Building on Needle Exchange to Optimize Prevention & Treatment
Phase: NA
Conditions: Intravenous Drug Usage, HIV/AIDS
Sponsor: Johns Hopkins University

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 1 of 34 
 
 
 
Building on Needle Exchange to Optimize Prevention and Treatment 
 
 
 
 
Sponsored by: 
 
US National Institute on Drug Abuse 
 
 
 
 
ClinicalTrials.gov Protocol Number: 
NCT03567174 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol Co-Chairs: 
Gregory M. Lucas, MD, PhD 
Kathleen Page, MD 
 
 
 
 
 
Version 1.0 
25 APR 2022 
 
 
 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 2 of 34 
 
 
 
Table of Contents 
1. 
TEAM ROSTER AND KEY ROLES ........................................................................................ 4 
2. 
LIST OF ABBREVIATIONS .................................................................................................. 7 
3. 
PROTOCOL SUMMARY ..................................................................................................... 8 
Purpose: .......................................................................................................................................... 8 
Design: ............................................................................................................................................. 8 
Study Population: ............................................................................................................................ 8 
Study Size: ....................................................................................................................................... 8 
Treatment Regimen: ........................................................................................................................ 8 
Study Duration: ............................................................................................................................... 8 
Primary Objective: ........................................................................................................................... 9 
Secondary Objectives: ...................................................................................................................... 9 
Exploratory Objectives: .................................................................................................................. 10 
Study Sites: .................................................................................................................................... 10 
Overview of Study Design and Randomization Scheme: ................................................................. 11 
4. 
INTRODUCTION ............................................................................................................. 12 
4.1 
Background Information .................................................................................................... 12 
4.2 
Rationale ........................................................................................................................... 12 
4.3 
Study Hypotheses .............................................................................................................. 13 
5. 
OBJECTIVES ................................................................................................................... 13 
5.1 
Primary Objective: ............................................................................................................. 13 
5.2 
Secondary Objectives: ....................................................................................................... 13 
5.3 
Exploratory Objectives: ..................................................................................................... 14 
To evaluate ICV cost and assess the potential cost-effectives of the ICV as a service delivery 
modality for PWID. ........................................................................................................................ 14 
6. 
STUDY DESIGN .............................................................................................................. 14 
7. 
STUDY POPULATION ...................................................................................................... 15 
7.1 
Inclusion/Exclusion Criteria ............................................................................................... 15 
7.1.1 
Participant Inclusion Criteria ............................................................................................................... 15 
7.1.2 
Participant Exclusion Criteria ............................................................................................................... 15 
7.2 
Recruitment Process .......................................................................................................... 16 
7.3  
Participant Retention ........................................................................................................ 16 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 3 of 34 
 
8. 
INTERVENTIONS ............................................................................................................ 16 
8.1 
Control Condition .............................................................................................................. 17 
8.2 
ICV Intervention ................................................................................................................ 17 
9. 
STUDY PROCEDURES/EVALUATIONS .............................................................................. 18 
9.1 
Clinical Evaluations and Procedures ................................................................................... 18 
9.2 
Laboratory Evaluations ...................................................................................................... 18 
9.2.1 
Biohazard Containment ....................................................................................................................... 19 
9.2.2 
Total Blood Volume ............................................................................................................................. 19 
9.3 
Schedule of Procedures/Evaluations: Timing and Definitions ............................................. 19 
9.3.1 
Screening ............................................................................................................................................. 19 
9.3.2 
Enrollment ........................................................................................................................................... 21 
9.3.3 
Follow-up ............................................................................................................................................. 21 
9.3.4 
COVID-19 Impact on Study .................................................................................................................. 21 
10. 
ASSESSMENT OF SAFETY ............................................................................................ 21 
10.1 
Safety Assessment Overview ............................................................................................. 21 
10.2 
Definition of Adverse Events (AE) ...................................................................................... 21 
10.3 
Definition of serious adverse events (SAE) ......................................................................... 22 
10.4 
Adverse Event Procedures and Reporting Requirements ................................................... 22 
11. 
CLINICAL MANAGEMENT ........................................................................................... 22 
11.1 
Clinical Management of Adverse Events ............................................................................ 22 
11.2 
Criteria for Permanent Intervention Discontinuation or Premature Study Discontinuation 22 
12. 
STATISTICAL CONSIDERATIONS .................................................................................. 23 
12.1 
Overview and General Design Issues .................................................................................. 23 
12.2 
Study Endpoints ................................................................................................................ 23 
12.2.1 
Primary Endpoint ............................................................................................................................ 23 
12.2.2 
Secondary Endpoints ...................................................................................................................... 23 
12.2.3 
Exploratory Endpoints .................................................................................................................... 24 
12.3 
Study Hypothesis ............................................................................................................... 24 
12.4 
Sample Size Considerations ............................................................................................... 24 
12.5 
Study Site Selection and Pair Matching .............................................................................. 25 
12.6 
Randomization and Masking Procedures ........................................................................... 25 
12.7 
Analysis Plan ..................................................................................................................... 25 
12.7.1 
Analysis plan for primary and secondary endpoints ....................................................................... 25 
12.7.2 
Analysis plan for qualitative evaluation of HIV treatment incentives ............................................. 28 
12.7.3 
Analysis plan for cost-effectiveness ................................................................................................ 28 
13. 
REFERENCES .............................................................................................................. 29 
14. 
APPENDIX .................................................................................................................. 33 
 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 4 of 34 
 
 
 
 
 
 
 
 
1. 
TEAM ROSTER AND KEY ROLES 
 
Protocol Co-Chairs 
Gregory Lucas, MD PhD 
Johns Hopkins University School of Medicine 
Division of Infectious Diseases 
1830 E. Monument Street, Room 435A 
Baltimore, MD  21287  USA 
Phone: 410-614-0560 
Fax: 410-205-2777 
glucas@jhmi.edu 
 
Kathleen Page, MD 
Johns Hopkins University School of Medicine 
Division of Infectious Diseases 
1830 E. Monument Street, Room 402 
Baltimore, MD  21287  USA 
Phone: 410-614-3269 
kpage2@jhmi.edu 
 
Qualitative Co-Investigators 
Susan Sherman, PhD 
Johns Hopkins University School of Public Health 
Department of Health, Behavior and Society 
Hampton House 749 
Baltimore, MD  21205  USA 
Phone: 410-614-3518 
Fax: 410-955-7241 
ssherma1@jhu.edu 
 
Suzanne Grieb, PhD 
Johns Hopkins University School of Medicine 
Department of Medicine 
Mason F Lord building, suite 4200 
5200 Eastern Avenue 
Baltimore, MD  21224  USA 
Phone: 410-550-4115 
sgrieb1@jhmi.edu 
 
 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 5 of 34 
 
 
 
 
 
 
 
 
Co-Investigator 
Oluwaseun Falade-Nwulia, MBBS, MPH 
Johns Hopkins University School of Medicine 
Division of Infectious Diseases 
4940 Eastern Avenue B3N, Suite 351 
Baltimore, MD  21224  USA 
Phone: 410-396-9410 
ofalade1@jhmi.edu 
 
Protocol Statistician 
Brian Weir, PhD MPH 
Johns Hopkins University School of Public Health 
Department of Health, Behavior and Society 
624 N. Broadway, Room 261 
Baltimore, MD  21205  USA 
Phone: 410-502-4877 
Fax: 410-502-4333 
bweir3@jhmi.edu 
 
Research Manager 
Katie Zook 
Johns Hopkins University 
Division of Infectious Diseases 
1830 E. Monument Street, Room 8032 
Baltimore, MD  21287  USA 
Phone: 410-614-2938 
Fax: 410-205-2777 
kcook7@jhmi.edu 
 
Research Supervisor 
Donald Brown 
Johns Hopkins University 
Division of Infectious Diseases 
2213 McElderry Street 
Baltimore, MD  21205  USA 
Phone: 410-502-9520 
dbrow140@jhmi.edu 
 
Research Field Team 
Jeffrey Green, jgree165@jhmi.edu  

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 6 of 34 
 
Tameka Brodie, tcassel4@jhu.edu 
Johns Hopkins University 
Division of Infectious Diseases 
2213 McElderry Street 
Baltimore, MD  21205  USA 
Phone: 410-502-9639 
 
Miles Landry 
Johns Hopkins University 
Division of Infectious Diseases 
1830 E. Monument Street, 8th floor 
Baltimore, MD  21287  USA 
Phone: 410-502-5210 
mlandry4@jhmi.edu 
 
 
 
 
 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 7 of 34 
 
2. 
LIST OF ABBREVIATIONS 
 
AIDS 
Acquired immunodeficiency syndrome 
ART 
Antiretroviral therapy 
BCHD 
Baltimore City Health Department 
ED 
Emergency department 
HCV 
Hepatitis C virus 
HIV 
Human immunodeficiency virus 
ICV 
Integrated care van 
JHU 
Johns Hopkins University 
MOUD 
Medication for opioid use disorder 
PrEP 
Pre-exposure prophylaxis 
PWID 
People who inject drugs 
SSP 
Syringe service program 
STI 
Sexually transmitted infection 
 
 
 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 8 of 34 
 
3. 
PROTOCOL SUMMARY 
 
Building on Needle Exchange to Optimize Prevention and Treatment 
 
Purpose: 
Biomedical interventions that have direct applicability to people who inject drugs 
(PWID) have flourished over the past 15 years (HIV treatment as prevention, pre-
exposure prophylaxis [PrEP], office-based medication for opioid use disorder [MOUD] 
with buprenorphine, and hepatitis C virus [HCV] treatment with direct acting agents). 
However, penetration of these interventions among PWID is low relative to the potential 
benefits. Syringe service programs (SSP) are an essential risk reduction service for 
PWID, and represent a potential, although under-used, interface to provide additional 
PWID services. The Baltimore City Health Department (BCHD) and investigators at 
Johns Hopkins University (JHU) have developed a dedicated integrated care van (ICV) to 
complement the city’s mobile SSP, with the goal of extending needed biomedical 
interventions to PWID. The primary purpose of this trial is to determine if the ICV 
intervention reduces risk, improves health, and increases uptake of evidence-based 
services among PWID. Secondary purposes are to examine the ICV implementation, 
acceptability, coverage, and sustainability using a mixed methods approach, and to assess 
costs and cost-effectiveness. 
 
