Scaling up HIV Prevention Trials Network (HPTN) 074: a Cluster Randomized Implementation Trial of an Evidence-based Intervention for Antiretroviral Therapy for PWID in Vietnam
Phase: NA
Conditions: HIV Infections, Drug Use
Sponsor: University of North Carolina, Chapel Hill

 
 
Scaling up HPTN 074: a Cluster Randomized Implementation Trial of 
an Evidence-based Intervention for Antiretroviral Therapy for PWID in 
Vietnam 
 
NCT number NCT03952520 
Document Date 09/13/2022 
 

 
 
SUMMARY OF CHANGES 
INCLUDED IN THE FULL PROTOCOL AMENDMENT OF: 
 
Scaling up HPTN 074: a Cluster Randomized Implementation Trial of an Evidence-based 
Intervention for Antiretroviral Therapy for PWID in Vietnam 
 
 
 
 
  
 
 
 
 
Sponsored by: 
US National Institute on Drug Abuse 
US National Institutes of Health 
 
 
 
Principal Investigators: 
Vivian Go, PhD, MPH, MA 
Department of Health Behavior, Gillings School of Global Public Health 
The University of North Carolina at Chapel Hill 
 
William Miller, MD, PhD, MPH 
Division of Epidemiology, College of Public Health 
The Ohio State University 
 
 
 
THE AMENDED PROTOCOL IS IDENTIFIED AS: 
Version 3.0 /13 September 2022 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Summary of revisions and rationales 
 
Revisions have been made to update these changes throughout the protocol. 
 
We are requesting to add a 3-question survey, the Provider REport of Sustainment Scale 
(PRESS), into the SNaP study. We plan to administer this scale to site staff (including 
counselors and navigators) who were involved with the delivery of SNaP 6-10 months following 
the completion of the SNaP study at each site. The purpose of the scale will be to assess the 
sustainment of the SNaP intervention at each of the sites, as well as characteristics of high and 
low sustaining sites. Study staff will contact site staff at the 42 HIV test sites that were involved 
in the SNaP study to invite them to participate in the survey. About 252 clinic staff (6 per site) 
will participate in the survey. Clinic staff who are interested in participating will be emailed 
electronic consents via a Qualtrics database to read and sign (if they choose to participate in the 
survey). They will then complete the fully self-administered survey on Qualtrics. The survey 
should take no more than 5 minutes to complete. 
 
We are requesting to add qualitative interviews at 6-10 months post-endline into the SNaP 
study. We plan to conduct the interviews with clinic navigators/counselors (n=12) and site staff 
or site directors (n=24) from a sub-sample of 12 of the SNaP scale-up sites. Based on their 
scores on the Provider REport of Sustainment Scale, we will randomly select 6 “high sustainer” 
and 6 “low sustainer” clinics for these interviews. The purpose of these interviews is to 
understand how SNaP and SNaP implementation strategy adaptations influence normalization 
and sustainment of the SNaP intervention into HIV testing clinics after the removal of external 
study support. SNaP study staff will contact clinic navigators, site staff, and site directors and 
will invite them to participate in the interviews. All interviews will be conducted over Zoom in 
Vietnamese by bilingual Vietnamese research assistants trained in qualitative interviewing. 
Participants will provide informed consent before being interviewed. The interviews are 
expected to last approximately one hour. All interviews will be audio-recorded, transcribed 
verbatim, and translated to English.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Scaling up HPTN 074: a Cluster Randomized Implementation Trial of an Evidence-based 
Intervention for Antiretroviral Therapy for PWID in Vietnam 
 
 
 
 
Sponsored by: 
US National Institute on Drug Abuse 
US National Institutes of Health 
 
 
 
Principal Investigators: 
Vivian Go, PhD, MPH, MA 
Department of Health Behavior, Gillings School of Global Public Health 
The University of North Carolina at Chapel Hill 
 
William Miller, MD, PhD, MPH 
Division of Epidemiology, College of Public Health 
The Ohio State University 
 
 
 
THE AMENDED PROTOCOL IS IDENTIFIED AS: 
Version 3.0 /13 September 2022 
 
 
Protocol 
Version 2.0  
13 September 2022 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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TABLE OF CONTENTS 
 
1. 
INTRODUCTION ................................................................................................................. 10 
1.1. 
Background .................................................................................................................. 10 
1.2. 
Rationale ...................................................................................................................... 11 
1.3. 
Theoretical Basis for the Implementation Trial ............................................................. 12 
2. 
STUDY OBJECTIVES AND DESIGN .................................................................................. 13 
2.1. 
Study Objectives ........................................................................................................... 13 
2.2. 
Study Design ................................................................................................................ 14 
3. 
STUDY SETTING AND POPULATION ............................................................................... 14 
3.1. 
Study Setting ................................................................................................................ 14 
3.2. 
Study Population .......................................................................................................... 14 
3.3. 
Inclusion Criteria ........................................................................................................... 15 
3.4. 
Exclusion Criteria .......................................................................................................... 16 
3.5. 
Recruitment Process .................................................................................................... 16 
3.6. 
Co-Enrollment Guidelines ............................................................................................. 17 
3.7. 
Participant Retention .................................................................................................... 17 
3.8. 
Participant Withdrawal .................................................................................................. 17 
4. 
STUDY INTERVENTION AND IMPLEMENTATION PACKAGES ....................................... 17 
4.1. 
Evidence-based Intervention: Systems Navigation and Psychosocial Counseling 
(SNaP) .................................................................................................................................... 17 
4.2. 
Implementation Packages ............................................................................................ 18 
5. 
STUDY PROCEDURES ...................................................................................................... 21 
5.1. 
Pre-implementation Study Procedures ......................................................................... 21 
5.2. 
Cluster Randomized Implementation Trial Initiation (Aim 1)......................................... 23 
5.3. 
Cost-effectiveness Data (Aim 2) ................................................................................... 24 
5.4. 
Procedures to Identify and Characterize High and Low Performing Sites (Aim 3) ....... 24 
5.5. 
Participant Study Procedures ....................................................................................... 27 
5.6. 
Study Procedures for System Navigators and Counselors at Sites ............................. 31 
6. 
SAFETY MONITORING AND ADVERSE EVENT (AE) REPORTING ................................ 33 
6.1. 
Safety Monitoring .......................................................................................................... 33 
6.2. 
Adverse Event Reporting .............................................................................................. 33 
6.3. 
Social Impact Reporting ............................................................................................... 33 
7. 
STUDY ASSESSMENTS AND OUTCOMES ...................................................................... 34 
7.1. 
Site-level Assessments ................................................................................................ 34 
7.2. 
Implementation Outcomes (Aim 1) ............................................................................... 34 
7.3. 
Effectiveness Outcomes ............................................................................................... 35 

 
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7.4. 
Cost-Effectiveness Measurements (Aim 2) .................................................................. 36 
7.5. 
High and Low Performing Sites (Aim 3)  ...................................................................... 36 
8. 
STATISTICAL CONSIDERATIONS ..................................................................................... 37 
8.1. 
Power and Sample Size Considerations ...................................................................... 37 
8.2. 
Statistical Analyses and Data Management ................................................................. 38 
8.3. 
Potential Biases and Solutions ..................................................................................... 40 
9. 
HUMAN SUBJECTS CONSIDERATIONS .......................................................................... 41 
9.1. 
Ethical Review .............................................................................................................. 41 
9.2. 
Informed Consent ......................................................................................................... 41 
9.3. 
Risks ............................................................................................................................. 42 
9.4. 
Benefits ......................................................................................................................... 43 
9.5. 
Incentives ..................................................................................................................... 44 
9.6. 
Confidentiality ............................................................................................................... 44 
10. 
LABORATORY SPECIMENS AND BIOHAZARD CONTAINMENT ................................. 46 
10.1. 
Specimen Collection, Storage, Processing ............................................................... 46 
10.2. 
Biohazard Containment ............................................................................................ 46 
11. 
DISSEMINATION PLAN .................................................................................................. 46 
12. 
ADMINISTRATIVE PROCEDURES ................................................................................. 47 
12.1. 
Study Team Roles .................................................................................................... 47 
12.2. 
Study Coordination ................................................................................................... 48 
12.3. 
Study Monitoring ....................................................................................................... 49 
12.4. 
Protocol Compliance ................................................................................................. 49 
12.5. 
Use of Information and Publications ......................................................................... 49 
12.6. 
Timeline .................................................................................................................... 49 
13. 
REFERENCES ................................................................................................................. 50 
 

 
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List of abbreviations and acronyms 
 
AE 
Adverse event 
ART 
Antiretroviral therapy 
CDC 
Center for disease control and prevention 
CFIR 
Consolidated Framework 
CFR 
Code of Federal regulations 
Co-I 
Co-Investigator 
DALY 
Disability-adjusted life year 
EBI 
Evidence-based intervention 
EC 
Ethics committee 
FDA 
Food and drug administration 
GNI 
Gross national income 
HIV 
Human immunodeficiency virus 
HMU 
Hanoi Medical University 
HPTN 
HIV prevention trials network 
ICH 
International Conference on Harmonisation 
IDI 
In-depth interview 
IGHID 
Institute for global health and infectious diseases 
IM 
Intervention mapping 
IRB 
Institutional review board 
JHU 
John Hopkins University 
MAT 
Medication-assisted treatment  
MID 
Masked identification number 
MMT 
Methadone maintenance treatment 
MoH 
Ministry of Health 
NGO 
Non-governmental organization 
NIDA 
National institute on Drug Abuse 
NIH 
National Institute of Health 
OHRP 
Office for Human Research Protections 
ORIC 
Organizational readiness to change 
OSU 
Oregon State University 
PC 
Psychological counseling 
PI 
Principle Investigator 
PID 
Patient identification number 
PWID 
People who inject drugs 
SA 
Standard approach 
SMC 
Safety monitoring committee 
SN 
System navigation 
SNaP 
Systems navigation and psychosocial counseling  
SoC 
Standard of care 
SOP 
Standard operating procedure 
TA 
Tailored approach 
TIM 
Tailored intervention mapping 
UNC 
University of North Carolina 
US 
United States 
VAAC 
Vietnam Authority of AIDS Control 
 
 
 
 

 
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Scaling up HPTN 074: a Cluster Randomized Implementation Trial of an Evidence-based 
Intervention for Antiretroviral Therapy for PWID in Vietnam 
 
SCHEMA 
 
Purpose:  
To conduct a pragmatic implementation trial comparing two Intervention 
Mapping implementation approaches for scale-up of the evidence-
based intervention (EBI), referred to as SNaP, in Vietnam, considering 
effectiveness, cost, and the characteristics of HIV test sites achieving 
successful or unsuccessful implementation. The two implementation 
approaches based on Intervention mapping, which are the one size fits 
all standard approach (SA) and the tailored approach (TA). 
 
Design: 
This study is a cluster randomized, controlled implementation trial 
designed to assess two implementation approaches (standard and 
tailored) for scaling-up the SNaP intervention. The SNaP intervention 
combines systems navigation and psychosocial counseling for people 
who inject drugs (PWID), and it is designed to facilitate PWID’s 
engagement in HIV and substance use care. 
 
Study  
Population:  
The study population will consist of the following participant types, 
recruited from selected HIV test sites across Vietnam: 
 
• 
PWID who present to the HIV test sites and test HIV-positive 
using the standard confirmatory HIV test  
• 
HIV test site directors and staff  
 
Study Size:  
PWID: Approximately 6200 HIV-infected PWID will be recruited for 
medical record assessment at baseline; of those, a subsample cohort of 
1500 PWID will be enrolled for detailed assessments at baseline, 12 
and 24 months, including questionnaires and viral load determination. 
 
 
HIV test site directors and staff: All site directors and staff at the 42 
selected test sites, including the navigators and counselors in each site, 
will be recruited for the study. 
 
Treatment  
Regimen: 
HIV test sites (n=42) will be randomized 1:1 to either: 
• 
the one size fits all standard approach (SA); or  
• 
the tailored approach (TA).  
 
Study Duration: 
Study activities will span across 5 years, with approximately 27 months 
at each site and recruitment of PWID participants over 21 months. For 
PWID not in the subsample cohort, participation is a one-time visit. For 
the Subsample Cohort PWID or PWID selected for qualitative 

 
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interviews, maximum study participation time is 24-27 months. For HIV 
test site directors and staff, maximum time in the study is 24-33 months. 
 
Primary  
Objectives:  
 
1) To compare the standard approach (SA) to tailored approach (TA) 
to scale-up an integrated intervention, SNaP, for PWID in HIV test 
sites in Vietnam. (Aim 1) 
2) To measure the incremental costs of SA compared to TA for SNaP 
implementation in Vietnam. (Aim 2) 
 
Secondary  
Objectives: 
 
1) To explore the key characteristics of HIV test sites and clinics that 
successfully or unsuccessfully implement and sustain SNaP for 
each study arm. (Aim 3) 
  
 
Study Sites: 
42 HIV test sites across Vietnam 
 
 

 
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Scaling up HPTN 074: a Cluster Randomized Implementation Trial of an Evidence-based 
Intervention for Antiretroviral Therapy for PWID in Vietnam 
 
OVERVIEW OF STUDY DESIGN AND RANDOMIZATION SCHEME 
 
Figure 1: Study design overview and randomization scheme. Test sites are randomized 1:1 (21 
sites per trial arm). 

 
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1. INTRODUCTION 
 
1.1. 
Background  
 
In early 2018, HIV Prevention Trials Network (HPTN) 074, a 
randomized, controlled, vanguard study for HIV-infected people 
who inject drugs (PWID), yielded exciting findings for HIV-
infected PWID. Conducted in Vietnam, Indonesia, and Ukraine, 
HPTN 074 compared a systems navigation and psychosocial 
counseling integrated intervention (SNaP) to standard of care 
(SoC). SNaP, a scalable, flexible intervention, markedly 
increased antiretroviral (ART) use (Figure 2), viral suppression, 
and medication-assisted treatment (MAT) use, while also 
reducing mortality.1 Transmission to HIV-uninfected partners 
also appeared to be reduced.  
 
