AC and study staff will rely on VSee platform or 
a comparable HIPAA compliant videoconferencing platform. When using VSee, participants will 
have the option to use VSee in several formats:  face-to-face video chat, video chat in which 
 
2445

they can see the interviewer but the interviewer cannot see them, audio chat only, or a text 
based conversation. The consent form for each research project will include a full description of 
VSee, their options for using VSee, and will also make it clear what they can opt not to do. VSee 
is compatible on PCs, tablets, and smartphones. Unlike other video-chat platforms (e.g. Skype), 
VSee is HIPAA-compliant. VSee includes the following functions to protect users:  
End-to-end encryption without a man-in-the-middle listener.  In WebEx, Vidyo, Tandberg, and 
Polycom architectures, media is sent to a server (also called a video relay or MCU). Although 
encryption is applied from the user’s computer to these servers, the servers still have full access 
to the user’s media. In contrast, VSee uses end-to-end encryption where no server, including 
VSee servers, has the decryption key. VSee uses public/private RSA keys to exchange a 256-
bit AES session key with the property that only the endpoints have the AES session key. VSee 
uses FIPS 140-2 certified 256-bit AES encryption.  
One port.  VSee uses a single port for call signaling and media. The VSee protocol is structured 
so that only the outgoing port needs to be open because return traffic is always structured as 
responses to outgoing traffic. This allows administrators to set a policy where if users inside 
their network are using VSee, then their firewall lets VSee traffic securely cross the firewall; 
however, if users inside their firewall stop using VSee, then the firewall will block external port 
scans.  
Automatic HTTP/SSL tunneling.  VSee prefers to use UDP since it allows higher performance 
video. However, if the firewall does not allow UDP, VSee will automatically switch to HTTP/SSL 
tunneling.  
Cloud Control.  VSee's cloud solution allows enterprises to maintain central control of their 
security policies to a large number of end points even though the service is hosted by VSee. It 
does this by having VSee clients always connect first to VSee servers in the cloud, where the 
policies are controlled. The cloud servers determine whether any of these security policies 
should be applied and enforces them as the VSee client. This allows us to set our own security 
settings and to record the sessions.  
No-install client.  Video conferencing software clients tend to be large and to leave a big 
footprint on the user’s system. Almost all of them require administrator permissions to install. 
Once the client software gains administrator permissions, they can severely compromise 
computer security. VSee is a lightweight client that does not require administrator permissions 
or installation.  
VSee offers the HIPAA-required Business Associate Agreement (BAA) where VSee agrees to 
be responsible for keeping all patient information secure and to immediately report any breach 
of personal health information. In this study, the iTech Technology core will enter into a BAA with 
VSee, and this will be extended to cover the proposed activities. The VSee sessions will include 
identifying information (e.g. images of the participant, voice recordings). All identifying 
information will be stripped from the recorded VSee sessions before they are sent to the 
analysis team for content analysis.  
7.3.5 Zoom Platform Description  
In addition to VSee, Zoom may be used to conduct qualitative interviews remotely. Participants 
will have the option to conduct face-to-face video chat, video chat in which they can see the 
interviewer, but the interviewer cannot see them, or audio chat only. Zoom is compatible on 
PCs, tablets, and smartphones; as well as maintains the option to conduct an audio conference 
without the video component. Emory University has entered into a BAA with Zoom, where Zoom 
agrees to be responsible for keeping all patient information secure and report any breaches of 
 
2545

protected health information (PHI). 
End-to-end encryption. Zoom encrypts all presentation content at the application layer using the 
Advanced Encryption Standard (AES) 256-bit algorithm. Zoom end-to-end (E2E) chat 
encryption allows for a secured communication where only the intended recipient can read the 
secured message. Zoom uses public and private keys to encrypt the chat session with Advance 
Encryption Standard (AES256), and session keys are generated with device unique hardware 
ID to avoid data being read from other devices. This ensures that the session cannot be 
eavesdropped or tampered with. 
Cloud Control Infrastructure. A distributed network of low-latency multimedia routers (software) 
resides on Zoom’s communications infrastructure. With these low-latency multimedia routers, all 
session data originating from the host’s device and arriving at the participants’ devices is 
dynamically switched — never stored persistently through the Zoom communications 
infrastructure. Zoom’s communications infrastructure for real-time video, audio, and data 
communications resides on Zoom dedicated servers, which are housed in SSAE 16 SOC2 
compliant datacenters on opposite sides of the US. Zoom sessions are completely temporary 
and operate analogously to the popular mobile conversation over the public mobile network. In 
addition to unique security beneﬁts, Zoom’s communications infrastructure also enables an 
extremely scalable and highly available meeting infrastructure unrestricted by the limitations of 
physical data centers. 
The Zoom client communicates with the multimedia router to establish a reliable and secure 
connection. At the time of instantiation, the Zoom client will determine the best method for 
communication, attempting to connect automatically using udp and tcp port 8801, 8802 and 
8804 or HTTPS (port 443/TLS). 
The Zoom sessions will contain identifying information, as in VSee above, but this information 
will be stripped form the recorded Zoom sessions before they are sent to the analysis team for 
content analysis.  
7.4 
Data Submission 
7.4.1 CRFs 
Although the iTech projects will involve substantial online follow-up, CRFs will be used to collect 
key study visit data (e.g., enrollment and randomization assignment), study milestones such as 
completion or discontinuation, study laboratory results, and adverse events (AE). AC staff will 
work with study investigators and the MC to develop and design the CRFs. During study 
conduct, the SRVs will maintain the CRFs in secured locations, and transmit CRF data to the 
AC either electronically using DFexplore or by submitting scanned paper forms using DFSend. 
DFexplore and its DFdiscover platform is a leading multi-site database environment for HIV 
RCT that can receive and transcribe CRF data via scanned PDFs, or allow for direct electronic 
data entry. It provides for monitoring form completion and data quality, and a system for data 
querying and resolution with SRVs, while maintaining an audit trail. The AC uses DFexplore for 
MSM studies and RCTs and data is maintained by the parent company DF/net on a cloud-based 
server with Microsoft Azure.  
7.4.2 Audio/Video Data  
Audio-recorded data for the focus groups and audio and video data for exit interviews will 
initially be stored as a digital file on a secure encrypted server. Focus group discussions will be 
transcribed verbatim from the digital audio-recording and de-identified by assigning unique 
numerical codes. All qualitative interviews will be transcribed. Transcripts of the interviews will 
not use the names of the participants, only their pseudonyms for FGs or study ID for the IDIs. 
 