Design: 
Matched-pair cluster randomized trial. 
 
Study Population: 
PWID who are 18 years of age or older. 
 
Study Size: 
The study will be conducted at 12 neighborhood sites or clusters in Baltimore that are 
visited by the SSP. We aim to enroll 60 participants at each site (720 participants 
overall). 
 
Treatment Regimen: 
In addition to continuing weekly visits from the mobile SSP, sites assigned to the 
intervention will receive weekly visits by the ICV. Staffed by 1-2 medical providers, a 
case manager, and phlebotomist, the ICV will provide a spectrum of PWID services (e.g., 
rapid HIV and HCV testing, naloxone overdose kits, HIV treatment and linkage, HCV 
treatment and linkage, buprenorphine-based MOUD, and PrEP). The ICV will visit 
neighborhood sites once a week and offer services to anyone seeking them, irrespective 
of enrollment in the study cohort 
 
Sites assigned to usual care will continue to receive weekly visits from the mobile SSP, 
but no additional services.  
 
 
Study Duration: 
The study duration will be approximately 36 months. Site selection and preparatory work 
will take 8 months. Participants will be enrolled by site, in staggered fashion, over 14 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 9 of 34 
 
months, and followed for an additional 14 months. 
 
Primary Objective: 
To determine if the ICV intervention increases uptake of evidence-based services, 
reduces risk behaviors, and reduces adverse outcomes among PWID (assessed by a 
composite PWID score), compared with the control condition. 
  
Secondary Objectives: 
• To determine if the ICV intervention improves the HIV care continuum (among HIV-
positive participants), compared with the control condition 
 
• To determine if the ICV intervention increases HIV testing rates (among HIV-negative 
participants), compared with the control condition. 
 
• To determine if the ICV intervention improves the PrEP continuum (among HIV-
negative participants), compared with the control condition. 
 
• To determine if the ICV intervention improves the HCV care continuum (among HCV-
positive participants), compared with the control condition. 
 
• To determine if the ICV intervention increases HCV testing rates (among HCV-negative 
participants), compared with the control condition. 
 
• To determine if the ICV intervention increases use of MOUD (among all participants), 
compared with the control condition. 
 
• To determine if the ICV intervention increases use of SSP (among all participants), 
compared with the control condition. 
 
• To determine if the ICV intervention increases possession of a naloxone overdose kit 
(among all participants), compared with the control condition. 
 
• To determine if the ICV intervention reduces injection drug use (among all participants), 
compared with the control condition. 
 
• To determine if the ICV intervention reduces recent drug use (among all participants), 
compared with the control condition. 
 
• To determine if the ICV intervention reduces sharing of drug paraphernalia (among all 
participants), compared with the control condition. 
 
• To determine if the ICV intervention reduces non-fatal drug overdoses (among all 
participants), compared with the control condition. 
 
• To determine if the ICV intervention reduces emergency department use (among all 
participants), compared with the control condition. 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 10 of 34 
 
 
• To determine if the ICV intervention reduces HIV seroconversion (among HIV-negative 
participants), compared with the control condition. 
 
• To determine if the ICV intervention reduces HCV seroconversion (among HCV-
negative participants), compared with the control condition. 
 
• To determine if the ICV intervention decreases mortality (among all participants), 
compared with the control condition. 
 
• To describe and characterize service utilization on the ICV including, but not limited to, 
number of visits and unique clients served, client demographics, use of individual 
services (HIV testing, HCV testing, PrEP, buprenorphine-based MOUD, etc.), and 
overlap between ICV clients and the neighborhood PWID cohorts enrolled for the study.  
 
Exploratory Objectives: 
• To conduct a qualitative evaluation of barriers to service delivery for PWID, 
perceptions about the ICV, interest in services provided by and not provided by the 
ICV, and sustainability of the ICV from in-depth interviews with SSP, ICV staff, and 
PWID; and by key-informant interviews with policy stakeholders. 
 
• To evaluate ICV cost and assess the potential cost-effectives of the ICV as a service 
delivery modality for PWID. 
 
Study Sites: 
The study will be conducted at 12 neighborhood locations (cross streets) where the 
Baltimore City mobile SSP provides clean needles and syringes  
 
 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 11 of 34 
 
Overview of Study Design and Randomization Scheme: 
 
 
 
 
 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 12 of 34 
 
4. 
INTRODUCTION 
4.1 
Background Information 
Since the introduction of combination antiretroviral therapy (ART), studies (including 
many from our team) have consistently identified barriers and lower access to ART 
among PWID compared with other HIV risk groups.1-6 While active substance use is a 
well-established barrier to adherence, it is also clear that clinicians often believe PWID 
are incapable of taking ART.7 Despite dramatic strides in treating HIV-positive persons 
overall, PWID disparities remain. A large consortium of HIV cohorts in North America 
recently found that (compared with other risk groups) PWID were significantly less likely 
to initiate ART and to achieve viral suppression at 6- and 12-months after reaching 
guideline-eligibility for ART.8 Strikingly, female PWID were 36% less likely (95% CI: 
25%, 46%) to initiate ART when eligible than MSM. In another study by the NA 
ACCORD, of all factors assessed, PWID had the strongest association with non-retention 
to HIV care (68% increased risk of non-retention; 95% CI: 49%, 89%) compared with 
non-PWID. This pattern has emerged again with pre-exposure prophylaxis (PrEP) and 
hepatitis C virus (HCV) treatment. In a systematic review, PWID expressed similar levels 
of PrEP interest as other risk groups;9 however a survey study found that primary care 
providers were significantly less willing to provide PrEP for PWID compared to all other 
risk groups.10 In a PubMed search we combined the term “pre-exposure prophylaxis” 
with “MSM” or “men who have sex with men” and identified 373 published articles. In 
contrast when we combined “pre-exposure prophylaxis” with “PWID” or “people who 
inject drugs,” only 34 published articles were identified. Tellingly, of the 34 articles, only 
2 manuscripts reported actual implementation of PrEP among PWID, both from the 
Bangkok Tenofovir Study.11,12 Finally, unpublished data by our group from the ALIVE 
study – a community-based cohort of PWID in Baltimore – found that among 269 HCV-
positive participants enrolled in 2016-17, less than 10% reported linkage to HCV care 
and only 3% reported HCV treatment with cure. These data highlight the persistent 
pattern of disparities in access to evidence-based biomedical services by PWID. 
 
4.2 
Rationale 
A substantial body of literature supports the feasibility, acceptability, and efficacy of 
models in which substance use treatment and medical management are integrated in a 
single venue.13,14 One small trial from over 20 years ago makes this simple point clearly: 
51 methadone clients who had an untreated medical condition were randomized to either 
on-site treatment at the methadone clinic or referral to a nearby medical clinic, with 
treatment costs covered by the study. 76% assigned to integrated care attended ≥ 2 
medical visits compared with 6% referred off-site (P<0.001).15 Other randomized 
controlled trials, including work by our group, have found that integration of medication 
for opioid use disorder (MOUD) within general medical or HIV specialty clinics was 
associated with higher patient satisfaction, increased retention to medical and substance 
abuse treatment, and higher rates of negative urine drug tests, compared with separate 
models of care.16-19 Pioneering work by Altice and colleagues has shown that a mobile 
health platform is acceptable, feasible, and effective for serving PWID populations, 
including vaccination, screening and treatment of latent tuberculosis, buprenorphine-
based MOUD, HCV screening, and ART facilitation for HIV-positive persons.20-24 We 
propose to build on the prior work of our team and others to implement and evaluate a 
PWID-focused multi-service van to bring needed biomedical services to this 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 13 of 34 
 
population. 
 
4.3 
Study Hypotheses 
We hypothesize that a multi-service ICV will reduce risk behaviors, improve health, and 
increase uptake of evidence-based services among PWID. 
 
5. 
OBJECTIVES 
5.1 
Primary Objective: 
To determine if the ICV intervention increases uptake of evidence-based services, 
reduces risk behaviors, and reduces adverse outcomes among PWID (assessed by a 
composite PWID score), compared with the control condition. 
  
