Adaptive Antiretroviral Therapy Adherence Interventions for Youth Living With HIV Through Text Messaging and Cell Phone Support Embedded Within the Sequential Multiple Assignment Randomized Trial (SMART) Design
Phase: NA
Conditions: HIV Infections
Sponsor: Florida State University

ADOLESCENT MEDICINE TRIALS NETWORK FOR HIV/AIDS INTERVENTIONS 
PROTOCOL 
Adaptive Antiretroviral Therapy (ART) Adherence Interventions for Youth Living with 
Human Immunodeficiency Virus (HIV) through Text Messaging (SMS) and Cell Phone 
Support (CPS) Embedded within the Sequential Multiple Assignment Randomized Trial 
(SMART) Design 
NCT03535337 
Sponsor: 
NaƟonal InsƟtute of Child Health and Human Development 
(NICHD) 
NaƟonal InsƟtute on Drug Abuse (NIDA) 
U19HD089875 
Study Chair/Lead: 
Marvin E. Belzer, M.D. 
Children’s Hospital Los Angeles 
Los Angeles, CA, USA 
Study Co-Chair/Co-Lead: 
Karen MacDonell, Ph.D. 
Wayne State University 
Detroit, MI, USA 
Recruitment & Enrollment Center: 
Hunter College PRIDE Health Research 
ConsorƟum 
AnalyƟc Core Analyst: 
Samiran Ghosh, Ph.D. 
Wayne State University 
Study Procedure Guide Version Date: 
June 17, 2021 

PROTOCOL TITLE: ATN 144 SMART
Page 1 of 48
Submitted: June 17, 2021
PROTOCOL TITLE:
Adaptive Antiretroviral Therapy Adherence Interventions for Youth Living 
with HIV through Text Messaging and Cell Phone Support Embedded 
within the Sequential Multiple Assignment Randomized Trial (SMART) 
Design
PRINCIPAL INVESTIGATOR:
Name Naar, Sylvie
Department COLLEGE OF MEDICINE
Telephone Number (248) 207-2903
Email Address sylvie.naar@med.fsu.edu
Co-Investigators/Research Staff
Name Belzer, Marvin E.; Protocol Lead
Department NON-FSU DEPARTMENT
Telephone Number (323) 361-2112
Email Address mbelzer@chla.usc.edu 
Name MacDonell, Karen Kolmodin; Protocol Co-Lead
Department NON-FSU Department
Telephone Number (313) 577-6996
Email address karen.macdonell@wayne.edu
VERSION NUMBER/DATE:
REVISION HISTORY
Revision 
#
Version Date
Summary of Changes
Consent 
Change?
0
10.09.2019
Resubmission into new RAMP template
No
1
10.09.2019
Change of Study Specific Screener welcome 
script; updated Consent/Assent Form with 
audio recordings deletion timeline; updated 
Study Personnel with 5 new Research 
Assistants; added CITI refresher for Dilones; 
removed confirmation page from the Locator 
Form; updated call guides, email templates, 
and SMS templates with minor wording 
changes; and added OneFlorida approval letter 
Yes

PROTOCOL TITLE: ATN 144 SMART
Page 2 of 48
Submitted: June 17, 2021
and estimate for utilizing OneFlorida research 
infrastructure for SMART recruitment.
2
11.06.2019
Addition of data collection sheet (i.e. a list of 
variables with a brief description) to be used 
for the OneFlorida database. Updating 
procedures for using OneFlorida database for 
recruitment. See section 6.0 Procedures 
Involved on page 9 and section 13.0 
Recruitment Methods on page 17-18.
No
3
01.03.2020
Reduced the N=90; increased the subject 
compensation; changed the compensation 
structure; added bonus incentives; addition of 
OneFlorida participant email script and 
provider letter; drafted email notification for 
currently enrolled participants RE revised 
compensation
Yes
4
01.30.2020
Revised the scripts drafted for OneFlorida 
providers and participants 
Addition of ATN 144b Project DABS sub-
study
Addition 
of 2nd 
consent 
for new 
study
5
02.24.2020
Project DABS: addition of 4 new items 
(invitation call script; kit registration form; test 
kit ID card; and sharing VL result script) and 
minor edits on consent/assent (added end of 
consent script); locator form (added 1 question 
and end of contact script, reformatted some 
items); and measures (added 2 discrimination 
scales)
No
6
04.03.2020
Provided COVID updates and plans; added 
COVID update email script for SMART 
participants; revised SMART email templates 
to include language for splitting VL+ART 
submission forms; revised SMART email 
templates to temporarily remove clinic visits 
and Quest options; revised DABS invitation 
email script to provide temporary contact 
information due to office closure from COVID 
outbreak; revised DABS kit registration form; 
addition of DABS QR code; and revised CASI 
measures to change terminology and addition 
of “Everyday Discrimination” scales for sexual 
orientation and race
No
7
04.23.2020
SMART: added email notification about NO 
clinical visits during COVID; revised email 
templates to include language for full 
No

PROTOCOL TITLE: ATN 144 SMART
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Submitted: June 17, 2021
compensation despite of missing VL due to 
COVID
DABS: Added 4 new items – CASI completion 
reminder email with office phone number; 
CASI completion reminder email with 
temporary phone number due to COVID; Exit 
interview with office phone number; Exit 
interview with temporary phone number due to 
COVID
8
05.22.2020
SMART: Added COVID-related measures to 
CASI; expanded 12-month window due to 
COVID-19 (see page 16 track changes)
No
9
07.02.2020
SMART: Resume recruitment and enrollment 
in July; increase sample size from 90 to 120; 
Added pandemic stress index to screening 
measure; revised CASI measures with 
formatting language
No
10
07.23.2020
DABS: Added 2 new items – a study screener 
and short version of the locator form.
No
11
10.28.2020
SMART: Piloting new social media platform, 
Reddit as a recruitment strategy, a final push to 
enrollment of youth with HIV (see page 25). 
We will be using the currently existing 
recruitment materials. 
No
12
11.25.2020
SMART and DABS: Addressed modifications 
requested on parental consent of minors (see 
page 42-49). Modified study-specific screener, 
assent, and locator forms.
Yes
13
12.08.2020
SMART: Added updated assent and consent 
for those who will be enrolled in Jan-Feb 2021 
as they will be able to participate in the study 
only up to 9-months. However, we will 
continue to use the existing assent/consent for 
those enrolled in the study by December 2020. 
Yes
14
06.17.2021
SMART: Added 1 new item: Email template 
for unpausing Quest appointment. 
DABS: Replaced the Clinical Microbiology 
Lab at the SUNY Downstate Medical Center 
with the Caliendo Molecular Lab at the Miriam 
Hospital (see page 18).  
No
Table of Contents
1.0
Study Summary ........................................................................................................3
2.0
Objectives* ...............................................................................................................4
3.0
Background*.............................................................................................................5
4.0
Study Endpoints*......................................................................................................6
5.0
Study Intervention ....................................................................................................6

PROTOCOL TITLE: ATN 144 SMART
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6.0
Procedures Involved* ...............................................................................................8
7.0
Data and Specimen Banking*.................................................................................11
8.0
Sharing of Results with Subjects* ..........................................................................11
9.0
Study Timelines*....................................................................................................11
10.0
Subject Population*................................................................................................12
11.0
Vulnerable Populations*.........................................................................................12
12.0
Local Number of Subjects ......................................................................................13
13.0
Recruitment Methods..............................................................................................13
14.0
Withdrawal of Subjects*.........................................................................................14
15.0
Risks to Subjects*...................................................................................................16
16.0
Potential Benefits to Subjects* ...............................................................................16
17.0
Data Management* and Confidentiality.................................................................16
18.0
Provisions to Monitor the Data to Ensure the Safety of Subjects*.........................18
19.0
Compensation for Research-Related Injury............................................................19
20.0
Economic Burden to Subjects.................................................................................20
21.0
Consent Process......................................................................................................20
22.0
Process to Document Consent in Writing...............................................................21
23.0
Setting.....................................................................................................................22
24.0
Resources Available ...............................................................................................22
25.0
Multi-Site Research* ..............................................................................................22
Study Summary
Study Title
Adaptive Antiretroviral Therapy Adherence Interventions for 
Youth Living with HIV through Text Messaging and Cell 
Phone Support Embedded within the Sequential Multiple 
Assignment Randomized Trial (SMART) Design
Study Design
This study will use a Type 1 effectiveness-implementation 
hybrid design to adapt adherence interventions to improve 
self-management and maintain VL suppression, and enhance 
the potential for scale up. A Sequential Multiple Assignment 
Randomized Trial (SMART) will be utilized to maximize 
real-world implementation and identify effective sequences 
of treatments and their cost-benefit ratio.
For the sub-study, to collect pilot data on the development 
and implementation of DBS procedures, this study seeks to 
conduct a mixed-method analysis to examine suitability, 
feasibility and acceptability of utilizing DBS to obtain viral 
load (VL) data.
Primary Objective(s)
Compare Cell Phone Support (CPS) versus Text Messaging 
(SMS) for youth living with HIV (YLH) who are not virally 
suppressed.
Understand the benefit of incentives for non-responders, 
identify how to taper interventions for responders, and 
describe potential moderators of treatment effect.

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Study the barriers and facilitators to wide-spread 
implementation as well as cost-effectiveness of treatment 
sequences.
Sub-study:
Assess the suitability, feasibility and acceptability of using 
dried blood spot (DBS) collection to obtain timely data on 
VL monitoring for human immunodeficiency virus (HIV)-
positive youth between 15-24 years old.
Secondary 
Objective(s)
Conduct an exploratory evaluation of tapering the intensity 
of CPS and SMS (among responders) vs. termination after 
completion of the 3-6 month intervention to determine if 
this improves the durability of intervention effects.
Explore the relative effectiveness and cost-effectiveness of 
the individual intervention sequences embedded within the 
SMART design for responders and non-responders.
Assess the five components of the Self-Management Model 
and how these components vary over time, are directly 
improved by the intervention, and mediate intervention 
effects.
 Assess barriers and facilitators to the implementation and 
sustainment of intervention sequences in adolescent HIV 
care 
settings 
using 
mixed 
methods 
(Exploration, 
Preparation, Implementation, and Sustainment [EPIS] 
surveys, qualitative interviews, fidelity measurements and 
sequential analysis).
Sub-study:
1. Examine barriers and facilitators of using DBS collection 
for VL monitoring and expand access to VL monitoring 
for HIV-positive youth between 15-24 years old. 
2. Adapt VL collection methods (i.e., construction and 
distribution of at-home testing kits and surveys, tracking 
and monitoring testing kit completion, tracking and 
monitoring at-home survey completion) for DBS in this 
population. 
3. Use a central laboratory to measure VL and evaluate the 
accuracy and lower limit of detection of a DBS. 
Currently, the lower limit is estimated at 500 to 800 
copies/mL. This is not consistent with the latest 
definition of VL below detection (e.g., 200 copies/mL). 
Explore utilizing DBS collection to screen and monitor VL 
for ATN 144 SMART and future protocols.
Research 
Intervention(s) 
The intervention will consist of CPS or SMS. CPS will be 
provided by an adherence facilitator (AF) who will assess if 
participants have taken their antiretroviral therapy (ART) 
medication(s) and provide brief problem solving support. 
SMS will act as a reminder to participants to take their 

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medication and participants will text back a confirmatory 
response. The CPS intervention will occur on weekdays, 
excluding holidays. The SMS intervention will occur every 
day. The tapered intervention will occur on two weekdays per 
week, excluding holidays. Incentives will be added to the 
intervention for those participants who do not meet viral 
suppression requirements at 3 months.
Sub-study: Project DABS does not implement any 
interventions.
Study Population
The study population will consist of HIV-positive youth (15-
24 years old, inclusive) who have: a VL ≥200 copies/mL 
within 12 months prior or self-reported adherence (SRA) ≤ 
80% in the past 4 weeks after being on a prescribed ART 
medication regimen for three months prior to eligibility VL; a 
cell phone and service plan; and the ability to understand 
written and spoken English.  
Sub-study:
Youth (15-24 years of age) living with HIV (YLH) who are 
willing to provide DBS specimens for HIV VL measurement 
and have the ability to understand written and spoken 
English.
Sample Size
We will enroll 120 HIV-positive youth living with HIV aged 
15-24. 
Sub-study: 50
Study Duration for 
individual 
participants
The total duration of the study for participants is 
approximately 12 months for both groups. 

