INTEGRA: A Vanguard Study of Health Service Delivery in a Mobile Health Delivery Unit to Link Persons Who Inject Drugs to Integrated Care and Prevention for Addiction, HIV, HCV and Primary Care
Phase: NA
Conditions: HIV Infections, Drug Use, Opioid Use, Opioid-use Disorder
Sponsor: HIV Prevention Trials Network

 
 
 
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HPTN 094 
 
INTEGRA: A Vanguard Study of Health Service Delivery in a Mobile 
Health Delivery Unit to Link Persons who Inject Drugs to Integrated 
Care and Prevention for Addiction, HIV, HCV and Primary Care 
 
DAIDS Document ID: 38715 
 
A Study by the HIV Prevention Trials Network (HPTN) 
 
 
 
Sponsored by: 
Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious 
Diseases (NIAID), US National Institutes of Health (NIH) 
 
 
 
Funded by: 
US National Institute on Drug Abuse 
 
 
 
 
Protocol Chair: 
Steve Shoptaw, PhD 
 
 
Protocol Co-Chair: 
Nabila El-Bassel, PhD 
 
 
 
 
 
Final Version 2.0 
20 February 2023 

 
 
 
HPTN 094, Final Version 2.0 
 
2 of 99 
20 February 2023 
HPTN 094 
INTEGRA: A Vanguard Study of Health Service Delivery in a Mobile Health 
Delivery Unit to Link Persons who Inject Drugs to Integrated Care and Prevention 
for Addiction, HIV, HCV and Primary Care 
 
 
TABLE OF CONTENTS 
 
PROTOCOL SIGNATURE PAGE .............................................................................................. 5 
LIST OF ABBREVIATIONS AND ACRONYMS ..................................................................... 6 
PROTOCOL TEAM ROSTER .................................................................................................... 8 
SCHEMA ...................................................................................................................................... 11 
1. 
INTRODUCTION ............................................................................................................. 16 
1.1 
BACKGROUND AND RATIONALE ................................................................................................. 16 
1.2 
RATIONALE FOR STUDY DESIGN ................................................................................................ 17 
1.2.1 
Implementation Science Framework ..................................................................................................... 20 
2.0 
STUDY OBJECTIVES ..................................................................................................... 21 
2.1 
PRIMARY OBJECTIVE .................................................................................................................. 21 
2.2 
SECONDARY OBJECTIVES ........................................................................................................... 21 
2.3 
PROCESS OBJECTIVES ................................................................................................................. 22 
2.4 
EXPLORATORY OBJECTIVES ....................................................................................................... 22 
3.0 
STUDY DESIGN ............................................................................................................... 23 
3.1 
PARTICIPATING SITES/INSTITUTIONS.......................................................................................... 24 
3.2 
STUDY DURATION ...................................................................................................................... 24 
4.0 
STUDY POPULATION ................................................................................................... 24 
4.1 
INCLUSION CRITERIA .................................................................................................................. 24 
4.2 
EXCLUSION CRITERIA ................................................................................................................. 25 
4.3 
RECRUITMENT PROCESS ............................................................................................................. 25 
4.4 
CO-ENROLLMENT GUIDELINES................................................................................................... 26 
4.5 
PARTICIPANT RETENTION ........................................................................................................... 26 
4.6 
PARTICIPANT WITHDRAWAL FROM STUDY ................................................................................ 27 
5.0 
STUDY INTERVENTIONS ............................................................................................. 28 
5.1 
INITIAL ASSESSMENT AND PROVISION OF SERVICES IN THE MOBILE UNIT - ALL PARTICIPANTS
 
28 
5.2 
PROVISION OF MEDICAL SERVICES ............................................................................................ 29 
5.2.1 
Medical Services - Intervention Arm ..................................................................................................... 29 
5.2.2 
Medical Services - Active Control Arm ................................................................................................ 30 
5.3 
PROVISION OF PEER NAVIGATION SERVICES.............................................................................. 30 

 
 