5.2 
Secondary Objectives: 
• To determine if the ICV intervention improves the HIV care continuum (among HIV-
positive participants), compared with the control condition 
 
• To determine if the ICV intervention increases HIV testing rates (among HIV-negative 
participants), compared with the control condition. 
 
• To determine if the ICV intervention improves the PrEP continuum (among HIV-
negative participants), compared with the control condition. 
 
• To determine if the ICV intervention improves the HCV care continuum (among HCV-
positive participants), compared with the control condition. 
 
• To determine if the ICV intervention increases HCV testing rates (among HCV-negative 
participants), compared with the control condition. 
 
• To determine if the ICV intervention increases use of MOUD (among all participants), 
compared with the control condition. 
 
• To determine if the ICV intervention increases use of SSP (among all participants), 
compared with the control condition. 
 
• To determine if the ICV intervention increases possession of a naloxone overdose kit 
(among all participants), compared with the control condition. 
 
• To determine if the ICV intervention reduces injection drug use (among all participants), 
compared with the control condition. 
 
• To determine if the ICV intervention reduces recent drug use (among all participants), 
compared with the control condition. 
 
• To determine if the ICV intervention reduces sharing of drug paraphernalia (among all 
participants), compared with the control condition. 
 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 14 of 34 
 
• To determine if the ICV intervention reduces non-fatal drug overdoses (among all 
participants), compared with the control condition. 
 
• To determine if the ICV intervention reduces emergency department use (among all 
participants), compared with the control condition. 
 
• To determine if the ICV intervention reduces HIV seroconversion (among HIV-negative 
participants), compared with the control condition. 
 
• To determine if the ICV intervention reduces HCV seroconversion (among HCV-
negative participants), compared with the control condition. 
 
• To determine if the ICV intervention decreases mortality (among all participants), 
compared with the control condition. 
 
• To describe and characterize service utilization on the ICV including, but not limited to, 
number of visits and unique clients served, client demographics, use of individual 
services (HIV testing, HCV testing, PrEP, buprenorphine-based MOUD, etc.), and 
overlap between ICV clients and the neighborhood PWID cohorts enrolled for the study.  
 
5.3 
Exploratory Objectives: 
• To conduct a qualitative evaluation of barriers to service delivery for PWID, perceptions 
about the ICV, interest in services provided by and not provided by the ICV, and 
sustainability of the ICV from in-depth interviews with SSP, ICV staff, and PWID; and 
by key-informant interviews with policy stakeholders. 
 
• To evaluate ICV cost and assess the potential cost-effectives of the ICV as a service 
delivery modality for PWID. 
 
6. 
STUDY DESIGN 
This is a comparative effectiveness, two-arm, matched-pair cluster randomized trial. The 
study will be conducted in 12 neighborhood sites in Baltimore City that receive services 
from the mobile SSP. Eligible PWID will be recruited at each site prior to randomization. 
In each site pair, one site will be assigned to the control condition and the other site to the 
ICV intervention. 
 
1. Control condition – Sites assigned to usual care will continue to receive weekly 
visits from the mobile SSP, but no additional services. 
2. Intervention – In addition to continuing weekly visits from the mobile SSP, sites 
assigned to the intervention will receive weekly visits by the ICV. Staffed by a 
medical provider, nurse, and phlebotomist, the ICV will provide a spectrum of 
PWID services (e.g., rapid HIV and HCV testing, naloxone overdose kits, HIV 
treatment and linkage, HCV treatment and linkage, buprenorphine-based MOUD, 
and PrEP). The ICV will visit neighborhood sites once a week and offer services 
to anyone seeking them, irrespective of enrollment in the study cohort 
 
In addition to the quantitative endpoints from the trial, we will also collect qualitative 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 15 of 34 
 
data to understand whether the ICV was recognized by clients and how ICV service 
provision was perceived by different stakeholders. Additionally, a cost-effectiveness 
evaluation is planned. 
 
The study duration will be approximately 36 months. Site selection and preparatory work 
will take 8 months. Participants will be enrolled by site, in staggered fashion, over 14 
months, and followed for an additional 14 months. 
 
7. 
STUDY POPULATION 
We will recruit cohorts of PWID at each neighborhood site, with roll-out of the study arm 
allocation (intervention or control condition) near the conclusion of cohort enrollment. 
Cohort participants will be followed for 14 months during the intervention phase. The 
exploratory objectives require i) collection of qualitative data from key stakeholders, 
including PWID, SSP staff, ICV staff, and policymakers, ii) conduct cost-benefit 
analyses. 
 
7.1 
Enrollment Criteria 
The enrollment criteria were designed to enroll high-risk PWID. To optimize enrollment 
of HIV-positive individuals, we structured the inclusion criteria so that HIV-positive 
individuals did not have to be recent injectors. HIV point-of-care rapid testing (with pre- 
and post-test counseling) will be conducted as part of study screening. An important 
component of study recruitment (and follow-up) will be the use of biometric 
identification (iris scans) to prevent duplicate enrollments of participants at different 
neighborhood sites (and to ensure proper attribution of follow-up visits). We have found 
this method to be highly acceptable to the target population, rapid (about 20 seconds), 
accurate, and safe (the program uses a proprietary algorithm to generate a unique, 
reproducible code from iris images, but does not store photographic images). 
   
7.1.1 Participant Inclusion Criteria 
Inclusion criteria for cohort participants 
Men and women who meet all of the following criteria are eligible for inclusion as a 
cohort participants: 
• 18 years of age or older 
• Injection drug use history according to HIV status 
o If HIV-negative 
§ Injected 4 or more days in the prior 30 days 
or 
§ Shared needles/syringes in the prior 6 months 
o If HIV-positive 
§ History of injection drug use 
 
7.1.2 Participant Exclusion Criteria 
Exclusion criteria for cohort participants 
Men and women who meet any of the following criteria are ineligible for inclusion as a 
cohort participants: 
• Not competent to provide written informed consent 
• Unwilling or unable to provide a blood sample 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 16 of 34 
 
 
7.2 
Recruitment Process 
We will enroll cohorts of participants at each of the 12 study sites, with a target 
enrollment of 60 participants at each site (720 overall). Data from the cohorts will be 
used to draw inferences about the acceptability and effectiveness of the ICV. We have 
taken steps to minimize selection or follow-up bias between the ICV and cohort 
activities. First, cohorts will be recruited prior to randomization (so research staff will not 
know which sites will receive the intervention when they are recruiting the cohorts). 
Second, the cohorts will be recruited and followed by a dedicated research team on a 
research van that is separate from the mobile SSP and the ICV. This separation of 
research from the ICV will minimize the risk that research activities affect ICV service 
utilization. The goal will be to recruit PWID clients of the mobile SSP and other PWID in 
the neighborhood who might access services on the ICV.   
 
We will use a dedicated research van to recruit individuals at each of the neighborhood 
sites (near cross-street locations where the Baltimore City mobile SSP makes regular 
stops). The research van will accompany the SSP van to sites where it is actively 
recruiting cohorts. We will post study recruitment flyers on the SSP van and staff on the 
van will refer interested clients to the research van. Additionally, research staff will 
encourage word-of-mouth referrals from participants. 
 
7.3  
Participant Retention 
Our experienced team is well aware of the challenges of PWID study retention. Once a 
participant enrolls in the cohort study, the research team will make every effort to retain 
him/her for the full study period (~14 months). Study site staff will develop and 
implement local standard operating procedures to target this goal. Components of such 
procedures include: 
• Thorough explanation of the study visit schedule and procedural requirements 
during the informed consent process and re-emphasis at each study visit. 
• An experienced van research team with a lifelong knowledge of Baltimore City. 
• Collection of detailed and multifaceted locator information at the baseline visit, 
and active review and updating of this information at each subsequent visit. 
• Use of mapping techniques to establish the location of participant residences and 
other locator venues. 
• Visit reminder calls and letters. 
• Reimbursed “check-in” phone contacts between the scheduled study visits (i.e., 
~3 months and ~9 months) 
• Regular communication with the PWID community at large to increase awareness 
about follow-up and the research van’s current and future location. 
• Use the van to visit participants’ last known residence (“knocking on doors”). 
 