The study population of HPTN 074 were actively injecting, HIV-
infected PWID, ages 18-60 years with viral loads >1000 
copies/mL (indexes) who were recruited and enrolled if they recruited an HIV-uninfected 
injection partner. Up to 5 injection partners could be enrolled per index.  
 
Injection partnerships were randomized in a 3:1 ratio (standard of care (SoC) : SNaP) In the 
SNaP arm, HIV-infected indexes received an integrated intervention that included: 1) systems 
navigation to facilitate engagement, retention and adherence in HIV care and medication-
assisted treatment (MAT, i.e. methadone in Vietnam), including negotiation of required 
laboratory testing, transportation, and ART initiation regardless of CD4+ cell count; and 2) 
psychosocial counseling using motivational interviewing, problem solving, skills building, and 
goal setting to facilitate initiation and adherence of ART and MAT. All navigator/counselors had 
addiction-related experience, but had a variety of education levels. 
 
The effectiveness of SNaP was striking, but its effects were observed in a controlled trial 
environment. Many evidence-based interventions (EBI), such as SNaP, fail to fulfill their promise 
during implementation. Implementation may fail due to barriers that vary across target 
populations, providers, organizations and systems. Implementation of EBI is commonly one size 
fits all, with a Ministry of Health decreeing a nationwide, single implementation strategy. This 
approach was effective in bringing HIV counseling and testing and ART to many people, but 
some populations, such as PWID were left behind. To implement SNaP at scale, a one size fits 
all approach may suffice, but HIV test site-specific barriers may need to be addressed to reach 
this vulnerable population.  
 
Intervention Mapping (IM), a multistep implementation process, incorporates theory, evidence, 
and stakeholder perspectives to ensure that intervention components effectively address key 
barriers to change. Intervention Mapping may improve centralized, one size fits all decision-
making prior to implementation.  
 
Intervention Mapping may also be extended to tailor implementation strategies to specific 
contexts using a multi-step process with initial development of a menu of implementation 
Study Week
Proportion Alive and o
0
4
13
26
39
52
0
0.2
0.4
0.6
0.8
1
SOC
Intervention
Figure 2: Proportion of HIV-infected PWID who were 
alive and self-reported ART use by week with 95% 
confidence intervals. Intervention = SNaP 

 
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strategies centrally, rapid assessment of local implementation barriers in each HIV test site, and 
selection of implementation strategies to match site-specific barriers.  
 
In 2015, we collaborated with the Vietnam Administration for HIV/AIDS Control (VAAC) to 
identify implementation strategies to facilitate the MoH’s plan to integrate MAT and HIV 
services.2 Our approach comprised 3 steps: 1) 16 qualitative interviews with key stakeholders 
(MoH, clinic directors, staff) in Vietnam; 2) a matrix of facilitators and barriers to align potential 
implementation strategies; and 3) a poll with Vietnamese stakeholders and implementation 
science experts to select appropriate implementation strategies. Stakeholders noted patient 
benefits from integration, but clinic leaders and staff voiced concerns related to staff training and 
morale. We then designed an acceptable and feasible package of 3 implementation strategies: 
local champion, technical assistance, and audit and feedback, and presented it to the MoH as 
they rolled-out MAT/HIV integration. This approach was similar to IM, as it linked barriers and 
strategies using stakeholder feedback. Our use of the formal IM process in this study will ensure 
that these decisions are also strongly grounded in theory and empirical literature. 
 
Standard Intervention Mapping may be sufficient to produce an appropriate national 
implementation package for the scale up of SNaP, but barriers at the local HIV test site-level 
may impede this approach. However, a tailored approach addresses contextual needs and 
may improve scale up of EBI for PWIDs. Unlike standard, MoH-decreed one size fits all 
approaches, tailored implementation allows for flexibility through a two-step local process: 1) 
rapid assessment of implementation barriers and facilitators in each site; and 2) selection of 
site-specific strategies using a pre-identified menu of potential strategies to address barriers.3 
 
This study addresses priorities in the field of implementation science by: 1) using a rigorous 
method for selecting and tailoring implementation strategies,2–4,6,7 2) comparing a tailored 
approach to a standard multifaceted implementation strategy (rather than a more passive “straw 
man” strategy such as dissemination of educational materials or training alone),4 and 3) 
assessing the incremental costs of a standard vs. tailored approach to implementation.4 
 
1.2. 
Rationale 
 
Despite decades of research and millions of dollars spent to develop EBI, PWID continue to 
bear a disproportionate HIV infection burden. This burden will only be reduced when EBI are 
effectively implemented at scale. But scale-up of any EBI, including SNaP, poses challenges 
that are often underestimated or not considered at all. Without effective implementation, SNaP 
will either languish with the other EBI that have never been implemented or fall short of its 
potential impact on the PWID epidemic because of poor implementation.  
 
As mentioned, the SNaP intervention significantly increased ART use, viral suppression and 
medication-assisted use, and reduced mortality in Vietnam and Ukraine, two countries with very 
different health care systems. Barriers to implementing SNaP will vary by countries and health 
care systems. However, in this study, we are evaluating two approaches to selection of 
implementation strategies (Intervention Mapping vs. Tailored Intervention Mapping), not 
implementation strategies themselves, to address specific barriers.  
 
Both Standard Approach (SA) and Tailored Approach (TA) are implementation approaches for 
identifying barriers and strategies to address those barriers that can be used in virtually any 
health care system. This trial, comparing SA to TA, will allow us to identify appropriate 
implementation strategies for use globally, including cost and critical factors for 

 
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success. This trial will allow us to determine which approach, SA or TA, is best to implement 
SNaP in terms of effectiveness, cost and the characteristics of HIV sites. This study will provide 
critical guidance to Ministries of Health worldwide regarding the most effective, cost-efficient 
approach to SNaP implementation. With this guidance, widespread implementation has the 
potential to significantly reduce mortality and improve health for HIV-infected PWID in resource-
limited settings. 
 
PWID need impactful interventions to reduce their HIV-associated morbidity and mortality and 
slow their HIV epidemic. SNaP provides such an opportunity. This implementation trial will 
provide critical guidance to policymakers worldwide who are charged with the task of reducing 
the burden of HIV infection among PWID. This guidance will accrue regardless of the trial 
outcome, based on the composite results of implementation outcomes, effectiveness outcomes, 
cost, and characterization of high and low performing test sites. 
 
1.3. 
Theoretical Basis for the Implementation Trial 
 
We will assess the effectiveness of two different approaches to implementation: 1) a “standard” 
multifaceted implementation approach (SA) and 2) a “tailored” approach to implementation (TA). 
Both will be based upon a rigorous approach to designing the implementation strategies called 
Intervention Mapping,1 which is a systematic intervention development protocol that 
incorporates theory, evidence, and stakeholder perspectives to ensure that intervention 
components address key determinants of change.  
 
Consistent with best practices in implementation science, our study is guided by theoretical 
frameworks to inform implementation processes (Intervention Mapping),4 identify 
implementation barriers and facilitators (Consolidated Framework for Implementation Research; 
CFIR),5 and assess implementation outcomes6 (Proctor et al.’s implementation outcomes 
framework).7 Intervention Mapping provides a methodological framework that will yield standard 
and tailored approaches to implementation. The CFIR is a comprehensive framework that 
identifies 39 factors that influence implementation outcomes. We will primarily focus on one of 
the five CFIR domains, the “inner setting,” which will drive our assessment of HIV test site 
contextual factors that are likely to vary across sites. These factors include the age, maturity, 
and size of the test site; norms of the test site; organizational readiness to change; 
implementation leadership; and implementation climate. We posit that tailoring implementation 
strategies to address test site context will improve test site context and lead to better 
implementation and effectiveness outcomes. Proctor et al.’s framework also guides our 
assessment of key implementation outcomes: fidelity, penetration, acceptability, and cost.  
 
As depicted in the conceptual framework (Figure 3), the effectiveness of SNaP scale-up will be 
determined by the implementation processes as operationalized through the SA and TA 
approaches. The two implementation approaches, SA and TA, must be implemented well (e.g. 
with fidelity), which in turn, affects SNaP implementation. Successful implementation of SNaP, 
with high fidelity, penetration and acceptability will lead to better effectiveness outcomes (ART 
uptake).   
 

 
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FIGURE 3. CONCEPTUAL FRAMEWORK 
 
2. STUDY OBJECTIVES AND DESIGN 
 
2.1. 
Study Objectives 
 
The primary objectives of this study are:  
 
1) To compare the standard approach (SA) to tailored approach (TA) to scaling-up an 
integrated intervention, SNaP, for PWID in HIV test sites in Vietnam. (Aim 1) 
 
We will conduct a two-arm, pragmatic cluster randomized implementation trial among HIV 
test sites in Vietnam. HIV test sites (n=42) will be randomized to receive one of two 
implementation approaches: a) SA—a standard, one size fits all multifaceted 
implementation package identified through Intervention Mapping, or b) TA—a tailored 
implementation package using Intervention Mapping with tailoring to each test site.  
• 
The primary outcomes are HIV test site-level EBI fidelity (implementation outcome) 
and ART uptake (effectiveness outcome).  
• 
Secondary implementation outcomes include penetration, acceptability, and cost.  
• 
Secondary effectiveness outcomes include viral suppression and MAT use.  
• 
We will conduct outcome assessments at 12 and 24 months. 
 
2) To measure the incremental costs of SA compared to TA for SNaP implementation 
in Vietnam. (Aim 2) 

 
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Comprehensive costing of SA and TA will be performed using a micro-costing or “bottom-
up” approach. This costing will include the intervention and the full implementation 
process, inclusive of Intervention Mapping and tailoring.  
• 
The primary cost-effectiveness outcome will be the incremental cost-effectiveness 
ratio, expressed as the incremental cost per incremental ART uptake, comparing 
TA to SA. 
 
The secondary objective of this study is: 
 
1) To explore the key characteristics of HIV testing sites and clinics that successfully 
or unsuccessfully implement SNaP for each study arm. (Aim 3) 
 
We will use qualitative and quantitative site-level data collected at baseline and study 
completion to explore critical site characteristics, such as test site size, readiness to 
change, or implementation climate, of high and low performing sites. Test site-level 
success will be defined based on a high SNaP fidelity score and ART uptake exceeding 
70% in newly diagnosed or previously diagnosed and not currently on ART HIV-infected 
PWID. We will also assess sustainment of the SNaP intervention at 6-10 months post- 
completion of 24 months at a given site.  
 
2.2. 
Study Design 
 
This study is a cluster randomized, implementation trial. The trial is designed to assess two 
implementation approaches (the one size fits all Intervention Mapping approach (SA) and the 
tailored approach (TA) for implementing SNaP, an evidence-based intervention (EBI). The 
SNaP intervention combines systems navigation and psychosocial counseling for people who 
inject drugs (PWID). The intervention is designed to facilitate PWID’s engagement in HIV and 
substance use care. 
 
The study is cluster randomized, and the unit of randomization is HIV test sites. These test sites 
will be randomized to receive either a standard approach (SA) procedure or a tailored approach 
(TA). The cluster sample size is 42 test sites with 1:1 allocation to each study arm. 
 
3. STUDY SETTING AND POPULATION 
 
3.1. 
Study Setting 
 
The study will be conducted in 10 provinces in Vietnam. The provinces are located in the 
mountainous northern, northern delta, northern center, center and Cuu Long delta areas. In 
each of these areas, HIV test sites (n=42 sites) have been chosen based on a high prevalence 
of PWID in the area and in the specific test sites. The study will be performed in these test sites. 
 
3.2. 
Study Population 
 
3.2.1 PWID Participants:  
PWID at the test sites will be enrolled with two levels of engagement for assessment of 
effectiveness outcomes (Aim 1):  

 
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1) For ART and MAT uptake outcomes, eligible participants will: test HIV-positive using 
the standard confirmatory HIV test in Vietnam; be 18 years or older; report a history 
of injection drug use in the past 6 months; and live in the HIV treatment catchment 
area.  
 
Only PWID, not all HIV-infected persons, will be offered SNaP at the selected HIV 
test sites. We conservatively estimate ~6200 eligible PWID over 21 months, after 
accounting for deaths. Most PWID will provide consent only for medical record 
assessment and will not be re-contacted.  
 
2) For viral suppression, a subset of enrolled HIV-infected PWID will be selected and 
asked to additionally consent to re-contact. This subset (n=1500, target n=1200 with 
20% loss to follow-up) will provide contact information and undergo an interview at 
baseline. This group will be re-contacted (see Sections 3.5.1 and 5.5 for retention 
strategy) for interview and assessment of viral suppression at 12 and 24 months 
after site implementation.   
 
A sample of PWID (Sections 5.4, 5.5.1) will also be selected to participate in qualitative 
interviews after 24 months post-implementation, to assess high and low site 
performance characteristics (Aim 3). 
 
Women are a minority of PWID and HIV-infected persons in Vietnam. We will engage 
women in the study in a proportion representative of the HIV-infected PWID population. 
 
3.2.2  HIV Test Site Directors and Staff:  
Site directors and staff will be considered study participants to assess implementation 
outcomes (Aim 1), costs (Aim 2), and high and low site performance characteristics (Aim 
3). Eligible participants will include all site directors and staff at test sites including the 
navigators and counselors in each site. All site directors and staff will provide informed 
consent. 
 