 
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5.3.1 
Navigation Services - Intervention Arm ................................................................................................ 31 
5.3.2 
Navigation Services- Active Control Arm ............................................................................................. 31 
5.4 
MEDICATION CONSIDERATIONS ................................................................................................. 31 
5.4.1 
Medications for HIV and MOUD .......................................................................................................... 32 
5.4.2 
Centrally Supplied Medication Acquisition and Accountability ........................................................... 32 
5.4.3 
Accountability for Centrally Supplied Medications .............................................................................. 33 
6.0 
STUDY PROCEDURES ................................................................................................... 40 
6.1 
SCREENING VISIT ........................................................................................................................ 40 
6.2 
ENROLLMENT VISIT .................................................................................................................... 40 
6.3 
CLINICAL CARE AND NAVIGATION VISITS BETWEEN ENROLLMENT AND WEEK 26 ................. 41 
6.4 
WEEK 26 VISIT ............................................................................................................................ 42 
6.5 
WEEK 52 VISIT ............................................................................................................................ 43 
6.6 
PROCEDURES FOR PARTICIPANTS WHO DO NOT HAVE HIV AT ENROLLMENT AND HAVE A 
REACTIVE OR POSITIVE HIV TEST AFTER STUDY ENROLLMENT.............................................................. 43 
6.7 
IMPLEMENTATION EVALUATION AND COST-EFFECTIVENESS DATA COLLECTION PROCEDURES
 
44 
6.8 
STUDY VISIT WINDOWS .............................................................................................................. 46 
7.0 
SAFETY MONITORING AND SERIOUS ADVERSE EVENT REPORTING ........ 47 
7.1 
ADVERSE EVENT DEFINITION AND REPORTING ......................................................................... 47 
7.1.1 
Grading Severity of Events .................................................................................................................... 48 
7.1.2 
Reporting Timeframe ............................................................................................................................. 48 
7.1.3 
SUSAR Assessment ............................................................................................................................... 48 
7.1.4 
AE Reporting to DAIDS ........................................................................................................................ 48 
7.1.5 
EAE Reporting to DAIDS ..................................................................................................................... 48 
7.2 
SOCIAL IMPACT REPORTING ....................................................................................................... 49 
7.3 
OTHER UNANTICIPATED PROBLEMS ........................................................................................... 50 
7.4 
SAFETY MONITORING AND CLINICAL DATA REVIEW ................................................................ 51 
7.5 
PREGNANCY ................................................................................................................................ 51 
8.0 
STATISTICAL CONSIDERATIONS ............................................................................ 52 
8.1 
REVIEW OF STUDY DESIGN ......................................................................................................... 52 
8.2 
ENDPOINTS .................................................................................................................................. 52 
8.2.1 
Primary Endpoints ................................................................................................................................. 52 
8.2.2 
Secondary Endpoints ............................................................................................................................. 52 
8.2.3 
Process Endpoints .................................................................................................................................. 56 
8.3 
SAMPLE SIZE ............................................................................................................................... 56 
8.4 
ACCRUAL AND RETENTION ......................................................................................................... 57 
8.5 
RANDOM ASSIGNMENT/STUDY ARM ASSIGNMENT ................................................................... 57 
8.6 
BLINDING .................................................................................................................................... 57 
8.7 
DATA AND SAFETY MONITORING OVERSIGHT ........................................................................... 57 
8.8 
STATISTICAL ANALYSIS .............................................................................................................. 57 
8.8.1 
Primary Analyses ................................................................................................................................... 57 
8.8.2 
Secondary Analyses ............................................................................................................................... 57 
9.0 
HUMAN SUBJECTS CONSIDERATIONS ................................................................... 58 
9.1 
ETHICAL REVIEW ........................................................................................................................ 58 

 
 