8. 
INTERVENTIONS 
Study sites (clusters) will be randomly allocated to either the ICV intervention or to the 
control condition.  
 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 17 of 34 
 
Table 1. Comparison of services with the mobile SSP alone (control) and the SSP combined with the ICV 
(intervention). 
Type of service 
SSP (control) 
ICV intervention 
Risk reduction 
 
 
SSP 
Confidential (ID-based) SSP using 
hybrid exchange/distributive model 
Same 
Overdose prevention 
/response 
SSP program leads city-wide 
initiative to train and provide 
naloxone overdose kits to PWID, 
their friends, and family 
Same, although ICV will provide increased 
opportunities for naloxone kit training and 
distribution 
PrEP 
Refer to PrEP program offered at 
BCHD clinics  
Onsite provision of PrEP education, clinical 
/lab screening for PrEP eligibility, PrEP 
prescription, and monitoring 
HIV care cascade 
 
 
HIV testing 
Free (non-rapid) HIV and syphilis 
testing offered on the van once or 
twice a year 
Free rapid HIV testing offered daily 
Linkage to HIV care 
No routine service 
Intervention team tracks care cascade using 
Data to Care program, peer navigators link 
clients to care. 
ART adherence /viral 
suppression 
No routine service on mobile SSP. 
ICV team communicates with HIV treatment 
providers in city, tracks patients who have 
lapsed with ART prescription fills, on-site 
case management to address barriers, 
laboratory testing on van to assist clinic, ART 
refills provided 
Substance abuse 
treatment 
Referral to buprenorphine- or 
methadone-based MOUD with 
dedicated slots for SSP clients 
Low-barrier, same-day prescription of 
buprenorphine, with transition community-
based MOUD 
Additional PWID 
services 
 
 
HCV care cascade 
Referral to BCHD clinics or 
elsewhere for testing, disease 
staging, and treatment 
HCV antibody and HCV RNA testing on ICV, 
initiate HCV treatment on ICV with case 
management support. Referral for advanced 
liver disease. 
Wound care 
Referral to primary care provider or 
emergency department 
Wound care-certified NP offers acute and 
chronic wound care management on the van, 
with referral for specialized treatment25 
 
8.1 
Control Condition 
Control (usual care) sites will receive services currently provided by 2 Baltimore City 
Health Department mobile SSPs. Together, these vans visit ~15 sites around Baltimore 
City each week (busy sites are visited more than once per week).  In 2015, the SSP had 
16,164 visits by 4512 unduplicated clients, and distributed 1,071,927 clean syringes.  In 
addition to needle/syringe services, the SSP vans offers outreach HIV and syphilis testing 
(not rapid testing) approximately twice a year (the SSP van is not normally staffed for 
phlebotomy). Second, the SSP provides opioid overdose reversal training and distributes 
naloxone nasal spray kits directly to clients. Third, the SSP can refer clients to opioid 
agonist treatment programs that have dedicated treatment slots for SSP referrals. For 
other services (HIV management, PrEP, HCV testing and treatment evaluation, wound 
care, etc.) the SSP provides no direct services. 
 
8.2 
ICV Intervention 
The integrated care van (ICV) is a medically-staffed, mobile health facility that will 
provide PWID-oriented medical services and case management. ICV services will 
include 1) linkage, support, and medical management for HIV-positive clients, 2) 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 18 of 34 
 
screening and initiation of pre-exposure prophylaxis (PrEP) for high-risk HIV-negative 
PWID, 3) low-barrier initiation of buprenorphine/naloxone and transfer to community-
based medication assisted treatment, 4) HCV testing, liver disease staging, and HCV 
treatment with direct acting agents, and 5) wound care. The ICV will visit different 
neighborhood stops/sites according to an established weekly schedule. The ICV is a 
structural intervention that will provide the staff, physical space, equipment, and 
information technology to bring a package of evidence-based biomedical services to the 
outermost public health-PWID interface. The ICV is a 40-foot Freightliner that includes 2 
patient exam rooms, a waiting space, a phlebotomy/laboratory area, and a bathroom.  
Electricity is provided by an on-board generator. The ICV will be staffed by BCHD 
employees, including one or two medical providers (physicians and mid-level 
practitioners), a case manager, and a phlebotomist/driver. The clinical staff are 
experienced in HIV treatment, PrEP screening and management, HCV treatment, 
buprenorphine (with Drug Enforcement Agency waiver), and wound care. Under the 
auspices of the BCHD, the ICV will provide services to anyone who visits the unit.  
 
9. 
STUDY PROCEDURES/EVALUATIONS 
9.1 
Clinical Evaluations and Procedures 
Eligible participants who meet inclusion criteria and provide written informed consent 
will be enrolled to the local cohort. Cohort participants will complete a baseline study 
visit, most often on the day of screening, and will be asked to complete follow-up visits at 
7 months and 14 months, for a total of 3 study visits. Study visits will include the 
following evaluations: 
• Biometric capture (iris scan) to assure identity 
• Blood draw and urine sample 
• Collection of contact and locator information 
• Interviewer-administered survey covering the following domains 
o Demographics 
o Quality of life 
o Engagement/experience with HIV, HCV, PWID services 
o Alcohol and drug use 
o Injection- and sex-related risk behaviors 
o Depression symptoms 
o Health care utilization 
 
9.2 
Laboratory Evaluations 
 
Table 2. Laboratory testing for cohort participants 
 
Test 
CLIA status 
Visits measured 
Participants included 
HIV-
negative 
HIV-
positive  
bioLytical Laboratory INSTI 
HIV-1/HIV-2  point-of-care 
Rapid HIV test 
Waived 
SCR 
● 
● 
CD4 cell count, flow 
cytometry, JHH 
Certified 
V00 
 
● 
HIV-1 antibody test 
Certified 
V14 
● 
 
HIV RNA 
Certified 
V00, V07, V14 
 
● 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 19 of 34 
 
Table 2. Laboratory testing for cohort participants 
 
Test 
CLIA status 
Visits measured 
Participants included 
HIV-
negative 
HIV-
positive  
Tenofovir diphosphate 
concentration in peripheral 
blood mononuclear cells 
Non-certified 
V00, V07, V14 
(among subset 
reporting linkage to 
PrEP) 
● 
 
Hepatitis C virus (HCV) 
serology 
Certified 
V00 
● 
● 
HCV RNA 
Certified 
V00 & V14 (in 
HCV seropositive 
only) 
● 
● 
Urine drug screening, high 
resolution accurate mass 
spectrometry 
Certified 
V00, V07, V14 
● 
● 
SCR, screening; V00, baseline visit, V07, 7-month visit; V14, 14-month visit 
 
9.2.1 Biohazard Containment 
As the transmission of HIV and other blood-borne pathogens can occur through contact 
with contaminated needles, blood, blood products and body fluids, 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 
United States Centers for Disease Control and Prevention. All infectious specimens will 
be transported in accordance with United States regulations (42 CFR 72). 
 
9.2.2 Total Blood Volume 
We will draw a blood volume of 25 cc at the baseline, 7 month, and 14-month visits. The 
maximum amount of blood drawn over an 8-week period is 25 cc. 
 
9.3 
Schedule of Procedures/Evaluations: Timing and Definitions 
Follow-up visits at ~7 months and ~14 months following the baseline visit.   
 
9.3.1 Screening 
Following oral consent (OCS) for screening (see Figure for flow diagram), participants 
will be asked to complete an iris scan to check for duplicate enrollment (individuals will 
not be able to enroll more than once). The iris scans are converted by proprietary 
software into long encrypted codes that are used to identify persons who have 
participated previously in the study (Iris ID, Inc.: EAC2500 Software and iCAM TD100 
dual iris imager. The iris scan system protects participant confidentiality because the iris 
images are not saved in the system and codes derived from the scans cannot be used to 
reconstruct iris scan images. Finally, the codes generated by the iris scans at screening 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 20 of 34 
 
will not be stored – they will only be used to cross-reference with the database to quickly 
identify individuals who have already participated and prevent such individuals from 
entering the study a 
second time.  
Participants with no 
match in the iris scan 
code database will be 
asked to answer 
screening questions.  
Participants that remain 
eligible after completing 
the screening questions, 
will be asked to provide 
written informed 
consent.  
 
Following written 
informed consent, 
participant iris scan 
codes will be registered 
in the database to 
prevent duplicate 
enrollment in the future. 
Study staff will 
complete a State of 
Maryland HIV testing 
form and provide pre-
test counseling.  
Participants will be 
asked to provide blood 
and urine samples, and 
have a fingerstick for a 
rapid HIV test. We will 
use the INSTI HIV-1/HIV-2 rapid test (bioLytical Laboratories, Richmond, BC, Canada), 
a 3rd generation HIV 1/2 test, which is also used by the BCHD.   After specimen 
collection and rapid testing, research staff will provide post-test HIV counseling, discuss 
eligibility for the cohort study, and offer cohort enrollment to eligible individuals. 
Participants with negative HIV test results will be counselled to resume routine testing 
(every 6 to 12 months) depending on ongoing risk factors. Participants with invalid 
results will be advised to retest in the next 1 month. Participants with a positive HIV test 
(and who have not previously tested positive) will be referred to a BCHD facility for 
confirmatory HIV testing and linkage to care. After HIV post-test counseling, we will 
make a final eligibility determination on the basis of 1) the screening survey, 2) ability to 
provide a blood sample, and 3) results of the rapid HIV test. These data will be applied to 
the study inclusion/exclusion criteria described in Section 7.1 to determine eligibility to 
join the cohort. 
 
 
 
Figure. Screening/Enrollment Diagram 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 21 of 34 
 
9.3.2 Enrollment 
Participants that are eligible for the cohort will be offered enrollment. Research staff will 
conduct the baseline visit as soon as possible following screening (usually the same day). 
 