2645

After transcripts are verified by the research team and one year after the study is over, audio 
and video files will be destroyed.  
All qualitative interviews may also be recorded using a back-up digital audio recorder. Audio files 
will be erased after being transcribed and transcripts will be de-identified. All audio files will be 
kept confidential and stored in a locked/limited access folder on secured servers, which is only 
accessible to designated study staff. All members of the research team will be trained in 
confidentiality and have signed confidentiality agreements. A professional transcription service, 
experienced in the handling of confidential data, will be used to fully transcribe verbatim all 
audio files. Prior to receipt of the first audio file, the transcription service will be instructed to 
exclude from the typed transcript identifying information (e.g., a name) that may have been 
verbalized during the course of the focus groups.  
All CASI data will only be identified with a unique study number and stored on a secure 
encrypted server by the AC team. Only SRV research staff, the AC team, and the research team 
at the San Diego State University will have access to the data. 
7.4.3 CASI Data Transmission 
Only authorized users with a login name and password will be able to access and open the 
survey through the internet site. To ensure data privacy, as soon as data is entered (in real-
time), it will be encrypted during transmission to the AC using Secure Socket Layer technology. 
The data will then be immediately stored in a secure database on an AC server at Emory 
University. 
7.4.4 Retention data  
The study will use a HIPAA-compliant web-based platform entitled Study Management and 
Retention Toolkit (SMART), which is a SaaS (Software as a Service) based mobile application 
aiding studies with various aspects of participant recruitment, study implementation, and 
retention. The application has the ability to securely manage participant information across 
multiple studies and customers simultaneously, stratifying participant information by study and 
site. SMART includes an admin web portal and a participant facing mobile app (optional), which 
allows for secure messaging, study calendar management, self-scheduling by participants, 
secure photo uploads, and longitudinal tracking of participants from screening to study 
completion. The ability to designate specific roles to all SMART users allows for greater control 
around permissions and accessibility to participant information. Users can even be limited to a 
reporting only role, which allows for study oversight through real time aggregate reporting, but 
no access to PHI. SMART is a licensed service of the Center for AIDS Research (CFAR) at 
Emory University, Prevention Science Core. Utilization of the mobile app is optional and the 
admin web portal will fully function without it. 
The following information outlines the security of the three SMART components: (1) the admin 
web portal, (2) the participant app, and (3) a web service that acts as a liaison between the 
mobile app and the study database. 
Admin Web Portal. The admin web portal is a web-based application developed using 
Microsoft .NET technologies. It uses SQL server as backend database. The application requires 
two servers to host: (1) Web server [Windows server with IIS] and (2) SQL server [Standard or 
 
2745

Enterprise version]. Both these servers are to be placed behind a firewall. Web server will have 
a public IP to access the server using VPN. SSL certificate is to be installed on the web server. 
The admin website will be rendered over SSL (https). 
The application uses form authentication (no integrated authentication such as AD). All 
passwords are stored encrypted within the database. System will also be using database level 
encryption, which will prevent any copying of information from one database to another. Web 
application also uses an automatic logout feature after a certain period of inactivity. By default, 
the inactivity duration is set to three minutes. 
Study staff can only first gain access to the admin web portal if granted by a study or site 
administrator. Their assigned user role will determine their permissions to perform different 
actions and even view PHI. Email notifications are sent from the system (without the need to 
login) when: (1) a staff member requests to reset their password, (2) role assignments to a 
study are made, (3) an event/visit staff are scheduled to work is nearing, (4) a new task is 
assigned to a staff member, or (5) they are designated as a staff member to receive alerts of 
positive test results. All participant communications are performed using secure messaging 
through the message center (inbox) implementation within the mobile app. If the mobile app is 
not utilized by a study, communications are sent as standard email or text messages to 
participants. 
Mobile App. The mobile app, developed natively for iOS and Android platforms and available 
for free in the App Store and Google Play Store, is an optional feature the study can utilize for 
self-scheduling, communication, photo uploads, and updating contact information. The study will 
indicate during the initial setup within the admin web portal whether the participant mobile app is 
utilized or not. If the app is utilized, participants will receive download instructions after their 
information is entered into the admin web portal. Only participants listed in an active study who 
validate their email or phone number against the contact information listed in the admin web 
portal will be able to proceed into the app. For validation, the app uses both traditional form 
authentication as well as social login (Facebook and Google). The social login feature will only 
work if the email associated with either social account matches the contact information within 
the admin web portal. The app does not request anything other than basic information from 
these authentication services. Participants cannot “remember” their password on the mobile 
device for automatic logins to ensure privacy. All participant data and activity status is 
maintained within a secure and encrypted SQL Server database. To create the connection 
between the admin web portal and the mobile app, each participant is assigned a unique ID 
within the application, which is associated with their login credentials. When a participant has 
been successfully authenticated through the mobile app, the admin web portal will send their 
specific information to their phone through the established secure session (web APIs using 
SSL). The app will not store the information presented locally on the phone. Local data storage 
is used only for storing some minimal non-PHI information, such as app settings. The mobile 
app implements an automatic logout when there is inactivity for more than three minutes. If a 
participant should need to re-download the app on a new device, login and password 
authentication will be required again. 
The mobile app has push notifications that are primarily used for reminders and notifications of 
new messages. Push notifications displayed on the participant’s phone will be generic in nature 
and not contain any PHI. Reminders and notifications within the mobile app inbox will also be 
generic in nature, with any message containing sensitive information requiring a pin, established 
during registration as a secondary authentication, to open within the mobile app. Firebase cloud 
messaging service is used as a communication channel for these notifications. No PHI is 
passed through Firebase. Push notifications are customizable in the study setup, and samples 
of system notifications include: “You have a new message in your inbox,” “You have an 
upcoming event for March 7, 2018,” and “You have a pending task.” 
 
2845

Web Service. A web service will also be hosted on the web server. This service is used by the 
mobile application to retrieve and store data. The service will utilize secure socket layer (SSL) 
for communication. 
7.5 
Data Quality Assurance 
Investigators receiving federal funding must adhere to the Code of Federal Regulations (CFR) 
to protect research participants and produce reliable study information. Sites participating in 
research sponsored by the NICHD need to have an internal quality assurance (QA) plan that will 
identify problems and correct errors in research study records.  
7.6 
Role of Data Management 
The MC will provide instructions concerning the recording of study data on the CRFs, entry of 
the data into RDC, and administration and transmission of CASI data.  
  
7.7 
Study Site Monitoring and Record Availability 
Site monitors from the MC will visit participating study sites to review a selected portion of the 
individual participant records, including assent/consent forms, CRFs, and supporting source 
documentation to ensure the protection of study subjects, compliance with the protocol, and 
accuracy and completeness of records. Regulatory files, as required, will also be inspected to 
ensure that regulatory requirements are being followed. 
The site investigator will make study documents (e.g., assent/consent forms, case report forms) 
and pertinent hospital or clinic records readily available for inspection by the local IRB, the 
single IRB, the site monitors, the NICHD, the Office for Human Research Protections (OHRP), 
or the sponsor’s designee for confirmation of the study data. 
PARTICIPANT MANAGEMENT 
8.1 
Tracking Participants / Follow-up 
All subjects will be contacted before each follow-up study visit/assessment (i.e., enrollment and 
5-month time points). Multiple contact methods will be used for youth who are difficult to reach 
(e.g., mail, alternate phone numbers, e-mail, text message, social media contact information). 
Subjects will be asked whether or not messages can be left for each of the phone numbers that 
they provide.  They will be informed that messages will not contain any information regarding 
the nature of the project.  
8.2 
Compensation 
The method for compensation will be determined separately by each site, listed in the site’s 
informed consent/assent form, and approved by the single IRB (the UNC-CH IRB). 
If a subject is unable to go into the clinic to complete a follow-up study visit, the web-based 
CASI survey could be completed on their own. Site study staff will be notified when a subject 
has completed a CASI survey on their own and the compensation will be provided to the 
subject. Additional compensation will be provided for participants who are asked to return to 
clinic site for laboratory/clinical testing or asked to complete a self-administered VL test. Site 
study staff will determine the appropriate amount of compensation. Compensation can be 
provided in person, or sent to participants electronically or via mail, if allowed at the site. 
 