 
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9.2 
INFORMED CONSENT................................................................................................................... 59 
9.3 
RISKS .......................................................................................................................................... 59 
9.4 
BENEFITS .................................................................................................................................... 60 
9.5 
POPULATION-SPECIFIC CONSIDERATIONS .................................................................................. 60 
9.6 
INCENTIVES ................................................................................................................................. 61 
9.7 
CONFIDENTIALITY ...................................................................................................................... 61 
9.8 
COMMUNICABLE DISEASE REPORTING REQUIREMENTS ............................................................ 62 
9.9 
STUDY DISCONTINUATION ......................................................................................................... 62 
10.0 
LABORATORY SPECIMENS AND BIOHAZARD CONTAINMENT ................. 62 
10.1 
LOCAL LABORATORY SPECIMENS .............................................................................................. 62 
10.2 
HPTN LABORATORY CENTER SPECIMENS ................................................................................. 63 
10.2.1 Stored Specimens ................................................................................................................................... 63 
10.2.2 Virology ................................................................................................................................................. 64 
10.2.3 Pharmacology and Toxicology Testing ................................................................................................. 64 
10.3 
QUALITY CONTROL AND QUALITY ASSURANCE PROCEDURES.................................................. 65 
10.4 
QC FOR HIV DIAGNOSTIC TESTING ........................................................................................... 65 
10.5 
HIV RNA MONITORING ............................................................................................................. 65 
10.6 
CD4 CELL COUNT DETERMINATION .......................................................................................... 66 
10.7 
SPECIMEN STORAGE AND POSSIBLE FUTURE RESEARCH TESTING ............................................ 66 
10.8 
BIOHAZARD CONTAINMENT ....................................................................................................... 66 
11.0 
ADMINISTRATIVE PROCEDURES ........................................................................ 66 
11.1 
PROTOCOL REGISTRATION ......................................................................................................... 66 
11.2 
STUDY ACTIVATION ................................................................................................................... 67 
11.3 
STUDY COORDINATION ............................................................................................................... 67 
11.4 
STUDY MONITORING .................................................................................................................. 67 
11.5 
PROTOCOL COMPLIANCE ............................................................................................................ 68 
11.6 
INVESTIGATOR’S RECORDS ........................................................................................................ 68 
11.7 
USE OF INFORMATION AND PUBLICATIONS ................................................................................ 69 
REFERENCES ............................................................................................................................. 70 
APPENDIX IA: SCHEDULE OF STUDY VISITS AND PROCEDURES ............................ 73 
APPENDIX IB: ADDITIONAL PROCEDURES FOR PARTICIPANTS WHO HAVE A 
REACTIVE OR POSITIVE HIV TEST AFTER ENROLLMENT ....................................... 77 
APPENDIX II: SAMPLE INFORMED CONSENT FORM - MAIN STUDY ...................... 78 
APPENDIX III: SAMPLE INFORMED CONSENT FORM- QUALITATIVE 
INTERVIEWS ............................................................................................................................. 94 
 
 
 

 
 
 
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HPTN 094 
INTEGRA: A Vanguard Study of Health Service Delivery in a Mobile Health 
Delivery Unit to Link Persons who Inject Drugs to Integrated Care and Prevention 
for Addiction, HIV, HCV and Primary Care 
 
 
 
PROTOCOL SIGNATURE PAGE 
 
 
DAIDS Document ID # 38715 
 
Final Version 2.0 
20 February 2023 
 
 
 
 
 
I will conduct the study in accordance with the provisions of this protocol and all applicable 
protocol-related documents. I agree to conduct this study in compliance with United States (US) 
Health and Human Service regulations (45 CFR 46); applicable US Food and Drug 
Administration regulations; standards of the International Conference on Harmonization 
Guideline for Good Clinical Practice (E6); Institutional Review Board/Ethics Committee 
determinations; all applicable in-country, state, and local laws and regulations; and other 
applicable requirements (e.g., US National Institutes of Health, Division of AIDS) and 
institutional policies. 
 
I have read and understand the information in this protocol and will ensure that all associates, 
colleagues, and employees assisting in the conduct of the study are informed about the 
obligations incurred by their contribution to the study.  
 
 
__________________________________ 
Name of Investigator of Record (print name) 
  
 
 
_____________________________________        ____________________ 
Signature of Investigator of Record                         Date (MM/DD/YYYY) 
  

 
 
 
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HPTN 094 
INTEGRA: A Vanguard Study of Health Service Delivery in a Mobile Health 
Delivery Unit to Link Persons who Inject Drugs to Integrated Care and Prevention 
for Addiction, HIV, HCV and Primary Care 
 
LIST OF ABBREVIATIONS AND ACRONYMS 
 
Ab 
 
Antibody 
AE 
 
Adverse Event 
AIDS  
Acquired immunodeficiency syndrome 
ALT 
 
Alanine Aminotransferase 
aPTT  
Activated Partial Thromboplastin Time 
ART 
 
Antiretroviral therapy 
ARV 
 
Antiretroviral  
AST 
 
Aspartate Aminotransferase 
CAB 
 
Community Advisory Board 
CDC 
 
(United States) Centers for Disease Control and Prevention 
CEA 
 
Cost-effectiveness analyses 
CFR 
 
Code of Federal Regulations 
CLIA  
Clinical Laboratory Improvement Amendments of 1988 
CMC  
Clinical Management Committee 
COWS  
Clinical Opiate Withdrawal Scale 
COVID-19 
Coronavirus Disease 2019 
CPQA  
Clinical Pharmacology Quality Assurance 
CRM  
Clinical Research Manager 
CRS  
 