Baseline Assessment

Follow Up Assessment (post baseline)
o
3-Month Follow Up
o
6-Month Follow Up
o
9-Month Follow Up
o
12-Month Follow Up
Sub-study: approximately 1 month
Study Specific 
Abbreviations/ 
Definitions 
Adherence Facilitator (AF)
Adolescents Medicine Trials Network (ATN)
Cell Phone Support (CPS)
Cell Phone Support + Incentives (CPS-I)
Cell Phone Support Tapered (CPS-T)
Sequential Multiple Assignment Randomized Trial 
(SMART)
Text Messaging (SMS)
Text Messaging + Incentives (SMS-I)
Text Messaging Tapered (SMS-T)
Youth living with HIV (YLH)
ART – antiretroviral therapy
CASI – computer assisted self-interviewing

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DBS – dried blood spot
HIV – human immunodeficiency virus
PI – principal investigator
VL – viral load

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1.0
Objectives*
Specific Aims:
1. To compare CPS versus SMS for youth living with HIV who are not virally 
suppressed.
2. To understand the benefit of incentives for non-responders, identify how to taper 
interventions for responders, and describe potential moderators of treatment 
effect.
3. To study the barriers and facilitators to wide-spread implementation as well as 
cost-effectiveness of treatment sequences.
Secondary Aims:
1. Conduct an exploratory evaluation of tapering the intensity of CPS and SMS 
(among responders) vs. termination after completion of the 3-6 month 
intervention to determine if this improves the durability of intervention effects.
2. Explore the relative effectiveness and cost-effectiveness of the individual 
intervention sequences embedded within the SMART design for responders and 
non-responders.
3. Assess the Five Components of the Self-management Model and how these 
components vary over time, are directly improved by the interventions, and 
mediate intervention effects.
4. Assess barriers and facilitators to the implementation and sustainment of 
centralized national recruitment, enrollment, intervention delivery, and retention 
using mixed methods (EPIS surveys, qualitative interviews, fidelity measurements 
and sequential analysis).
The proposed project is highly innovative because it focuses on a critical area for 
intervention, adherence to ART in YLH, and goes beyond what has been done previously 
in several key ways:
1. It directly compares two successful, potentially sustainable, and youth-friendly modes 
of mobile health (mHealth) youth adherence intervention delivery.
2. The project uses a SMART design to explore a number of key issues surrounding 
sequencing mHealth interventions in a cost effective manner that would be practical in 
clinical settings.
3. The CPS intervention uniquely addresses multiple barriers to antiretroviral therapy 
(ART) adherence in real-time using a social support framework.
4. The study will explore the clinical and public health costs of sequencing of 
interventions based on viral suppression and sexual transmission risk.
Sub-Study:
The primary aim of this sub-study “ATN 144b Dried At-Home Blood Science” (Project 
DABS) is to leverage our current ATN 144 SMART recruitment and screening methods 
and patient population to develop and test DBS implementation procedure to promote 
home-based DBS collection and change the landscape of adherence research in youth 
living with HIV. Additionally, if feasible, DBS collection implementation may enhance 
ATN 144 SMART protocols for obtaining VL, both at enrollment and follow-ups. DBS 

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collection has the potential to help identify additional youth who are eligible for ATN 
144 SMART, thereby increasing enrollment in this difficult patient population, and aid in 
improving retention for those who do not provide VL via a clinic or testing facility. 
Specific Aims:
1. Assess the suitability, feasibility and acceptability of using DBS collection to 
obtain timely data on VL monitoring for HIV-positive youth between 15-24 years 
old. 
2. Examine barriers and facilitators of using DBS collection for VL monitoring and 
expand access to VL monitoring for HIV-positive youth between 15-24 years old. 
3. Adapt VL collection methods (i.e., construction and distribution of at-home 
testing kits and surveys, tracking and monitoring testing kit completion, tracking 
and monitoring at-home survey completion) for DBS in this population. 
4. Use a central laboratory to measure VL and evaluate the accuracy and lower limit 
of detection of a DBS. Currently, the lower limit is estimated at 500 to 800 
copies/mL. This is not consistent with the latest definition of VL below detection 
(e.g., 200 copies/mL). 
5. Explore utilizing DBS collection to screen and monitor VL for ATN 144 SMART 
and future protocols.
2.0
Background*
Adherence to ART is a critical factor contributing to low rates of viral suppression among 
YLH. At the end of 2015, there were approximately 60,300 YLH ages 13-24 in the U.S., 
and this number continues to increase. In 2016, YLH made up 21% of new HIV 
diagnoses—the equivalent of 8,451 new cases in that year alone. National treatment 
guidelines recommend initiating treatment with ART as soon as an individual is ready. 
Even with simpler, more potent, and better tolerated medications, viral suppression is 
difficult to achieve in youth. Only 41% of YLH in 2014 received HIV-related care, 31% 
were retained in care, and 27% were virally suppressed, the lowest percentage of any age 
group. 
Adherence to ART is critical to sustain health, reduce transmission, and minimize the 
development of ART resistance. Non-adherence has both public health implications and 
personal health risks. High viral load (VL) increases the likelihood of viral transmission, 
and non-adherent individuals may be more likely to transmit drug-resistant strains of the 
virus. Conversely, treatment adherence decreases the pool of infectious individuals when 
condom use is poor, even among youth aware of their HIV status. 
The Centers for Disease Control and Prevention (CDC) released a statement in 2017 that 
further underscored the importance of ART adherence and VL suppression. The CDC’s 
statement acknowledged that individuals living with HIV who have an undetectable viral 
load are not able to transmit HIV. This is commonly known by the slogan launched by 
the Prevention Access Campaign: Undetectable=Untransmittable, or U=U, and has 

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ushered in a new era of treatment as prevention for HIV, as well as contributed to 
reduced stigma for those living with HIV. 
While it has been abundantly clear for over two decades that adherence to ART is a 
critical problem, the field has identified only a limited number of modestly successful 
interventions available for YLH, including motivational interviewing, directly observed 
therapy, multisystemic therapy, and cell phone reminder calls. These failed to 
demonstrate lasting impact on VL beyond the intervention. All of the interventions, 
except the cell phone reminder pilot studies, require in-person sessions, which may be 
difficult for non-adherent youth to complete. Interventions that reach youth more 
frequently, using modern and youth-friendly means of intervention delivery, such as cell 
phones, may hold promise for improving both short and long-term adherence. 
Cell phones may be a powerful tool for HIV prevention and treatment intervention. 
Interventions delivered via cell phone may offer an advantage over traditional, in-person 
interventions in cost, flexibility, and ease of adapting the intervention to the participant. 
Our pilot study found that daily phone call reminders were both acceptable and feasible 
for non-adherent youth. Cell phone intervention delivery allows for tapering of the 
frequency of calls or texts in response to the needs of each participant, which could help 
sustain the impact of the intervention over a longer period of time for a lower cost. 
However, few interventions utilizing cell phones as a stand-alone mode of intervention 
(vs. as part of a larger intervention) have been tested, and even fewer have targeted YLH. 
Supportive Accountability: A theoretical rationale for CPS to improve medication 
adherence. The intervention is guided by the conceptual model of supportive 
accountability. This model was developed to guide research into human support 
components of mHealth interventions. The model is based on the premise that human 
support increases adherence through accountability to a coach (in the intervention, an 
Adherence Facilitator or AF) who is perceived as trustworthy, knowledgeable, and 
benevolent. Accountability should involve clear, process oriented expectations that the 
patient is involved in determining (e.g., reporting adherence, problem-solving). The 
effect of accountability may be moderated by patient motivation so that patients with 
higher intrinsic motivation may actually require less support. 
The process of support is also mediated by the mode of communication (e.g, phone, text 
messages, computer), with different advantages and disadvantages for each mode. There 
is evidence that “lean media,” or those modes of communication with less face-to-face 
contact and fewer visual social cues, may be associated with more positive, even 
idealized, attributions of communication partners. This is because people tend to form 
stronger impressions based on more limited social and interpersonal cues. Interactions via 
lean media, including CPS and text messages, have the potential to foster social 
accountability towards improved adherence.
Multiple studies have demonstrated that social support is a strong predictor of good 
adherence to ART, and retention to HIV care is predicted by clients' perceptions of 

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providers as engaging and validating. While overall social support was predictive in these 
studies, specific aspects such as instrumental support (i.e., practical assistance) and 
informational support (advice or problem-solving) were found to be predictive of 
adherence in adults with HIV. The content of conversations in the CPS study were 
designed to validate the importance of adherence, prompt problem solving (through 
informational support), and provide instrumental assistance (through referrals) to address 
barriers as they emerge. This intervention utilizes social support constructs to provide 
tailored conversations to improve both short- and long-term adherence. 
Sub-Study:
Use of DBS technology, a method introduced by the World Health organization (WHO) 
guidelines in 2015 for routine VL monitoring of HIV-positive individuals on ART1,2 is 
currently underutilized in the United States. HIV biomarker, VL testing, has been 
increasingly recognized as the gold standard for monitoring treatment efficacy and 
detecting treatment failure.3 According to a systematic review of 13 articles evaluating 
the performance of DBS samples, DBS is still an emerging method for monitoring VL 
and has been mostly used for detecting HIV.3 Only two studies have found the lower 
detection limit to be 550 and 800 copies/mL.3 More recently, a study of 205 young adults 
with HIV living in the Chicago metropolitan area reported a significant percent (34%) of 
subjects with a detectable VL at the time of study visit self-reported an undetectable VL 
at their last medical visit.4 However, performing traditional serological testing requires 
youth to schedule an appointment either with their primary care provider or a laboratory 
such as Quest Diagnostics to extract the serum from blood specimens. In the context of a 
research study such as ATN 144 SMART, this requires a release of information. In 
addition, youth often fail to make or keep these appointments. ATN 144 SMART has 
faced multiple challenges to enrollment, primarily difficulty obtaining VL and/or youth 
who are ineligible due to self-reported VL level. 
3.0
Study Endpoints*
The ultimate goal of this study is an adaptive adherence intervention designed to improve 
self-management and achieve and maintain VL suppression while understanding the 
context for wide-scale implementation in an effectiveness-implementation Type 1 Hybrid 
trial.
Sub-study:
The use of traditional treatment methods for engagement and retention to care may not be 
well-suited for YLH. The ultimate goal of this pilot study is to develop and test DBS 
implementation procedure for obtaining VL and promote self-management. 
4.0
Study Intervention
Cell Phone Support. Each participant randomized to CPS will be assigned a lead and 
back up Adherence Facilitator (AF). At the time of study entry, the AF and the 

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participant will choose a start date and arrange a call time that is after their daily ART 
dosage time and within office hours. For those participants taking their medication after 
dinner/before bed, the AF will call in the morning to confirm they took their ART the 
night before. While the study allows flexibility in planning for the timing of taking the 
medication and the phone call that follows it based on the participant’s schedule, the call 
time should be mutually agreeable to the AF and the participant. All calls must take place 
during the agreed upon time range. 
Preferably, calls should begin the next Monday following the baseline visit and/or within 
two weeks of study entry. Calls from the AF will occur Monday through Friday, once a 
day, and continue for three months, except for major holidays. While the initial call will 
last 10-15 minutes, it is expected that most calls will last less than five minutes. AFs will 
take an additional five minutes to document the content of the call. To protect the 
confidentiality of the participant, the AF will confirm that the person who answered the 
cell phone is the participant enrolled into the study. Voice recognition can be used as the 
primary confirmation; however, participants will also be offered the use of a code word 
for identification purposes to further protect their privacy. AFs will use cell phones to 
conduct the daily calls, send/receive texts, and have voice messages 
On each call, AFs will assess if the participant has taken their medication for that day and 
if medication was taken during days when calls to participants are not completed (i.e., 
weekends and holidays). If the participant has not yet taken their ART medication(s), the 
AFs will wait for the participant to retrieve and take their medication, if available. If the 
participant usually takes their ART the night before, then the AF will not request that the 
participant take their medication during the call. If the participant is non-adherent, the 
AFs will assess reasons for non-adherence and will engage the participant in brief 
problem solving around these identified barriers. The AFs will also discuss any new or 
ongoing problems in the participant’s life (e.g., related to housing, transportation, or 
food), and provide support around problem-solving to address these issues. In addition, 
they will reinforce prioritizing medications, remind participants about scheduled 
appointments, and suggest scheduling any relevant referrals (e.g., case management, 
mental health services, substance use counseling) through their healthcare providers. 
Youth needing more intensive assistance will be referred to their care team using the 
information provided on the participant’s locator form, and with the youth’s permission, 
the AF will contact the care team to share the concerns.
Text Message Support. Participants enrolled in the SMS intervention will receive daily 
personalized SMS adherence reminders for three months. Participants will be able to 
choose the timing and the wording of the text message. Participants will be asked to text 
back if they did or did not take their ART medications. The texts will be sent through 
Trumpia, a robust, customizable technology to deliver text messages to participants and 
track their responses. Trumpia is compliant with HIPAA laws as all personal identifiable 
data are encrypted. 
Incentives and Tapering. After three months of either the CPS or SMS intervention, 
participants will be sorted into new intervention arms depending on their VL. Participants 

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will submit proof of VL and complete a computerized survey. Participants whose VL is 
<200 copies/mL are categorized as “responders,” because they were able to successfully 
reduce their VL by adhering to their ART medication during the past three months. 
Participants whose VL is ≥200 copies/mL are categorized as “non-responders.”
All responders will be randomized into the tapered intervention arm or into standard care, 
where no interventions (calls or texts) will be made. Those originally in the CPS group 
will receive the CPS tapered (CPS-T) intervention; likewise, those in the SMS group will 
receive the SMS tapered (SMS-T) intervention. In the tapered interventions, calls and 
texts will be reduced to two days a week. CPS-T and SMS-T will last for three months 
until the six month follow-up, after which participants will go into standard care. At this 
point, all responders will be in standard care, and will continue throughout the nine- and 
twelve-month follow-ups.
Participants who were non-responders after the first three months will be re-randomized 
to CPS or SMS, but with the addition of an incentive. They will receive incentives for 
text messaging or cell phone support participation. Those participants who answer the 
cell phone support call or respond to the text messages 75% of the time or more each 
month will receive an additional $50 during the incentive phase. This will be 
implemented for three months until the six month follow-up, after which the intervention 
will be tapered to two times per week. Those in CPS-I will enter CPS-T, and those in 
SMS-I will enter SMS-T. After the nine-month follow-up, participants will enter standard 
care until completion of the study at the last twelve-month follow-up.
The three-, six-, nine-, and twelve-month follow-up assessments for all participants 
include a viral load and a computerized survey.
Sub-Study:
Project DABS does not implement any interventions.
5.0
Procedures Involved*
Enrollment Procedures. Enrollment in this study may occur at any time during the 
recruitment period. Potential participants recruited utilizing the OneFlorida Data Trust 
will receive a “text-in” number, in which interested persons will be able to text-in to 
receive instructions for screening and enrollment. Potential participants through the 
OneFlorida Data Trust who do not “opt-out” of being contacted could also be directly 
contacted by the study team to be inform of the study and screening/enrollment options 
for preliminary eligibility.
Screening and enrollment may occur on the same day, as long as the appropriate VL and 
ART regimen data are appropriately obtained. If a participant is determined to be eligible 
for the study, a unique Qualtrics link will be sent to the participant for submitting proof 
of HIV VL ≥200 copies/mL and ART regimen. After final eligibility is determined, study 
staff sends the potential participant the SMART enrollment link, which contains the study 