2945

8.3 
Intervening on “Social Harms"  
(Describe potential harms that may occur as a result of participating in the study, and what steps 
will be taken to reduce or counteract the negative effects. These measures can be preventive or 
reactive.) 
We identified the following 6 items as possible risks to subjects and described how we plan on 
addressing those risks: 
1.
Protecting against going to the site by mistake. We have a secure site (https:) with an 
introductory page clearly specifying the nature of the study. Sensitive survey or 
intervention content is protected behind screening questions and a username/password, 
and therefore in the opening study webpage, we could not think of anything that would 
be deemed offensive by any persons or those who might be vulnerable. In this way, we 
have minimized the risk to a level that is negligible.  
2.
Protecting against others finding out about their sexual behavior, sexual orientation 
identity, or HIV status. Participants will be alerted to this and provided basic information 
on how to best protect themselves. Specifically, those who qualify for the study will have 
access to an informational page describing how we protect their confidentiality and what 
steps participants can take to protect their confidentiality during the study. The 
description of the purpose of the study will clearly state that the study is designed so that 
participants are encouraged to interact with one another virtually, and we will 
recommend that persons who are highly uncomfortable with such exchanges may be 
better served by not enrolling in the study. Once enrolled, we also minimize this risk of 
identification to participants in the following ways:  a) participants will be required to 
create usernames that do not contain personally identifying information and the site will 
be continuously monitored to maintain high levels of confidentiality and b) participants 
may utilize the features of the intervention that they choose, although we will encourage 
the exploration of all features. Thus, although we cannot guarantee their anonymity, we 
will take appropriate safeguards to minimize this risk.  
3.
Protecting against discomfort in answering personal questions during the focus group 
discussions, the assessments, and/or revealing aspects of themselves during the 
intervention period with other participants. This risk is similar to #2 above, and we will 
use comparable safeguards to protect against it. Thus, we intend to fully inform 
participants of the purpose and nature of the study prior to their participation. 
Participants in all of the protocols are informed that they are free not to answer questions 
or utilize study features, and they may stop participation at any time. Since a “refuse to 
answer” option is provided to every self-report question in the study surveys, there is a 
constant reminder of their participant rights throughout the study. Internet-based studies 
may be less invasive than conventional study methodologies, as it provides users total 
control over their participation and they may opt out of the study by simply exiting the 
study website. We believe the risk to participants is minimal and we have adequately 
anticipated and set into place protocols to address potential risks that may arise. 
4.
Protecting against hostile interactions and inaccurate information from one participant to 
another. Participants will be informed during the consent process of the “group rules” 
regarding interactions with one another (e.g., “Honesty is important; however, hostile or 
abusive language will not be tolerated and may be grounds for immediate removal from 
the study”). These “rules” will also be available with a link on all intervention web pages 
for review by participants at any time. The project coordinator will manually review an 
automated compilation of posts participants make on a daily basis to flag hostile 
interactions and inaccurate information. Hostile interactions between participants will be 
handled by, first, reminding the participants in the interaction of the “group rules” 
regarding appropriate interactions. If the hostility continues, the offending participants 
 
3045

will be given a warning that the continued hostility will result in withdrawal from the study 
if it continues. On the third offense, the offending participant will be withdrawn from the 
study. Text containing hostile exchanges will be removed from the study website and 
unavailable to view. In cases in which inaccurate information is found, project staff be 
guided by experts on the team to post a comment that provides accurate information on 
the topic. In extreme cases, the PI’s may decide to withdraw a participant before the 
third offense. We will ensure all clinic sites have a clear clinical protocol to address major 
issues that may come up at study visits or in online interactions. The major issues 
addressed in the procotol will be suicidal ideation, homicidality or violent ideation, 
emotional and cognitive disregulation, violent/aggressive or disruptive behavior, and 
intoxication. If research staff from San Diego State University see concerning comments 
or messages online from participants regarding self-harm or harm of others, they will 
contact clinicians at the site and take immediate precautions.  
5.
Protecting against concerns about the security of their data. Well-established security 
protocols will be followed, that include the following: 
1.
Participants’ identifying information is kept separate from the data set, in a separate 
file on a separate computer in the offices of the PI’s, accessible only by authorized 
study staff. 
2.
All data will be encrypted and stored on a password-protected computer behind a 
firewall to ensure access is provided only to those involved directly in data collection 
or analysis.  
3.
Payment to subjects will be administered by research staff during the baseline, and 
immediate post-intervention follow-up.  
4.
At the end of the study, the identifying information (participants’ names and contact 
information) is destroyed. The original data records will be archived for 7 years (in 
accord with good data practices), and three copies of the de-identified dataset will be 
maintained (a working one and two archived at different sites). 
5.
All project staff will be required to complete the NIH online training in research ethics. 
Further training and supervision will focus research staff on confidentiality concerns 
both during and after the study. The project coordinator in conjunction with the PI are 
responsible for ensuring that all research staff involved in this study document their 
NIH training.  
6.
Minimizing the risk and discomfort from phlebotomy and VL testing. Trained and certified 
phlebotomists will perform all blood draws done in person in order to minimize the risk of 
bruising or infection. In order to minimize discomfort, an experienced and/or certified 
medical assistant will perform these procedures. They are routinely done in medical 
settings, and therefore potential risks are no greater than those encountered during 
routine medical exams.   SRV staff will make every effort to align participants’ data 
collection time points with standard clinic viral load measures. When these do not align, 
an additional blood draw or self-collected VL testing will be needed. For both standard 
VL testing and self-administered VL testing, physical harms are minimal. The type of 
safety lancet selected for use in the study was designed to minimize the potential for 
infection or significant injury. Cleaning the area with an alcohol pad first lowers the 
already low infection risk further; pads are included in every kit. The spring-loaded lancet 
retracts fully after one firing, and thus does not pose a risk for “needle stick” injury to 
anyone after the device has been used. Subjects could experience dizziness, 
diaphoresis and nausea associated with the procedure but in prior clinical studies using 
self-administered testing, adverse events have been rare.  
 