3.3. 
Inclusion Criteria 
 
PWID participants: 
1) HIV infection: 
• 
Newly diagnosed HIV infection, based on confirmatory test at the test site, and not 
currently on ART at the time of the study; or 
• 
If previously diagnosed with HIV infection, then not currently on ART at the time of 
study enrollment (self-reported) 
2) Age 18 years or older 
3) Injection drug use within the past 6 months (self-reported at time of screening) 
4) Willingness to provide informed consent 
 
Site directors and staff: 
1) All site directors and staff, including the navigators and counselors, at the selected HIV 
test sites 
2) Willingness to provide informed consent 
 
 

 
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3.4. 
Exclusion Criteria 
 
PWID participants: 
1) Residence outside of the catchment area of local antiretroviral therapy (ART) and 
medication-assisted treatment (MAT, e.g. methadone) clinics 
2) Currently on ART at time of study enrollment (self-reported) 
3) Planning to move out of the catchment area within the next 24 months.  
 
3.5. 
Recruitment Process 
 
 
The study population comprises HIV-infected PWID not on ART and HIV test site directors and 
staff.   
 
HIV-infected PWID participants will be either newly-diagnosed HIV infected or previously 
diagnosed HIV-infected who are not on ART. PWID participants will provide consent for medical 
record review. A subset of enrolled PWID will also be consented to allow re-contact at a later 
date. This subset will be re-contacted for collection of a dried blood spot for viral suppression 
and a brief questionnaire at baseline, 12, 18 and 24 months. 
 
Test site directors and staff will undergo interviews for measurement of implementation-related 
outcomes. 
 
3.5.1 Persons who inject drugs (PWID) 
All persons meeting the eligibility criteria presenting to 42 HIV test sites in Vietnam will be 
approached for inclusion in the study. Recruitment will immediately follow routine post-test 
counseling procedures. Eligible persons will be informed of the study and consent will be 
requested to access their medical records at local HIV and methadone clinics. In addition, 
consent will be requested for audio-recording of psychosocial counseling sessions. 
Retention for the primary study participants is not required, as the only follow-up is through 
medical record review.  
 
In a subset of the primary study participants (n=1500), we will also obtain consent for re-
contact at a later date. These participants will be contacted by telephone and undergo a 
brief interview. Retention will be facilitated by quarterly contact by telephone to ensure that 
the number has not changed. If we are unable to reach a participant, we will contact a 
family member or friend, using a contact number provided during the original consent 
process. 
 
The expected overall number of PWID is ~335 per month for 21 months or 7035. After 
accounting for approximately 12% mortality, as seen in a previous study, the expected 
number of PWID for outcome measurement is ~6200. 
 
We will enroll a subsample cohort of 1500 PWID to obtain a sample of 1200 PWID for 
detailed assessments, including questionnaires and viral load determination. We recruit all 
eligible PWID into this subsample cohort, until we reach the 1500 sample size. The 1500 
allows for a 20% loss to follow-up (evaluable n=1200).  
 
3.5.2 Site staff & site directors 

 
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All HIV test site staff, including site directors, will be recruited for participation in this 
implementation science study. The study will be explained by the Vietnam Administration 
for HIV/AIDS Control (VAAC) representatives to the site directors. Consent will be 
obtained from all test site staff prior to data collection procedures. 
 
3.6. 
Co-Enrollment Guidelines 
 
Participants should not be currently participating in any other HIV study. 
 
3.7. 
Participant Retention 
 
 
3.7.1 Persons Who Inject Drugs (PWID) 
Retention for the primary PWID study participants is not required, as the only follow-up is 
through medical record review.  
 
In a subset of the primary study participants (n=1500), retention will be facilitated by 
quarterly contact by telephone to ensure that the number has not changed. If we are 
unable to reach a participant, we will contact a family member or friend, using a contact 
number provided during the original consent process. 
 
3.8. 
Participant Withdrawal 
 
Participants may voluntarily withdraw from the study for any reason at any time. The 
investigators may also withdraw participants from the study in order to protect the participant’s 
safety. 
 
Participants may also be withdrawn from the study if the study sponsor, UNC or local IRBs or 
the SMC terminate the study prior to study completion. 
 
Participants will be considered terminated from the study if the participant actively withdraws or 
dies during the course of the study. 
 
4. STUDY INTERVENTION AND IMPLEMENTATION PACKAGES 
 
4.1. 
Evidence-based Intervention: Systems Navigation and Psychosocial Counseling 
(SNaP) 
 
PWID with confirmed HIV infection at the test site will receive the SNaP integrated intervention 
that includes: 1) systems navigation to facilitate engagement and retention in HIV care and MAT 
(currently methadone in Vietnam), and to negotiate required laboratory tests (e.g. CD4 counts) 
or transportation; and 2) psychosocial counseling using motivational interviewing, problem 
solving, skills building, and goal setting to facilitate ART and MAT initiation and adherence.  
 
As an implementation study, navigators/counselors will not be compensated by the study. 
 

 
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Systems navigators will initially meet participants twice, in-person or by telephone, within 8 
weeks of enrollment. Subsequent sessions, based on participants’ needs, will be conducted in-
person, by telephone, or SMS text.  
 
Psychosocial counselors will provide participants with a minimum of one counseling session 
within 4 weeks of enrollment. The session will focus primarily on ART initiation,  ART adherence 
and MAT. To determine the need for additional sessions, the counselor will use a standardized 
inventory to assess the participants’ need for counseling on risk reduction, drug treatment entry 
and retention, HIV medical care, ART and MAT adherence, depression, alcohol dependence, 
and social support. Counseling session content will be incorporated in a manual, similar to that 
used in HPTN 074, which will be used by the counselors to ensure coverage of key topics and 
specific psychosocial counseling techniques.  Participants will be offered the opportunity for 
additional booster sessions, if needed, at ~1 and 3 months after enrollment. Participants who 
have not initiated ART, have low levels of adherence to ART, or have not begun MAT will be 
able to receive additional counseling sessions through self-referral or referral by the systems 
navigators. 
 
We will train existing HIV test site staff, selected by test site directors, to become systems 
navigators and psychosocial counselors for SNaP. 
 
4.2. 
Implementation Packages 
 
Overview:  
Maximizing the public health impact of EBI requires the judicious use of implementation 
strategies, defined as “methods or techniques used to enhance the adoption, implementation, 
and sustainment of a clinical program or practice.”8 Over 70 discrete implementation strategies 
(e.g., audit and feedback, supervision, opinion leaders) have been identified,9,10 but specific 
strategies must be matched to the EBI.11  
 
Effective implementation typically requires selection of multiple discrete strategies to address 
multilevel determinants (barriers and facilitators).12-14 Tailoring implementation strategies to 
address context-specific barriers may be more effective than one size fits all approaches.15 In 
this study, we will use a systematic intervention development protocol, Intervention Mapping,4 to 
develop both standard and tailored implementation strategies. IM is a multistep process that is 
inherently ecological and incorporates theory, evidence, and stakeholder perspectives to ensure 
that intervention components effectively address key barriers to change.   
 
Description of Intervention Mapping: 
Intervention Mapping is one of the most rigorous and relevant approaches to designing 
implementation strategies.2,3 It will be used to identify a core set of discrete strategies for the 
standard condition and that may be used for the tailored condition. We believe that the standard 
multifaceted strategy will address the primary barriers faced by the majority of clinics. However, 
there is evidence that implementation strategies may be more effective if they are tailored to 
specific contexts,4 and emerging perspectives on tailoring suggest that barriers may need to be 
assessed and addressed in an iterative fashion throughout the process of implementation.5 
Thus, while clinics in the tailored condition will have access to the multifaceted implementation 
strategy developed for the standard condition, it will differ in several important ways.  
 
First, the tailored condition will also have access to an additional menu of implementation 
strategies derived from the Intervention Mapping process that will be connected to potential site-

 
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specific barriers. Second, they will receive three 1-hour coaching sessions with the central 
implementation team that will focus on identifying and prioritizing site-specific barriers and 
identifying theory and evidence-based implementation strategies to address them. Third, the 
tailoring approach will be dynamic in that monthly calls with the central implementation team will 
afford the opportunity to identify new barriers and strategies throughout all phases of 
implementation.  
 
The tailored strategies that each clinic deploys may be less intensive than the “standard” 
condition if they have strong infrastructure and implementation support already in place, or more 
intensive if numerous site-specific barriers need to be addressed. We believe that both the 
standard and tailored conditions will be effective in improving implementation and clinical 
outcomes, but that the tailored condition will outperform the standard condition as it more 
appropriately addresses site-specific needs.  
 
Central Implementation Teams: 
A central implementation team will be used to conduct the Intervention Mapping that occurs 
prior to randomization (Figure 1). 
 
After randomization, two central implementation teams (one for each arm) will facilitate study 
implementation. Implementation will be done for both arms simultaneously in a rolling process, 
working systematically through the regions of Vietnam.  
 
Central implementation teams will have separate group calls with the SA and TA test sites every 
6 months to share experiences and lessons learned. 
 
Each central implementation team will comprise:  
1) A UNC-Vietnam Hanoi staff member,  
2) A VAAC representative, and  
3) A Hanoi Medical University (HMU) representative. 
 
Summary of SA and TA Procedures:  
Prior to randomization (see Figure 1), standard intervention mapping approach (SA) arm will be 
conducted at the central level, by our study’s IM central implementation team, for all 42 sites. 
As the SA will be conducted at the central level (i.e., not site-level), it will not be specific to a 
particular site. The SA will be applied to all 42 sites as the standard implementation package. 
Then, after randomization, the 21 sites randomized to the Tailored Approach (TA) arm will 
receive additional tailored Intervention Mapping. The TA central implementation teams will 
conduct tailored Intervention Mapping at each TA site, tailoring the implementation strategies to 
fit each TA site specifically. 
 
4.2.1 Standard Implementation Package:  
 
 Intervention Mapping (SA arm): 
 
  
In Year 1, during the Pre-implementation Phase of this study (see Section 5.1), the 
central implementation team will engage our local partners to accomplish the following 
steps of Intervention Mapping: 
 
Step 1: Conduct a needs assessment to identify determinants (barriers and 
facilitators) of implementation. The needs assessment will draw upon data from 
HPTN 074, which included qualitative interviews with navigators, counselors, 

 
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clinic directors, and PWID on their experiences with SNaP and surveys among 
PWID on acceptability of SNaP. We will partner with our OAB and the VAAC to 
identify additional determinants 
 
Step 2: State outcomes (e.g., implementation outcomes such as fidelity, 
penetration, acceptability, and costs; effectiveness outcomes such as ART 
uptake, viral suppression, and MAT uptake) and performance objectives (e.g., 
who needs to do what to implement and sustain SNaP).  
 
Step 3: Create matrices that relate determinants (Step 1) to performance 
objectives (Step 2), and list specific change objectives that will serve as “targets” 
that need to be addressed by theory and evidence-based implementation 
strategies.  
 
Step 4: Identify appropriate implementation strategies. This step will draw upon 
previously published compilations of implementation strategies, as well as 
behavior change techniques and methods that are useful in specifying the 
theoretical mechanisms by which these strategies may exert their effects. 
 
Based upon our preliminary work from HPTN 074, we anticipate that the implementation 
strategy will include opinion leader, leadership buy-in, and external technical assistance, 
but additional strategies will undoubtedly emerge during Intervention Mapping. The 
protocol for this strategy will be formalized for use in both SA and TA arms. 
 
The initial Intervention Mapping process will yield a multifaceted implementation strategy 
that we believe will be feasible for national scale-up (SA condition). It will also yield a 
more extensive list of implementation strategies that can be used by HIV test sites to 
address site-specific barriers in the TA condition. 
 
4.2.2 Tailored Implementation Package: 
  
 Tailored Approach (TA): Intervention Mapping + tailoring (TA) 
 
In addition to having access to the standard implementation package, TA sites will have 
access to a broader menu consisting of 4-6 strategies identified through the Intervention 
Mapping process. Participating agencies (provincial health officials, HIV test sites) in TA 
will receive resources and coaching to assist them in tailoring their implementation 
strategy to address key determinants of change throughout the implementation process. 
Consistent with our guiding determinant framework8 (CFIR9), we will assess inner setting 
factors that may influence implementation processes, including: organizational readiness 
to change, implementation leadership, and implementation climate, and available 
resources.  
 
We will conduct this assessment using a structured form to be completed by each of the 
21 clinics in the TA arm electronically, prior to implementation. These assessments will 
suggest site-specific targets for change that could be addressed through tailored 
implementation strategies. 
 
Each TA site will also receive three 1-hour coaching sessions from the central TA 
implementation team via video-conference. These calls will address additional site-
specific barriers to implementation through a structured brainstorming process,16 

 
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prioritizing barriers that are most important and modifiable, and selecting theory and 
evidence-based strategies from the Intervention Mapping-based menu that address 
them. Some test sites will need to engage in strategies in addition to the standard 
implementation package to address site-specific needs. However, some sites may not 
need to use all strategies outlined in the standard IM implementation package. For 
example, if a test site already has strong supportive leadership in place, it may not need 
to use the leadership buy-in activities. 
 
A central TA implementation team will have monthly calls with local implementation 
teams to monitor each TA site. Calls will focus on site-specific challenges and assess 
ongoing implementation. If adjustment is needed, site-specific standard operating 
procedures (SOP) will be updated by the site and reviewed centrally, and the central TA 
implementation team will re-train TA site implementation staff by video-conference. 
 
5. STUDY PROCEDURES 
 
An overview of study visits and procedures is presented below. Summaries of the participant 
schedules of visit procedures are presented in Appendices I, II, and III. Detailed instructions to 
guide and standardize study procedures across test sites will be provided in the SOPs. The 
UNC and UNC-Vietnam staff are responsible for developing all SOPs.  
 