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consent/assent form, HIPAA Authorization form, and the baseline web-based survey. 
These are programmed in Qualtrics by the REC. The baseline survey can be completed at 
the participant’s convenience (ideally within 14 days before and 28 days after their 
scheduled assessment date). Upon completion of all portions of the enrollment link, 
participants are considered enrolled in SMART. Study staff will then randomize and 
stratify the participants into their respective intervention arms (CPS or SMS) for the first 
period of the study. Stratification is based on method of contraction: Perinatal vs 
Behavioral (and other). 
Participants randomized to the CPS intervention group will speak with the AF to 
determine the start day and call time for intervention phone calls. This phone call should 
be completed within 30 days from entry. Participants randomized to the SMS 
intervention will speak with the Project Coordinator (PC) to identify the start day, timing, 
and content of the text messages they will begin receiving daily.  
At each follow-up, participants will complete  web-based surveys programmed in 
Qualtrics by the REC. A link to these computerized surveys will be sent to each 
participant by the REC and can be completed at the participant’s convenience (ideally 
within 14 days before and 28 days after their scheduled assessment date). Participant VL 
data will need to be obtained before the study procedures for the respective assessment 
period is considered complete and the participant is compensated. Data files will be 
downloaded via Qualtrics by the Data Management Team of the REC. The REC will 
maintain a linkage of PID and subject name, and these will be stored in password 
protected files. These web-based surveys will take approximately 60-90 minutes to 
complete.
Randomization Process/Systems. Participants will be randomized at the end of their 
baseline assessment into one of two intervention conditions: (1) CPS or (2) SMS. Both 
intervention conditions will receive 3 months of intervention (i.e., 3 months of CPS or 
SMS). Each participant’s condition will be tracked in REDCap. At the 3-month follow-
up, a second stratified randomization will occur in blocks with 8 possible intervention 
trajectories as follows:

CPS responders (VL <200 copies/mL) will be randomized to either 9 months of 
standard care (SC) or 3 months of CPS-T followed by 6 months of SC;

CPS non-responders (VL ≥200 copies/mL) will be randomized to 3 months of 
CPS-I or SMS-I followed by 3 months of CPS-T or SMS-T, respectively, and 
then 3 months of SC for both groups thereafter;

SMS responders (VL <200 copies/mL)  will be randomized to either 9 months of 
SC or 3 months of SMS-T followed by 6 months of SC; and

SMS non-responders (VL ≥200 copies/mL)  will be randomized to 3 months of 
CPS-I or SMS-I followed by 3 months of CPS-T or SMS-T, respectively, and 
then 3 months of SC for both groups thereafter.
Participants who are unable to provide a valid HIV VL result at the 3-month time point 
have approximately 30 days to obtain a HIV VL performed at Quest Diagnostics or have 
a physician release this information to PRIDE. Participants who are unable to provide this 

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information within the timeframe i.e. 30 days after their 3 month follow-up assessment 
will be treated as non-responders to the intervention and will be re-randomized to an 
incentive arm. The 30 day window follows the same timeframe as the 30 day window for 
calls to begin following baseline.  
Retention and Follow-up. The REC will have automated procedures to communicate 
with participants about remembering to complete their surveys, and also to complete VL 
testing.  Participants will be reminded of upcoming study procedures, including VL blood 
draw logistics. The locator form will be reviewed with the participant during these 
reminder calls, and any changes will be noted. Multiple contact methods will be used for 
difficult to reach youth (e.g., alternate phone numbers, email, text messaging, family 
members, or friends and healthcare providers). We will have a mechanism in place for 
troubleshooting text-message bounce-backs and retaining hard to reach participants. 
All participants are retained in the intervention regardless of their missing the 75% 
monthly requirement or missing several consecutive weeks. The incentive is provided 
only for the months that participants reach the 75% target. This is expected to increase 
the overall number of calls and SMS completed over the 3-month CPS-I and SMS-I 
interventions.
Study staff will use Trumpia to text participants during the duration of their participation 
in the study to remind them of upcoming follow-up visits. Participants will receive both 
an email and a text message reminder simultaneously. The text message will inform a 
participant that an email reminder was sent and will ask the participant to respond 
accordingly with a number notifying staff that they received the email, or if there are any 
problems. (e.g., “text back ‘1’ if you received the email or ‘2’ if you DID NOT receive 
the email.”). Study staff will utilize an Access database using an Application Program 
Interface connected to Trumpia’s secure server to track responses and respond to 
participants accordingly. 
Specimen Collection. VL will be collected for baseline and follow-up assessments (i.e., 
months 3, 6, 9 and 12) for all participants. This is the only study component that cannot 
be completed by the participant online or by phone. Participants have several options for 
how they would like this data submitted to the REC.
VL measurements collected during screening or after will be used for the baseline 
assessment, as long as the remaining components of the baseline assessment are 
completed no later than 1 month from the VL collection date (exceptions to this must be 
approved by the REC).
Participants may submit VL test results from their standard care providers (at both SRV 
and non-SRV clinics) as long as they were measured using a level of detection of <200  
copies/mL or below and the VL collection dates are within 6 months prior to screening or 
the baseline assessment, and within 2 weeks prior to or 4 weeks after all other study 
follow-up assessments. VL measurements using a level of detection ≥200 copies/mL will 
not be accepted. If participants have a standard care provider, but no VL test results 

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within the required window period, they may request a new VL test from their usual 
provider and invoice the REC. 
If participants decide to obtain a copy of their standard care VL test results, they will be 
given two choices on how to submit their VL test results. The REC will inform the 
participant that they may take a picture of their newly obtained standard care VL test 
result using their personal cell phone and submit the picture through a secure Qualtrics 
online submission form. Participants may also request their providers directly send their 
newly obtained lab results to the REC. This option may require youth to provide a release 
of information (ROI) if one is not already in place. 
If standard of care results are not available, participants who have access to a clinical 
SRV, but have not completed a VL test within the required window period may request a 
new VL test for research purposes. The REC will refer participants to a clinical SRV; 
participants do not need to be an existing patient or establish care at this clinic in order to 
complete this study component. This new test will be invoiced to the REC and not billed 
to the patient’s insurance. Clinical care VL measurements can be used as long as they 
were measured using a level of detection of <200 copies/mL or below. VL measurements 
using a level of detection ≥200mL  will not be accepted. Participants should complete 
this VL test within 1 month of screening before the baseline assessment, and within 2 
weeks of each follow-up assessment. The REC will contact providers to submit VL 
measurements via fax or Qualtrics.
Participants who cannot or do not wish to visit a medical provider may be referred to 
local Quest Diagnostics labs for VL testing. The REC will order and pay for these labs, 
and receive VL data directly via online.
One way the Privacy Rule protects the privacy of protected health information (PHI) is 
by generally giving individuals the opportunity to agree to the uses and disclosures of 
their PHI by signing an authorization form for uses and disclosures not otherwise 
permitted by the Rule. 
The Privacy Rule establishes the right of an individual, such as a research subject, to 
authorize a covered entity to use and disclose their PHI for research purposes. This 
requirement is in addition to the informed consent to participate in research required 
under the Department of Health and Human Services (HHS) Protection of Human 
Subjects Regulations and other applicable Federal and State law. 
Incentives and Compensation. Participants will be compensated up to $500 total for 
completing all study assessments, not including compensation for completing the 
intervention. Participants will be compensated $60 after completing the baseline survey 
and providing the proof of viral load. A $10 increased compensation will be offered over 
time each time participants complete the survey and submit viral load results. We will 
also offer a $10 bonus for participants who complete the survey within one week of the 
date is sent out and a $10 bonus for participants who submit the viral load results within 
two weeks of the date link is sent out. See table below for a summary of the 

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compensation amounts for each study assessment. At the end of each month for 
participants in the CPS-I and SMS-I interventions, those participants who reach the 75% 
monthly adherence to calls/text responses will receive $50. Compensation will be 
provided via electronic gift cards (e.g., Amazon, Target, or Walmart).
Baseline Assessment Compensation
 $      80.00 
Submission of the viral load result
 $   30.00 
Completion of the survey
 $   30.00 
Submitting the viral load result within two weeks of the screened eligible date (bonus)
 $   10.00 
Completing the survey within one week of the date is sent out (bonus)
 $   10.00 
3-Month Assessment Compensation
 $      90.00 
Submission of the viral load result
 $   35.00 
Completion of the survey
 $   35.00 
Submitting the viral load result within two weeks of the date link is sent out (bonus)
 $   10.00 
Completing the survey within one week of the date is sent out (bonus)
 $   10.00 
6-Month Assessment Compensation
 $    100.00 
Submission of the viral load result
 $   40.00 
Completion of the survey
 $   40.00 
Submitting the viral load result within two weeks of the date link is sent out (bonus)
 $   10.00 
Completing the survey within one week of the date is sent out (bonus)
 $   10.00 
9-Month Assessment Compensation
 $    110.00 
Submission of the viral load result
 $   45.00 
Completion of the survey
 $   45.00 
Submitting the viral load result within two weeks of the date link is sent out (bonus)
 $   10.00 
Completing the survey within one week of the date is sent out (bonus)
 $   10.00 
12-Month Assessment Compensation
 $    120.00 
Submission of the viral load result
 $   50.00 
Completion of the survey
 $   50.00 
Submitting the viral load result within two weeks of the date link is sent out (bonus)
 $   10.00 
Completing the survey within one week of the date is sent out (bonus)
 $   10.00 
Total Compensation (upon completion of all 5 assessments)
 $    500.00 
Measures. Baseline data collections should be completed all within the same day, and 
ideally no later than 7 days after the beginning of the baseline. Follow-up data collections 
should be collected up to 14 days prior to target date and up to 28 days after the target 
date. Due to COVID-19 pandemic, 12-month assessment window will be extended to 90 
days. Those who are overdue for 12-month assessment will be allowed to complete the 
CASI and submit the VL after their window is closed. These participants will receive 90 
days extension to complete the last component of the study. The REC Data Management 
Team will monitor reports of when participants are due for follow-up assessments. Self-
report measures will be collected via a link to Qualtrics which can be accessed via 
smartphone, laptop, or PC. Site characteristics, including resources and supports available 
for non-adherent youth living with HIV, will be recorded into a Qualtrics survey and 
managed by the REC.

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Web-based CASI Measures
Baselin
e
Follow-
Up
Demographics
Demographics/Socioeconomic Characteristics (ATN)
X
Primary Outcomes
HIV Positive Cascade: Medication Adherence Variables 
X
X
Viral Load 
X
X
Other Self-Reported Measures
HIV Positive Cascade: Other Participant Characteristics
X
X
Self-Efficacy for Medication Adherence 
X
X
Sexual Risk Behavior Questionnaire (harmonized + 
additional questions)
X
X
Additional Self-Management Measures
Substance Use: ASSIST 
X
X
PHQ-8 (Depression)
X
X
GAD7
X
X
PROMIS: Emotional Support, Informational Support, 
Instrumental Support, Companionship, Social Isolation
X
X
BRIEF-A: Plan/Organize and Task Monitor Scales; 
Plan/Organize and Shift Scales; Behavioral Regulation 
Subscales (Inhibit, Self-Monitor)
X
X
PAM (Patient Activation Measure)
X
X
Modified Healthcare Access Measure 
X
X
HIV Positive Cascade Biomedical Data – Chart Abstraction
HIV Positive Cascade Biomedical Data (harmonized + ART 
Regimen)
X
X
Supplement Measures
HIV Stigma Scale
X
X
Knowledge of HIV Treatment Scale
X
X
Internalized Homophobia Scale
X
X
Sub-Study:

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Study Design. To collect pilot data on the development and implementation of DBS 
procedure, this study seeks to conduct a mixed-method analysis to examine suitability, 
feasibility and acceptability of utilizing DBS for obtaining VL data. We will conduct 
recruitment for this study by reaching out to contacts who have been previously screened 
and not currently enrolled in SMART due to enrollment criteria or those who were unable 
to complete the components of the enrollment phase. We will develop survey measures 
and structured interview guide to collect both quantitative and qualitative data. 
Figure 1. Project DABS’ three study components.
HemaSpot™-HF Blood 
Sampling Kit 
• Approximately 5 
minutes to complete.
Online Computer 
Assissted Self Interview 
(CASI)
• Approximately 30 to 
45 minutes to 
complete.
Qualitative Interview
• Apprimately 30 to 45 
minutes to complete.
Study Assessments
Hemaspot™-HF Blood Sampling Kit. Once the protocol team has received the 
subject’s consent/assent to participate, the protocol team will mail the HemaSpot™-HF 
blood sampling kit to the address provided by the participant. The HemaSpot-HF 
collection kit is a cartridge with absorbent paper covered by a surface with a small spot to 
direct blood onto the paper. After drawing 3 drops of blood, the paper is sufficiently 
saturate; a desiccant within the cartridge rapidly dries the blood to preserve it for transit 
to the laboratory, which can occur at ambient temperature. The HemaSpot cartridge will 
be placed within appropriately labeled specimen packaging and returned to the PRIDE 
Health Research Consortium at Hunter College with prepaid mailing labels. After 
receiving kits, study staff will store samples to be sent to the laboratory for testing in 
batches. The kit contains instructions on how to perform the blood collection and 
properly store and handle the kit (see below). Participants will also receive a brief survey 
that contains an instructional video along with the kits received and sent dates to allow 
for more accurate tracking and monitoring of the samples in transit. The Caliendo 
Molecular Laboratory at the Miriam Hospital in Rhode Island will then perform a 
quantitative analysis of VL using the participant’s DBS sample. We will use the 
AmpliPrep/COBAS TaqMan HIV-1 Test, v2.0 assay to analyze samples collected. 