3145

All sites have specific policies governing the treatment of human subjects. These policies 
specify that medical and psychological assistance will be available in the immediate 
environment in the event a participant should experience any adverse reactions resulting from 
study procedures.  
While participants will be informed that they may refuse to answer any question at any time, 
responses or reactions to certain questions may indicate distress on the part of the participants. 
If at any time during the study, a participant divulges that they are at risk for harm, including but 
not limited to being abused or experiencing violence, if harm is suspected or likely, or if the 
participant states they are suicidal/homicidal, measures will be taken to ensure their safety. 
Reporting will be done as appropriate to the situation and the legal statutes, including reporting 
to child protection agencies or other appropriate agencies, and referrals will be provided to 
appropriate support, counseling, or treatment resources. 
8.4 
Criteria for Premature Study Discontinuation 
Subjects will be prematurely discontinued from the study if any of the following occurs:  
•
The subject withdraws consent/assent;  
•
The subject becomes incarcerated or placed in detention 
•
The participant is unwilling or unable to comply with study procedures 
•
The investigator believes that ongoing participation may cause harm to the participant or 
study staff 
•
The investigator believes that ongoing participation may impact the integrity of the study 
data 
•
The study is cancelled by the NIH (or iTech, or other administrative entity); 
•
The study is cancelled for other administrative reasons;    
•
The subject becomes incarcerated or placed in detention during the study; or  
•
Death of the subject. 
The Study Stop CRF will be completed when participants are study stopped. No medical record 
data on participants will be abstracted past the date of study discontinuation. 
Subjects who are prematurely discontinued from the study may be allowed to re-enroll into the 
study on a case-by-case basis. The Protocol Team will review the number of slots opened for 
replacements on a monthly basis, or more frequently, as needed.  
MONITORING UNTOWARD EFFECTS ASSOICATED WITH OR RESULTING FROM STUDY  
Site research staff must first follow their own IRB’s procedure for reporting and managing 
untoward effects.  
There are three types of untoward effects to be identified:  (1) those related to the participant, 
(2) those related to the study staff, and (3) those related to the neighborhood/community (if 
applicable). 
First, the study will catalogue any untoward effect related to the participant. Reporting is 
required for occurrences including social harms, psychological distress, and serious life-
threatening events such as suicide attempts. These may be immediately apparent to the study 
staff, such as the participant’s emotional upset state requiring referral for counseling; or they 
may be delayed and reported later to study staff, such as physical harm to an individual for 
having participated in the study. Study staff will notify the iTech team of any untoward effects 
using the iTech QNS accessible through the iTech website (www.itechnetwork.org) within 24 
hours of becoming aware of these untoward effects. Study staff will be briefed during the 
training on the scope of possible untoward effects and instructed to report events. 
 
3245

Second, study staff may encounter untoward events during sessions that personally affect them. 
Training and guidance will seek to minimize this risk. Nonetheless, an assessment of the cost of 
conducting this study must include cataloguing these events as well. The protocol chairs should 
be notified of these events so that they may be immediately addressed, evaluated, and 
guidance modified or expanded to minimize similar risk to other study staff. 
Third, a critically important area any community-based study intends to evaluate is the impact, 
including untoward effects, of the project on the community. This will be done informally for this 
protocol with untoward events being reported to the protocol team. 
All untoward effects/adverse events/unanticipated problems will also need to be reported to the 
UNC IRB if they meet all three of the following criteria: 
 “Unanticipated problems involving risks to subjects or others” (UPIRSO) refers to any incident, 
experience, or outcome that:  
1) is unexpected (in terms of nature, severity, or frequency) given (a) the research 
procedures that are described in the protocol-related documents, such as the IRB-
approved research protocol and informed consent document; and (b) the 
characteristics of the subject population being studied;  
2) is related or possibly related to a subject’s participation in the research; and  
3) suggests that the research places subjects or others at a greater risk of harm 
(including physical, psychological, economic, or social harm) than was previously 
known or recognized.  
Events that meet the criteria for an UPIRSO and are also serious adverse events should be 
reported to the UNC IRB within one (1) week of the investigator becoming aware of the event.  
Any other events that meet the criteria for a UPIRSO should be reported to the IRB within two 
(2) weeks of the investigator becoming aware of the problem.  
If the report cannot be completed in its entirety within the required time period, a preliminary 
report should be submitted. The report should be amended once the event is resolved and/or 
more information becomes available. 
STATISTICAL/ANALYTIC CONSIDERATIONS 
10.1 
Introduction 
10.1.1  Focus Groups Overview  
We will conduct six focus groups with approximately 8 youth (15-19 years old) and young adults 
(20-24 years old) each at 3 SRVs (Chicago, Houston, and New York) to obtain:  1) information 
about barriers to ART adherence and other challenges of living with HIV; 2) feedback from 
YLWH about the “look and feel” and content of the original TWM intervention; 3) suggestions for 
adapting the intervention for youth/young adults similar to themselves. Focus groups (as 
opposed to in-depth quantitative interviews) were chosen to gain feedback in these areas 
because this setting will allow participants to explore together the ways in which the TWM 
intervention meets their needs and how the intervention can be adapted to be community 
appropriate.   
10.1.2 Usability Testing 
A total of 12-20 YLWH across 6 SRVs (Bronx, Chicago, Houston, Philadelphia, Tampa, and 
Atlanta) will be recruited to provide feedback on the first full version of the YT intervention. 
 
3345

Usability testing is done to identify any technical problems with the program and any design 
features that are likely to impede engagement with the program. 
10.1.3 RCT Overview  
We propose to evaluate the YT intervention in a randomized controlled efficacy trial of 300 
YLWH at 8 SRVs. YLWH will be recruited from the 8 SRVs, screened, and randomized to 
receive either the YT intervention or HIV-information only control condition. VL testing will be 
assessed at the enrollment visit and immediate post-intervention (5-month follow-up). We will 
evaluate interviews with up to 20 active users to obtain:  1) information about barriers to ART 
adherence and other challenges of living with HIV; 2) feedback from YLWH about the YouTHrive 
intervention; 3) suggestions for adapting potential future iterations of the intervention. 
10.2 
Power Estimates  
10.2.1 Focus Groups Power Considerations 
The purpose of focus groups is not to obtain generalizable data, but rather to obtain collective 
qualitative information to inform adaptation of the TWM intervention for youth. We are balancing 
feasibility with the need to obtain information from a spectrum of YLWH. As such, we will 
conduct 6 focus groups, targeting younger (15-19) and older youth (20-24) at 3 different SRVs 
with the goal of reaching 48 YLWH. Given our prior experience and best practices for the 
conduct of focus groups, this will provide us with information from enough youth to inform the 
adaptation process. 
10.2.2. Usability Testing Power Considerations 
Power is not a concern for usability testing as it is performed to collect feedback from a small 
number of members from the target population about a preliminary version of the intervention. 
10.2.3 RCT of YT Power Considerations  
We will continue to collect as much biologic data on viral load at baseline and month 5; 
however, given the difficulty in obtaining viral load measurements due to COVID, we will also 
utilize measures contained within our surveys to assess the impact of the intervention on self-
reported HIV care continuum outcomes and possible mediating (social support) and moderating 
(depression) factors. We are already collecting this data, and thus will not need to modify our 
measures. We have been in discussions with SRVs about how many participants per month 
they believe that they could enroll. On average, sites reported that they would be able to recruit 
4 participants per month each. If we begin the new inclusion criteria in April, then sites could 
potentially recruit up to 288 additional participants by ….. The study statistician (Dr. MacLehose) 
conducted a power analysis to ensure our proposed changes will still allow for meaningful 
detection of primary study outcomes. Assuming approximately 85% follow-up, we 
based our updated power calculations on 240 participants. The primary outcome, self-reported 
adherence is a continuous measure. A study by Belzer et al. suggest a standard deviation of 43; 
assuming a type 1 error of 5% and equal allocation of participants between the 2 arms, we have 
80% power to detect a difference of 15.6 points between the two groups. For instance, if the 
control arm had an adherence of 48% (as seen in Belzer et al.), we could detect a significant 
difference of 63.6% adherence in the intervention arm. This is a clinically meaningful difference.  
We have also assessed the impact of these proposed study changes on important secondary 
outcomes that have been shown to impact ART adherence among YLH (including depression 
 