5.1. 
Pre-implementation Study Procedures 
 
In Year 1, pre-implementation activities will include: 
1) Develop assessment instruments and SOPs 
2) Meet with provincial leaders 
3) Conduct Intervention Mapping 
4) Randomize test sites 
5) Conduct baseline assessment of site context 
6) Trainings: 
o Train navigators and counselors 
o Train on seek strategies 
o Train on implementation strategies 
 
5.1.1  Developing assessment instruments and SOPs 
Our study investigators and UNC staff will develop assessment instruments for the 
baseline assessments and trial, and UNC and UNC-Vietnam staff will develop SOPs for 
the study. 
 
5.1.2  Meetings with provincial leaders  
Our centralized implementation team comprised of UNC-Vietnam, VAAC, and HMU staff 
will meet with each provincial AIDS committee in the study provinces to disseminate HPTN 
074 findings and introduce SNaP, SA and TA processes, and the cluster randomized 
implementation trial. 
 
5.1.3  Intervention Mapping  
Prior to randomization and baseline assessment, we will apply Intervention Mapping to 
systematically identify implementation strategies for the SA arm and the menu of 

 
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implementation strategies for the TA arm. See Section 4.2.1 for detailed Intervention 
Mapping steps to be conducted in Year 1. 
 
5.1.4  Randomization  
We obtained a complete list of the 136 HIV test sites in Vietnam, including the number of 
persons tested per month, positivity rates, and proportion of PWID. These data have been 
used to identify 42 proposed test sites for inclusion in this implementation study.  
 
Test sites will be stratified by region and size, then randomized to either arm at a 1:1 ratio 
(21 sites per trial arm). Randomization will be blocked within strata to ensure equal 
distribution by arm. 
 
5.1.5  Baseline assessment of site context (see also Section 7.1) 
After randomization and prior to SNaP intervention implementation (Figure 1), we will ask 
each of the 42 test sites to complete a survey assessing the following baseline 
measurements at each site: 
 
Site demographic characteristics (in the past 12 month): 
• 
Number of HIV tests performed 
• 
PWID size (number of HIV tests performed who are PWID) 
• 
PWID proportion (number of PWID over total tests performed) 
• 
Sex distribution (men and women who are PWID) 
• 
Staff information 
• 
Current support from Non-governmental organizations (NGOs) 
 
Baseline test site context measurements (see Table 1 for details): 
• 
Organizational readiness to change  
• 
Implementation leadership 
• 
Implementation climate  
 
Sites will be asked to complete a Qualtrics survey assessing each of these measurements 
and return it within 1 week.  
 
Table 1. Test site context measures 
Test site context 
measure 
Definition 
Measure or Scale* 
Organizational 
readiness to change 
Organizational members’ shared resolve 
to implement change and shared belief in 
collective capability to do so. 
ORIC: 12-item scale used to measure 
readiness for implementation.17  
Implementation 
leadership  
Degree to which a leader is proactive, 
knowledgeable, supportive in evidence-
based practice implementation. 
Implementation Leadership Scale (ILS): 
12-item scale with 3 items measuring 
each of the 4 dimensions.18 
Implementation 
climate 
The extent to which organizational 
members perceive that innovation use is 
expected, supported and rewarded.19 
Implementation Climate Scale 
6-item scale measuring expectations, 
support & rewards.20 
 
The assessments of the 21 TA sites will be used to tailor and finalize implementation 
packages for each TA site (see Section 4.2.2). 
 
5.1.6  Trainings 
• Selection and training of navigators and counselors:  

 
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We will train existing HIV test site staff, selected by test site directors, to become 
systems navigators and psychosocial counselors for SNaP. Test sites will 
nominate up to three staff per test site as systems navigators and/or counselors. 
Similar to HPTN 074, the roles of navigators and counselors may be performed 
by a single person or two distinct persons at the discretion of the test site.  
 
We will conduct regional (north, south, central) trainings for navigators and 
counselors for all study test sites to ensure that SNaP training is uniform across 
study arms prior to notifying the sites of their SA/TA allocation.  
 
The 2-day, in-person training will be conducted by the centralized training 
team and rely heavily on the training manual developed for HPTN 074, which will 
be minimally modified for use at scale. The training will include introduction to 
motivational interviewing, counseling techniques practices, and a series of 
guided role play activities, in which real-time feedback will be provided by the 
training team. Any new navigators or counselors will be trained similarly. 
Refresher trainings will be held annually. 
 
• Training on seek strategies:  
At the regional training, implementation teams will provide strategies to reach out 
to PWID in their catchment area. Strategies will include communicating with 
needle exchange sites, MAT clinics and other substance use treatment centers 
(including mandatory 06/07 detoxification centers). The goal is to ensure active 
referrals of MAT patients to HIV test sites and provide information cards about 
HIV testing to PWID to distribute in their networks. These strategies were used to 
effectively “seek” PWID in HPTN 074. 
 
• Training on implementation strategies for SA and TA:  
During or immediately after the navigator/counselor regional training, a 2-day 
regional training will be held for all test sites to introduce the project, orient to 
common implementation barriers and facilitators across sites, and train teams on 
the SA implementation package. TA implementation teams will subsequently visit 
each TA site in the region to conduct trainings on site-specific implementation 
strategies.   
 
5.2. 
Cluster Randomized Implementation Trial Initiation (Aim 1) 
 
After training completion, sites will implement the SNaP intervention and initiate the trial (Time 0 
in Figure 1). SNaP will be implemented as the study rolls out. Specifically, upon trial initiation, 
trained navigators and counselors will provide SNAP to all accepting PWID testing positive for 
HIV at the test sites. Time 0 for each site will be the first day that the SNaP intervention is 
offered at that site.  
 
Each site will consent PWID with a positive confirmatory test at the post-test counseling visit 
who are willing to allow medical chart review at MAT and ART clinics. Injecting drug use 
information is collected as part of routine protocol at HIV test sites and will be used to identify 
eligible participants for the study.  
 
 
5.2.1  Central Implementation Teams (see also Section 4.2) 
As stated in Section 4.2, distinct central implementation teams (one for each arm) will 
facilitate study implementation. Each implementation team will comprise:  

 
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1) A UNC-Vietnam Hanoi staff member,  
2) A VAAC representative, and  
3) An HMU representative.  
 
Implementation will be done for both arms simultaneously in a rolling process, working 
systematically through the regions of Vietnam. Central implementation teams will have 
separate group calls with the SA and TA test sites every 6 months to share experiences 
and lessons learned. 
 
 
 
5.3. 
Cost-effectiveness Data (Aim 2) 
 
Measurements: Based on our prior experience with costing behavioral interventions to reduce 
hazardous alcohol use in Vietnam we will conduct an empirical costing study of SNaP—
including SA and TA and the actual process of implementation itself—from a societal 
perspective.  
 
We will estimate implementation costs prospectively by: 
- 
Embedding a trained costing specialist within each central implementation team (one per 
arm),  
- 
Documenting all resources used (e.g., staff training level and time, travel costs, supplies, 
etc.) and  
- 
Estimating the unit cost of each resource.  
 
To estimate the unit health system cost of each intervention, we will perform detailed budgetary 
analysis including: 
- 
Interviews of key staff,  
- 
Review of logbooks/timesheets, and  
- 
Time-and-motion studies to record navigator, counselor, and other staff time devoted to 
various activities on ≥15 randomly selected days,  
o This will be conducted by the costing specialists, in each of 12 clinic sites (6 sites 
per arm, selected purposively to provide representation of patient volume, 
urban/rural status, and geography) over the course of the trial.  
 
To estimate patient costs, we will: 
- 
Administer a survey to a smaller subset of the 1500 PWID subsample cohort at baseline 
and at a single follow up visit of 12 or 18 or 24 months (depending on enrollment time of 
PWID participants)- to collect data on direct and indirect (lost wages, child care, etc.) 
costs of clinic visits and other elements (e.g., medication side effects) associated with 
ART, MAT, and SNaP itself. We will randomly sample up to 420  PWID participants 
among the 1500 PWID subsample cohort to administer this survey. 
 
Cost data collection will be based on the Tool to Estimate Patient Costs, which we have 
adapted and used in Uganda.21 
 
5.4. 
Procedures to Identify and Characterize High and Low Performing and 
Sustaining Sites (Aim 3)  
 
We will identify high and low performing sites in both study arms based on SNaP fidelity and 

 
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ART uptake targets for PWID clients. We will assess these characteristics qualitatively and 
quantitatively.  
 
To assess characteristics of high and low performing sites in depth, we will conduct qualitative 
interviews with: 
- 
HIV-infected PWID, including those that received SNaP and those that declined,  
- 
systems navigators and psychosocial counselors, clinic staff, and clinic directors in both 
SA and TA arms.  
- 
Health providers and/or adherence counselors at HIV outpatient clinics near these test 
sites in both SA and TA arms 
 
We will also assess the characteristics of high and low performing sites based on quantitative 
characteristics derived from the implementation outcomes, test site demographics, and test site 
context.  
 
To assess characteristics of high and low sustaining sites in depth, we will conduct qualitative 
interviews with: 
- 
Systems navigators and psychosocial counselors, clinic staff, and clinic directors in both 
SA and TA arms.  
 
We will also assess the characteristics of high and low sustaining sites based on quantitative 
characteristics derived from the implementation outcomes, test site demographics, and test site 
context.  
 
Our a priori definition of successful implementation at 24 months is: 
• 
A site with a fidelity score of 136 (see Section 7.2) and 70% ART uptake among its 
newly diagnosed or previously diagnosed and not currently on ART PWID clients.  
 
The fidelity score and ART uptake are based on the Vietnam site’s experience in HPTN 074. In 
the SNaP arm of HPTN 074, 72% of PWID were using ART at 12 months; in Vietnam, 88% of 
PWID were using ART at 12 months. Based on these results, 70% is a reasonable target for this 
implementation trial.  We will consider any person lost to follow up as having failed ART use and 
not virally suppressed.  
 
5.4.1 High and Low Performing and Sustaining Sites Data Collection: 
 
In-depth interviews - PWID at high and low performing sites: We will conduct six semi-
structured in-depth interviews (IDIs) with PWID in each of three sites of the following four 
site performance types (12 test sites; 72 interviews): 1) SA low performers; 2) SA high 
performers; 3) TA low performers; and 4) TA high performers. Three PWID will have 
participated in SNaP and three PWID will have declined SNaP. We will ask participants 
about barriers and facilitators to uptake of ART and MAT and ART adherence, attitudes 
and experiences in the HIV test site, with test site staff, and if appropriate, with 
navigators and counselors.   
 
In-depth interviews - navigators and counselors, clinic staff, and clinic directors: In these 
same 12 test sites, we will conduct semi-structured IDIs with navigators/counselors 
(n=12-24), site staff (n=12), site directors (n=12) and HIV providers (n=12) to inform the 
context and processes that may underlie SNaP success and failures (total n=48-60, 
depending on the number of navigators and counselors at each site). Topics will include 
PWID-related stigma; attitudes toward and experience with SNaP, SA, and TA 

 
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implementation packages; competing site priorities; perceptions of rewards and 
leadership support around SNaP; perceptions of effectiveness of SNaP, SA and TA; 
availability of technical assistance; beliefs around sustainability of SNaP at their test site; 
collaboration between HIV test sites and HIV outpatient clinics. 
 
Quantitative characterization of high and low performing clinics: We will use the 
implementation test site context scales for readiness to change, implementation 
leadership, and implementation climate to characterize each clinic before and after 
implementation of SNaP. We will also characterize the test sites in terms of overall size 
(number of HIV tests performed), PWID size (number of HIV tests performed who are 
PWID),PWID proportion (number of PWID over total tests performed), staff information 
and current support from NGOs Clinic and PWID characteristics will be assessed before 
and after implementation. 
 
Sustainment survey: We will administer the 3-question Provider REport of Sustainment 
Scale (PRESS) scale to site staff (including counselors and navigators) who were 
involved with the delivery of SNaP 6-10 months following the completion of the SNaP 
activities at each site. The purpose of the scale will be to assess the sustainment of the 
SNaP intervention at each of the sites, as well as characteristics of high and low 
sustaining sites. Study staff will contact site staff at the 42 HIV test sites that were 
involved in the SNaP study to invite them to participate in the survey. About 252 clinic 
staff (6 per site) will participate in the survey. Clinic staff who are interested in 
participating will be emailed electronic consents via a Qualtrics database to read and 
sign (if they choose to participate in the survey). They will then complete the fully self-
administered survey on Qualtrics. The survey should take no more than 5 minutes to 
complete.  
 
Sustainment in-depth interviews: We will conduct in-depth interviews with clinic 
navigators/counselors (n=12) and site staff or site directors (n=24) from a sub-sample of 
12 of the SNaP scale-up sites at 6-month post-endline. Based on their scores on the 
PRESS, we will randomly select 6 “high sustainer” and 6 “low sustainer” clinics for these 
interviews. The purpose of these interviews is to understand how SNaP and SNaP 
implementation strategy adaptations influence normalization and sustainment of the 
SNaP intervention into HIV testing clinics after the removal of external study support. 
SNaP study staff will contact clinic navigators, site staff, and site directors and will invite 
them to participate in the interviews. All interviews will be conducted over Zoom in 
Vietnamese by bilingual Vietnamese research assistants trained in qualitative 
interviewing. Participants will provide informed consent before being interviewed. The 
interviews are expected to last approximately one hour. All interviews will be audio-
recorded, transcribed verbatim, and translated to English.  
 
 

 
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5.5. 
Participant Study Procedures 
 
Pre-implementation assessment of site context will be conducted among site directors and site 
staff. After implementation of the SNaP intervention at test sites (Time 0), post-implementation 
assessments will occur to evaluate implementation and effectiveness study outcomes. 
 
 
PWID Data  
 
PWID enrollment: All PWID who are confirmed HIV-infected will be given a brief consent 
form during post-test counseling. This consent will address permission to: 1) extract ART 
uptake from medical records at local ART clinics and 2) extract MAT uptake from medical 
records at MAT clinics. Note that consent for SNaP will not be explicitly requested, as it 
will be considered a routine clinical activity at that site upon trial initiation. 
 