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Figure 2. Spot*On Sciences’ HemaSpot™-HF blood collection sampling kit 
instructions. 
Online Computer Assisted Self-interviewing (CASI). The protocol team will send an 
online CASI questionnaire, supported by the Qualtrics platform, via a hyperlink to the 
email and phone number provided by the subject. The online CASI will ask questions 
pertaining to the following: demographics, modules on suitability, feasibility, and 
acceptability of using DBS, social determinants of health, HIV cascade, and the last 
section focused on feedback for future trials. 
Web-based CASI Measures
Baseline
Section A: Demographics (Aims 1, 2, and 5)
ATN Standard Domain: Demographic Characteristics
X
Section B: Suitability, Feasibility, and Acceptability (Aim 1)
Module 1: Suitability
Intervention Appropriateness Measure (IAM)
X
Module 2: Feasibility
Feasibility of Intervention Measure (FIM)
X

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At-Home Dried Blood Spots Testing Usability Scale
X
Psychometric Analysis of the Perceptions of At-Home DBS 
Testing Questionnaire
X
Module 3: Acceptability
Post-test Questionnaire on Acceptability and Preference of 
HIV Self-testing
X
Acceptability of Intervention Measure (AIM)
X
Section C: Social Determinants of Health (Aim 2)
Module 1: Economic Stability
Module 2: Education
Module 3: Health and Health Care
Health Care Utilization
X
Medical Research Distrust Scale
X
Module 4: Neighborhood and Built Environment
Module 5: Social and Community Context
HIV Stigma Scale
X
Experiences of  Discrimination Scale
X
Section D: HIV Cascade (Aims 2 and 5)
ATN Standard Domain: HIV Positive Cascade Participant 
Characteristics
X
SMART Self-Efficacy for Medication Adherence
X
Section E: Feedback for Future Trials
Qualitative Interview. After the protocol team has received both completed 
HemaSpot™-HF blood collection sampling kit and online CASI from the subject, the 
protocol team will invite the subject via email, phone, or text, to participate in a 
qualitative phone interview aimed to gather the subject’s thoughts on the suitability, 
acceptability and feasibility of the at-home blood sampling kit to determine the kit’s 
utility as a VL monitoring and self-management tool for YLH. Completion of the 
qualitative interview concludes the subject’s participation in this study.
Qualitative Interview Measures. Qualitative interview measures assess the suitability, 
acceptability, and feasibility of the adoption and use of the at-home DBS; anticipated 
barriers and facilitators of receiving at-home DBS collection kits; perspectives on 
implementation and recommendations on the delivery and pickup methods; cost and 
compensation; perspectives on implementation and engagement of participants; and 

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suggestions for future trials (see Appendix for the qualitative interview guide). The 
PRIDE Hunter Team will be responsible for conducting the qualitative interviews, audio 
recordings, and coding the data.
Referral to ATN 144 SMART. Subjects that produce an unsuppressed VL (≥ 200 
copies/mL) could potentially join ATN 144 SMART as a subject. The protocol team will 
notify the subject of their lab result via phone and/or email and offer them the 
opportunity to enroll in ATN 144 SMART, a study aimed to assist YLH adhere to their 
ART so that they may achieve a suppressed VL (< 200 copies/mL). The subject will then 
follow ATN 144 SMART’s study procedures if enrolled, which includes providing VL 
lab results every 3 months. If viable, the HemaSpot™-HF blood sampling kit could 
potentially serve as a mechanism for collecting VL data for these subjects during ATN 
144 SMART’s retention phase. This referral will be offered at the end of their 
participation in this study. A participant cannot be concurrently enrolled in DBS and 
SMART. 
Compensation. Subjects will receive $20.00 compensation for successfully completing 
and mailing the DBS sampling kit and $20.00 compensation for completing the online 
CASI and the qualitative phone interview. Subjects can therefore receive up to $40.00 
total compensation for completing all study assessments. Subjects will receive 
compensation in the form of an electronic gift card sent directly to the email they provide.
6.0
Data and Specimen Banking*
Data for Future Use
Participants consent to these procedures as part of the consent/assent process.
The research team, authorized staff, and government agencies that run this type of 
research may have access to research data and records in order to check on the research. 
Research records given to approved researchers will be de-identified. If a researcher 
requests the data, they will be special permission from the Research Compliance 
Administrator. Data collected during this research study may be used for future research 
purposes. The data stored will be de-identified.
Data that cannot be linked to participants (i.e., de-identified data) will be kept 
indefinitely; this data will be saved for future use and may be shared with other 
researchers. 
Biological samples collected for the purposes of this study will not be used to conduct 
any future research. They will be destroyed after analysis is completed
At the end of the study data collected will be made available, in accordance with the NIH 
Data Sharing Policy (http://grants.nih.gov/grants/policy/data_sharing). These data will be 
saved for future use and may be shared with other researchers. By participating in this 
study, you are agreeing to allow us to save and share your data anonymously.

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Sub-Study: 
Data Banking. Participants consent to these procedures as part of the consent/assent 
process. Data collected during this research study may be used for future research 
purposes. The data stored will be de-identified. Data that cannot be linked to participants 
(i.e., de-identified data) will be kept indefinitely; this data will be saved for future use and 
may be shared with other researchers without additional informed consent. The research 
team, authorized staff, and government agencies that run this type of research may have 
access to research data and records in order to check on the research. Research records 
given to approved researchers will not have identifying data. Publications and/or 
presentations that result from this study will not include the identifying data. 
At the end of the study data collected will be made available, in accordance with the NIH 
Data Sharing Policy (http://grants.nih.gov/grants/policy/data_sharing). These data will be 
saved for future use and may be shared with other researchers. By participating in this 
study, participants are agreeing to allow us to save and share their data anonymously.
Specimen Banking. This study will not bank the DBS specimens for future use. 
Biological samples collected for the purposes of this study will not be used to conduct 
any future research. They will be destroyed after analysis is completed. 
7.0
Sharing of Results with Subjects*
If participants go to Quest Diagnostics for VL testing, the research team will share with 
them the lab results produced by Quest. These results are not shared with any other 
individuals.
 
Sub-Study: The research team will share with subjects their VL lab results produced from 
the HemaSpot™-HF blood collection device. The protocol team will not share these 
results with any other individuals. Participants will receive their VL results by phone and 
may request a written copy be emailed to them. The protocol team will develop 
phone/email templates for sharing both detectable and undetectable results. The templates 
will include a brief introduction of the research staff delivering the results followed by 
either detectable or undetectable VL results and the meaning of those results. For those 
who had undetectable VL, no further step is needed. For those who had detectable VL, 
referral to SMART as well as any necessary referrals will be provided. Participants will 
also be recommended to follow up with health care provider. 
8.0
Study Timelines*
Individual participants are in the study for 12 months (baseline assessment, 3 months of 
the intervention, and follow-up assessments at 3, 6, 9, and 12 months post-baseline).
All study subjects will be enrolled over the course of 15 months. 
Sub-Study:

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Participation Duration. The HemaSpot™-HF blood collection device takes 
approximately 5 minutes to complete. The online CASI takes approximately 1 hour to 
complete. Lastly, the qualitative interview will take approximately 45 minutes to 
complete. The duration of an individual subject’s participation in this study depends on 
multiple factors, such as the delivery time of the DBS collection kit to the subject’s 
desired address and delivery time to the lab.  Assuming a subject manages to complete 
the study’s components in a timely manner their participation should not exceed more 
than a month. 
Study Duration. Project DABS expects to begin enrolling study subjects by January 
2020 and to complete enrollment of all study subjects by November 2020. The protocol 
team aims to enroll 5 subjects per month to achieve the enrollment goal of 50 study 
subjects.
9.0
Subject Population*
Inclusion Criteria. To be considered eligible for enrollment, an individual must meet the 
following criteria:

A youth living with HIV (ages 15 years and zero days through 24 years and 364 
days, inclusive, at the time of signed informed consent or assent) ;

Willing to provide proof of VL ≥200 copies/mL or blood specimens for HIV VL 
measurement within 12 months prior to baseline enrollment or self-reported 
adherence (SRA) ≤80% in the past 4 weeks;

Prescribed an ART medication regimen for a minimum of 3 months prior to 
eligibility VL;

The sole owner of a device capable of sending and receiving calls and text 
messages;

Able to provide consent for research team to communicate with participant’s HIV 
care provider team
Exclusion Criteria. Exclusionary criteria includes:

Participants whose mental, physical or emotional capacity does not permit them to 
complete the protocol as written;

Inability to understand written or spoken English;

Concurrent participant in any behavioral research intervention designed to impact 
medication or care adherence, as indicated in screener.
We will include individuals who are not yet adults: 
Study procedures involve no more than minimal risk. The nature and scope of the 
proposed research study, communication skills training and the CHTC intervention do 
not pose more than "minimal risk" to participants as defined in 45 CFR Part 46.102, "the 
probability and magnitude of harm or discomfort anticipated in the research are not 
greater in and of themselves that those ordinarily encountered in daily life or during the 
performance of routine physical or psychological examinations or tests".

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We will not include individuals who are adults unable to consent, pregnant women, and 
prisoners. 
Sub-Study: 
Inclusion Criteria. This study will include individuals who are not yet adults and 
pregnant women. Subjects must meet the following study criteria:

YLH ages 15-24.

Willing to provide DBS specimens for HIV viral load measurements.

Living in the U.S.
Exclusion Criteria. This study will exclude prisoners and those who are unable to 
consent. This sub-study also excludes subjects that meet the following criteria:

Subjects whose mental, physical or emotional capacity does not permit them to 
complete the protocol as written.

Inability to understand written or spoken English.

Subjects with hemophilia or on anti-coagulation therapy.
10.0
Vulnerable Populations*
We will enroll research participants 15-24 years of age. The nature and scope of the 
proposed research study and SMART intervention do not pose more than “minimal risk” 
to participants, as defined in 45CFR Part 46, 102, “the probability and magnitude of harm 
or discomfort anticipated in the research are not greater in and of themselves than those 
ordinarily encountered in daily life or during the performance of routine physical or 
psychological examinations or tests.” Given that some participants will be under the age 
of 18, adequate provisions will be made for soliciting informed assent.
We will not require parental consent for study enrollment. Parental consent may decrease 
participation rates because some youth will fear that they may be "outed" as a result of 
participation. Disclosure of HIV status may place participating youth at risk for parental 
harassment, abuse or expulsion from the home.
The intervention and measures utilized in this study are standard in this population, as are 
waivers of parental permission for survey and interview studies. Additionally, consistent 
with national policy recommendations from the Society for Adolescent Medicine, 
requiring parental permission for the proposed study would have a number of possible 
negative effects, including: (1) reducing the validity of the findings by effectively 
eliminating potential participants unwilling to share permission forms with their 
parents/guardians; (2) increasing risk to some youth whose parents have a negative 
response to the material in the permission forms that would suggest their child has a 
minority or alternative sexual orientation; and (3) adding little in the way of actual 
subject protection, given the minimal risk of study participation. Our procedures for the 
waiver of parental consent are consistent with the guidelines provided by the Department 
of Health and Human Services: http://www.hhs.gov/ohrp/humansubjects/ 
guidance/45cfr46.html#subpartd.

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We will obtain assent from participants who are under 18 years of age.
This research does not include neonates, prisoners, or cognitively impaired adults. 
(same as sub-study)
11.0
Local Number of Subjects
We will enroll 120 HIV-positive youth living with HIV aged 15-24.
Sub-Study:
This study aims to enroll 50 YLH, ages 15-24, nationally.
12.0
Recruitment Methods
A number of recruitment strategies previously utilized by the Hunter College Center for 
HIV Educational Studies and Training (CHEST) will be implemented by the Scale It Up 
Recruitment and Enrollment Center (REC). To ensure the desired sample of 120 
participants is reached, both site referrals and national media campaigns will be used. The 
following are methods through which recruitment will take place: (1) referrals from Scale 
It Up clinical subject recruitment venues (SRVs), (2) social media ad campaigns, (3) 
geosocial networking data application ads, (4) nationwide flyers and recruitment material 
distribution, and (5) indirect recruitment through CHEST’s Online Master Screener 
(OMS). 
Clinical SRVs involved in Scale It Up will refer potentially eligible patients to the Text-
In option or provide the REC screening phone number. Flyers and other recruitment 
materials will be distributed to SRVs to inform patients about the study. SRV staff will 
not screen patients directly, but will discuss the study and refer interested patients to 
complete the Study Screener online or by phone.
REC team will run national ad campaigns on social media sites (e.g., Facebook, 
Instagram, Reddit, etc.). Filtering features will be used during the ad set-up to target 
social media users who indicated in their profiles that they are between 15-24 years old 
and live within the United States. Other “Interest” categories will be used to target 
individuals based on Facebook algorithms, which will identify young men who have sex 
with men or young men and women who have interacted with HIV-related pages and 
status messages on Facebook. Similar to Facebook and other social media platforms, 
Reddit’s ad platform will be utilized to target individuals by demographics and regions. 
Both free and paid advertising methods will be used to recruit participants through 
Reddit. Paid advertising enables the study to be promoted post pinned to the top of a 
given subreddit to boost its reach and engagement to targeted audiences. Users 
subscribed to the communities of HIV related discussion forums within the Reddit 
platform will learn about the study. Interested participants will click the ad and will be 
routed to an online Study Screener to determine eligibility.