3445

and social support). Based on a literature review, depression is estimated to have a prevalence 
between 25% and 40% in this population. Using the same assumptions as above, we have 80% 
power to detect a difference of 13.9% (if the prevalence is as low as 25% in the control arm) or 
16.7% (if the prevalence is as high as 40% in the control arm). We are also assessing social 
support as measured by the PROMIS-ES scale. A study by Shensa et al allows estimation of 
a standard deviation of 0.63 for this score, giving us 80% power to detect a different of 0.23 
units. For example, if the control arm indicates a mean social support of 4, we could detect a 
difference if the intervention arm had a social support scale of 4.23.  
10.3 
Statistical Analysis Plan 
10.3.1 Analyses of Focus Group Data.  
Focus group discussions will be transcribed verbatim from the digital audio-recording, de-
identified by assigning unique numerical codes, and entered into Dedoose software to assist 
with theme identification, coding textual data, and describing relationships among codes (via 
code co-occurrence and memoing functions). Following established focus group analysis 
guidelines, we will create a codebook of a priori and emergent themes including operational 
definitions of all codes and sample quotations to illustrate how to apply each code. Two study 
team members will then use the codebook to independently code the compiled user profiles 
while a third team member will review these sections of coded data and resolve discrepancies. 
We will draw a random sample of 20 instances for the coders to begin with and calculate an 
inter-rater reliability score based on their code assignments. If this score is <95%, we will refine 
the codebook definitions and retrain the coders. Coders will then complete the coding of the 
remaining instances and we will calculate an inter-rater reliability score. Discrepancies will then 
be reviewed and resolved by the research team. Coding and analytic activities will be discussed 
during weekly team meetings. 
10.3.2 Primary Analyses for Usability Testing 
A usability report will be compiled by Protocol Chair and reviewed by the investigator team and 
the AC. The report will include:  a) a list of common problems like navigation problems; and b) 
recommended design-improvements that will be used in the final iterative stages of intervention 
adaptation. 
10.3.3 Primary Analyses for RCT of YouTHrive 
Stata version 15 (StataCorp) and SAS version 9.4 (SAS Institute) were used for power 
calculations and will be used for all analyses. The primary study outcome is HIV viral 
suppression at 5 months, measured as undetectable VL based on the standard level of 
detectability. The primary statistical test of intervention efficacy for YT will be the comparison 
between intervention and control arms of the proportion of participants with undetectable VLs at 
the 5-month follow-up, using a chi-square test. If there is evidence of baseline imbalance 
between intervention arms for important predictors of viral suppression, we will fit logistic 
regression models that adjust for those covariates.  
10.3.4 Secondary Analyses for RCT of YouTHrive  
 
3545

As a secondary aim, we will investigate whether there is greater benefit from the YT intervention 
for substance-using participants compared with nonsubstance-using participants. We will use 
the same modeling approach described above to address this aim. First, we will examine the 
association between the intervention and viral detection separately among those who did and 
did not self-report current (since the last visit) substance use (i.e., yes/no for problematic alcohol 
use and/or illicit drug use). Second, to formally test whether there is an interaction between 
intervention arm and substance use, the models described above will be refit including an 
interaction term between substance use and interaction arm. Interactions will be evaluated on 
the additive scale. We will carefully examine the distribution of potential confounders of the 
substance use and VL association and adjust for them as necessary. As mentioned previously, 
we will adjust for covariates where appropriate. 
The models described use logistic regression to model the outcomes. We will use estimates 
from these models to report prevalence differences and ratios. However, alternative (log-linear 
and Poisson) models may be explored to allow easy interpretation of parameters in the 
presence of common outcomes. In the event of loss-to-follow-up among study participants, we 
will perform sensitivity analyses of an alternative outcome. We will define an additional outcome 
where a failure is defined as either detectable VL or loss-to-follow-up. The analyses described 
above will be repeated with this alternative outcome. All of the models mentioned above can be 
modified to accommodate missing values in the outcome or covariates over time without 
dropping participants. Although attempts will be made to limit missing data, in the event that this 
occurs, we will carefully examine patterns of missingness. Multiple imputation will be 
implemented, as needed, to deal with missing covariate data. 
Finally, we will examine models that include covariates that quantify the degree of site usage 
and which components were used. The additional outcome of self-reported ART adherence will 
be examined. The outcome will be defined as the percentage of ART taken in the past 30 days. 
Differences in this proportion by study arm will be evaluated using the same approach as 
described above. To explore the effects of the YT intervention on the intermediate theory-based 
processes of change, we will use the IMB-AAQ informational and motivational scales, 
adherence self-efficacy, and social support measures at each time point. These scales will be 
included as outcome variables in linear regression models to test the main effect of intervention 
arm. 
Note: Any deviations from the analysis plans outlined above or in the sections that follow will be 
documented and justified in the Statistical Analysis Plan developed for this protocol. 
10.4 
Missing Data 
Several procedures will be used to conduct data analysis when data for either outcomes or 
covariates are missing. The first step will be to assess the extent and pattern of missing data. If 
data are missing for only a few cases, then data analysis will be conducted only on study 
participants with complete data. However, when such a strategy would result in loss of data from 
a substantial proportion of participants, or if this approach would lead to biased or inaccurate 
results, then some form of imputation will be performed. The form of imputation used will 
depend on the nature of the data that are missing. For example, data that are collected 
repeatedly might be imputed using the “last value carried forward” method; and in some 
instances, interpolation between neighboring points might also be used.  
 