9.3.3 Follow-up 
There will be 2 follow-up cohort visits at ~7 and ~14 months.  Study visits will include 1) 
collection of contact information, 2) an interviewer-administered questionnaire, 3) blood 
draw, and 4) urine sample. The questionnaire will cover the following domains: socio-
demographics (age, race, sex, education, employment, geo-coding, incarceration), 
substance use (injection and non-injection drugs, alcohol [AUDIT]), drug using network, 
overdose history, injection practices (frequency, needle/syringe sharing, drugs used), 
sexual transmission risk behaviors (number of partners, concurrency, condom use, MSM, 
sex work), depression (PHQ-9), quality of life (SF-12), social support, and resource 
utilization (SSP, HIV care, HCV care, PrEP, MOUD, other substance abuse treatment 
modalities, emergency department use, hospitalizations, time and money spent obtaining 
medical care). 
 
9.3.4 COVID-19 Impact on Study 
The COVID-19 pandemic initially struck Baltimore, MD in March 2020 and had 
substantial effects on this study. The pandemic led to suspension of both study cohort 
follow-up visits and the ICV intervention for many months. The study achieved full 
enrollment (N=720, n=60 at each of the 12 sites) between July 2018 and August 2019. 
Two cohort follow-up visits were planned at 7 months and 14 months. At the time of 
pandemic-related shut downs we had completed the 7-month visits at all 12 sites. 
Additionally, we had completed the 14-month visit at 4 of the 12 sites. We switched to 
telephone-based follow-up visits, which included the participant survey but not 
laboratory tests. We also added questions to assess the effects of COVID-19 among the 
study cohort. We resumed in-person visits in July 2021. For the purposes of this trial, we 
decided to base primary analyses on the baseline visit and the first follow-up visit (7 
months). Although this does not include the longer follow-up that we planned, it includes 
only data that was collected prior to the pandemic. In secondary analyses we will 
consider data collected during and after pandemic-related shut downs.  
 
10. 
ASSESSMENT OF SAFETY 
 
10.1 
Safety Assessment Overview 
This section provides information on the definition of adverse events (AE), serious 
adverse events (SAE) and the procedures for reporting. Procedures for prompt reporting 
of AE and SAE will be standardized across the field sites. 
 
10.2 
Definition of Adverse Events (AE) 
An AE is any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or diagnosis that occurs in a study participant during the conduct of 
the study regardless of the attribution (i.e., relationship of event to medical 
treatment/study product/device or procedure/intervention). This includes any occurrence 
that is new in onset or aggravated in severity or frequency from the baseline condition.  
 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 22 of 34 
 
10.3 
Definition of serious adverse events (SAE) 
An SAE is defined as any untoward medical occurrence that: 
 
 
• Results in death 
• Is life-threatening  
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity  
• Is a congenital anomaly/birth defect 
• Is an important medical event that may not be immediately life-threatening or 
result in death or hospitalization but may jeopardize the patient or may require 
intervention to prevent one of the other outcomes listed in the definition above). 
 
10.4 
Adverse Event Procedures and Reporting Requirements 
The research procedures in our study include study visits with cohort participants and 
key-informant interviews. These research procedures are minimal risk (involve only a 
blood draw), and do not include a drug or medical device. Furthermore, study sites (or 
clusters) are the unit of randomization, not individual participants. Participants at 
intervention sites have access to the intervention (ICV), but are not required to seek or 
accept the intervention. The intervention itself is being rolled out by the BCHD, and this 
study is a formalized assessment of the intervention. Finally, the study population of 
active PWID have substantially higher risks of morbidity and mortality than persons in 
the general population. Given these considerations, our reporting obligations for the trial 
focus only on events that are more likely than not to be associated with study procedures 
(study visits or key-informant interviews. Two types of events will be reportable: 
 
1. Unanticipated problems involving risks to participants or others will be reported to 
the JHM IRB within 10 working days (unless the event is death, in which case # 2 
applies).  Such events are defined as: 
a. The information is unexpected in terms of nature, severity, or frequency, 
given: 
i. The research procedures described in the protocol and informed 
consent document; and 
ii. The characteristics of the subject population being studied 
b. The information indicates that the participants or others are at greater risk 
of harm (including physical, psychological, economic, or social harm) 
than was previously known or recognized. 
2. Deaths of study participants in close association with study procedures will be 
reported to the IRB within 3 working days. 
 
11. 
CLINICAL MANAGEMENT 
11.1 
Clinical Management of Adverse Events 
Research staff will interact with participants at study visits and during the intervention 
(dispensing non-cash incentives). Research staff will refer participants to a clinic or 
hospital for medical conditions that arise. 
 
11.2 
Criteria for Permanent Intervention Discontinuation or Premature Study 
Discontinuation 
Potential reasons for discontinuation of intervention or study are: 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 23 of 34 
 
• Request by the participant to stop. 
• Request of study coordinator if s/he thinks the intervention is no longer in the best 
interest of the participant. 
• At the discretion of the IRB/Ethics Committee, Office for Human Research 
Protections (OHRP), other government agencies as part of their duties, or 
investigator 
 
12. 
STATISTICAL CONSIDERATIONS 
12.1 
Overview and General Design Issues 
The primary objective of this study is to determine whether provision of an ICV at 
neighborhood sites, served by the mobile SSP in Baltimore, reduces risk, improves 
health, and increases uptake of evidence-based services among PWID. We will address 
this objective with a two-arm, matched-pair, 12-site cluster randomized trial. 
Neighborhood sites allocated to the control condition, will continue to receive SSP 
services. Neighborhood effects will be assessed in cohorts of PWID participants enrolled 
at each study site, prior to intervention roll-out, and followed for up to 14 months. During 
the trial, we will collect qualitative data from PWID (who used and did not use ICV 
services), ICV staff, and other stakeholders. Finally we will collect costing data to 
facilitate evaluation of cost-effectiveness.  
 
12.2 
Study Endpoints 
Primary and secondary study endpoints will be assessed at follow-up cohort visits on the 
basis of laboratory testing, structured interviews, and external sources of data, including 
treatment episodes (emergency department visits, hospitalizations, outpatient clinic visits) 
captured by Chesapeake Regional Information System for Our Patients (CRISP) and the 
National Death Index. Exploratory endpoints will be assessed on the basis i) costing data 
collected during the study, and ii) qualitative key informant interviews. 
 
12.2.1 Primary Endpoint 
Composite PWID score (service access, risk behaviors, adverse outcomes). This outcome 
will be assessed in participants at all visits. To capture the multi-faceted nature of the 
ICV intervention and the array of health issues relevant to PWID, we developed a 
composite score that will be captured at baseline and recalculated at each follow-up visit. 
We developed a scoring rubric (Appendix) based on WHO guidelines for evidence-based 
PWID services,26 a predictive risk model for HIV seroconversion among PWID 
developed by the Baltimore-based ALIVE study,27 the HCV care continuum,28 and the 
overdose epidemic.29 
 
12.2.2 Secondary Endpoints 
• HIV care continuum (among HIV-positive participants). 
 
• Recent HIV testing (among HIV-negative participants). 
 
• PrEP continuum (among HIV-negative participants). 
 
• HCV care continuum (among HCV-positive participants). 
 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 24 of 34 
 
• HCV testing (among HCV-negative participants) 
 
• Engagement in MOUD (among all participants). 
 
• Engagement in SSP 
 
• Possession of a naloxone overdose kit (among all participants). 
 
• Injection drug use (among all participants) 
 
• Recent drug use (among all participants) – Urine drug test positive for fentanyl 
(metabolite), heroin (morphine or 6MAM), cocaine (metabolite), or amphetamines 
 
• Sharing drug paraphernalia (among all participants) 
 
• Non-fatal drug overdoses (among all participants) 
 
• Emergency department use (among all participants). 
 
• HIV seroconversion 
 
• HCV seroconversion 
 
• All-cause mortality (among all participants). 
 
12.2.3 Exploratory Endpoints 
• Qualitative assessments among key stakeholders. 
 
• Costs and cost-effectiveness 
 
12.3 
Study Hypothesis 
We hypothesize that the availability of an ICV that provides evidence-based PWID-
focused services will reduce risk, improve health, and increase uptake of evidence-based 
services among PWID.     
 
12.4 
Sample Size Considerations 
To estimate the power to correctly reject a null hypothesis, we used simulation methods 
assuming a normally distributed composite PWID score. We adapted the methods of 
Arnold et al.30 for using mixed effects logistic regression random intercepts for cluster 
(SD = .22) and participant (SD = 1.05) with one baseline and one follow-up assessment, 
80% retention, and a similar treatment effect at each follow-up. With an initial sample 
size of 720 participants, we would have 80% power if the true person-level composite 
scores were .33 standard deviations higher at follow-up at the target sites than at the 
control sites, controlling for composite scores at baseline, random variation across study 
sites, and random variation across individuals. Using Cohen’s criteria, this would 
correspond to a small-medium effect size.31 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 25 of 34 
 
 
12.5 
Study Site Selection and Pair Matching 
We will use a parallel cluster randomized trial, in which random allocation to the 
experimental condition occurs at the site- (or cluster-) level rather than at the participant-
level. Like other randomized designs, cluster randomized trials are methodologically 
rigorous and yield strong inferences about intervention effectiveness.32,33 Cluster 
randomized trials are well-suited to implementation research because participant-level 
randomization is often impractical with multi-faceted or structural interventions and is 
susceptible to contamination bias in this setting.  The SSP vans currently serve 15 
neighborhood sites across the city. We will select 12 of the sites to include in the cluster 
randomized trial.  Several factors are relevant to site selection. We must consider 
proximity of the sites. If two sites are very close together, there may be contamination, 
where the intervention delivered at one of sites affects the proximal site as well.  Where 
there is a high risk of overlap between two sites, we will exclude one of the sites or 
consider the two sites to be a single site in the trial. 
 