ART and MAT uptake data: To initiate ART, all persons in Vietnam must present a 
confirmation of diagnosis to the ART clinic. Using participants’ study masked ID (MID), we 
will then review the medical record at ART clinics to confirm ART initiation. A similar 
process will be used for MAT uptake data. These data will be extracted semi-annually.  
 
Viral suppression and interview data: During months 0-6 and 12-18 after implementation in 
each test site, a random sample of PWID will be identified for participation in the 
subsample cohort. These PWID will have an additional consent to allow re-contact and to 
obtain locator information, including a family member. A few days after diagnosis, the 
PWID subsample cohort will undergo a brief demographic, behavioral, mental health, and 
costing questionnaire, administered through the phone by a test site staff member trained 
and compensated to collect these data.  
 
To enhance retention, the subsample cohort of 1500 PWID will be re-contacted every 
3-4 months to maintain contact. If contact with the PWID cannot be established, the family 
member will be contacted in an attempt to update the locator information. Trained study 
staff (including training in confidentiality) will attempt to contact family members by phone. 
If after several attempts the family members are not reached by phone, our trained study 
staff will attempt to visit the home. (See also Section 9.6.1.)  
 
At 12 months post-implementation at a test site, the PWID group enrolled at 0-6 
months will be contacted to return to the test site, where a dried blood spot specimen will 
be collected for viral load testing. A brief questionnaire will also be administered through 
the phone. The questionnaire will address PWID’s perceptions of SNaP and factors that 
may affect uptake of ART and MAT, including sociodemographic characteristics, injecting 
behaviors,, and costs (costing questionnaire will be administered to only a smaller subset 
of the 1500 PWID subsample cohort). The PWID will be given an incentive for participation 
in the subsample cohort.  
 
At 18 months post-implementation, this process will be repeated with PWID group 
enrolled at 0-12 months. The costing questionnaire will only be administered at this follow-
up to only a smaller subset of the 1500 subsample cohort enrolled at 7-12 months. 
 
At 24 months post-implementation, this process will be repeated with PWID group 
enrolled at 0-18 month. The costing questionnaire will only be administered at this follow-
up to a only a smaller subset of the 1500 subsample cohort enrolled at 13-18 months. With 
this approach, all PWID in the subsample cohort will be assessed for viral suppression 6-
12 months after diagnosis (n=1200) (see Section 3.5.1 for explanation of n=1200); the 0-6 
month group will have the 12 18, and 24 month assessments and the 13-18 month group 
will have the 24 month assessment (Figure 1). 

 
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Routine HIV Testing Data: Each test site routinely maintains a log of persons tested for 
HIV, including associated risk behaviors, such as injection drug use and sexual behavior. 
These data will be de-identified and used to provide the denominator for the total number 
of PWID diagnosed with HIV infection. 
 
 
HIV Test Site and HIV outpatient Clinic Staff and Director Data 
 
In each test site, directors, physicians, nurses, and other site staff will undergo brief 
quantitative interviews (up to 1 hour in length) at pre-implementation and at 12 and 24 
months post-implementation. These interviews will be administered with Qualtrics to 
assess acceptability of the intervention and site context including organizational readiness 
to change, implementation leadership, and implementation climate (Table 1). Site staff will 
also undergo a 3-question survey at 6-10 months post endline, as described in Section 
5.4.  Qualitative in-depth interviews will be conducted after 24 months post-implementation 
and 6-10 months post-endline, as described in Section 5.4, at HIV test sites and HIV 
outpatient clinics. 
 
 
5.5.1 Visit Procedures for PWID Participants: Post-implementation (Appendices I-III) 
 
 
If the PWID accepts the SNaP intervention and is eligible and willing to participate in the 
implementation trial, the following procedures will occur as part of study enrollment:  
 
5.5.1.1  PWID Not in Subsample Cohort (n= approx. 5000) 
PWID who present to one of the 42 selected HIV test sites at any time point post-
implementation of SNaP at that site will be offered the SNaP intervention, regardless of 
PWID participation in the implementation trial (see also Appendix I):  
 
 
Enrollment Procedures: 
 
Administrative, Behavioral, and Regulatory Procedures 
• 
Informed consent to participate in the implementation trial 
o Consent will be obtained during post-test counseling at the site 
• 
Bar code sticker placed on PWID’s HIV confirmation test result card  
 
 
Laboratory Evaluations 
• 
No laboratory evaluations 
 
 
 
12-Month and 24-Month Follow-up Procedures: 
 
 
Administrative, Behavioral, and Regulatory Procedures 
• 
None 
o No direct contact with participant for follow-up procedures 
o Only the participant’s ID will be used at ART and/or MMT clinic if 
the participant presents to either of those clinics after enrollment 
 
 
Laboratory Evaluations 
• 
None 
 
 

 
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Post-24-Month Assessment Qualitative Interview Procedures [among 
randomly selected PWID at 12 selected sites] (see Section 5.4.1): 
 
 
Administrative, Behavioral, and Regulatory Procedures 
• 
Informed consent to participate in qualitative in-depth interview 
• 
Qualitative in-depth interview 
 
 
5.5.1.2  PWID Subsample Cohort (n=1500) 
The subset of 1500 enrolled PWID will be selected to participate in a PWID subsample 
cohort that will provide locator and contact information, and be re-contacted to 
participate in study follow-up procedures (see also Appendix II). We will recruit all 
eligible PWID into this subsample cohort, until we reach the 1500 sample size. A subset 
of the PWID subsample cohort will be selected to complete additional costing questions 
at baseline and a single follow-up visit of 12 or 18 or 24 months, depending on PWID 
enrollment time. 
 
 
Enrollment Procedures: 
 
Administrative, Behavioral, and Regulatory Procedures 
• 
Informed consent to participate in the implementation trial 
o Consent will be obtained during post-test counseling at the site 
• 
Additional informed consent  
o To allow for re-contact and follow-up study procedures 
• 
Provide locator information 
• 
Quantitative questionnaire (through phone interview) 
 
Laboratory Evaluations 
• 
No laboratory evaluations at enrollment 
 
 
 
12-Month Follow-up Procedures: 
 
Administrative, Behavioral, and Regulatory Procedures 
• 
Quantitative questionnaire (through phone interview) 
 
  
 
Laboratory Evaluations 
• 
Dried blood spot specimen collection 
 
 
18-Month Follow-up Procedures: 
 
Administrative, Behavioral, and Regulatory Procedures 
• 
Quantitative questionnaire (through phone interview) 
 
  
 
Laboratory Evaluations 
• 
Dried blood spot specimen collection 
 
 
24-Month Follow-up Procedures: 
 
Administrative, Behavioral, and Regulatory Procedures 
• 
Quantitative questionnaire (through phone interview) 
 
  
 
Laboratory Evaluations 
• 
Dried blood spot specimen collection 
 

 
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Post-24-Month Assessment Qualitative Interview Procedures [among 
randomly selected PWID at 12 selected sites] (see Section 5.4.1): 
 
 
Administrative, Behavioral, and Regulatory Procedures 
• 
Informed consent to participate in qualitative in-depth interview 
• 
Qualitative in-depth interview 
 
 
5.5.2 Visit Procedures for Test Site Directors and Site Staff Participants  
 
 
 
See also Appendix III. 
 
 
 
 Pre-Implementation Baseline Assessment Procedures: 
 
 
Administrative, Behavioral, and Regulatory Procedures 
• 
Informed consent to participate in the implementation trial 
• 
Quantitative questionnaire via Qualtrics 
o To assess HIV test site characteristics (site demographics and 
site context) 
 
 
 
  
12-Month Post-Implementation Assessment Procedures: 
 
 
Administrative, Behavioral, and Regulatory Procedures 
• 
Quantitative questionnaire via Qualtrics 
o To assess HIV test site characteristics (site demographics and 
site context) 
o To assess acceptability of the intervention 
 
 
 
  
24-Month Post-Implementation Assessment Procedures: 
 
 
Administrative, Behavioral, and Regulatory Procedures 
• 
Quantitative questionnaire via Qualtrics 
o To assess HIV test site characteristics (site demographics and 
site context) 
o To assess acceptability of the intervention 
 
 
Post-24-Month Assessment Qualitative Interview Procedures [among site 
staff (n=12), site directors (n=12) and HIV providers (n=12) at 12 selected sites] 
(see Section 5.4.1): 
 
 
 
Administrative, Behavioral, and Regulatory Procedures 
• 
Informed consent to participate in qualitative in-depth interview 
• 
Qualitative in-depth interview 
 
 
6-10 Months Post-endline Assessment Procedures (see Section 5.4.1): 
 
 
Administrative, Behavioral, and Regulatory Procedures 
• 
Informed consent to participate in PRESS survey 
• 
PRESS survey  
 

 
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Administrative, Behavioral, and Regulatory Procedures [among site 
navigators/counselors (n=12), site directors/staff (n=24) at 12 selected 
sites] (see Section 5.4.1): 
 
• 
Informed consent to participate in qualitative in-depth interview 
• 
Qualitative in-depth interview 
 
 
5.6. 
Study Procedures for System Navigators and Counselors at Sites  
 
Navigators and counselors are part of the Site Staff and, if they consent, they will participate in 
the visit procedures for Site Directors and Staff in Section 5.5.2.  
 
Separately, as part of their work as site staff navigators/counselors at the HIV test site, at each 
navigator and counselor session, navigators and counselors will complete the following: 
 
• 
Maintain a log of PWID engaged in their care.  
o This log will capture, in a simple format, the PWID’s name, medical record 
number, and the type of encounter.  
• 
After each navigation or counseling session, complete a brief encounter form, based 
on those used in HPTN 074:  
o The navigation form will capture the mode of communication (in-person, 
telephone, SMS text), ART/MAT status, availability of a social support person, 
duration of the encounter, and encounter content (HIV care, ART, MAT, sexual 
health, etc.).  
o The counseling form will capture the type of session (initial or booster), 
availability of social support, session focus, barriers addressed, duration, and 
need for systems navigation.  
o These forms will be forwarded monthly to the Hanoi study site for data entry.  
• 
All counseling sessions will also be audio-recorded and reviewed periodically by 
site supervisors to provide feedback to counselors, as a standard procedure. Consent 
for audio-recording will be obtained from the study participant. 
 
5.6.1  Quality of navigation sessions  
The quality of navigation sessions will be measured by rating the navigator encounter 
forms. For each site, the central implementation teams will review the first 10 navigation 
encounter forms and a randomly selected 50% of all remaining navigation encounter 
forms, and rate each encounter on a 5-point quality scale from poor to excellent.  
 
5.6.2  Quality of counseling sessions 
For each site, the central implementation teams will also review the first 5 counseling 
session audio-recordings and a randomly selected 50% of all remaining counseling 
session audio-recordings and rate each on a 10-point quality scale.  
For central review of recordings, identifying information of the PWID will not be provided to 
the central team. The quality rating forms and recordings will be forwarded monthly to the 
Hanoi team.   
 
Navigators/counselors will be compensated for time as Site Staff study participants at study 
visits (Section 5.5.2), such as for their time answering study questionnaires 

 
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 and in-depth interviews. However, as an implementation study, navigators/counselors will not 
be compensated by the study for their work as navigators/counselors at each HIV test site, as 
their work delivering the SNaP intervention will be run by the HIV test site. 
 
 
 

 
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6. SAFETY MONITORING AND ADVERSE EVENT (AE) REPORTING 
 
6.1. 
Safety Monitoring 
 
The study will be monitored through close collaboration of the study principal investigators, 
implementing sites, Vietnam collaborators, and the appropriate institutional review boards. 
Particular care is given due to the high-risk nature of this study population. 
 
At each contact with PWID and HIV test site directors and staff, the study team will ask about 
any social harms experienced as a result of study. We will also provide all participants with 
study contact information and ask that they contact us immediately if they experience any social 
harm or other adverse event, such as disruption of families, acts of discrimination or physical 
harm. Study staff will refer people to appropriate care should an adverse event come to our 
attention that needs professional or medical intervention. If a social harm is reported, a short 
questionnaire will be administered to characterize the social harm and describe its impact. All 
reported social harms will be documented and communicated to the HMU IRB and the UNC IRB 
within 7 days.  
 
We will establish a safety monitoring committee (SMC) comprising at least three people. The 
SMC will meet at the outset of the study in person then semi-annually by telephone or in person. 
The semi-annual SMC meeting will assess whether study objectives are being met and will 
ensure that benefit exceeds harm. The SMC will review the protocol, assessments, and consent 
forms prior to study initiation. The SMC will receive all reports of AEs at the same time that the 
AEs are forwarded to the HMU and UNC IRBs. Severe AEs will trigger an immediate meeting of 
the SMC. Additional meetings of the SMC can be scheduled, as needed, to discuss and resolve 
AE issues. Members of the SMC will include representatives of the government sponsored HIV 
test sites, an infectious disease physician, epidemiologist or other expert, and a methodologist. 
The SMC will submit minutes following every meeting to UNC IRB and the HMU IRB. 
 
6.2. 
Adverse Event Reporting 
 
Non-serious adverse events will be collected and recorded in the source documentation with 
referrals as necessary, but not reported in the database as part of this research protocol for all 
study participants. Non-serious adverse events will be collated and reported to the SMC for 
each SMC meeting. This report will be shared with the appropriate institutional review boards. 
 
Serious AEs (SAEs) are defined per International Conference on Harmonisation (ICH) guidance 
and will be collected and reported on case report forms (CRFs) for all study participants. Only 
SAEs leading to death, life threatening SAEs and suspected unexpected serious adverse 
events (SUSAEs) will be reported to the PIs within 24 hours of the study site learning of the 
SAE, and reported to the SMC within 72 hours and the appropriate institutional review boards 
within 7 days from the time site staff learned of the SAE. Other SAEs will follow the reporting of 
non-serious adverse events. 
 