3645

When the primary endpoint is missing, one data analysis will be conducted using only cases 
with the endpoint. Subsequent analysis will be done where missing endpoints are imputed. Hot-
deck imputation or regression imputation may also be used in this context. 
HUMAN SUBJECTS 
This study will be conducted in compliance with the protocol, ICH Good Clinical Practice (GCP) 
guidelines, and 45 CFR Part 46. 
11.1 
Participants’ Confidentiality 
All laboratory specimens, questionnaires, evaluation forms, reports, transcripts, and other 
records will be identified by a coded number and participant code to maintain participant 
confidentiality. All records with personally-identifying information will be kept in a locked file 
cabinet in a limited secure access area at each SRV site. All computer entry and networking 
programs will be done with coded numbers only. Clinical information will not be released without 
written permission of the participant, except as necessary for monitoring by the MC or NICHD. 
Every effort will be made to ensure that study participants are protected from risks. The main 
risk specific to the role of the AC is breach of confidentiality.  
Breach of Confidentiality:  A potential risk to participants is violation of confidentiality. We will 
take the utmost caution to protect the confidentiality of all responses. We will minimize this risk 
by maintaining confidentiality and discretion throughout all iTech research procedures and data 
management and analysis.  
Participants may be concerned about the security of their data, particularly since it is collected 
and stored electronically. The AC has significant experience developing security protocols for 
Internet-based studies, and we will take a variety of steps to ensure participant security, 
including using a dedicated server behind a firewall, encryption of data, separation of identifiers 
from responses, and password-protected access to data. Therefore, we believe that this risk will 
be minimal. All of the apps and websites included in the iTech have features to ensure app 
security and privacy.  
For the YT intervention in Aim 3 - RCT, participants will create a unique username that does not 
contain any identifying information but will be their social media handle on the YT website. 
Intervention participants will have the option to upload a profile picture in keeping with the site 
guidelines or select an anonymous avatar to represent themselves on the site. Participants are 
told at the enrollment visit and in multiple places on the YT website that it is a violation of 
community guidelines to reveal identifying information including name, address, phone number, 
email address, social media handles, places of employment, or locations to meet for personal or 
business use. Participants will not be able to privately communicate with each other on the YT 
website - all conversations are viewable on the main feed. Trained research staff at the San 
Diego State University (SDSU) will monitor the website daily to ensure violations to privacy, 
even through self-disclosure, are addressed. Participants will also be able to flag others’ 
postings if they feel they have violated community guidelines. The YT website will use an 
“htpps” URL and entry into the website that is also password-protected.   
11.2 
Certificate of Confidentiality 
This research specifically targets a vulnerable population, children - YMSM ages 15-17. We will 
take every available step to minimize the risk of identifying/linking data being subpoenaed, 
stolen, or inadvertently released. First, the iTech will request a Certificate of Confidentiality from 
the NIH. Second, all research staff members are required to complete ethical clearance 
certification regarding protection of human subjects through their relevant IRBs. Third, all 
 
3745

studies will have documented procedures to safeguard against the risk of the linking information 
being stolen by keeping such information in locked spaces to which only essential study 
personnel who have completed CITI certification for human subjects research ethics training 
(http://citiprogram.org) will have access.  
A Certificate of Confidentiality for the iTech will be sought prior to enrolling participants. As noted 
on the NIH website (http://grants.nih.gov/grants/policy/COC/faqs.htm#187), a Certificate of 
Confidentiality will help the research team “...avoid compelled ‘involuntary disclosure’ (e.g., 
subpoenas) of names and other identifying information about any individual who participates as 
a research subject (i.e., about whom the investigator maintains identifying information) during 
any time the Certificate is in effect.” We have applied for and received Certificates of 
Confidentiality for other NIH-funded research projects, and given the sensitive nature of the data 
collected for this project, do not foresee difficulty securing one for this study.  
11.3 
Risks and Benefits 
11.3.1 Risks 
Risks to participants in this research study may include:   
By misspelling a web address or “surfing” the net, some individuals may unintentionally go to 
the study website. We deem this unlikely as we will use the prefix “https:” to prohibit persons 
from coincidentally viewing the site. Nonetheless, if someone were to mistakenly view the study 
website home page, we anticipate that the information contained on the homepage will be 
benign to viewers. 
Potential participants or participants enrolled in the study may have concerns about others 
finding out about their HIV status or other personal behavior (e.g., sexual behavior or substance 
use). We anticipate that the likelihood of this occurring is high given that a major feature of the 
intervention is for participants to network with one another and that eligibility for enrollment in 
the study requires participants to identify as a HIV-positive. We anticipate these concerns to be 
even higher for focus group participants as well, since they will be meeting in-person with other 
YLWH. Subjects will be informed of the inclusion criteria and general questions that will be 
asked during focus groups during the recruitment period. Since subjects will be recruited directly 
within clinics, they will have the opportunity to discuss with clinic staff whether they feel 
comofrtable being a part of such discussions. Clear consent procedures and an introduction 
from the PI will also give opportunities for subjects to withdraw if they no longer feel comfortable 
participating in focus group discussions. For those in the RCT, subjects will be informed during 
the consent process of the basic features of the intervention and those who are not comfortable 
interacting with other HIV-positive persons will be encouraged to not participate in the study. 
Those who do enroll will be given the option of utilizing intervention features with which they feel 
comfortable, although utilization of all features will be encouraged. 
The measurements that are involved in this study require venipuncture and self-administered 
finger pricks to collect blood samples. This procedure may cause local discomfort, bleeding, or 
bruising; rarely small clot or infection can occur at the blood draw site. This measurement 
should not be considered greater than minimal risk in and of itself given its routine use in 
general health care delivery.  
To minimize the risk of participants feeling uncomfortable about answering personal questions, 
we will use CASI methods for the study's surveys. In CASI, participants read survey questions 
on a laptop computer or mobile phone and use a combination of mouse click and keyboard/
touchscreen entry to input the answers themselves. Study staff may be available to assist 
participants with questions or technical difficulties on the CASI. Participants will also be able to 
refuse to answer any question that makes them uncomfortable.  
 
3845

Participants may receive hostile communications or incorrect information from other participants 
during the course of the intervention. It is possible that some participants may respond 
aggressively or with hostility to other participants. Likewise, although well-intended, participants 
may provide inaccurate information about adherence or its risk factors to other participants by 
interactions through the website message boards/social networking wall. The YT intervention 
website includes a clear section on Community Guidelines and will be monitored daily by 
research staff. Users have the option to “flag” objectionable content. We have protocols in place 
for addressing hostile interaction in the site up to and including termination of participation in the 
study.  
To minimize risks to confidentiality, we will secure study data with all appropriate physical, 
electronic, and operational protections. Data will be stored in a physically secure environment. 
All data files will have encryption and strong password protection. Any identifiable data will 
either be stored on Emory University's secure servers or will be on fully encrypted laptops. CASI 
surveys and online eligibility screening will take place on an encrypted commercial survey 
website, Alchemer. This site has been used by the investigators for thousands of online surveys 
with MSM with no data security breaches. Access to data will be on a role-based standard; only 
those study staff who require access to each type of data to complete their study-related roles 
will be allowed access. All study staff will be trained in security and confidentiality procedures, 
and will sign a confidentiality agreement before receiving access to any participant data.  
We will also develop procedures to minimize indirect disclosure that a participant is participating 
in an HIV-related research study, or a study that enrolls MSM. For each mode of contact 
information, we will ask specifically whether anyone else potentially has access to that mode of 
communication, and if it is acceptable to leave a non-specific message about participation in a 
health study. No study-related messages will ever mention HIV prevention or the nature of the 
research study. Additionally, all scripts for email, text message, and telephone contact with 
participants will be reviewed and approved by the UNC IRB before being used for contact with 
participants.  
We use SSL encryption for transfers of information online, and Alchemer has a business partner 
HIPAA agreement with Emory. Alchemer’s servers are HIPAA compliant.  
The AC will use Dedoose software to perform all qualitative analyses. Dedoose is a web-based 
application for organizing and analyzing textual, audio, and video data (qualitative) along with 
outstanding functionality for their integration with survey, test score, ratings, and demographic 
data (quantitative). Dedoose employs the highest levels of data encryption available for a web 
application in all data storage, back up, and transmission. Dedoose allows for project specific 
encryption feature. When using this feature, only Dr. Kate Muessig or her designee will hold the 
additional encryption key needed to be entered in order to view the project. This gives Dr. 
Muessig exclusive control over who can view the project under any circumstances.  
In addition to a Certificate of Confidentiality, we will protect participants in the following ways 
(which correspond to the potential risks described earlier):  
1. Breach of confidentiality. We will take every precaution to minimize risks to study participants. 
All AC research staff members are required to complete ethical clearance certification regarding 
protection of human subjects through UNC-CH or Emory University. We also have a strong data 
and safety monitoring plan in place to protect participants. Adverse events will be reported to the 
UNC-CH and Emory IRBs, individual research PI institutional IRBs, and SRV site-specific IRBs 
per each institution’s IRB reporting requirements using Adverse Event Reporting Forms created 
by the AC. When possible, reports will be sent within 24 hours of notification by the PIs. Annual 
updates on enrollment and retention will also be sent to the IRBs.  
 