Because the number of randomly allocated units in this cluster randomized trial is small, 
we anticipate using a matched-pair design. The idea is to identify pairs of sites that are 
similar to one another in important characteristics, with one site in each pair randomized 
to the intervention and the other site to usual care. To assess for good site pairings, we 
will review all available BCHD data about the different SSP sites – number of clients 
accessing services each week, client demographic characteristics, and HIV prevalence.  
Additionally, we will interview current SSP staff to capture qualitative aspects of the 
different sites. At the conclusion of this process we will identify 12 sites (6 pairs) for the 
trial. Of note, cohort recruitment at the sties will be staggered, whereby recruitment will 
begin at the first 2 pair (4 sites), then move to a second set of 2 pair, and finally to a third 
set of 2-pair. 
 
12.6 
Randomization and Masking Procedures 
Once the randomization scheme is finalized (including consideration of pair-matching) a 
statistician, who is independent of the study will randomize sites in pairs using a 
commercial software program. The statistician will withhold results until cohort 
enrollment is complete or nearly complete for a given pair of sites. When cohort 
enrollment in a given pair is complete or near complete, the statistician will notify the 
team of the random assignments for the sites in a given pair. The nature of the 
intervention precludes masking. 
 
12.7 
Analysis Plan 
12.7.1 Analysis plan for primary and secondary endpoints 
We will estimate the impact of the ICV on the composite primary outcome which 
incorporates the following: HIV prevention, testing, and treatment; HCV prevention, 
testing, and treatment; substance use and treatment; overdose; and healthcare utilization 
(see Appendix). We will also estimate the impact of the ICV on the separate measures 
that make up the composite outcome, including the HIV care cascade, the PrEP 
continuum, MAT engagement, and linkage to HCV treatment. The outcomes will be 
continuous (composite primary outcome), ordinal (HIV care cascade, PrEP continuum, 
HCV linkage), and dichotomous (MAT), and the analytic samples will vary depending on 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 26 of 34 
 
the outcome. For all outcomes, the data will have the same structure, with time (t) nested 
within participants (i) nested within SSP sites (j).  The three-level structure of the data 
will induce correlations in the outcomes within sites and within participants, and this will 
be addressed by using random intercepts for site and random intercepts for participants. 
Fixed effects will include covariates for calendar time (a linear, quadratic, spline terms, 
or indicators as indicated by exploratory data analysis), indicator for 6-month follow-up 
assessment, a time-varying indicator for ICV exposure status, and follow-up-by-ICV-
status interaction terms. This general linear model can be expressed as: 
 
 
where: 𝜋!"# denotes the linearized expected outcome for participant 𝑖 at SSP site 𝑗 on 
occasion 𝑡 ; 𝛽$ is the overall intercept; 𝑈$! and 𝑈$" are normally distributed person-level 
and site-level random intercepts; 𝐼𝐶𝑉!"# is an indicator for participation being at an ICV 
site, 𝐹𝑈!"# is a binary indicator for the 6-month follow-up assessment; 𝐼𝐶𝑉𝑥𝐹𝑈!"# is an 
ICV-by-follow-up interaction term; 𝒙!"# is a vector of participant-level covariates with 𝜸 
the vector of corresponding fixed-effects regression parameters; 𝒛′" is a vector of SSP site 
covariates (including intervention phase) with 𝜻 the vector of corresponding fixed effects; 
and 𝜀!"# are error terms. The null hypothesis of no significant group-by-time interaction at 
the follow-ups can be tested using a 1-df F-test of 𝐻$: 𝛽& = 𝟎. The form of 𝜋!"# and the 
expected distribution of the residuals will be specified based on the specific outcome. For 
the composite outcome, we will use mixed effects linear regression with an identity link 
function and normally distributed residuals.  
The above-described model does not have a coefficient for matched-pair, and therefore 
“breaks the pairing.” This approach may be more statistically powerful when the 
matching accounts for little variability among clusters,33 and we expect that to the case 
given the limited information that was available for conducting the matching. How much 
variability is accounted for by the matching will be based on reduction in the variance of 
the cluster-level random intercept when including fixed effects for matched-pairs, and a 
likelihood ratio test comparing models with and without fixed effects for matched-pairs.  
For ordinal outcomes, such as an individual’s location along the HIV care cascade or 
PrEP continuum, mixed effects ordinal logistic regression is a natural analytic approach. 
Such a method assumes an underlying continuum of propensity for viral suppression or 
PrEP adherence. In a classic example, Aiken and colleagues34 used ordinal logistic 
regression in a randomized trial to model movement along a mammography continuum 
with ordered outcome categories including doing nothing, contacting a healthcare 
provider, making an appointment, and actually receiving a mammogram—these 
outcomes parallel the care cascade and PrEP continuum. Gibbons and Hedeker35 
described using ordinal logistic regression in a three-level random effects model, as we 
propose here. 
 
The ordinal logistic model is also referred to as the proportional odds model as it assumes 
that ICV exposure has the same effect on transitioning across the various 
cascade/continuum thresholds. Thus, the interaction between follow-up and ICV status 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 27 of 34 
 
would be interpreted as the change in the log-odds of being past any given threshold in 
the care cascade (e.g., recent prescription for ART) with ICV exposure, controlling for 
other factors in the model, including person-specific and site-specific, random intercepts. 
In our analyses, we will evaluate the proportional odds assumption through the use of the 
Score test.31 If the proportional odds assumption is violated, we will proceed with a 
nested dichotomies approach using a logit link function. It is also possible that the three-
level ordinal logistic model may not converge. In that case, we will also use nested 
dichotomies. With nested dichotomies,31 we would first dichotomize outcomes between 
the first and second steps of the care cascade (or PrEP continuum) and evaluate the effect 
of the intervention on the odds of being at least linked to care; in a second model limited 
to those at least linked to care, we would evaluate the effect of the intervention on the 
odds of being engaged in care; and so forth. 
 
For the dichotomous outcome of MOUD use in the last 30 days, we will follow the same 
general formula described above using mixed effects logistic regression with a logit link 
function and a binomial residual distribution. Outcome analyses will be preceded by 
preliminary analyses examining bias in intervention assignment and potential baseline 
confounders of the relationship between assignment and the primary outcomes. We shall 
evaluate and adjust for any potential confounders in adjusted outcome analyses. All 
analyses will be conducted in Stata and will include the use of the random effects gllamm 
procedures with Huber/White variance-covariance estimators. 
 
The composite PWID score will be calculated for each participant at each study visit 
according to the rubric in the Appendix, where a higher score indicates higher risk for 
adverse events or lower use of evidence-based PWID services. At the follow-up visits, 
we will calculate each participant’s change in score from baseline. We will estimate the 
association between ICV cluster and change in the score with a multi-level linear 
regression model, similar to that shown above. In a supplementary analysis, we will 
convert follow-up scores to binary outcomes that indicate whether the score has 
decreased from baseline (improved) or not. In this case we will use a logistic regression 
model. 
 
We are aware of the risk of attrition in this study, and our sample size estimates have 
accounted for up to 20% attrition, despite intensive retention efforts. We will examine 
whether missingness is associated with observed data using standard methods.36-38 If we 
do identify predictors of missingness (i.e., data are not missing completely at random 
[MCAR]), we will conduct a second set of outcome analyses using multiple imputation to 
evaluate the robustness of the primary outcome analyses to missingness and report 
estimates based on multiple imputation that would be valid based on the assumption that 
the data are missing at random (MAR) as opposed to not missing at random (NMAR). As 
missing data are expected to follow multiple distributions, we will impute using chained 
equations.39 We will produce imputed datasets (m > 10), run outcome analyses on all 
sets, and derive point and standard error estimates for treatment effects and other 
parameters from the distribution of estimates from the outcome analyses with imputed 
datasets. We will implement multiple imputation using the Stata “mi impute chained” and 
“mi estimate” procedures. 
 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 28 of 34 
 
12.7.2 Analysis plan for qualitative evaluation of HIV treatment incentives 
Qualitative data analysis involves the search for patterns in data and for ideas that help to 
explain the presence of those patterns. Transcripts from in-depth interviews (IDIs) with 
ICV and SSP staff, PWID participants, and city and state health department officials will 
be entered and managed in NVivo.  Separate coding schemes will be developed for 
PWID (ICV and non-ICV clients) and the other two groups of city and state health 
department staff (city and state health department officials, ICV and SSP service 
providers). An iterative coding process in NVivo will be used to conceptually name the 
data and reduce it to manageable units of information that cover broad and general 
categories. Codes will be informed by the questions in the qualitative guides, and new 
themes that emerge from the data will be analyzed through a grounded theory approach, 
allowing for themes to emerge and ensuring that the knowledge assembled from the 
observational data is not subjected to the themes solely established through the interview 
guide. Two coders will conduct open-coding on three transcripts to develop initial coding 
schemes. After discussion and development of a combined draft scheme, two more 
interviews will be coded, and these will be further discussed and inform a final coding 
scheme under the guidance of Dr. Sherman. Through weekly meetings, a team approach 
to data analysis will be employed, whereby different analysts provide feedback on 
emerging interpretations and check emerging categories against the raw data. In this way, 
an “audit trail” will be used to help ensure trustworthiness of findings, gather input from 
multiple perspectives, and enhance reliability. 
 