6.3. 
Social Impact Reporting  
 
It is possible that participants' involvement in the study could become known to others, and that 
a social impact may result (i.e., because participants could be perceived as being HIV-infected 

 
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or at risk or "high risk" for HIV infection). For example, participants could be treated unfairly, or 
could have problems being accepted by their families and/or communities. A social impact that 
is reported by the participant and judged by the PIs to be expected or not. If a social impact is 
not unexpected, site staff will complete a detailed description of the impact using the UNC IRB’s 
New Safety Information. This report will be reported to the SMC within 72 hours and the 
appropriate institutional review boards within 7 days from the time site staff learned of the 
unexpected social impact. 
 
Given the status of illegal drug use, the associated social stigma and perceptions of drug users 
held by many members of the communities in which the study will be conducted, social harms 
could occur purely as a result of participation in a study targeting drug users. These could 
include discriminatory treatment and violence associated with possible disclosure of participants' 
drug or sex-related behaviors or of their HIV serostatus. 
 
 
7. STUDY ASSESSMENTS AND OUTCOMES  
 
7.1. 
Site-level Assessments  
 
To assess the site characteristics, we will ask test sites (site directors and staff) to provide 
information at the start of the study (i.e., at baseline, pre-implementation), and at 12- and 24- 
months post-implementation on the following site characteristics: 
 
Site demographic characteristics (in the past 1 month): 
a. Number of HIV tests performed 
b. PWID size (number of HIV tests performed who are PWID) 
c. PWID proportion (number of PWID over total tests performed) 
d. Sex distribution (men and women who are PWID) 
 
Site context characteristic measures (Table 1): 
a. Organizational readiness to change – ORIC scale 
b. Implementation leadership – Implementation Leadership Scale 
c. Implementation climate – Implementation Climate Scale 
 
7.2. 
Implementation Outcomes (Aim 1) 
 
7.2.1  Primary Implementation Outcome 
The primary implementation outcome will be fidelity to SNaP intervention procedures 
(Table 2). Fidelity is measured as follows: 
 
Fidelity = (% navigation sessions completed * % quality score +  
% counseling sessions completed * % quality score) 
 
Fidelity will be measured at the test site level by assessing each site’s success in 
completing the three protocol-specified sessions (two navigation, one counseling) within 
the required eight- or four-week period, respectively, weighted by the central 
implementation team’s quality rating of those sessions. Session completion will be 
assessed by reviewing the navigator and counselor logs, while session quality will be 

 
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assessed by central implementation team review and scoring of the first 10 and 5 of all 
forms (navigation) and audio-recordings (psychosocial counseling) respectively and a 
random 50% of all remaining forms and audio-recordings at each site, as described in 
Section 5.6 above. Reviewers will be masked to the arm when reviewing navigation forms 
or audio-recordings. For context, in HPTN 074, the Vietnam site achieved >85% 
completion of the 4 sessions in the protocol-specified windows, showing that in the context 
of a carefully monitored trial, high completion of appointments within an eight-(SN) or four-
week (PC) window by this population is feasible.   
 
The test site fidelity score will range from 0-200. The score will be the percentage of 
expected navigation sessions that are completed, multiplied (weighted) by the average 
quality rating of navigation sessions; plus the percentage of expected counseling sessions 
that are completed, multiplied by the average quality rating of counseling sessions. Thus, 
a site completing all navigation sessions with a perfect quality rating (100 points) and all 
counseling sessions with a perfect rating (100 points) would receive the maximum fidelity 
score of 200 points, whereas a site completing 90% of navigation sessions with an 80% 
average quality score (100*0.9*0.8 = 72 points) and 80% of counseling sessions with an 
80% average quality score (100*0.8*0.8 = 64 points) would receive a total score of 72 + 64 
= 136 points.   
 
7.2.2  Secondary Implementation Outcomes 
Secondary implementation outcomes will be penetration, acceptability, and 
implementation costs (Table 2): 
• 
Penetration, defined as the proportion of newly diagnosed or previously diagnosed 
and not currently on ART PWID at test sites who are contacted by a counselor 
and/or systems navigator and who participate in SNaP sessions 
• 
Acceptability, measured with the OADRI 12-item scale, is the perception that SNaP 
is agreeable or satisfactory by both PWID clients and test site staff. 
• 
Costs, measured directly as non-research costs, see Sections 7.4 and 8.2.2. 
 
7.3. 
Effectiveness Outcomes  
 
7.3.1  Primary Effectiveness Outcome 
The primary effectiveness outcome is ART uptake among eligible PWID (Table 2). ART 
uptake will be defined as the proportion of PWID receiving SNaP with evidence of an ART-
related visit in an ART clinic. Acceptable evidence will include a clinic documentation of 
ART use or an ART prescription. 
 
7.3.2  Secondary Effectiveness Outcomes 
The secondary effectiveness outcomes include the following two measures (Table 2): 
• 
Viral suppression, defined as an undetectable viral load on a dried-blood spot 
sample. 
• 
MAT uptake, evidence of MAT use from MAT clinic records, defined as MAT 
initiation among those not currently on MAT 
 
 

 
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Table 2. Study Outcomes 
Outcome 
 
Definition 
 
Measure or Scale* 
 
Primary Integration Implementation Outcome 
Fidelity to 
SNaP protocol 
Delivering SNaP as 
intended. 
 (systems navigation % * average quality score) + (counseling session 
% * average quality score) [see text for example] 
Secondary SNaP Implementation Outcomes 
Penetration 
% of PWID contacted, & 
enrolled in SNaP 
Proportion of newly diagnosed or previously diagnosed and not 
currently on ART PWID at test sites who are contacted by a navigator 
and/or counselor and participate in a SNaP session.  
Acceptability 
 
Perception that SNaP is 
agreeable, palatable, or 
satisfactory. 
OADRI (adapted): 12-item scale, staff and client acceptability of an 
innovation in a clinic setting.25  and qualitative interviews 
Implementation 
costs 
Costs of SNaP & its 
implementation 
Directly measured non-research costs (Aim 2)  
Primary Effectiveness Outcome 
Uptake of ART % PWID who initiated ART ART clinic records of consenting PWID 
Secondary Effectiveness Outcomes 
Viral 
suppression 
% PWID virally suppressed Undetectable viral load on DBS**, in PWID subsample cohort 
Uptake of MAT % of PWID on MAT  
MAT clinic records of consenting PWID 
*All measures will be adapted to SNaP; **DBS=dried blood spot 
 
7.4. 
Cost-Effectiveness Measurements (Aim 2) 
 
We will conduct an empirical costing study of SNaP—including SA and TA and the actual 
process of implementation itself—from a societal perspective. We will estimate implementation 
costs prospectively by embedding a trained costing specialist within each Intervention Mapping 
team, documenting all resources used (e.g., staff training level and time, travel costs, supplies, 
etc.) and estimating the unit cost of each resource. To estimate the unit health system cost of 
each intervention, we will perform detailed budgetary analysis including interviews of key staff, 
review of logbooks/timesheets, and time-and-motion studies to record navigator, counselor, and 
other staff time devoted to various activities on ≥15 randomly selected days, conducted by the 
costing specialists, in each of 12 clinic sites (6 sites per arm, selected purposively to provide 
representation of patient volume, urban/rural status, and geography) over the course of the trial. 
To estimate patient costs, we will administer a survey to a smaller subset of the 1500 PWID 
subsample cohort at baseline, and a single follow-up visit of 12 or 18 or 24 months, depending 
on PWID enrollment time to collect data on direct and indirect (lost wages, child care, etc.) costs 
of clinic visits and other elements (e.g., medication side effects) associated with ART, MAT, and 
SNaP itself. Cost data collection will be based on the Tool to Estimate Patient Costs, which we 
have adapted and used in Uganda.21  
 
We will use, in our primary analysis, an “ingredients” or bottom-up approach, with comparison to 
“top-down” costing. Our comprehensive costing will include costs associated with each 
component of each delivery strategy (e.g., staff, equipment, consumables, overheads, etc.), and 
will follow international conventions for all procedures including economic costing, discounting, 
and reporting.26,27  
 
7.5. 
High and Low Performing Sites (Aim 3)  
 
Our a priori definition of successful implementation at 24 months is a site with a fidelity score of 

 
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136 (see Section 7.2) and 70% ART uptake among its newly diagnosed or previously diagnosed 
and not currently on ART PWID clients.  
 
8. STATISTICAL CONSIDERATIONS 
 
8.1. 
Power and Sample Size Considerations 
 
8.1.1  Implementation Outcomes Sample Size Calculations 
 
The primary implementation outcome is fidelity, based on an index with a score 
ranging from 0-200 (see Section 7.2). The unit of analysis is test site (n=42 test sites 
total, 21 per arm).  
 
In HPTN 074, the Vietnam site achieved 86%-88% completion of navigation and 
counseling sessions in the protocol-specified window, and in our counseling studies we 
consistently achieve 90-95% quality scores on supervisor-rated counseling sessions. This 
track record suggests a “best case” upper bound to the fidelity score of ~150 
[(100*0.85 navigation sessions completed * 0.9 quality) + (100*0.85 counseling sessions 
completed * 0.9 quality) = 76.5+76.5 = 153].  
 
We expect TA to achieve close to this “best case” upper bound, with ≥80% 
appointment completion and ≥85% quality scores, or a fidelity score of ≥136= 
(100*0.8*0.85 + 100*0.8*0.85). We expect IM to achieve lower session completion and 
lower quality.  
 
Using two-tailed tests and α=0.05 and assuming a conservatively large standard deviation 
of 40, 42 sites will give us 80% power to detect a difference between a fidelity score 
of 136 in the TA arm and 100.5 in the SA arm.   
 
A score of 100.5 in the TA arm corresponds to 75% session completion and 67% average 
quality ratings (100*0.75*0.67 + 100*0.75*0.67 =100.5).  
 
With a more plausible standard deviation of 28, we would have 80% power to detect the 
difference between a score of 136 in the TA arm and 111 (75% completion,74% quality) in 
the SA arm. Thus, we have power to detect operationally meaningful differences in 
session completion and quality scores.   
 
8.1.2  Effectiveness Outcomes Sample Size Calculations 
 
The primary effectiveness outcome is ART uptake, measured as a dichotomous 
variable at the PWID level. After accounting for up to 12% mortality during follow-up, we 
estimate an available sample of 6200 PWID, with cluster (test site) size ranging from 7-
764 PWID (mean≈148). Loss to follow-up does not affect this outcome, as patients not 
retained in clinic will be assumed not to be on ART.  
 
To calculate the design effect, we estimate that the intra-cluster correlation coefficient 
may range from 0.01-0.05, as is typical in clinic-level behavioral interventions, implying a 
design effect between 2.5 and 8.4.28-31  
 

 
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Using two-tailed tests and α=0.05, we will have >80% power to detect a difference as 
small as 10 percentage points (e.g., 70% vs. 60% ART uptake) if the ICC is as large as 
0.05, and as small as 6 percentage points (e.g., 70% vs. 64% ART uptake) if the ICC is as 
small as 0.01. Thus, we are well powered to detect operationally meaningful differences in 
our primary effectiveness outcome of ART uptake.  
 
For viral load, which is based on a sample of n=1200 (~30 per clinic), assuming the 
same ICC of 0.01-0.05, we will have 80% power to detect differences of 10-14 
percentage points in viral suppression between arms (e.g. 40% vs. 30% if ICC=0.01; 40% 
vs. 26% if ICC=0.05). 
 
8.2. 
Statistical Analyses and Data Management  
 
8.2.1 Implementation and Effectiveness Outcomes Analyses (Aim 1) 
 
We will conduct intent-to-treat comparisons between arms, using a generalized linear 
regression model with an identity link and Gaussian error distribution to compare means 
(e.g., fidelity scores) or an identify link and binomial error distribution to compare 
proportions (e.g., ART uptake). For patient-level outcomes (e.g. ART uptake), the design 
effect introduced by clinic-level randomization will be addressed using a robust variance 
estimate. 
  
Data for all aims will be managed at the UNC-Vietnam. Each site will undergo explicit 
training in data quality. All data sources, including electronic surveys, paper forms, and 
audio-recordings will be monitored for quality and completeness. Data queries will be 
made promptly to the sites, typically within one week. The central data team head will 
have group quarterly calls with site data representatives to address any ongoing data 
issues. Specific sites will have calls as needed.  
 
8.2.2 Cost-Effectiveness Analyses (Aim 2) 
 
We will estimate and compare the unit cost (per patient) of the SNaP intervention under 
SA or TA. Second, if there is a difference in effectiveness between arms (and the more 
effective option is also the more expensive one), we will conduct a comparative cost-utility 
analysis to identify the economically preferred option, assuming a willingness to pay of 
Vietnam’s per-capita gross national income (GNI) per disability-adjusted life year (DALY) 
averted.  
 
Cost analysis: The primary outcome will be a unit cost per patient covered and per ART 
uptake under SA or TA, reported both as an average cost (relative to no SNaP 
intervention) and an incremental cost (of tailored implementation relative to standard 
implementation), using the empirical cost measurements, as described above. We will also 
describe the major cost components and key drivers of cost (e.g., patient volume or cost of 
ART), and conduct sensitivity and scenario analyses around these major cost items to 
describe the likely variation in per-patient costs across different settings. For patient-level 
factors, we will use multivariable regression techniques (likely after log-transformation of 
cost measurements, depending on the distribution of the data) to develop cost functions 
that describe the relationships between patient-level variables (e.g., gender, distance from 
clinic) and patient costs under each implementation strategy. 
 