Clinical Research Site 
CT 
 
Chlamydia trachomatis  
DAIDS  
Division of AIDS 
DBS 
 
Dried Blood Spot 
DHHS  
US Department of Health and Human Services 
DSM 
 
Diagnostic and Statistical Manual of Mental Disorders 
FDA 
 
(United States) Food and Drug Administration 
FQHC  
Federally-Qualified Health Centers 
GC 
 
Neisseria gonorrhoeae 
GCLP  
Good Clinical Laboratory Practice 
HAV 
 
Hepatitis A Virus 
HBV 
 
Hepatitis B Virus 
HCG 
 
Human Chorionic Gonadotropin 
HCV 
 
Hepatitis C Virus 
HIV 
 
Human Immunodeficiency Virus 
HLA 
 
Human Leukocyte Antigen 
HPTN  
HIV Prevention Trials Network 
ICER  
Incremental Cost Effectiveness Ratio 
ICF 
 
Informed consent form 
IgG 
 
Immunoglobulin G 
IoR 
 
Investigator of Record 
IRB 
 
Institutional Review Board 
LC 
 
(HPTN) Laboratory Center 
LDMS  
Laboratory Data Management System 
LOC 
 
Leadership and Operations Center 

 
 
 
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mL 
 
Milliliter 
MOP 
 
Manual of Operations 
MOUD  
Medication for Opioid Use Disorder 
MSM  
Men who have Sex with Men 
NAAT  
Nucleic Acid Amplification Test 
NAESM 
National AIDS Education & Services for Minorities 
NHBS  
National HIV Behavioral Surveillance 
NIAID  
(United States) National Institute of Allergy and Infectious Diseases 
NIDA  
National Institute on Drug Abuse 
NIH 
 
(United States) National Institutes of Health 
OHRP  
Office of Human Research Protections 
OUD 
 
Opioid Use Disorder 
PrEP 
 
Pre-Exposure Prophylaxis 
PRISM  
Practical, Robust Implementation and Sustainability Model 
PRO 
 
(DAIDS) Protocol Registration Office 
PT 
 
Prothrombin Time 
PWID  
People Who Inject Drugs 
QA 
 
Quality Assurance 
QALY  
Quality-Adjusted Life Year 
QC 
 
Quality Control 
RE-AIM 
Reach, Effectiveness, Adoption, Implementation, Maintenance 
RNA 
 
Ribonucleic acid 
RSC 
 
Regulatory Support Center 
SAE 
 
Serious Adverse Event 
SARS-CoV-2    Severe Acute Respiratory Syndrome Coronavirus 2 
SDMC  
(HPTN) Statistical and Data Management Center 
SEP 
 
Syringe exchange program 
SMC 
 
Study Monitoring Committee 
SNS 
 
Social Network Strategy 
STI 
 
Sexually transmitted infection 
SOC 
 
Standard of Care 
SOP 
 
Standard Operating Procedures 
SSP 
 
Study Specific Procedures  
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TAM  
Time and Motion 
US 
 
United States 
VL 
 
Viral load 
 
 

 
 
 
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HPTN 094 
INTEGRA: A Vanguard Study of Health Service Delivery in a Mobile Health 
Delivery Unit to Link Persons who Inject Drugs to Integrated Care and Prevention 
for Addiction, HIV, HCV and Primary Care 
 
 
PROTOCOL TEAM ROSTER 
 
PROTOCOL CHAIR: 
Steve Shoptaw, PhD 
University of California Los Angeles 
Departments of Family Medicine and 
Psychiatry and Biobehavioral Sciences  
10880 Wilshire Blvd, Suite 1800 
Los Angeles, CA 90024 
Phone: 310-740-7021 
Email: sshoptaw@mednet.ucla.edu 
 
PROTOCOL CO-CHAIR 
Nabila El-Bassel, PhD 
Columbia University 
Professor, School of Social Work 
Director, Global Health Research Center 
of Central Asia 
Director, Social Intervention Group 
(SIG) 
1255 Amsterdam Avenue 
New York, NY 10025 
Phone: 212.851-2391 
Email: ne5@columbia.edu 
 
 
Philip Andrew, RN 
Senior Research Clinician   
HPTN Leadership and Operations 
Center   
FHI 360  
359 Blackwell Street, Suite 200  
Durham, NC 27701  
Phone: 919-544-7040 Ext. 11213  
Email: pandrew@fhi360.org  
 
  
 