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REC team will also recruit through ads on geosocial networking dating applications 
(apps). Two methods of ads will be used to recruit participants: (1) a pop-up message 
shown when a user first logs in, encouraging users to click through to determine 
eligibility for the study, and (2) a message sent by the app directly to the user’s inbox. 
Similar to Facebook, once a participant clicks the ad, they will be taken to the Study 
Screener and will be provided with more information on how to enroll in the SMART 
study. Although the REC team is unable to use filters to target users who fit within study 
age restrictions and HIV status, they will be able to use geo-targeting, similar to those 
used with social networking websites, to target potential participants within the United 
States.
Flyers and other recruitment materials with a text-in number will be distributed to AIDS 
service organizations (ASOs) and other clinics that provide care for youth living with 
HIV. In order to diversify recruitment and reach individuals outside of an online setting, 
the REC will identify ASOs/clinics including Ryan White funded recipients and other 
community-based organizations (CBOs) where potential participants can learn about the 
study. The REC team will set up a keyword through Trumpia™, a popular text-
messaging marketing service. Interested individuals will text a keyword (e.g., 
“RESEARCH”) to a five-digit number (e.g., 99-000) to learn about how to screen for the 
study. Once a potential participant sends the keyword to the five-digit number, they will 
receive an automated text-message with a link to a landing page where they may 
complete the preliminary screener specific to this study (e.g., chestnyc.org/SMART). 
 
REC team will download the list-serve from the Health Resources & Services 
Administration (HRSA) website (https://data.hrsa.gov/data/download?data=HAB#HAB). 
By accessing the HRSA website, email address of Ryan White recipients will be filtered 
using Ryan White as the Grant Program Name on the Active Grants Data Downloads 
page. REC team will also launch a website where providers outside of the ATN network 
can learn about the SMART study and request recruitment materials or further 
information (http://chestnyc.org/smart-provider). Outreach emails will be sent to Ryan 
White funded recipients with links to the website and recruitment materials order form. 
Our plan is to send emails in batches of ~50 providers at a time and follow up with all 
engaged sites 2 weeks after recruitment materials are shipped to ensure materials are 
delivered and to answer any additional questions.   
Potential participants can also be routed to the SMART study through the PRIDE OMS. 
The OMS determines potential eligibility for several PRIDE studies. If the interested 
individual is potentially eligible for SMART, a screen will be displayed informing them 
that they might be eligible for the study, followed by a separate online form, which will 
collect contact information.
Recruitment Strategy Utilizing OneFlorida Data Trust. We would like to utilize the 
OneFlorida Research Infrastructure to assist with recruitment for the SMART study. An 
initial Data Trust query was conducted and resulted in identifying at least 127 youth that 
fit the inclusion criteria of the SMART study.  Following approval from the OneFlorida 

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Executive committee and IRBs, we would like to use the OneFlorida Honest Broker system 
to re-identify this data and provide us with information on those clinicians and sites that 
are interested in participating in this project, and that are providing services to the identified 
youth. Additional requested data from the Honest Broker, which will be outlined in the 
data release cover sheet, includes: Patient Demographics, contact information (address), 
Clinical encounter details , Diagnosis, Procedures, Lab Results, Medications, Provider ID 
(provider NPI info), Geographical location, i.e. Facility location (3 digit zip), and Numbers 
of eligible adolescents at each site. 
 
Prior to data release, the PI and study team will need permission from OneFlorida partners 
to receive the re-identified data from the Honest Broker. After identifying which partners 
would like to participate, we would proceed to engage these OneFlorida partners in the 
SMART study by informing them of study objectives and recruitment plan. Additionally, 
we will seek permission from partners and providers for the study team to send letters to 
potential participants on behalf of their clinical providers, approval typically provided at 
the clinic or department level. The letter sent to participants will include study information 
and an opportunity to “opt-out” of being contacted by the study team. Additionally, letters 
will include a “text-in” number, in which interested persons will be able to text-in for 
enrollment, and receive instructions for enrollment screening. After the warm hand-off via 
letters process, the study team will directly contact potential participants (those that did not 
opt-out of being contacted) to inform them of the study and screening/enrollment options 
for preliminary eligibility. 
 
Prior to reaching out to potential participants, we will receive permission from interested 
OneFlorida partners and the potential participant’s healthcare providers. Initial outreach 
without partner and provider permission will not be conducted. 
 
Should recruitment rates fall below an acceptable threshold, the study team will work with 
the providers and their clinical staff to add a recruitment process wherein patients will be 
referred for the study during clinic visits, representing a direct and in-person warm handoff.
Sub-Study:
ATN 144b At-Home DBS Recruitment Methods. The protocol team will recruit 
subjects from the United States beginning in January 2020 until November 2020. The 
protocol team will send an invitation email to potential subjects that screened ineligible 
for ATN 144 SMART or those who were unable to complete the procedures to be 
enrolled in SMART and consented to being contacted for other studies. This email will 
contain a link to a locator form where the subject can provide their contact information if 
they wish to participate in Project DABS. The electronic locator form will also include 
items on whether a participant will be willing to receive DBS collection kit and mail it 
back to us along with the exclusion criteria. In addition, they will be asked to provide 
their preferred mailing address which maybe home address or USPS/UPS pick up/drop 
off locations. Upon submitting their contact information, the Qualtrics software will 
generate a unique subject ID (PID) number for the subject. The protocol team will then 
send the consent/assent, with the PID embedded within the electronic form, to the subject 
via email to begin the consent/assent process.

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ATN 144 SMART Recruitment Methods. To achieve this sub-study’s aims, we will use 
ATN 144 SMART’s recruitment and screening methods, to enroll 50 YLH aged 15-24 
years old living in the United States. A number of recruitment strategies previously 
utilized by Hunter College will be implemented5-7 by the Scale It Up Recruitment and 
Enrollment Center. Both site referrals and national media campaigns will be used. The 
following are methods through which recruitment will take place: (1) referrals from Scale 
It Up clinical subject recruitment venues, (2) social media ad campaigns, (3) geosocial 
networking data application ads, (4) nationwide flyers and recruitment material 
distribution, and (5) indirect recruitment through Hunter College’s Online Master 
Screener (OMS).
ATN Subject Recruitment Venues (SRVs). Clinical subject recruitment venues 
involved in Scale It Up will refer potentially eligible patients to the text-in option or 
provide the REC screening phone number. Flyers and other recruitment materials will be 
distributed to SRVs to inform patients about the study. SRV staff will not screen patients 
directly, but will discuss the study and refer interested patients to complete the study 
screener online or by phone.
Table 1. Scale it Up SRVs.
Subject Recruitment Venue
Location
Johns Hopkins University 
Baltimore, MD
University of Alabama at Birmingham
Birmingham, AL
State University of New York Downstate 
Brooklyn, NY
Children's Hospital Los Angeles 
Los Angeles, CA
St. Jude Children's Research Hospital 
Memphis, TN
University of Miami
Miami, FL
Children's Hospital of Philadelphia 
Philadelphia, PA
University of California San Diego 
San Diego, CA
University of South Florida 
Tampa, FL
Children's National Health System 
Washington, D.C.
Social Media. REC team will run national ad campaigns on social media sites (e.g., 
Facebook, Instagram, etc.). Filtering features will be used during the ad set-up to target 
social media users who indicated in their profiles that they are between 15-24 years old 
and live within the United States. Other “Interest” categories will be used to target 
individuals based on Facebook algorithms, which will identify young men who have sex 
with men or young men and women who have interacted with HIV-related pages and 
status messages on Facebook. Interested subjects will click the ad and will be routed to an 
online Study Screener to determine eligibility.
Geosocial Networking Apps. REC team will also recruit through ads on geosocial 
networking dating applications (apps). Two methods of ads will be used to recruit 
subjects: (1) a pop-up message shown when a user first logs in, encouraging users to click 

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through to determine eligibility for the study, and (2) a message sent by the app directly 
to the user’s inbox. Similar to Facebook, once a subject clicks the ad, they will be taken 
to the Study Screener and will be provided with more information on how to enroll in the 
SMART study. Although the REC team is unable to use filters to target users who fit 
within study age restrictions and HIV status, they will be able to use geo-targeting, 
similar to those used with social networking websites, to target potential subjects within 
the United States.
Short Message Service. Flyers and other recruitment materials with a text-in number 
will be distributed to AIDS service organizations (ASOs) and other clinics that provide 
care for youth living with HIV. In order to diversify recruitment and reach individuals 
outside of an online setting, the REC will identify ASOs/clinics including Ryan White 
funded recipients and other community-based organizations (CBOs) where potential 
subjects can learn about the study. The REC team will set up a keyword through 
Trumpia™, a popular text-messaging marketing service. Interested individuals will text a 
keyword (e.g., “RESEARCH”) to a five-digit number (e.g., 99-000) to learn about how to 
screen for the study. Once a potential subject sends the keyword to the five-digit number, 
they will receive an automated text-message with a link to a landing page where they 
may complete the preliminary screener specific to this study (e.g., 
chestnyc.org/SMART).
REC team will download the list-serve from the Health Resources & Services 
Administration (HRSA) website (https://data.hrsa.gov/data/download?data=HAB#HAB). 
By accessing the HRSA website, email address of Ryan White recipients will be filtered 
using Ryan White as the Grant Program Name on the Active Grants Data Downloads 
page. REC team will also launch a website where providers outside of the ATN network 
can learn about the SMART study and request recruitment materials or further 
information (http://chestnyc.org/smart-provider). Outreach emails will be sent to Ryan 
White funded recipients with links to the website and recruitment materials order form. 
Our plan is to send emails in batches of ~50 providers at a time and follow up with all 
engaged sites 2 weeks after recruitment materials are shipped to ensure materials are 
delivered and to answer any additional questions.
Online Master Screener. Potential subjects can also be routed to ATN 144 SMART 
through the Hunter College OMS. The OMS determines potential eligibility for several 
Hunter College studies. If the interested individual is potentially eligible for SMART, a 
screen will be displayed informing them that they might be eligible for the study, 
followed by a separate online form, which will collect contact information.
13.0
Withdrawal of Subjects*
Criteria for Premature Discontinuation
These are the categories of “dropping” participants along with their definitions. 

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Category: Definition
Procedure
Notes
Ineligible prior to BL 
(Prior to Consent):
Screened eligible, but 
finally ineligible after 
proof of suppressed viral 
load (VL) test result 
within the past 12 
months due to necessary 
VL eligibility 
confirmation
Remove from reminder 
call lists and mark as “Do 
Not Contact” in Access.
Counted towards screened 
number only.
Refused baseline (BL) 
(Prior to Consent): 
Screened eligible, but 
never provided consent 
during BL assessment 
and/or no longer wishes 
to be contacted.
Remove from reminder 
call lists and mark as “Do 
Not Contact” in Access.
Counted towards screened 
number only.
Withdrew during BL 
(After Consent): Provided 
consent but refused to 
finish BL assessment.
Remove from reminder 
call lists and mark as “Do 
Not Contact” in Access.
Counted up to and including 
magic number; these 
participants get marked as 
“Withdrew from Study” for 
IRB purposes.
Withdrew after BL (After 
Consent): Participant 
completed the BL but 
asked to be removed 
from the study 
thereafter.
Remove from Follow-Up 
Call Lists; should be 
Tracked as enrolled and 
have a condition assigned.
Counted up to and including 
randomized/enrolled and 
stays in all denominators for 
Follow-Up retention; these 
participants get marked as 
“Withdrew from Study” for 
IRB purposes.
Ineligible after BL (After 
Consent): Participant 
either completed the BL 
OR both BL and follow-
ups but was found 
ineligible for enrollment 
at a later date (e.g., 
found to have 
psychiatric conditions 
while collecting BL data)
Remove from Follow-Up 
Call Lists; should be 
Tracked as enrolled and 
have a condition assigned
Counted up to and including 
randomized/enrolled and 
stays in all denominators for 
Follow-Up retention; these 
participants get marked as 
“Withdrew from Study” for 
IRB purposes.
Refused intervention (if 
applicable), Still Enrolled: 
Participants who are no 
longer interested in the 
intervention, but have 
Remain in Database to be 
called for Follow-Up visits
Treated as other enrolled 
participants except they 
wouldn’t receive any future 
randomization or 
intervention.

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indicated a willingness to 
continue to be followed 
for Follow-Up Visits
Passed away: Participant 
was enrolled but later 
passed away
Notify Recruitment and 
Enrollment Center (REC) 
immediately with details 
regarding the situation (i.e. 
Date of Death, Date 
Notified, Cause of Death, 
Participant Age and Sex); 
Remove from Follow-Up 
Call Lists
Counted up to and including 
randomized/enrolled and 
stays in all denominators for 
Follow-Up retention; these 
participants get marked as 
“Withdrew from Study” for 
IRB purposes.
Other
If a participant withdraws 
for any other reason not 
listed here, please contact 
the REC immediately to 
discuss how to proceed. 
Sub-Study:
All subjects that have signed the consent form have enrolled in the study; however, a 
variety of scenarios may require discontinuation of participation and removal from the 
study. Removal from the study simply means we have stopped following them, but they 
remain enrolled. Anyone marked as “withdrew from study” for sIRB purposes should be 
included in the sIRB continuation, SIU Data Safety Monitoring Plan (DSMP) report, and 
the Research Performance Progress Report.
Below are the categories of removing subjects along with their definitions. These 
categories should be accurately used in the site’s tracking materials if one of the 
conditions below occurs.