 
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Cost-utility analyses: We will construct a Markov model to convert the incremental cost per 
ART uptake (primary cost-effectiveness outcome) into an estimated incremental cost per 
disability-adjusted life year (DALY) averted. We will calibrate this model to the 
demographics of the trial population and incorporate a Markov structure, simulating 10,000 
adults living with HIV over time steps of 6 months. Markov states will include engagement 
in care, ART status, viral suppression status, and engagement with MAT, and will project 
effectiveness outcomes observed in the trial over the lifetime of a cohort of simulated 
patients. We will incorporate into the model the annual probability of first-order 
transmission (i.e., transmissions of HIV occurring from individuals in each arm). We will 
adopt the societal perspective, with secondary analyses from the health system and 
patient perspectives. We will conduct one-way sensitivity analyses across all model 
parameters, multi-way sensitivity analyses for those parameters found to be most 
influential, and a probabilistic uncertainty analysis in which all parameters are varied 
simultaneously using Latin Hypercube Sampling. Additional sensitivity analyses will 
include different assumptions about the duration of effectiveness of SNaP and scenario 
analyses of different economic and epidemiological conditions (e.g., different country 
contexts). All analyses will be performed in R (R Foundation for Statistical Computing). 
 
8.2.3 High and Low Performing and Sustaining Site Characterization- Analyses (Aim 3)  
 
Aim 3 - Qualitative data analyses: All qualitative interviews will be audiotaped, 
transcribed, translated, coded and computerized for analysis using Atlas.ti v.8 software. 
Analysis will begin as data are collected so that topics for further exploration can be 
incorporated into ongoing fieldwork. Qualitative data analysis consists of the search for 
patterns in data and conceptualizing ideas that help explain the presence of those 
patterns.32 Textual data analysis will involve five steps: 1) reading for content; 2) 
deductive and inductive coding; 3) data display to identify emerging themes; 4) data 
reduction; and 5) interpretation. Memos will be written for each code. Codes will be 
refined during the process of analysis. Responses of navigators and counselors, test site 
staff, and test site directors will be compared within and across the staff groups and 
within and across high and low performing and sustaining sites. For example, we will 
compare navigator and counselors’ attitudes around implementing SNaP, including 
PWID-related stigma, competing job responsibilities at the site, perceived effectiveness 
of SNaP, and perceived status/value of being navigators and counselors, by high and 
low performing sites to understand if and how these attitudes may ultimately affect site 
performance. 
 
Aim 3 - Quantitative data analyses: The site characteristics will be assessed with 
exploratory analyses to examine associations with high and low performing and 
sustaining clinics. Site is the unit of analysis. Given the small sample size, we will assess 
each site measure separately. We will use a generalized linear model with a logit link 
and binomial error distribution to assess the dichotomous outcome of high or low 
performance and sustainment. Individual implementation or demographic measures will 
be included as an explanatory variable, with an indicator variable for study arm, and an 
interaction term (assessed with α=0.10). The interaction term will aid in interpreting 
whether a specific characteristic modified the effect of the implementation strategy. Two 
sets of models will be constructed: baseline measures only and change from baseline to 
evaluation.  
 
Data triangulation: IDI and quantitative data will be triangulated to understand SNaP 

 
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and SA and TA approaches within high and low performing and sustaining sites. For 
example, if in low performing sites, site directors scored low on the implementation 
leadership scale leading to low SNaP fidelity and penetration, the qualitative data could 
inform why site directors in these sites did not support and value SNaP (e.g. lack of 
prioritization of PWID clients due to PWID-related stigma), and how we can improve 
leadership investment (e.g. a stigma-reduction program combined with VAAC 
recognition of sites that improve SNaP implementation over a year). These integrated 
data will provide information about both clinics that “lag behind” and clinics that need 
less intervention for success. Although descriptive, these data will provide critical 
information for other settings seeking to implement and sustain SNaP. 
 
8.3. 
Potential Biases and Solutions  
 
Potential biases of this study, among both PWID and Site Directors/Site Staff participants, 
include selection bias during recruitment and social desirability bias during the assessments. 
 
Social Desirability Bias 
 
Some questions asked to the PWID subsample cohort may be sensitive. For example, we may 
ask about participants’ drug use, injection drug use, alcohol use, sexual behaviors, HIV testing 
history, HIV care seeking behaviors and ART adherence. Participants may provide answers 
they perceive the interviewers want to hear. Social desirability bias may also occur among the 
Site Directors and Site Staff, as they may feel pressure to show their clinic and/or staff in a 
positive light. 
 
Efforts to prevent social desirability bias and encourage accurate responses among participants 
include emphasizing confidentiality of all participant responses, and assuring participants that 
their responses and participation in the study will have no effect on the quality of their health 
care or access to health care (for PWID) and no effect on employment status or treatment in the 
workplace (for Site Directors and Staff). Also, interviewers and study staff will be trained to  
maintain strict confidentiality, to build rapport with participants and to ask questions in a 
respectful and non-judgmental way. Additionally, for Site Directors and Staff, we will ensure that 
their responses will not be shown to any other staff or supervisors at the clinics. 
 
Selection Bias 
 
Participation in the study is completely voluntary, and it is possible that those who agree and 
consent to participate in the study may have different characteristics from those who do not 
participate. In turn, difference in characteristics may be associated with differences in study 
results. We will minimize selection bias by assuring confidentiality to all potential participants 
and addressing any concerns that may arise among potential participants who are hesitant to 
join the study. We will also track the numbers who decline to participate in the study, providing 
an estimate of the extent of potential selection bias that may exist. 
 
 
 
 

 
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9. HUMAN SUBJECTS CONSIDERATIONS 
 
9.1. 
Ethical Review 
 
This protocol, the template informed consent form, participant education and recruitment 
materials, and other requested documents — and any subsequent modifications — will be 
reviewed and approved by the ethical review bodies responsible for oversight of research 
conducted at the study site.  
 
Subsequent to initial review and approval, the responsible IRBs/ECs will review the protocol at 
least annually. The Investigators will make safety and progress reports to the IRBs/ECs at least 
annually, and within three months of study termination or completion. These reports will include 
the total number of participants enrolled in the study, the number of participants who completed 
the study, all changes in the research activity, and all unanticipated problems involving risks to 
human subjects or others. The Principal Investigators and UNC Project Vietnam are responsible 
for the submission of continuing review to the required ethical review bodies. 
 
9.2. 
Informed Consent 
 
Electronic voluntary informed consent will be obtained from each study participant. Participants 
who consent to participation in the study will provide electronic signatures via tablets or laptops. 
The study site is responsible for developing study informed consent forms for local use that 
describes the purpose of the study, the procedures to be followed, and the risks and benefits of 
participation, in accordance with all applicable regulations. The study site also is responsible for 
translating the template form into the local Vietnamese language, and verifying the accuracy of 
the translation by performing an independent back-translation. 
 
Literate participants will document their provision of informed consent by signing their electronic 
informed consent forms. Non-literate participants will be asked to document their informed 
consent by marking their informed consent forms (e.g., with an X, thumbprint, or other mark) in 
the presence of a literate third party witness. Participant literacy will be determined according to 
local site SOPs. Any other local IRB/EC requirements for obtaining informed consent from non-
literate persons also will be followed. 
 
Participants will be provided with a copy of their informed consent forms if they are willing to 
receive them. 
 
PWID participants: All PWID participants who are confirmed HIV-infected (n=6200) will be 
given a brief consent form during post- test counseling. This consent will address permission to: 
1) extract ART uptake from medical records at local ART clinics and 2) extract MAT uptake from 
medical records at MAT clinics. Note that consent for SNaP will not be explicitly requested, as 
SNaP will be incorporated as a routine clinical activity. However, audio-recording of post-test 
counseling for purposes of fidelity measuring is not part of routine clinical activity, therefore we 
will obtain consent for all audio-recording the post-test counseling.  
 
The PWID subsample cohort (n=1500) will have an additional consent to allow re-contact at a 
later date and to obtain locator information, including information of a family member.  
 

 
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Site directors and site staff participants: HIV test site directors and staff will provide 
electronic informed consent prior to quantitative and qualitative interviews. 
 
9.3. 
Risks 
 
This study does not introduce new drugs, new therapies, or new indications for existing 
drugs, but rather aims to understand ways to best implement the SNaP intervention to 
increase ART and MAT uptake, and suppress viral load. 
 
Our study will not increase the risk of participants who present to HIV test sites. In Vietnam, it 
is illegal to share medical records outside the health system and this is clearly understood 
by all practitioners including those that provide HIV and MAT (specifically, methadone in 
Vietnam) related care. Based on our qualitative research with providers and law enforcement 
officers for HPTN 074, as well as more than a decade of experience conducting HIV studies 
in Vietnam, disclosure of ARV and MAT patients to law enforcement officials does not occur. 
Furthermore, methadone maintenance treatment (MMT) guidelines and DECREE 
96/2012/NĐ-CP state that MMT patients are exempt from mandatory detoxification centers, 
even if MMT participation is suboptimal. 
 
There may be some discomfort to directors and staff working in HIV test sites identified as 
low-performing/low-sustaining. However, we will work closely with the Vietnam Administration 
for HIV/AIDS Control (VAAC) to minimize this risk and minimize any risk that authorities will 
treat sites or staff differently based on performance identified by our study. In a pilot 
ART/MMT integration study among 18 clinics and 3 provinces conducted by VAAC in 2012, 
there were instances in which clinic staff and local leaders resisted ART/MMT integration and 
were not able to successfully integrate service. No punitive measures were taken against 
these clinics or their leaders or staff. Furthermore, during formative research our team has 
conducted on ART/MMT integration, clinic staff, local leaders, and VAAC representatives 
openly discussed barriers to integration and identified productive approaches that could be 
employed to overcome the difficulties that both leaders and staff may encounter. 
 
Similarly, we do not anticipate any punitive measures to HIV test sites that are less 
successful in SNaP implementation or sustainment. We have worked closely with the VAAC 
and the National AIDS Committee for over 15 years on several sensitive projects. The VAAC 
is engaged and committed to providing technical support for the scale-up of SNaP in 
Vietnam and strongly supports this proposed research. 
 
There will be no additional risks or side effects for participants presenting to SA sites 
compared to participants who presenting to TA sites. 
 
Dried blood spots will be collected from PWID who consented to participating in the subsample 
cohort. Dried blood spot collection consists of a finger prick to the participant. There are minimal 
risks to dried blood spots, such as a slight pain when the finger is pricked. To reduce the 
possibility of pain, dried blood spot collection will be taken by trained staff. Participants may 
decline the dried blood spot collection with no consequence to their care. Participants may 
return for their results, and trained staff will provide results referrals to appropriate health care 
services as requested or necessary. 
 
A small risk of psychological distress is posed by study questions such as those concerning HIV 
risk, drug use, and disclosure of HIV serostatus. Participants may find answering questions 

 
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about these issues upsetting: these questions will be asked in as sensitive a manner as 
possible, and participants may decline to answer at any time. If a participant experiences 
emotional upset during the interview, the research staff will be trained on how to handle these 
situations and the principal investigators will be available to speak with participants if needed. 
 
Specific and appropriate protocols will be in place to ensure a participant’s safety should a 
research staff member feel that a participant is in danger of harming himself or others during the 
course of a study visit. We will also remind participants that they can terminate the interview at 
any time. 
 
Although study sites will make every effort to protect participant privacy and confidentiality, it is 
possible that participants' involvement in the study could become known to others, and that 
social harms may result (i.e., because participants could become known as HIV-infected). For 
example, participants could be treated unfairly or discriminated against, or could have problems 
being accepted by their families and/or communities." 
 
Study-related visits will not be conducted in prisons or jails with study participants. Incarcerated 
participants will be eligible to resume study participation upon release. 
 
Steps taken to ensure that potential participants do not feel coerced to enter or remain in the 
study: Research staff recruiting participants will follow a standardized script to ensure that all 
ethical issues are adhered to and that study protocols are followed. For PWID participants, all 
written and oral communications about the study will emphasize that this study is completely 
voluntary and will not impact employment status, or the entitlement for the MAT or HIV services, 
hospital or other clinics or testing sites, and that they can drop out of the research at any time 
without jeopardizing their entitlement to any of these services. For HIV test site directors and 
staff participants, all written and oral communications about the study will emphasize that this 
study is completely voluntary and will not impact employment status, and that they can drop out 
of the research at any time without jeopardizing their jobs. In addition, interviewers reviewing 
consent with participants will be trained to probe for comprehension. 
 
 
9.4. 
Benefits 
 
All PWID presenting at the 42 HIV test sites will be offered the SNaP intervention. While PWID 
may likely benefit from the SNaP intervention, they may not directly benefit from enrolling as 
participants in the study. Participants may benefit from being able to share their experiences 
and opinions about the SNaP intervention. Participants in the Tailored Approach (TA) 
implementation arm may benefit from potentially more effective implementation of SNaP. 
Participants in the PWID subsample cohort may benefit from knowing their HIV viral load, to 
discuss with their HIV care provider. 
 
HIV site directors and staff participants may benefit from the additional service skills they 
observe, which may allow them to better serve their patients at the site. Site directors and staff 
participants may also benefit from being able to share their experiences and opinions about the 
different aspects of facilitating PWID into HIV care and learning about different implementation 
strategies and the importance of HIV test site context. 
 
Participation in the study may put one at risk of confidentiality breach if study staff are not well 
trained in rigorous confidentiality safeguards, or if data are not properly encrypted and securely 

 
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stored. However, because we have highly trained and experienced team in Vietnam, with over 
10 years of experience conducting complex and rigorous research studies among highly 
stigmatized populations in Vietnam, the risk of these data breaches is very small. Therefore the 
risks are reasonable in relation to the benefit of being in a study that will compare 
implementation strategies for a systems navigation and psychosocial counseling (SNaP) 
intervention. 
 