Dale Burwen, MD, MPH 
Medical Officer 
Clinical Prevention Research Branch  
Prevention Sciences Program, Division 
of AIDS, NIAID 
5601 Fishers Lane, Rm 8B49 
Rockville, MD 20852 
Phone: 240.669.2867 
Email: dale.burwen@nih.gov  
 
Redonna K. Chandler, Ph.D. 
Director, AIDS Research Program 
Director, HEALing Communities Study 
National Institute on Drug Abuse 
6001 Executive Boulevard, Room 5265 
Rockville, MD 20892-9581 
Phone: 301-443-1470 
E-mail: redonna.chandler@nih.gov 
 
William Clarke, PhD, DABCC 
Professor of Pathology 
HPTN LC Toxicology Core Director 
Johns Hopkins University School of 
Medicine 
1551 E. Jefferson Street/CRB II 3M03 
Baltimore, MD 21287 
Phone: 410-502-7692 
Email: wclarke@jhmi.edu 
 

 
 
 
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Melissa Cummings, MPH 
SCHARP Clinical Data Manager 
Fred Hutch 
1100 Fairview Ave N, E3-129 
Seattle, WA 98109 
Phone: 206-667-1232 
Email: mcumming@fredhutch.org 
 
Dobromir Dimitrov, PhD 
Mathematical Modeler 
HPTN Modeling Center 
Fred Hutch 
1100 Fairview Ave N 
Seattle, WA 98109 
Phone: 206-667-1933 
Email: ddimitro@fredhutch.org 
 
Deborah Donnell, PhD 
Biostatistician 
HPTN Statistics and Data Management 
Center 
Fred Hutch 
1100 Fairview Ave N 
Seattle, WA 98109 
Phone: 206-667-5661 
Email: deborah@fredhutch.org 
 
Lynda Emel, PhD  
Associate Director, HPTN SDMC  
SCHARP- Fred Hutch  
1100 Fairview Avenue North M2-C118  
Seattle, WA 98109  
Phone: 206-667-5803  
Email: lemel@scharp.org 
 
Jessica M. Fogel, PhD 
HPTN Laboratory Center 
Representative 
Johns Hopkins University School of 
Medicine 
720 Rutland Ave., Ross Bldg Rm 646 
Baltimore, MD 21205  
Phone: 410-614-6498 
Email: jfogel@jhmi.edu 
 
David Goodman-Meza, MD, MAS 
Assistant Professor 
UCLA, Division of Infectious Diseases 
10833 Le Conte Ave (Room 37-
121CHS) 
Los Angeles, CA, 90095-1688 
Phone: 310-825-8373 
Email: dgoodman@mednet.ucla.edu 
 
Brett Hanscom, PhD 
Biostatistician 
HPTN Statistics and Data Management 
Center 
Fred Hutch 
1100 Fairview Ave N 
Seattle, WA 98109 
Phone: 206-667-4534 
Email: bhanscom@fredhutch.org 
 
 Irene Kuo, PhD, MPH 
Associate Research Professor 
George Washington University  
Milken Institute School of Public Health 
950 New Hampshire Avenue NW, Suite 
500 
Washington, DC 20052 
Phone: 202-994-0367 
Email: ikuo@gwu.edu 
 
Timothy Skalland, PhD 
Biostatistician 
HPTN Statistics and Data Management 
Center 
Fred Hutch 
1100 Fairview Ave N 
Seattle, WA 98109 
Phone: 206-667-1186 
Email:  tskallan@fredhutch.org 
 
Jonathan Paul Lucas, MPH 
Senior Community Program Manager   
HPTN Leadership and Operations 
Center   
FHI 360  
359 Blackwell Street, Suite 200  
Durham, NC 27701  
Phone: 919-544-7040 Ext. 11458  
Email: jlucas@fhi360.org 
 

 
 
 
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Mia Moore, PhD 
Biomathematician 
HPTN Modeling Center 
Fred Hutch 
1100 Fairview Ave N 
Phone: 206-667-2252 
Email: jrmoore@fredhutch.org 
 
Cindy Parker, PharmD 
DAIDS Pharmacist 
DAIDS, Pharmaceutical Affairs Branch 
5601 Fishers Lane, 9D37 
Rockville, MD 20852 
Phone: 301-761-7199 
Email: cindy.parker@nih.gov 
 