Refused to participate prior to consent: Invitation email sent out, but never 
completes the locator form and/or no longer wishes for further contact.

Withdrew after consent: Provided consent, but refused to complete study-related 
components afterwards or subject asked to be removed from the study.

Ineligible after consent: Subject either completed the consent, DBS kit, CASI, 
and/or exit interview, but was found ineligible for enrollment at a later date (e.g., 
found to have psychiatric conditions).

Passed away: Subject enrolled, but later passes away.

Withdrawn from the study by the research team: Subject enrolled, but later 
dismissed from the study by the Protocol Lead.
14.0
Risks to Subjects*
The SMART Protocol Team has determined that this study does not involve greater than 
minimal risk (45 CRF Part 46.404 and 21 CFR Part 50.51). Participation in this study 
does not involve any physical risk above and beyond that which would ordinarily be 

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encountered in daily life, standard clinical practice, or physical or psychological 
evaluations and tests. However, there is some risk of emotional discomfort or distress due 
to the personal nature of some questions asked in behavioral assessments as well as by 
the AF during intervention phone calls and risk of breaching confidentially during the 
calls or text messages. Feedback from the AF is designed to be very respectful, but there 
is a chance that the AF and the participant may find parts of the phone calls distressing. 
Participants will be informed that they are free to decline to answer any questions, or 
withdraw from participation at any time without penalty. AFs will make every effort to 
ensure that the person who answers the cell phone is the participant enrolled into the 
study. This will be primarily conducted through voice recognition. If requested by the 
participant, the use of a code word can also be employed.  
The HIV VL measurement will be collected for participants who do not have a record of 
a VL result obtained within the specified timeframes. The collection requires 
venipuncture 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.
Sub-Study:
The protocol team has determined that this study does not involve greater than minimal 
risk (45 CRF Part 46.404 and 21 CFR Part 50.51). Participation in this study does not 
involve any physical risk above and beyond that which would ordinarily be encountered 
in daily life, standard clinical practice, or physical or psychological evaluations and tests. 
This study utilizes the HemaSpot™-HF blood sampling kit from Spot*On Sciences, who 
warns that persons with hemophilia or persons under anticoagulation therapy should 
consult their doctor or health care professional prior to using their kit; however, the 
protocol team will exclude subjects that indicate themselves as a person with hemophilia 
or under anticoagulation therapy. Furthermore, due to the personal nature of some 
questions asked in the CASI and/or exit interview, these study components do present 
some risk of emotional discomfort or distress.
15.0
Potential Benefits to Subjects*
This study includes assessment and monitoring of medication adherence and behavioral 
functioning. An assessment of these areas is considered standard of care for individuals 
infected with HIV, but is not always easily available in clinical settings. Thus, this study 
has the potential to provide participants (and their care providers, with participant 
permission) with clinical data that may be valuable in monitoring effects of HIV and its 
treatments.
Sub-Study:
Subjects do not receive any direct benefits for participating in this sub-study.

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16.0
Data Management* and Confidentiality
Data Management and Data Quality. The first randomization involves allocation to 
CPS vs. SMS using a 1:1 allocation ratio. This step will use stratified randomization in 
permuted blocks to achieve balance in distribution of behaviorally and perinatally 
infected youth. The REC data team will program the randomizer in Qualtrics and will not 
participate either in the intervention delivery or in the adherence reinforcement steps. The 
protocol team will monitor race, ethnicity, and gender to ensure balanced distribution at 
the first stage. After 6 months, stratified randomization will occur with permuted blocks 
within each trajectory. Since second stage randomization is dependent on first stage 
response status, we will only maintain the balance within each first stage treatment 
outcome when randomizing at the second stage.
Following the Analytic Core’s (AC) standard quality assurance, including checking for 
outliers and abnormal values using graphical methods, we will verify that the 
distributions of measures meet the assumptions of the statistical tests to be used, applying 
a formal test such as the Shapiro-Wilk’s test [60]. Transformations will be used when 
distributional assumptions are not fulfilled. Tests will be conducted to identify potential 
relationships among baseline demographic and clinical variables and our dependent 
variables and to see whether they are balanced between groups. If a baseline variable is 
not balanced between groups and is correlated with the dependent variable (r>.30), we 
will include this variable as a covariate in subsequent analyses. Since we will test more 
than one primary hypothesis with one primary outcome variable (VL suppression), the 
Hochberg step-up multiplicity adjustment will be used with a two-tailed family wise 
alpha-level of .05 [61]. All other tests described below will each have a two-tailed alpha-
level of 0.05. Outcome analyses will be based on the principle of intention-to-treat [62].
Quantitative Analysis Plan. The AC’s primary analysis will be a comparison of the VL 
suppression rate (primary outcome) between the CPS and the SMS group at the first stage 
of randomization (see Study Design). This will be performed using anχ^2test. We will 
also compare the drop in VL (measured in logarithmic scale with base 10) between the 
two groups. Since this is a continuous measure, we will use two-sample t-test to conduct 
this analysis. We will also compare medication adherence rate (secondary outcome) 
between the two groups using an χ^2 test. All the primary analyses will be based on 
initial assignment to groups, using the intention-to-treat (ITT) principle. Each of the 
primary hypotheses will be tested using linear mixed-effects (LMEs) regression analyses 
[63]. For testing primary hypothesis 1, the model will include up to 4 repeated 
assessments of VL suppression (months 0, 3, 6, 12) as the dependent variable. For 
primary hypothesis 2, we will only focus on non-responders (for both CPS and SMS at 
stage 1) and compare the VL suppression as dependent variable using a repeated measure 
LME (months 0, 3, 6, 12). Each LME model will include a random intercept and slope 
and fixed effects for adherence intervention group, and time, as well as the stratification 
variables: clinical site, age, gender. A likelihood ratio test will examine the incremental 
contribution of the group by time interaction, which represents the interaction of interest 
for Primary Hypothesis 1 and Primary Hypothesis 2, testing for a differential adherence 
intervention effect over time. The decision rule for each primary hypothesis calls for 

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rejection of null hypothesis if this interaction is statistically significant using the 
Hochberg’s step-up alpha adjustment [61]. A site by group interaction will be also 
examined and included in each model (above) if significant at the .05 level. In addition, 
likelihood ratio tests will be used to compare the model fit with that having a first order 
autoregressive (AR1) covariance structure, as described by Hedeker and Gibbons [63].
We will also conduct similar models as above however predicting adherence to ART 
(secondary outcome), which is measured at every time point. Each model will be a two-
level model in which time points (Level 1) are nested within participants (Level 2). This 
approach accounts for the non-independence of repeated measurements within 
individuals. The purpose of the LME based [64] analysis for the primary aim is to 
determine which of the first-stage intervention, CPS or SMS, is associated with the most 
improvement in VL and adherence, regardless of which second-stage treatment 
participants received. Also note in SMART design, we compare combinations of 
subgroups (as in two Specific aims), but not individual subgroups. The study is designed 
and powered to test the two primary hypotheses with one primary outcome. However, we 
expect that data based on SMART design will yield valuable information for hypotheses 
generation involving high quality embedded interventions, which can guide the design of 
subsequent confirmatory studies.
SMART Secondary Aims. The first of the secondary aims is to compare the effect of 
tapering with termination at the second randomization among those who received CPS 
and those who received SMS and achieved VL <200 copies/mL. The AC will compare 
viral suppression rates among the two groups (tapering vs. termination), followed by 
more refined analysis using LME modeling. We will first perform a χ^2 test between the 
two viral suppression rates, followed by mixed-effects modeling. 
The purpose of the second secondary aim is to determine which of the adaptive 
intervention arm leads to the greatest improvement in VL and adherence over the entire 
study period. To perform this, we will estimate the viral suppression and adherence rates 
following each of the 8 embedded interventions, and conduct a χ^2 test. Since both 
responders and non-responders are re-randomized, there is no need to use inverse-
probability weighting [65]. However, in order to account for the correlation induced by 
subjects shared between any two embedded interventions, we will use robust (sandwich) 
standard errors as in the generalized estimating equations approach [66]. 
Additionally, we will study the moderators of treatment effect. This is a potentially 
impactful goal, given the gradual but assured paradigm shift in behavioral interventions 
from “one-size-fits-all” approach to the modern personalized medicine. Potential 
moderators in the current context are subject’s demographics and the level of motivation 
– these can be incorporated in the analysis of the SMART data to deeply personalize the 
adaptive intervention for future patients. Because of the two-stage nature of the adaptive 
interventions, a straightforward regression analysis including potential moderators in the 
model as interaction terms is not suitable due to the possibility of unmeasured 
confounding induced by selection bias (also known as “collider-stratification bias”)  that 
can be present in time-varying settings, even in presence of randomization [67]. To avoid 

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this bias, one needs to employ 2 separate regressions corresponding to the 2 stages of 
SMART, and carefully move backward through the stages; such a state-of-the-art 
approach is known as Qlearning [68]. Each regression will contain interaction terms 
between the stage-specific treatments and the appropriate stage-specific moderators. If 
any come out significant, then patient characteristics can be used to deeply tailor the 
interventions for future patients. This will be performed using the R software package 
qLearn [69]. As customary, secondary aims are not powered and exploratory in nature.
Site Clustering Effects. Although some of the participants will be recruited via a site 
referral, we do not anticipate substantial site effects. A group identifier for each 
participant will be included in the merged analytic dataset, and the intra-class correlation 
(ICC) for each outcome within sites will be calculated prior to conducting multivariate 
analysis. If no significant variance (<0.05) is carried at the group level, we will reduce the 
model to a traditional two-level model (only clustering due to repeated measure). If 
significant group-level variance does emerge, dummy codes to control for site-specific 
variance will be used to enhance statistical power using a 3-level LME model. In other 
words, ICC will be included in the model at three-level to control for the clustering effect 
by design, provided third level is significant. The significance test is always at 0.05. We 
did not recommend a three-level model all the time as power analysis is conducted 
considering two-level models only i.e. ignoring site effect.  
Sample Size and Power. Statistical power analyses examined the sample size 
requirements to detect greater than chance group differences on primary outcome 
(Primary Hypotheses 1 and 2). Because two primary hypotheses have been proposed, the 
Hochberg alpha adjustment will be used in hypothesis testing. The smaller of those 
sequential alpha-levels of .025(=0.05/2) was used in our estimates of the multiplicity-
adjusted sample sizes. Preliminary data have traditionally been used for this purpose, but 
the small sample of the pilot data to provide estimates that are too imprecise for sample 
size calculations [70]. The power analyses examined the sample sizes required to detect 
clinically meaningful group differences in the VL suppression rate over time (i.e., the 
slope). Statistical power was estimated in a Monte-Carlo simulation study using SAS 
PROC MIXED over 1000 iterations. This represents the differential course for the two 
interventions over time. Based on the results, the protocol requires recruitment of 190 
participants (≈95/group at 1st stage) with ≈50% non-responder in 2nd stage. The power 
table above shows the statistical power to detect standardized interaction effects of 
various magnitudes (0.45 to 0.55) for the Ns and a two-tailed alpha-level of 0.025. The 
intra-class correlation coefficient within subjects varied (ICC: .30, .40, .50, based on pilot 
data). The sample size of 95/group provides sufficient statistical power to detect 
differences in slopes that results in endpoint differences of _0.45 sd. units with ICC=.30 
or .40 and 0.50. In the power analysis it is assumed about 50% responder state at the end 
of stage 1, thus resulting about 95 subjects in responder and non-responder group. 
Strategies for Attrition. Attrition introduces bias and reduces power, precision and 
generalizability [71]. In keeping with the Intent-to-Treat principle we distinguish between 
intervention and study termination (complete withdrawal). Accordingly, we will make 
every effort to continue assessments for the entire course of randomized intervention, 

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even among those who do not continue with randomized group [72]. The mixed-effects 
models will incorporate all available data, even from subjects who do not complete the 
study. Mixed-effects models yield valid inferences assuming ignorable attrition [73]. For 
conducting descriptive and two-group comparison Multiple Imputation will be used to 
replace missing values in the outcomes and other measures. Point estimates, standard 
errors, and all tests will be calculated using Rubin’s rules for combining the results of 
identical analyses performed on each of the imputed data sets [74].
Additional Secondary Aims. Self-management model analysis will be conducted based 
on the exploration, preparation, implementation, sustainment (EPIS) model. For the 
implementation aim, we will explore provider perceptions of the centralized 
implementation intervention and of the intervention as an evidence-based practice, 
through qualitative interviews and quantitative assessments based on the EPIS model. 
Data coding and analysis will proceed in a three-phase process with the EPIS Team. First, 
consistent with Morgan’s [75] recommendations for qualitative content analyses and 
Hsieh and Shannon’s [76] directed qualitative content analytic approach, standard 
definitions of the concepts to be coded in the text will initially be developed by the ISC 
based on the EPIS model. We will first systematically review each interview at each time 
point for all thematic mentions of EPIS model constructs, initially using existing theory 
to guide categorization, but also allowing themes to emerge from the data through open 
coding procedures [77, 78]. This combined inductive and deductive coding approach will 
allow us to both validate and extend the EPIS framework through our analysis. Revision 
of our initial coding categories will occur iteratively until we reach saturation in the 
identification of new codes. During this iterative process, categories and their definitions 
will be refined and sub-categories of codes consolidated, consistent with an axial-coding 
process. At this point, we will return to each interview and systematically apply the final, 
revised set of codes. In addition, case codes will be applied to each interview to reflect 
clinic role, site, cluster, and relevant demographic characteristics of the respondent. All 
coding will be conducted using NVIVO Version 10. For reliability, a random selection of 
30% of the interviews will be independently coded. Coding will be monitored to maintain 
a kappa coefficient of .90 or higher [79, 80]. Any discrepancies will be discussed and 
resolved. We will work closely with the EPIS team and then ISC to develop an 
Intervention Profile and Implementation Resources for replication and sustainment of the 
intervention. The Profile will synthesize intervention components and implementation 
analyses into intervention-specific practical guidance for further scale up. Additional 
resources to facilitate uptake, quality implementation, and sustainment of effective 
interventions are described in the ISC.
Cost-Effectiveness Analysis Plan. Detailed resource use for the interventions will be 
collected for the initial randomization and subsequent treatment assignment. These data 
will be assigned standard cost weights developed by the AC for the purpose of 
performing incremental cost effectiveness analyses across studies. The use of resource 
use measures with standard cost values will assure that the economic analyses associated 
with the clinical trial meet the International Society for Pharmacoeconomics and 
Outcomes Research (ISPOR) Good Practices for Economic Evaluation Alongside 
Clinical Trials [81]. We will use a modification of the approach described by Kim and 