3945

All data collection will take place in secure and supervised clinical settings. All study personnel 
have completed training and received certification in Human Subjects Research Protection (CITI 
Program) and HIPAA regulations. They will continue to renew this training in compliance with 
institutional policies.  
11.3.2 Benefits   
Participation in the YT arm may provide participants with information and exercises that help 
them build peer social support, monitor their medication adherence and HIV-related care 
appointments, and develop skills. Participants in the control group may gain basic knowledge 
about medication adherence and links to outside resources. In either the experimental or control 
condition, the primary benefit is access to health information that may assist participants to 
improve ART adherence and quality of life. Secondary benefits include positive feelings related 
to having assisted in the development and testing of a novel internet-based adherence 
intervention, and if proven effective, the future availability of this intervention to others. 
Compensation for participation is not considered a benefit, because we are simply reimbursing 
participants for their time, effort, and expenses (e.g., Internet access). 
11.4 
Institutional Review Board (IRB) Review and Informed Consent 
This protocol, the informed assent/consent documents, and any subsequent modifications will 
be reviewed and approved by the UNC IRB who is responsible for the oversight of the study. 
The informed assent/consent will describe the purpose of the study, the procedures to be 
followed, and the risks and benefits of participation.   
Consent/assent will be obtained to explain the nature, significance, and risks of the study.  
11.5 
Waiver of the Requirement for Parental Permission for Special Circumstances 
The site IRBs and the UNC IRB as the single IRB will be requested to grant a waiver of parental 
permission to participate in this research study for youth participants under (not inclusive of) the 
age of 18.   
Under 45 CFR 46.408 (c), an IRB has the authority to waive parental permission if it determines 
that “a research protocol is designed for conditions or a subject population for which parental or 
guardian permission is not a reasonable requirement to protect the subjects” and “an 
appropriate mechanism for protecting the children who will participate as research subjects is 
substituted” and “that the waiver is not inconsistent with Federal, State, or local law.” 
A request for a waiver of the requirement for parental permission is requested for 2 reasons:  1) 
many youth would be reluctant to participate in this study – which focuses on HIV and risks for 
poorer medication adherence – if they are required to get parental permission; and 2) many of 
the youth in our study are likely to be gay, bisexual, or have an attraction to persons of the same 
gender, but may not be out to their parents; requiring parental permission may place participants 
at risk for outing themselves as part of the LGBT community or having HIV. For these reasons, 
we believe it is important to be granted a waiver for parental permission for this study 
population. 
11.6 
Waiver of the Requirement for Signed Consent Form  
1.
For Study Participation 
 
4045

In order to maintain the anonymity of the survey and fully protect the privacy of the volunteer 
study participants, the UNC IRB will be requested to waive the requirement for a record of a 
signed consent form. A written consent form will be reviewed with each potential study 
participant and provided to each consenting one. This form describes the purpose of the study, 
the procedures to be followed, and the risks and benefits of participation.  
Under 45 CFR §46.117 (c) (1) and (2), an IRB may waive the requirement for the investigator to 
obtain a singed informed consent for some or all of the subjects if it finds either:  (1) That the 
only record linking the subject and the research would be the consent document and the 
principal risk would be potential harm resulting from a breach of confidentiality. Each participant 
will be asked whether they want documentation linking them with the research, and the 
participant’s wishes will govern; or (2) that the research presents no more than minimal risk of 
harm to the participants and involve no procedures for which written consent is normally 
required outside the research context.” 
The protocol team believes that both #1 and #2 applies to this study and, both combined, justify 
a waiver of written consent.   
11.6.2 For Eligibility Screening 
An online consent process for the eligibility screening is proposed. The introduction to the 
screening interview includes all the required elements for consent (45 CFR 46.116). No 
identifying information on volunteers is recorded during the online screening until a participant is 
determined eligible (i.e., by marking “I do consent to be screened for eligibility.”. Therefore, there 
will be no identifying link of who agreed to be screened or not screened for the study. In 
addition, the screening presents minimal risk to participants and involves no procedures that 
would require written consent outside of a research context. Under these conditions the IRB is 
authorized to modify the requirements to obtain a signed consent form for some or all subjects 
(45 CFR 46.117 [c]). 
11.7 Prisoner Participation 
NICHD has concluded that this protocol does NOT meet Federal requirements governing 
prisoner participation in human subjects research and should NOT be considered by local IRBs 
for the recruitment of prisoners. Subjects enrolled who subsequently become incarcerated or 
are placed in detention may not continue study participation. Study visits cannot be conducted 
during the period of incarceration or detention.  
11.8 
45 CFR Parts 160 and 164 Standards for Privacy of Individually Identifiable Health 
Information ("Privacy Rule" Pursuant to the Health Insurance Portability and 
Accountability Act - HIPAA) 
Each site is responsible for adherence to their individual institution’s HIPAA policies and 
procedures. 
11.9 
Study Discontinuation 
This study may be discontinued at any time by the UNC IRB, NICHD, or other government 
agencies as part of their duties to ensure that research participants are protected.  
PUBLICATION OF RESEARCH FINDINGS 
Any presentation, abstract, or manuscript will be made available for review by the study 
sponsor(s) prior to submission.   
 