12.7.3 Analysis plan for cost-effectiveness 
Overview. In accordance with the recommendations of the 2nd US Panel on Cost-
Effectiveness in Heath and Medicine,40 we will: inventory and value the resources 
consumed in the ICV intervention; estimate intervention effectiveness in regards to viral 
suppression, HIV infections averted, HCV treatment, and MOUD use; estimate treatment 
costs averted and QALYs saved for each type of effectiveness; and determine whether 
the ICV is cost-saving, cost-effective, or not cost-effective. 
Cost analysis. We will estimate the cost of delivering the program locally from payer, 
societal, and health care perspectives. The societal perspective will incorporate broader 
costs, including non-medical costs to participants and costs reflected in the newly-
recommended impact inventory.41 We will use a micro-costing approach42-44 to directly 
enumerate the cost of every output used in the intervention such as staff time spent on 
each intervention activity, facility space, equipment and materials. In-kind contributions 
will also be enumerated and costed. Sources of data will include project records, salaries, 
cost worksheets, project manager interviews and a project manager survey. The program 
manager will complete a survey to quantify per unit costs for program resources, 
including procedure-specific resources, general resources, fixed resources, and variable 
resources. The labor hours will be converted to labor cost by multiplying the staff time by 
hourly wage rate (including fringe benefits) of the specific staff person who performed 
the activity. Unit costs for in-kind contributions will be based on market rates. Costs for 
participant time, travel, and child or elder care will be based on prevailing local wage 
costs. Cost data for each type of resource will include a “best estimate”, and a credible 
range for unit costs will be established by asking program staff to provide upper and 
lower bounds for any uncertain cost estimates. Questions will be added to the 
questionnaire to capture participant time spent in the intervention and money spent in 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 29 of 34 
 
travel to and from the intervention. We will pilot-test and refine data collection 
instruments and methods during the formative phase. In addition to ongoing, integrated 
cost data collection, it is expected that intensive cost data collection will occur during at 
least two time periods during the intervention phase. During these periods members of 
the costing team will be on-site.  
 
Upon completion of cost data collection, the costing team will conduct a preliminary cost 
analysis of the ICV intervention. We will estimate the cost overall of delivery the 
intervention as well as the cost per visit and cost per person-year. The cost estimate will 
allow us to establish effectiveness thresholds required for the interventions to be cost 
saving, cost-effective, or highly cost-effective. Cost-effectiveness analysis will be 
conducted following the final outcome analyses. 
Effectiveness, medical costs, and QALYs. Expected outcomes among participants with 
and without the ICV will be based on the primary outcome analyses and will include HIV 
care engagement, adherent PrEP use, HCV treatment, and MOUD engagement. We will 
estimate HIV and HCV incidence among participants and contacts using Bernoulli 
process models45 of intercourse and injecting with transmission probabilities based on an 
updated review of the literature and behavioral patterns based on participant assessments. 
We will also rely on the literature for estimates of lifetime treatment costs and quality-
adjusted life years (QALYs) associated with different health states, both discounted at 
3% per annum.40,46 
Incremental cost-effectiveness. The cost-utility ratio will be computed based on the 
estimation of net incremental cost (difference between the incremental intervention costs 
and the incremental treatment costs averted) divided by the QALYs averted. The 
intervention will be considered cost-saving if the incremental intervention cost less than 
the incremental treatment cost averted, considered cost-effective if the net incremental 
cost per QALY saved is less than society’s willingness to pay to save 1 QALY, and not 
cost-effective if net incremental cost per QALY is greater than society’s willingness to 
pay.47 We will use sensitivity analyses to reflect uncertainty in our parameter estimates 
and to examine the robustness of the cost-utility estimates. 
 
 
13. 
REFERENCES 
 
1. 
Lucas GM. Substance abuse, adherence with antiretroviral therapy, and clinical outcomes 
among HIV-infected individuals. Life Sci. 2011;88(21-22):948-952. 
2. 
Lucas GM, Chaisson RE, Moore RD. Highly active antiretroviral therapy in a large urban 
clinic: risk factors for virologic failure and adverse drug reactions. Ann Intern Med. 
1999;131(2):81-87. 
3. 
Lucas GM, Cheever LW, Chaisson RE, Moore RD. Detrimental effects of continued 
illicit drug use on the treatment of HIV-1 infection. J Acquir Immune Defic Syndr. 
2001;27(3):251-259. 
4. 
Lucas GM, Gebo KA, Chaisson RE, Moore RD. Longitudinal assessment of the effects 
of drug and alcohol abuse on HIV-1 treatment outcomes in an urban clinic. AIDS. 
2002;16(5):767-774. 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 30 of 34 
 
5. 
Celentano DD, Galai N, Sethi AK, et al. Time to initiating highly active antiretroviral 
therapy among HIV-infected injection drug users. Aids. 2001;15(13):1707-1715. 
6. 
Shapiro MF, Morton SC, McCaffrey DF, et al. Variations in the care of HIV-infected 
adults in the United States: results from the HIV Cost and Services Utilization Study. 
JAMA. 1999;281(24):2305-2315. 
7. 
Gerbert B, Maguire BT, Bleecker T, Coates TJ, McPhee SJ. Primary care physicians and 
AIDS. Attitudinal and structural barriers to care [see comments]. JAMA. 
1991;266(20):2837-2842. 
8. 
Hanna DB, Buchacz K, Gebo KA, et al. Trends and disparities in antiretroviral therapy 
initiation and virologic suppression among newly treatment-eligible HIV-infected 
individuals in North America, 2001-2009. Clin Infect Dis. 2013;56(8):1174-1182. 
9. 
Koechlin FM, Fonner VA, Dalglish SL, et al. Values and Preferences on the Use of Oral 
Pre-exposure Prophylaxis (PrEP) for HIV Prevention Among Multiple Populations: A 
Systematic Review of the Literature. AIDS Behav. 2017;21(5):1325-1335. 
10. 
Edelman EJ, Moore BA, Calabrese SK, et al. Primary Care Physicians' Willingness to 
Prescribe HIV Pre-exposure Prophylaxis for People who Inject Drugs. AIDS Behav. 
2017;21(4):1025-1033. 
11. 
Choopanya K, Martin M, Suntharasamai P, et al. Antiretroviral prophylaxis for HIV 
infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a 
randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 
2013;381(9883):2083-2090. 
12. 
Martin M, Vanichseni S, Suntharasamai P, et al. Factors associated with the uptake of 
and adherence to HIV pre-exposure prophylaxis in people who have injected drugs: an 
observational, open-label extension of the Bangkok Tenofovir Study. Lancet HIV. 
2017;4(2):e59-e66. 
13. 
Weisner C, Mertens J, Parthasarathy S, Moore C, Lu Y. Integrating primary medical care 
with addiction treatment: a randomized controlled trial. JAMA. 2001;286(14):1715-1723. 
14. 
Willenbring ML, Olson DH. A randomized trial of integrated outpatient treatment for 
medically ill alcoholic men. ArchInternMed. 1999;159(16):1946-1952. 
15. 
Umbricht-Schneiter A, Ginn DH, Pabst KM, Bigelow GE. Providing medical care to 
methadone clinic patients: referral vs on-site care [see comments]. Am J Public Health. 
1994;84(2):207-210. 
16. 
Fiellin DA, O'Connor PG, Chawarski M, Pakes JP, Pantalon MV, Schottenfeld RS. 
Methadone maintenance in primary care: a randomized controlled trial. JAMA. 
2001;286(14):1724-1731. 
17. 
O'Connor PG, Oliveto AH, Shi JM, et al. A randomized trial of buprenorphine 
maintenance for heroin dependence in a primary care clinic for substance users versus a 
methadone clinic. Am J Med. 1998;105(2):100-105. 
18. 
Lucas GM, Chaudhry A, Hsu J, et al. Clinic-based treatment of opioid-dependent HIV-
infected patients versus referral to an opioid treatment program: A randomized trial. Ann 
Intern Med. 2010;152(11):704-711. 
19. 
Altice FL, Bruce RD, Lucas GM, et al. HIV treatment outcomes among HIV-infected, 
opioid-dependent patients receiving buprenorphine/naloxone treatment within HIV 
clinical care settings: results from a multisite study. JAcquirImmuneDeficSyndr. 2011;56 
Suppl 1:S22-S32. 
20. 
Altice FL, Bruce RD, Walton MR, Buitrago MI. Adherence to hepatitis B virus 
vaccination at syringe exchange sites. J Urban Health. 2005;82(1):151-161. 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 31 of 34 
 