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colleagues (2015)  and used in the economic evaluation of the Positive Charge multisite 
program aimed at linking HIV-infected youth to care in five states [82]. Data collection 
will be completed for this component by having each site’s financial management contact 
fill out a standard Excel spread sheet which contains resource use categories relevant to 
calculation the cost of the intervention.  The personnel cost data collected through this 
method will be combined with study contract and expenditure records to estimate the cost 
of the CPS and SMS conditions. The personnel data are collected using a standardized 
Excel spreadsheet to estimate the economic cost of alcohol and other drug treatment 
programs (e.g., personnel, facilities, supplies). Client case flow data is incorporated to 
determine the average weekly and annual cost/client for each service type, average cost 
per intervention episode, and marginal cost per contact. We will also collect data on 
resources used for tapering and incentives, which will be factored into calculating costs 
of the interventions. Data on sexual activity will be collected to be used with recent 
national estimates [54] of cost per HIV infection avoided, and/or on cost per HIV-
infection delayed, a more conservative measure. This will allow the estimation of 
potential cost savings in reduction in new HIV infections. If warranted by study findings, 
we will use a previously validated Markov decision analysis model [83] to estimate the 
expected treatment cost savings resulting from the increase in time with suppressed VL. 
The resource use measures and cost data collected will be used to develop budget impact 
scenarios to help inform “scale up” and diffusion planning for the most cost-effective 
intervention combinations.
Intervention Monitoring/Quality Control. It is critical to maintain consistency in the 
intervention delivery for all participants across all phone calls and the AFs at the REC. 
As previously described, the AFs will be trained to carry out the intervention. A fidelity 
evaluation will be conducted to assess whether the AF is collecting the correct 
information and providing an appropriate level of support.  This is to ensure fidelity to 
intervention delivery and to detect areas of the AF training that need to be improved. A 
Clinical Coordinator will conduct this fidelity evaluation.
All intervention phone calls between the AF and participant in this study will be digitally 
recorded utilizing the amplifier and recorder provided by the REC team. AFs will save all 
digital recordings in a secure network or review. The Clinical Coordinator will review 
20% of all audio files for each AF during the initial three months. The audio files will be 
randomly selected from all audio files saved by the AFs. If 90% of reviewed files are 
found to be adherent to the requirements listed above, the Clinical Coordinator will only 
review 10% of all audio files after the initial three months. The recordings will be 
assessed for: Adherence to the phone call script; 

Appropriate responses/advice/referrals;

Centering of participants in discussion;

Order of content discussed;

Appropriate length of call 
The Clinical Team will share any discrepancies and provide critical feedback to the AFs 
as soon as possible, and other feedback will be provided during the monthly AF 

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meetings. This ongoing feedback process will assist in ensuring the integrity of the 
intervention.
Documentation regarding follow up with the HIV care provider team will be reviewed to 
ensure that follow-up activities occurred when needed and follow up was conducted in a 
timely manner. Quality assurance activities will confirm that data captured on study 
forms are complete and accurate per source documentation. In addition, source 
documentation or forms will be compared to the data entered into the database to ensure 
that they match.
Participants’ Confidentiality. All laboratory specimens, questionnaires, evaluation 
forms, reports, and other records will be identified by a coded number only, to maintain 
participant confidentiality. All records with personally-identifying information will be 
kept in a locked, limited access area (such as a locked file cabinet). 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 (and parent or legally 
authorized representative, when applicable), except as necessary for monitoring by the 
ATN SIU or NICHD.
Certificate of Confidentiality. To further protect the privacy of the study participants, 
the ATN SIU has obtained a Certificate of Confidentiality from the U.S. Department of 
Health and Human Services (DHHS). With this Certificate in place, the ATN SIU 
researchers cannot be forced to turn over identifying information about a study 
participant in any Federal, State, or local criminal, administrative, legislative, or other 
proceedings. This Certificate does not prevent a study participant from volunteering to 
turn over their research information, nor does it prevent researchers from providing 
research-related information to others when requested by the study participant.
Sub-Study:
Data Management. The CASI data will be entered directly by the participant into 
Qualtrics. Data will reside on a secure server with firewall protection and SSL 
encryption. Only the Protocol Leads, Data Management and Statistical Team will have 
administrator privileges enabling them to download these data. The database, data 
structure, and data quality will be routinely reviewed by the Data Management and 
Statistical Team. Data will be downloaded into Dropbox Business account which will be 
used as the study’s file sharing site. Lab Manager and Project Manager will be creating 
specific folders for the Wayne State Statistician to have access to those folders. 
Dropbox provides secure shared folders for storing, sharing, and accessing files across 
sites. In order to allow others to access Dropbox files, the Lab Manager/Project Manager 
will deliberately share these folders. These folders will be accessible once an invitation 
sent by Lab Manager/Project Manager is accepted and Dropbox is installed by the site. 
Dropbox accounts and folders are password protected. At Dropbox, a dedicated security 
team using the best tools and engineering practices available to build and maintain 
Dropbox, and has implemented multiple levels of security to protect and back up files. 
There is also a two-step verification, a login authentication feature which one can enable 
to add another layer of security to the account. Other Dropbox users can't see our files in 
Dropbox unless the Lab Manager/Project Manager deliberately share links to files or 

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share folders. Dropbox employees are prohibited from viewing the content of files stored 
in the Project DABS folder. Employees may access file metadata (e.g., file names and 
locations) when they have a legitimate reason, like providing technical support. Like 
most online services, a small number of Dropbox employees will be able to access user 
data for the reasons stated in their privacy policy (e.g., when legally required to do so). 
But that's the rare exception, not the rule. Dropbox has strict policies and technical access 
controls that prohibit Dropbox employee access except in these rare circumstances. In 
addition, Dropbox employ a number of physical, technical, and heuristic security 
measures to protect user information from unauthorized access. 
 
Data Quality. Data quality will be examined before statistical analysis can be conducted, 
including examination of missing data, invalid responses, assessment of distributional 
assumptions, and identification of outliers.
Data Analysis Plan. To assess the feasibility of using DBS we will examine descriptive 
data to determine how many participants returned the DBS specimen. Descriptive 
statistics, frequencies, means and standard deviations, will be used to describe the 
samples’ demographic characteristics as wells as perceptions of their suitability, 
feasibility and acceptability. To identify potential barriers and facilitators of testing 
response rates we will conduct exploratory analyses comparing differences in 
demographics and perceptions in youth who did return the DBS specimen versus those 
who did not. We will examine proportional differences using chi-square tests for 
categorical variables and mean differences using t-tests for continuous outcomes (alpha = 
0.05). For the suitability, feasibility and acceptability scales we will calculate Pearson 
correlation coefficients to examine the relationship between these variables and potential 
barriers and facilitators. Point bi-serial correlations will be used when comparing the 
scales and dichotomous variables.    
Confidentiality. All laboratory specimens, questionnaires, evaluation forms, reports, and 
other records will be identified by a coded number only, to maintain participant 
confidentiality. All records with personally-identifying information will be kept in a 
locked, limited access area (such as a locked file cabinet). 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 (and parent or legally 
authorized representative, when applicable), except as necessary for monitoring by the 
ATN SIU or NICHD.
To further protect the privacy of the study participants, the ATN SIU has obtained a 
Certificate of Confidentiality from the U.S. Department of Health and Human Services. 
With this Certificate in place, the ATN SIU researchers cannot be forced to turn over 
identifying information about a study participant in any Federal, State, or local criminal, 
administrative, legislative, or other proceedings. This Certificate does not prevent a study 
participant from volunteering to turn over their research information, nor does it prevent 
researchers from providing research-related information to others when requested by the 
study participant.

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17.0
Provisions to Monitor the Data to Ensure the Safety of Subjects*
This research involves no more than Minimal Risk to subjects.
The protocol has a Data Safety Monitoring Plan and is reviewed semiannually by a Study 
Monitoring Committee. 
The Scale-It-Up (SIU) U19 Data Safety and Monitoring Plan will utilize a single 
monitoring system for all SIU protocols (including SMART) in order to harmonize 
review standards across protocols. The review process of the most vulnerable protocol 
will be applied to all SIU protocols thereby ensuring adequate oversight. We propose 
utilizing an independent study monitoring committee (SMC). A SMC was selected as the 
Clinical Research Management (CRM) as it is the highest level CRM needed for the most 
vulnerable SIU protocol. The proposed SMC will be composed of three independent 
experts who possess the relevant expertise (e.g., HIV-related research and prevention, 
adolescent medicine, and sexual health) to evaluate each SIU protocol and whom do not 
have a conflict of interest. Mary Velasquez, Jim (Xinguang) Chen, and Dushyantha 
Jayaweera have formally agreed to serve on the SIU SMC. Together, they represent an 
academically diverse and highly experienced team capable of providing the necessary 
foresight and oversight to ensure data safety monitoring plans are diligently designed and 
implemented. SIU has the appropriate funding available to financially support the 
activities of the SMC. The SMC will review each research protocol and plan for data and 
safety monitoring every 6 months, with additional ad-hoc reviews as necessary. All SMC 
meetings and reviews will be held via telephone conference.
Adverse Events Reporting. Data for monitoring participants’ safety will be captured 
within the Access database as part of the required study data. There are no additional 
study-specific reporting requirements. Information on unexpected events including 
serious adverse effects will be reported to the sIRB.
Sub-Study:
This study does not involve more than minimal risk to subjects.   
18.0
Provisions to Protect the Privacy Interests of Subjects
We protect the privacy interests of participants in several ways. The team of research 
staff working on this study is trained and committed to advancing the rights, regard, and 
sexual health of youth living with HIV. We utilize sex-positive and non-judgmental 
approaches in developing standard operating procedures, surveys, and intervention 
guides. Staff training in contacting participants highlights creating a comfortable 
interaction for the participant, having good listening skills, adopting non-judgmental 
approach, paying close attention to detail, being very knowledgeable about the study so 
as to answer questions participants may have, and being sensitive and flexible to 
participant’s personal situations that may impede completing a study assessment within 
their window. The research team is permitted to access participants’ information only 

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after completion of a comprehensive training followed by post-training mocks and 
feedback. 
19.0
Compensation for Research-Related Injury
The research and the sub-study do not involve more than Minimal Risk to 
subjects.
20.0
Economic Burden to Subjects
Research subjects are responsible for co-pays that may be incurred during any 
medical visits to a healthcare provider for viral load testing. 
Sub-Study: The protocol team expects enrolled subjects to incur no financial costs as a 
result of their participation in this study.
21.0
Consent Process
Once it is determined that a potential participant may qualify for the study, study details 
will be discussed and all questions answered by phone. During this screening process, 
potential participants will be asked if they verbally consent to being screened and 
complete a phone screener. Electronic informed consent/assent and HIPAA authorization 
will be obtained from each participant before any study-related procedures are performed. 
Since this is a nation-wide study, the consent process is not done in person. Instead 
participants receive the consent/assent form via an emailed link from Qualtrics. The 
electronic consent/assent form contains a set of “True or False” statements at the end of 
the form to verify that the participant understands the study and its components. The 
consent/assent form asks the following questions:
1. True or False: Participating in the study is my choice and I can choose to stop 
participating at any time, even if I agree today.
2. True or False: Every participant will be asked to complete online surveys and 
provide HIV viral load results or complete HIV viral load testing every three 
months for the full year of this study.
3. True or False: If I ask, the SMART research team may contact my provider to 
share information such as whether I need a refill of my medications or other 
quality of life matters.
4. True or False: The HIV viral load testing performed for this study is free. I am not 
responsible for the cost of a study related HIV viral load test.
5. True or False: If I already have HIV viral load results I can provide these to the 
research team if the results are recent.
If one response is incorrect, the form redirects to a page that contains all of the correct 
responses to the above statements for the participant’s review.
Non-English Speaking Subjects. Eligibility includes criteria that participants must speak 
English. No separate plan for obtaining consent is needed for non-English speakers.