4145

 
4245

REFERENCES 
1. 
Centers for Disease Control and Prevention. HIV Surveillance Report, 2014; vol. 26. 
November 2015; http://www.cdc.gov/hiv/library/reports/surveillance/. . Accessed June 6, 
2016. 
2. 
Centers for Disease Control and Prevention. HIV among youth. 2016; http://
www.cdc.gov/hiv/group/age/youth/index.html Accessed July 28, 2016. 
3. 
Zanoni BC, Mayer KH. The adolescent and young adult HIV cascade of care in the 
United States: exaggerated health disparities. AIDS Patient Care STDS. Mar 
2014;28(3):128-135. 
4. 
Kapogiannis B, Xu J, Mayer K, et al. The HIV continuum of care for adolescents and 
young adults (12-24 years) attending 13 urban US centers of the NICHD-ATN-CDC-
HRSA SMILE collaborative. . 8th International AIDS Society Conference on HIV 
Pathogenesis, Treatment, and Prevention (IAS 2015). Vancouver, CA2015. 
5. 
Frieden TR, Foti KE, Mermin J. Applying Public Health Principles to the HIV Epidemic--
How Are We Doing? The New England journal of medicine. Dec 3 
2015;373(23):2281-2287. 
6. 
The Antiretroviral Therapy Cohort Collaboration. Life expectancy of individuals on 
combination antiretroviral therapy in high-income countries: a collaborative analysis of 
14 cohort studies. The Lancet. 2008;372(9635):293-299. 
7. 
Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 Infection with Early 
Antiretroviral Therapy. New England Journal of Medicine. 2011;0(0). 
8. 
Pellowski JA, Kalichman SC. Recent Advances (2011-2012) in Technology-Delivered 
Interventions for People Living with HIV. Current HIV/AIDS reports. Aug 26 2012. 
9. 
Saberi P, Johnson MO. Technology-Based Self-Care Methods of Improving Antiretroviral 
Adherence: A Systematic Review. PLoS ONE. 2011;6(11):e27533. 
10. 
Amico KR. Evidence for Technology Interventions to Promote ART Adherence in Adult 
Populations: a Review of the Literature 2012–2015. Current HIV/AIDS reports. 
2015/09/28 2015:1-10. 
11. 
Pew Internet and American Life Project. Internet User Demographics. 2014; http://
www.pewinternet.org/data-trend/internet-use/latest-stats/. Accessed September 14, 
2015. 
12. 
Page TF, Horvath KJ, Danilenko GP, Williams M. A Cost Analysis of an Internet-Based 
Medication Adherence Intervention for People Living With HIV. JAIDS Journal of 
Acquired Immune Deficiency Syndromes. 2012;60(1):1-4 10.1097/
QAI.1090b1013e318250f318011. 
13. 
Simoni JM, Kutner BA, Horvath KJ. Opportunities and Challenges of Digital Technology 
for HIV Treatment and Prevention. Current HIV/AIDS reports. 2015/09/28 2015:1-4. 
14. 
Pew Research Center Internet Project. Teen Internet Access Demographics. 2012; http://
www.pewinternet.org/data-trend/teens/internet-user-demographics/. Accessed 
November 11, 2015. 
15. 
Pew Research Center Internet Project. Device Ownership by Teens Over Time. 2015; 
http://www.pewinternet.org/data-trend/teens/devices/. Accessed November 11, 2015. 
16. 
Pew Internet and American Life Project. Technology Device Ownership: 2015. 2015; 
http://www.pewinternet.org/2015/10/29/technology-device-ownership-2015/. Accessed 
December 28, 2015. 
17. 
Duggan M, Smith A. Social Media Update 2013. 2014; Available at: http://
pewinternet.org/Reports/2013/Social-Media-Update.aspx. Accessed August 20, 2014. 
18. 
Thompson MA, Mugavero MJ, Amico KR, et al. Guidelines for Improving Entry Into and 
Retention in Care and Antiretroviral Adherence for Persons With HIV: Evidence-Based 
Recommendations From an International Association of Physicians in AIDS Care Panel. 
Annals of Internal Medicine. 2012;156(11):817-833. 
 
4345

19. 
Horvath K, Danilenko G, Williams M, et al. Technology Use and Reasons to Participate 
in Social Networking Health Websites among People Living with HIV in the US. AIDS 
and Behavior. 2012/02/01 2012;16(4):900-910. 
20. 
Simoni JM, Huh D, Frick PA, et al. Peer support and pager messaging to promote 
antiretroviral modifying therapy in Seattle: a randomized controlled trial. J Acquir Immune 
Defic Syndr. Dec 1 2009;52(4):465-473. 
21. 
Horvath KJ, Michael Oakes J, Simon Rosser BR, et al. Feasibility, Acceptability and 
Preliminary Efficacy of an Online Peer-to-Peer Social Support ART Adherence 
Intervention. AIDS Behav. Jul 2013;17(6):2031-2044. 
22. 
Feldman BJ, Fredericksen RJ, Crane PK, et al. Evaluation of the single-item self-rating 
adherence scale for use in routine clinical care of people living with HIV. AIDS Behav. 
Jan 2013;17(1):307-318. 
23. 
Bush K, Kivlahan DR, McDonell MB, Fihn SD, Bradley KA. The AUDIT alcohol 
consumption questions (AUDIT-C): an effective brief screening test for problem drinking. 
Ambulatory Care Quality Improvement Project (ACQUIP). Alcohol Use Disorders 
Identification Test. Archives of internal medicine. Sep 14 1998;158(16):1789-1795. 
24. 
Walsh JC, Mandalia S, Gazzard BG. Responses to a 1 month self-report on adherence 
to antiretroviral therapy are consistent with electronic data and virological treatment 
outcome. AIDS. 2002;16(2):269-277. 
25. 
The LifeWindows Project Team. The LifeWindows Information Motivation Behavioral 
Skills ART Adherence Questionnaire (LW-IMB-AAQ): Center for Health, Intervention, and 
Prevention. University of Connecticut; 2006. 
26. 
McLellan AT, Kushner H, Metzger D, et al. The Fifth Edition of the Addiction Severity 
Index. J Subst Abuse Treat. 1992;9(3):199-213. 
27. 
Saunders JB, Aasland OG, Babor TF, de la Fuente JR, Grant M. Development of the 
Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early 
Detection of Persons with Harmful Alcohol Consumption--II. Addiction. Jun 
1993;88(6):791-804. 
28. 
Radloff LS. The CES-D scale: A self-report depression scale for research in the general 
population. Applied Psycholgical Measurement. 1992;1:385-401. 
29. 
Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. Journal of 
Health and Social Behavior. 1983;24:385-396. 
30. 
Wong MD, Sarkisian CA, Davis C, Kinsler J, Cunningham WE. The association between 
life chaos, health care use, and health status among HIV-infected persons. Journal of 
General Internal Medicine. 2007;22(9):1525-1497. 
31. 
Berger BE, Ferrans CE, Lashley FR. Measuring stigma in people with HIV: psychometric 
assessment of the HIV stigma scale. Res Nurs Health. Dec 2001;24(6):518-529. 
32. 
Mosack KE. Development and validation of the R-PLA: A resiliency measure for people 
living with HIV/AIDS (immune deficiency). US, ProQuest Information & Learning; 2002. 
33. 
Stephenson MT, Hoyle RH, Palmgreen P, Slater MD. Brief measures of sensation 
seeking for screening and large-scale surveys. Drug and Alcohol Dependence. 
2003;72(3):279-286. 
34. 
Potosky D. The Internet knowledge (iKnow) measure. Computers in Human Beahvior. 
2007;23(6):2760-2777. 
35. 
Sarason IG, Sarason BR, Shearin EN, Pierce GR. A Brief Measure of Social Support: 
Practical and Theoretical Implications. Journal of Social and Personal Relationships. 
November 1, 1987 1987;4(4):497-510. 
36. 
Sherbourne CD, Stewart AL. The MOS social support survey. Social science & medicine 
(1982). 1991;32(6):705-714. 
37. 
Brooke J. SUS: A quick and dirty usability scale. In: Jordan PW, Thomas B, 
Weerdmeester BA, McClellend I, eds. Usability Evaluation in Industry London: Taylor 
and Francis 1996. 
 
4445

 
4545