21. 
Altice FL, Springer S, Buitrago M, Hunt DP, Friedland GH. Pilot study to enhance HIV 
care using needle exchange-based health services for out-of-treatment injecting drug 
users. J Urban Health. 2003;80(3):416-427. 
22. 
Morano JP, Walton MR, Zelenev A, Bruce RD, Altice FL. Latent tuberculosis infection: 
screening and treatment in an urban setting. J Community Health. 2013;38(5):941-950. 
23. 
Schwarz R, Zelenev A, Bruce RD, Altice FL. Retention on buprenorphine treatment 
reduces emergency department utilization, but not hospitalization, among treatment-
seeking patients with opioid dependence. J Subst Abuse Treat. 2012;43(4):451-457. 
24. 
Morano JP, Zelenev A, Lombard A, Marcus R, Gibson BA, Altice FL. Strategies for 
hepatitis C testing and linkage to care for vulnerable populations: point-of-care and 
standard HCV testing in a mobile medical clinic. J Community Health. 2014;39(5):922-
934. 
25. 
Robinowitz N, Smith ME, Serio-Chapman C, Chaulk P, Johnson KE. Wounds on wheels: 
implementing a specialized wound clinic within an established syringe exchange program 
in Baltimore, Maryland. Am J Public Health. 2014;104(11):2057-2059. 
26. 
WHO, UNODC, UNAIDS technical guide for countries to set targets for universal access 
to HIV prevention, treatment and care for injecting drug users - 2012 revision. Available 
at http://wwwwhoint/hiv/pub/idu/targets_universal_access/en/. 
27. 
Smith DK, Pan Y, Rose CE, et al. A Brief Screening Tool to Assess the Risk of 
Contracting HIV Infection Among Active Injection Drug Users. J Addict Med. 
2015;9(3):226-232. 
28. 
Jordan AE, Perlman DC, Reed J, Smith DJ, Hagan H. Patterns and Gaps Identified in a 
Systematic Review of the Hepatitis C Virus Care Continuum in Studies among People 
Who Use Drugs. Front Public Health. 2017;5:348. 
29. 
Mattson CL, Schieber L, Scholl L, et al. Annual surveillance report of drug-related risks 
and outcomes--United States, 2017. Available at https://stackscdcgov/view/cdc/47832 
[Accessed 12/12/2017]. 2017. 
30. 
Arnold BF, Hogan DR, Colford JM, Jr., Hubbard AE. Simulation methods to estimate 
design power: an overview for applied research. BMC medical research methodology. 
2011;11:94. 
31. 
Cohen J, Cohen P, West SG, Aiken LS. Applied multiple regression/correlation analysis 
for the behavioral sciences. Routledge; 2013. 
32. 
Hemming K, Lilford R, Girling AJ. Stepped-wedge cluster randomised controlled trials: a 
generic framework including parallel and multiple-level designs. Stat Med. 
2015;34(2):181-196. 
33. 
Hayes RJ, Moulton LH. Cluster Randomised Trials. Baco Raton, FL: Chapman & Hall / 
CRC; 2009. 
34. 
Aiken LS, West SG, Woodward CK, Reno RR, Reynolds KD. Increasing screening 
mammography in asymptomatic women: evaluation of a second-generation, theory-based 
program. Health Psychol. 1994;13(6):526-538. 
35. 
Gibbons RD, Hedeker D. Random effects probit and logistic regression models for three-
level data. Biometrics. 1997;53(4):1527-1537. 
36. 
Enders CK. Applied missing data analysis. Guilford Press; 2010. 
37. 
Little RJ, Rubin DB. Statistical analysis with missing data. John Wiley & Sons; 2014. 
38. 
Rubin DB. Multiple imputation for nonresponse in surveys. Vol 81: John Wiley & Sons; 
2004. 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 32 of 34 
 
39. 
White IR, Royston P, Wood AM. Multiple imputation using chained equations: Issues 
and guidance for practice. Stat Med. 2011;30(4):377-399. 
40. 
Neumann PJ, Sanders GD, Russell LB, Siegel JE, Ganiats TG. Cost-effectiveness in 
health and medicine. Oxford University Press; 2016. 
41. 
Sanders GD, Neumann PJ, Basu A, et al. Recommendations for Conduct, Methodological 
Practices, and Reporting of Cost-effectiveness Analyses: Second Panel on Cost-
Effectiveness in Health and Medicine. JAMA. 2016;316(10):1093-1103. 
42. 
Weinstein M, Siegel J, Gold M, Kamlet M, Russell L. Cost-effectiveness in health and 
medicine. New York: Oxford University. 1996;55. 
43. 
Frick KD. Microcosting quantity data collection methods. Med Care. 2009;47(7 Suppl 
1):S76-81. 
44. 
Shrestha RK, Sansom SL, Farnham PG. Comparison of methods for estimating the cost 
of human immunodeficiency virus-testing interventions. J Public Health Manag Pract. 
2012;18(3):259-267. 
45. 
Lin F, Farnham PG, Shrestha RK, Mermin J, Sansom SL. Cost Effectiveness of HIV 
Prevention Interventions in the U.S. Am J Prev Med. 2016;50(6):699-708. 
46. 
Holtgrave DR. Handbook of economic evaluation of HIV prevention programs. Springer 
Science & Business Media; 1998. 
47. 
Neumann PJ, Cohen JT, Weinstein MC. Updating cost-effectiveness--the curious 
resilience of the $50,000-per-QALY threshold. N Engl J Med. 2014;371(9):796-797. 
 
 
 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 33 of 34 
 
14. 
APPENDIX 
 
Table.  Rubric for composite PWID score (service access, risk behaviors, adverse outcomes) 
Score component 
Denominator 
Category definitions 
Service access 
 
 
HIV care continuum 
HIV positive 
0 – Suppressed (HIV RNA <200 c/mL) 
1 – Not suppressed, and either i) took ARVs in prior 30 days (self-report) OR ii) had visit with HIV 
provider in prior 6 months 
2 – Not suppressed AND did not take ART in prior 30 days AND did not have visit with HIV provider 
in prior 6 months (includes those unaware of HIV+ status) at the visit 
HIV testing 
HIV negative 
0 – Had HIV test in past 6 months 
1 – Did not have HIV test in past 6 months 
PrEP continuum 
HIV negative 
0 – Used PrEP in prior 6 months (self-report) 
1 – Did not use PrEP in prior 6 months 
HCV care continuum 
HCV positive 
i. all Ab(+) + RNA(+)  
or  
ii. Ab(+) + RNA(-) + treated 
0 – HCV treatment history (self-report) and HCV RNA suppressed (<15) 
1 – Not suppressed and either treated for HCV OR evaluated by HCV provider in prior 6 months 
2 - Not suppressed AND not treated for HCV in prior 6 months AND not evaluated by HCV provider 
in prior 6 months. 
 
 
HCV testing 
HCV negative  
i. Ab(-) 
or  
ii. Ab(+) + RNA(-) + never treated 
0 – Had HCV test in past 6 months 
1 – Did not have HCV test in past 6 months 
MOUD use 
All 
0 – Used MOUD in past 6 months 
1 – Did not use MOUD in past 6 months 
SSP use 
Injected in prior 6 months 
0 – Used SSP in past 6 months 
1 – Did not use SSP in past 6 months 
Available naloxone kit 
All 
0 – Has naloxone kit on person or where drugs used 
1 – Does not have accessible naloxone kit 
Risk behaviors 
 
 
Injection drug use 
All 
0 – No injection drug use in prior 6 months (self-report) 
1 – Injection drug use in prior 6 months 
Recent drug use 
All 
0 – Urine drug test negative for drugs of concern (*see footnote) 
1 – Urine drug test positive for one or more drugs of concern (*see footnote) 
Sharing injecting 
equipment 
All 
0 – No sharing syringe/works OR not using/injecting in prior 6 months 
1 – Sharing works (cotton/cooker) only in prior 6 months 
2 – Sharing needle/syringe in prior 6 months 
Adverse outcomes 
 
 
 
 
 

 
 
Protocol Number NCT03567174 
 
 
Version 1.0 
 
 
25 APR 2022 
 
Page 34 of 34 
 
*Includes fentanyl (or metabolite), heroin (morphine or 6MAM), cocaine (or metabolite), amphetamine 
 
 
Revised scoring system 25 OCT 2021 
HIV status 
HCV status 
Maximum score 
- 
- 
15 
- 
+ 
15 
+ 
- 
13 
+ 
+ 
13 
 
Table.  Rubric for composite PWID score (service access, risk behaviors, adverse outcomes) 
Score component 
Denominator 
Category definitions 
Non-fatal overdose 
All 
0 – No overdose in prior 6 months 
1 – One or more overdose in prior 6 months 
Emergency department 
use 
All 
0 – No ED visits in past 6 months 
1 - One or more ED visits in past 6 months (Self-report, supplemented by CRISP 
Clinical status change assessed at follow-up only 
 
HIV seroconversion 
HIV negative 
0 – No HIV seroconversion 
2 -  HIV seroconversion occurring between baseline and follow-up 
HCV seroconversion 
HCV negative 
0 – No HCV seroconversion 
1 - HCV seroconversion occurring between baseline and follow-up 
Death 
All 
0 – Alive 
15 (maximum points) – Confirmed death during follow-up