9.5. 
Incentives 
 
Pending IRB approval, PWID subsample cohort participants and site directors and site staff 
participants will be compensated for their time and effort in this study, and/or be reimbursed for 
travel to study visits and time away from work. Reimbursement amounts will be specified in the 
study informed consent forms. PWID participants who are not in the subsample cohort will be 
compensated a small amount for their one-time visit. 
 
9.6. 
Confidentiality 
 
Procedures to safeguard confidentiality: All participants will receive a patient identification 
number (PID) and this number will be used for all interviews and collection of lab specimens. 
This PID will not be linked to the participant’s name, and no other information that would 
disclose the participant’s identity will be found on any interview or specimen label. Data will be 
kept without serostatus or injecting drug use identification in locked cabinets at the UNC-
Vietnam office in Hanoi or designated offices at sites. Only the consent form, tracker form and 
tracker computer will link the participant’s name to the identification number. If appropriate, we 
will maintain contact with participants using a computerized tracking system. In addition, 
interviewing and office staff will sign a “confidentiality pledge” prior to having contact with 
participants. 
 
All study interviews and procedures will be administered by trained study staff in a private room 
or over zoom (in the case of the 6 month post-endline in-depth interviews). If names and 
identifying information are collected, a logbook will be used to link a participant's identifying 
information with his/her PID; personal identifiers will not be stored in the data set. The logbook 
will be kept in a locked cabinet, separate from all other study file cabinets, in a locked project 
office room; an electronic copy will be saved on a password-protected, encrypted computer. All 
data, notes, and audio- recordings will also be kept on a password-protected, encrypted 
computer. Access to the locked files and security passwords will be given only to the PIs, UNC-
Vietnam In-Country Director, Research Manager and select well-trained project staff.  
 
The logbook will be destroyed and the electronic copy deleted 9 months after the end of data 
collection. Tapes of qualitative interviews will be destroyed within one year of being transcribed 
electronically. Raw data files will be destroyed one year after electronic coding. Blood samples 
will be incinerated after no more than 10 years of storage in lab facilities. 
 
Participant’s study information will not be released without the written permission of the 
participant, except as necessary for monitoring by the NIH/NIDA and/or its contractors; the US 
FDA, OHRP; other U.S., local Vietnamese, and international regulatory entities; and/or site 
IRBs. 
 
9.6.1 Re-contacting Subsample Cohort PWID 

 
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A subsample of participants (n=1500) will be re-contacted to return to the test sites post-
implementation for viral load assessments. We will ask the subsample cohort to provide contact 
information of family members who may be able to help us locate the participant during the 
study. We will only contact family members for the purpose of locating the participant; we will 
not ask the family members any questions other than where and when we can contact the 
participant. We will implement the following measures to protect the participant’s confidentiality 
and mitigate risks of disclosure of the participant’s HIV or drug use status: 
 
1. Study identification:  
 
When speaking with family members of participants, study staff will not identify the study 
as a study of PWID or HIV-infected persons. Instead, they will refer to the study broadly 
as a study to better understand health in the community.  Study staff will be trained in 
strategies to maintain the identification of the study as a general study on health in the 
community. They also will not disclose the study population as being PWID or HIV-
infected persons.  
 
 
Any referral card from the study to ART, MMT or other health services will not disclose 
the participant’s name, as it will contain a study ID to link the participant to the 
participant’s study records. The referral cards also will not disclose that the referred 
patient is coming from a research study, but rather from the participant’s local District 
Health Center. 
 
2. Staff training: 
 
Staff’s maintenance of confidentiality: Staff will sign confidentiality statements at 
recruitment and on annual basis regarding sharing any participant information, ensuring 
the privacy of participants. The confidentiality statement will give examples of the kinds 
of information that should be kept confidential, such as the HIV and drug use status of all 
participants. Additionally, all staff will maintain updated certifications in good clinical 
practice, human subjects protections and good participatory practice. Any staff members 
who do not adhere to protocols to maintain participant confidentiality will be immediately 
placed on 2 weeks of administrative leave and will be re-trained by one of the 
supervisors on the importance of and how to maintain participants’ confidentiality. The 
staff member will be closely monitored.  If the same staff is found in violation of 
participant confidentiality again, depending on the severity of the violation, that staff will 
be terminated from working for our study. 
 
Identifying social harms: We will train the staff in the collection and reporting of social 
harms, such as unintended disclosure of HIV or drug use status, and such events will be 
collected and reported by study staff to study leadership in a structured process. 
 
3. Study participation:  
 
All participants are identified on study materials by their participant ID number only, 
thereby preventing their name from being disclosed and linking them to a specific study. 
All participants will be provided with contact information of the In-country Director and 
Study Coordinator, which participants may use to privately inform study leadership of 
any issues or concerns they have regarding their study participation. 
 

 
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Procedures to maintain the integrity of the data: All files will be backed up daily on project 
computer hard drives and on external hard drives. Files will be protected by the use of a 
password and encryption security system and with firewall protection from the Internet. Weekly 
software updates will provide additional protection.  
 
10. 
LABORATORY SPECIMENS AND BIOHAZARD CONTAINMENT 
 
As described in Section 5.5.1.2, the following specimen will be collected at all study sites: 
  
• Dried blood spot for viral load testing, collected for PWID Subsample Cohort only 
 
10.1. Specimen Collection, Storage, Processing  
 
Dried blood spots (DBS) can be easily prepared at district labs, using blood drawn for routine 
clinical examination, without special processing requirements. The filter paper used is easily 
obtained and stored in Vietnam. DBS can be transported and stored at ambient temperature for 
up to 14 days after collection. After this time, DBS must be frozen at -200C or -700C at the 
provincial or district labs for up to 2 years. From the district/provincial labs, DBS can be shipped 
in dry ice to a genotyping lab. 
 
Site and study staff involved with specimen collection and/or management will adhere to 
standards of good clinical laboratory practice and SOPs for specimen collection, management, 
storage, and transport. 
 
10.2. Biohazard Containment  
 
As the transmission of HIV and other blood-borne pathogens can occur through contact with 
contaminated needles, blood, and blood products, appropriate blood and secretion precautions 
will be employed by all personnel in the drawing of blood and shipping and handling of all 
specimens for this study, as currently recommended by the US CDC. All infectious specimens 
will be transported in accordance with United States regulations (42 CFR 72). 
 
11. 
DISSEMINATION PLAN 
 
This study will comply with all NIH and U.S. Federal governments requirements related to the 
dissemination of the research findings upon completion of the study. Specifically, the research 
findings will be disseminated through several mechanisms: 
 
a) Presentation of the research findings at an appropriate international conference, such 
as CROI or the International AIDS Society conference. 
b) Publication of the research findings in a suitable scientific journal. 
c) Deposit of all journal publications in PubMed C in compliance with existing 
Federal rules and regulations. 
d) Registration of the study with ClinicalTrials.gov prior to study initiation, regular updating 
of the protocol on ClinicalTrials.gov, and submission of the research findings to 
ClinicalTrials.gov upon completion of the study. All activities with ClinicalTrials.gov will 
be completed within the timeframes specified in the official policy. 

 
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e) Presentation of the research findings to the Vietnamese Ministry of Health and any 
other interested parties (e.g. governmental representatives of other Southeast Asian 
countries, WHO representatives from the Southeast Asia Regional Office) 
 
In addition, to comply with current regulations, all informed consent forms will include a 
statement referencing that this study will be registered in ClinicalTrials.gov and will provide a 
link to the site to enable interested participants to review the trial information on the website. 
 
Oversight of these procedures will be completed with assistance from the Office of Sponsored 
Research and the Institute of Global Health and Infectious Diseases (IGHID) Regulatory 
Group at the University of North Carolina. The IGHID Regulatory Group regularly tracks all 
clinical trials for the UNC ACTG and HPTN studies, as well as all NIH-funded studies 
conducted in our research sites in Malawi, Vietnam, and South Africa. 
 
 
12. 
ADMINISTRATIVE PROCEDURES 
 
12.1. Study Team Roles  
 
UNC and OSU, where the PIs Drs. Go and Miller are based, respectively, will be responsible for 
the overall oversight and conduct of all aspects of the study (Figure 4). JHU will lead the cost-
effectiveness and intervention implementation aspects of the study along with UNC and OSU. 
UNC-Vietnam and HMU will be responsible for in-country management of the study. UNC-
Vietnam, HMU, and VAAC will work closely as the implementation teams for the study.  
 
 

 
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Figure 4. Overall structure of the study team; blue is US-based, green is Vietnam-based 
Note: Implementation Teams = Central Implementation Teams (see Sections 4.2 and 5.2.1) 
 
12.2. Study Coordination 
 
Study implementation will be directed by this protocol as well as the SOPs. The 
SOPs will outline procedures for conducting study visits, data and forms processing, AE 
assessment, management and other study operations. The study team will develop study case 
report forms and other study instruments. Data will be transferred to the central UNC-Vietnam 
office in Hanoi, processed, and cleaned. 
 
The data manager will be responsible for coordinating Quality Control reports and data queries 
resolutions. 
 
Close coordination between the PIs and UNC-Vietnam will be necessary to track study 
progress, respond to queries about proper study implementation, and address other issues 

 
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in a timely manner. Rates of accrual, retention, and AE incidence will be monitored closely by 
the PIs and UNC-Vietnam as well as the SMC. The PIs will address issues related to study 
eligibility and AE management and reporting as needed to assure consistent case management, 
documentation, and information-sharing across sites. 
 
 
12.3. Study Monitoring 
 
On-site study monitoring will be performed in accordance with SOPs. The PIs, UNC, and UNC-
Vietnam teams will visit the sites to: 
• Verify compliance with human subjects and other research regulations and guidelines; 
• Assess adherence to the study protocol, study-specific procedures manual, and local 
counseling practices; and 
• Confirm the quality and accuracy of information collected at the study site and entered into 
the study database. 
 
A site visit log will be maintained at the study site to document all visits. 
 
12.4. Protocol Compliance 
 
The study will be conducted in full compliance with the protocol. The protocol will not be 
amended without prior written approval by the PIs. All protocol amendments must be submitted 
to and approved by the relevant IRB(s)/Ethical Committees prior to implementing the 
amendment. 
 
12.5. Use of Information and Publications 
 
Publication of the results of this study will be governed by the PIs. Any presentation, abstract, or 
manuscript will be submitted by the authors to the PIs for review prior to submission. 
 
12.6. Timeline 
 
Figure 5 
Year 1 
Year 2 
Year 3 
Year 4 
Year 5 
Year 6 (NCE) 
 
1 
2 
3 
4 
1 
1 
2 
3 
1 
2 
3 
4 
1 
2 
3 
4 
1 
2 
3 
4 
1 
2 
3 
4 
Pre-Implementation Activities 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Final formative activities, approvals 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Aim 1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Implementation: Steps 1-5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Outcome measures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Aim 2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Costing & cost analyses 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Aim 3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Quantitative analyses 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Qualitative data collection & analyses 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Manuscript preparation & dissemination 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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31. 
Smeeth L, Ng ES. Intraclass correlation coefficients for cluster randomized trials in 
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Bernard HR. Research Methods in Anthropology. 2nd ed. Walnut Creek: Altamira Press; 
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APPENDIX I. Schedule of Procedures for the PWID participants not in the subsample cohort 
(n= approx. 5000) 
 
Pre-
Implementation 
Post-Implementation 
Enrollment 
12mo 
24mo 
Post-24mo 
Administrative, regulatory, and behavioral 
assessment procedures 
 
 
 
 
 
Enrollment informed consent 
 
X 
 
 
 
Additional consent 
 
 
 
 
 
Locator information 
 
 
 
 
 
Quantitative questionnaire via interviewer 
 
 
 
 
 
Qualitative interviews consent 
 
 
 
 
X* 
Qualitative assessment 
 
 
 
 
X* 
Laboratory procedures 
 
 
 
 
 
Dried blood spot collection 
 
 
 
 
 
 
*Only applies if participant was randomly selected to participate in post-implementation 
qualitative interviews. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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APPENDIX II. Schedule of Procedures and Evaluation for the PWID Subsample Cohort (n=1500) 
 
Pre-
Implementation 
Post-Implementation 
Enrollment 
12mo 
18mo 
24mo 
Post-24mo 
Administrative, regulatory, and behavioral 
assessment procedures 
 
 
 
 
 
 
Enrollment informed consent 
 
X 
 
 
 
 
Additional informed consent 
 
X 
 
 
 
 
Locator information 
 
X 
 
 
 
 
Quantitative questionnaire via interviewer 
 
X 
X** 
X*** 
X 
 
Qualitative interviews consent 
 
 
 
 
 
X* 
Qualitative assessment 
 
 
 
 
 
X* 
Laboratory procedures 
 
 
 
 
 
 
Dried blood spot collection 
 
 
X** 
X*** 
X 
 
 
*Only applies if participant was randomly selected to participate in post-implementation 
qualitative interviews. 
 
** Only applies if participant was enrolled in study within 0-6 months after implementation of the 
SNaP intervention at the test site. 
 
*** Only applies if participant was enrolled in study within 0-12 months after implementation of 
the SNaP intervention at the test site. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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APPENDIX III. Schedule of Procedures and Evaluation for HIV Test Site Directors and Site Staff 
participants (including HIV providers at nearby HIV clinics) at all 42 test sites 
 
Pre-
Implementation 
Post-Implementation 
 
Enrollment 
12mo 
24mo 
Post-24mo 
6-monts 
post-study 
Administrative, regulatory, and behavioral 
assessment procedures 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
X 
Locator information 
 
 
 
 
 
 
Quantitative questionnaire via Qualtrics 
X 
 
X 
X 
 
X 
Qualitative consent (*) 
 
 
 
 
X 
X** 
Qualitative assessment (*) 
 
 
 
 
X 
X** 
 
 
(*) For HIV providers at nearby HIV clinics only 
** For HIV providers at select clinics only