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Sub-Study:
Informed Consent. Once it is determined that a potential subject may qualify for the 
study, study details will be discussed through the online consenting process and all 
questions answered by email/phone. During this consenting process, potential subjects 
will be asked if they consent to complete an online survey, complete the at-home DBS 
testing component, and complete an exit qualitative interview. Electronic informed 
consent/assent will be obtained from each subject before any study-related procedures are 
performed. Additional electronic consent/assent will be provided for audio recordings as 
part of the qualitative exit interviews. Since this is a nation-wide study, the consent 
process is not done in person. Instead subjects receive the consent/assent form via an 
emailed link from Qualtrics. The electronic consent/assent form contains a set of “True or 
False” statements at the end of the form to verify that the subject understands the study 
and its components. The consent/assent form asks the following questions:

True or False: Participating in the study is my choice and I can choose to stop 
participating at any time, even if I agree today.

True or False: Every subject will be asked to complete a one-time online survey 
and provide DBS specimen for the participation of this study.

True or False: The HIV viral load testing performed for this study is free. I am not 
responsible for the cost of a study related HIV viral load test.
If one response is incorrect, the form redirects to a page that contains all of the correct 
responses to the above statements for the subject’s review.
22.0
Process to Document Consent in Writing
Consent will be obtained electronically using a consent or assent form which details all 
study procedures and expectations for participation. The participant will electronically 
sign the consent/assent form, which is then stored on Qualtrics. The consent and assent 
forms were written using the template consent document (HRP-502).
Sub-Study:
Consent will be obtained electronically using a consent or assent form which details all 
study procedures and expectations for participation. The subject will electronically sign 
the consent/assent form, which is then stored on Qualtrics. The consent and assent forms 
for this study comply with Florida State University’s template consent document (HRP-
502).
Waiver or Alteration of Consent. 
For children, age 15-17, whose parents or legal guardians already know about the 
children’s HIV status and who if told would not place the children at risk of harm, 
parental permission for these children will be obtained. We are requesting a waiver of 
parental consent for youth who indicate that involving their parent or guardian may put 
them at risk of harm. 
We are requesting a waiver of parental consent for participants aged 15-17. Our research 
protocol is designed for conditions or for a subject population for which parental or 

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Submitted: June 17, 2021
guardian permission is not a reasonable requirement to protect the YLH, age 15 – 17. 
Youth will be completing daily phone calls and online surveys that discuss sensitive topics 
such as their sexual behavior, sexual orientation, etc. It is also expected that there will be 
participants who have not disclosed their HIV status to parents/legal guardians, and the 
parents/legal guardians will not be aware of the subject’s sexual orientation or risk 
behaviors. 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 HIV-related research with youth. Parental permission 
would put those youth whose parents do not already know about their sexual behavior 
and/or HIV status, infrequency of HIV-related care, at risk of their parents learning about 
this by the nature of requesting their permission to participate in a study of this kind. This 
may then place these youth at risk for parental harassment, abuse or expulsion from the 
parental home. Requiring parental permission could not only place these youth at increased 
risk of harm, but it would also substantially limit the generalizability of our research. 
Our justification for this waiver is informed by prior research with the target population, 
which has demonstrated risks of parental victimization during coming out or discussions 
of sexual orientation. Most young men who have sex with men (YMSM) are unwilling to 
ask their parents' permission to be in an HIV-focused study and those who are willing are 
significantly different on key variables. In addition, research suggests that YMSM have the 
capacity to make an informed decision regarding participation (e.g., appreciation of 
risks/benefits to themselves, understanding research components such as randomization) 
despite this not meeting the legal definition of consent. As shown in prior research, parents 
with LGBT-identified children appreciate the rationale for waivers of their permission 
when the study and its purpose are explained. This evidence supports the fact that YMSM 
are a population for whom parental or guardian permission is not a reasonable requirement 
to protect the participants and a waiver of parental permission is appropriate under 45 CFR 
46.408(c). This determination was further supported by the fact that this study does not 
expose participants to greater risk than encountered in everyday life, and therefore the 
waiver could also be approved under 45 CFR 46.116(d) based on the evidence described 
above that the research is not possible if parental permission is required. Additionally, 
consistent with national policy recommendations from the Society for Adolescent 
Medicine, requiring parental permission for the proposed study would have a number of 
possible negative effects, including: (1) reducing the validity of the findings by effectively 
eliminating potential participants unwilling to share permission forms with their 
parents/guardians; (2) increasing risk to some youth whose parents have a negative 
response to the material in the permission forms that would suggest their child has a 
minority or alternative sexual orientation; and (3) adding little in the way of actual subject 
protection, given the minimal risk of study participation.
Under 45 CFR Part 46.4116 (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.” The study procedures involve research on individual on perspectives 

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through collection of data from individual interviews. Foreseeable harms from 
participating in this study are not greater than those encountered in everyday life or during 
the performance of routine physical or psychological examinations or tests. In addition, in 
all 50 states and the District of Columbia, minors are explicitly permitted to consent for 
STI services without parental permission.
For children whose parents or legal guardians do not know about the children’s HIV status 
and who if told would place the children at risk of harm, a waiver of parental permission 
for these children is requested. For children whose parents or legal guardians are aware of 
HIV status, but knowledge of participation in study would place the children at risk of 
harm, a waiver of parental permission for these children is requested. For children whose 
parents or legal guardians already know about the children’s HIV status and who if told 
would not place the children at risk of harm, parental permission for these children will be 
obtained.
Procedures to Obtain/Waive Parental permission for YLH, age 15- 17. 
The study team will put the following steps in place to ensure that parental permission for 
youth stakeholders, 15 – 17, is obtained or waived as set forth by the Institutional Review 
Board. 
Screening procedures. 

The study screener will inform interested participants under the legal age (18) will 
need parental or legal guardian consent to be part of this study

The study screener will inform prospective youths that although their parent’s 
permission is usually required before children under the age of 18 may take part in 
the study, this permission will not be obtained for children who will be placed at 
risk of harm if their parents were told about their children’s participation in this 
study. 

The screener will ask youth under 18 whether their parents or legal guardians know 
about their HIV status, and whether if told would will be placed at risk of harm.

Youth who report that their parent is aware of their HIV status, they will be asked 
whether they will be placed at risk of harm if their parents were told about their 
participation in the study.

Youth that indicate that they will not be at risk for harm, will be told that parental 
consent is required to participate in the study, and they must be able to comply with 
that requirement.

Key study team members will review these youth’s responses in the screener to 
ensure and document that only for children who indicated risk of harm was parental 
permission not obtained.
Consenting Procedures. 

The youth consent/assent form include a section to obtain parental consent for 
youth under 18 who will be not placed at risk of harm 

This section on the consent/assent form will inform youth under 18, who will 
not be placed at risk of harm that parental permission is required to take part 

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Submitted: June 17, 2021
in the study and includes 2 questions to allow parental permission to be 
obtained. 
The study team will ensure that youth whose parents or legal guardians already know about 
the children’s HIV status and who if told would not place the children at risk of harm, 
parental permission for these children will be obtained.
The study team will review and document youth stakeholders’ who whose parents or legal 
guardians do not know about the children’s HIV status and who if told would place the 
children at risk of harm, a waiver of parental permission for these children is requested. 
For children whose parents or legal guardians are aware of HIV status, but knowledge of 
participation in study would place the children at risk of harm, a waiver of parental 
permission for these children is requested. 
Additionally, the study team will ensure to review and document that study screener 
information and consent/assent forms are completed appropriately for all youth and 
document 
youth 
that 
indicate 
they 
would 
be 
at 
risk 
for 
harm.
For every jurisdiction in which the study will be conducted and for which parental 
permission will not be obtained for one or more of the youth under the age of 18, waiving 
parental permission for these youth is not inconsistent with the state law in those 
jurisdictions in which the study will be conducted.
23.0
Setting
This research is being conducted at the PRIDE Health Research consortium at Hunter 
College, New York, NY. All research procedures will be performed in the offices of the 
research facility. 
Potential Participants are identified through healthcare provider referrals (e.g., Ryan 
White clinic or ATN clinic referrals), online social media, and dating apps. Please see 
recruitment sections for more information. 
The Community Advisory Board for this protocol is a part of the national Youth 
Community Advisory Board for the Scale It Up program of research. They meet on a 
quarterly basis via skype to discuss study progress, recruitment strategies, and 
recommendations for youth engagement. 
Sub-study:
Potential subjects are identified through the pool of subjects that screened ineligible for 
ATN 144 SMART or those who were not able to complete the study components to be 
enrolled in the SMART trial. These subjects were recruited from healthcare provider 
referrals (e.g., Ryan White clinic or ATN clinic referrals), online social media, and dating 
apps. Please see recruitment sections for more information. PRIDE Health Research 
Consortium at Hunter College, New York, NY, will perform all research procedures, 
excluding quantitative analysis of VL (to be performed by a third party lab) and the study 
data analyses to be performed by the Wayne State University Team in the offices of the 
research facility. 

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Submitted: June 17, 2021
The Community Advisory Board for this protocol is a part of the national Youth 
Community Advisory Board for the Scale It Up program of research. They meet on a 
quarterly basis via skype to discuss study progress, recruitment strategies, and 
recommendations for youth engagement.
24.0
Resources Available
A number of recruitment strategies previously utilized by the Hunter College will be 
implemented by the Scale It Up REC. To ensure the desired sample of 120 participants is 
reached, both site referrals and national media campaigns will be used. The following are 
methods through which recruitment will take place: (1) referrals from Scale It Up clinical 
subject recruitment venues (SRVs), (2) social media ad campaigns, (3) geosocial 
networking data application ads, (4) nationwide flyers and recruitment material 
distribution, and (5) indirect recruitment through Hunter College’s OMS.
The duration of this study is 43 months. During Months 1-4, the research team will focus 
on finalizing protocols, hiring/training staff, and completing IRB-related documents. For 
Months 5-19, the REC will recruit and enroll participants. After closing recruitment and 
enrollment, Months 20-31 are dedicated to completing the follow-up assessments. 
Finally, Months 32-43 are devoted to data analyses and dissemination.
Hunter College's Promoting Resilience, Intersectionality, Diversity, and Equity in Health 
Research Consortium was created to serve as a hub for Hunter's expanding work in 
sexual and gender minority health and broader focus on sexuality, gender, and health. 
The PRIDE Consortium supports research at the nexus of psychology, public health, and 
the health and helping professions that is relevant to understanding and addressing the 
health needs of diverse SGM individuals. A major focus of studies supported by the 
PRIDE Consortium has been to understand the structural, social, and psychological 
determinants of health disparities for SGM communities and to design and implement 
empirically-supported interventions to reduce disparities in the pursuit of health equity. 
The research center is located in midtown Manhattan and all services are research-
related; no clinical services are provided at PRIDE.
Since this is a nation-wide study, youth needing more intensive assistance (medical or 
psychological) will be referred to their care team using the information provided on the 
participant’s locator form, and with the youth’s permission, the AF will contact the care 
team to share the concerns. Any adverse events reported by the participant to the AF will 
be triaged by the REC Clinical Team and appropriate procedures will be followed.
The MPIs of Scale It Up, and the MC, maintain responsibility for the overall conduct and 
implementation of the study; the MC is also responsible for management of recruitment 
and retention including enrollment and retention. The REC will also be responsible for 
Data Management while the AC will be responsible for analysis and reporting. The 
Protocol Leads are responsible for scientific leadership and dissemination. Protocol 
meetings are held bi-weekly to keep all assisting personnel informed about the protocol 

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Submitted: June 17, 2021
and its procedures. Moreover, Dropbox is utilized to facilitate the storage and sharing of 
study-related documents, which further informs protocol personnel about any updates to 
research procedures.
Sub-Study:
A number of recruitment strategies previously utilized by the Hunter College will be 
implemented by the protocol team. To ensure the achievement of the desired sample size 
of 50 subjects, the protocol team will contact all of ATN 144 SMART’s ineligible 
subjects or those who did not fulfill the enrollment components. These subjects were 
recruited using the following methods (1) referrals from Scale It Up clinical SRVs, (2) 
social media ad campaigns, (3) geosocial networking data application ads, (4) nationwide 
flyers and recruitment material distribution, and (5) indirect recruitment through Hunter 
College’s OMS.
The duration of this study is 17 months. During Months 1-5, the research team will focus 
on finalizing protocol, study instruments, identifying the central lab for analyzing DBS 
specimens, and completing IRB-related documents. For Months 6-11, the PRIDE Team 
will recruit and enroll subjects. In addition, Months 7-12 are also dedicated to data 
analyses and dissemination.
Hunter College's PRIDE Health Research Consortium was created to serve as a hub for 
Hunter's expanding work in sexual and gender minority health and broader focus on 
sexuality, gender, and health. The PRIDE Consortium supports research at the nexus of 
psychology, public health, and the health and helping professions that is relevant to 
understanding and addressing the health needs of diverse SGM individuals. A major 
focus of studies supported by the PRIDE Consortium has been to understand the 
structural, social, and psychological determinants of health disparities for SGM 
communities and to design and implement empirically-supported interventions to reduce 
disparities in the pursuit of health equity. The research center is located in midtown 
Manhattan and all services are research-related; no clinical services are provided at 
PRIDE.
The principal investigator of Scale It Up and the Protocol Leads maintain responsibility 
for the overall conduct and implementation of the study. The Management Core, as well 
as the Recruitment and Enrollment Center, are responsible for management of 
recruitment, enrollment, and retention. The Recruitment and Enrollment Center will also 
be responsible for programming surveys in Qualtrics and databases as well as protocol 
development, and IRB submissions while the Wayne State University Team will be 
responsible for data management and analysis. The protocol leads are responsible for 
scientific leadership and dissemination. Protocol meetings are held as necessary to keep 
all assisting personnel informed about the protocol and its procedures. Moreover, 
Dropbox is utilized to facilitate the storage and sharing of study-related documents, 
which further informs protocol personnel about any updates to research procedures.