Azizza K. Davis, PharmD [C] 
Clinical Pharmacy Advisor 
Pharmaceutical Affairs Branch 
OCSO, DAIDS, NIAID, NIH 
5601 Fishers Lane, Room 9E14 
Rockville, MD 20852 
Mobile Phone: 240-669-5248 
Email: azizza.davis@nih.gov 
 
Paul Richardson, MSc  
Senior International QA/QC 
Coordinator  
HPTN Laboratory Center  
Johns Hopkins University  
Pathology 306 
600 N. Wolfe St. 
Phone: 410-502-0435 
Email: pricha18@jhmi.edu  
 
James Rooney, MD 
Vice President Medical Affairs 
Gilead Sciences, Inc 
333 Lakeside Drive 
Foster City, CA 94404 
Phone: 650-522-5708 
Email: Jim.Rooney@gilead.com  
 
Laramie R. Smith, PhD 
Assistant Professor 
UC San Diego, School of Medicine 
9500 Gillman Dr. #0507 
La Jolla, CA 9209.-0507 
Phone: 858-822-1462 
Email: laramie@health.ucsd.edu  
 
Chloe Thio, MD 
Professor of Medicine 
HPTN Laboratory Center 
Johns Hopkins University School of 
Medicine 
855 N Wolfe Street, 5th floor 
Baltimore, MD 21205 
Phone: 410-614-6088 
Email: cthio@jhmi.edu 
 
Jessica Yeager, NCPRSS, PSS, PRS/ 
ICPR, RSPS, PM/ PRC 
HPTN Community Working Group 
Representative 
The University of Texas Health Science 
Center at Houston 
School of Biomedical Informatics 
7000 Fannin Street | Suite 190 | Houston 
Texas 77030 
Phone: 713.500.3597 
Email: Jessica.Yeager@uth.tmc.edu 
 
 
 
 

 
 
 
HPTN 094, Final Version 2.0 
 
11 of 99 
20 February 2023 
HPTN 094 
INTEGRA: A Vanguard Study of Health Service Delivery in a Mobile Health 
Delivery Unit to Link Persons who Inject Drugs to Integrated Care and Prevention 
for Addiction, HIV, HCV and Primary Care 
 
 
SCHEMA 
 
Purpose: 
 
The purpose of this study is to determine the efficacy of using a mobile 
health delivery unit (“mobile unit”) to deliver “one stop” integrated 
health services – particularly medication for opioid use disorder (MOUD) 
and medication for HIV treatment and prevention – to people who inject 
drugs (PWID) with opioid use disorder (OUD) to improve uptake and use 
of MOUD, and uptake and use of antiretroviral therapy (ART) or pre-
exposure prophylaxis (PrEP). The intervention arm receiving health 
services in the mobile unit will be supported by peer navigation. An 
active control arm will receive peer navigation to health services 
available at community-based agencies. Impact (cost-effectiveness, 
mathematical modeling) and implementation factors (mixed methods to 
identify barriers and facilitators of the interventions) will contextualize 
findings from the efficacy analysis. The impact of the COVID-19 
epidemic in the study population will also be assessed. 
 
Design: 
 
A two-arm, individually randomized, controlled, open label study 
 
Population: 
 
People living with and without HIV and who inject drugs, have OUD, 
and are not receiving MOUD  
 
Study Size: 
 
A total of 450 participants allotted in a 1:1 ratio to intervention and active 
control arms, with targets of a minimum 25% women and 25% 
participants under 30 years of age, and 10% people living with HIV at 
enrollment. 
 
Study 
Duration: 
 
Approximately three and a half years total with individual participants on 
study for approximately 52 weeks (26 weeks receiving the intervention or 
peer navigation and then an evaluation for durability of effect at the end 
of 52 weeks). 
 
Study Sites: 
 
Five urban sites in the United States (US) with substantial populations of 
PWID with OUD. See the Study Specific Procedures (SSP) Manual for 
site listing. 
 
Study 
Regimen: 
 
All potential study participants will provide biological samples and self-
reported data via interview in the mobile unit at Screening and Enrollment 
Visits. Samples will be tested for HIV, hepatitis A (HAV), B (HBV) and C 
(HCV) and sexually transmitted infections (STIs). At the Enrollment Visit, 
participants who meet all inclusion and no exclusion criteria will be 
randomized to the intervention or active control arm and will receive 
harm reduction services and empiric treatment for STIs if symptomatic. 
Participants will also be assessed for COVID-19 at study visits; participants 

 
 
 
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with suspected COVID-19 or recent exposure will be referred for further 
evaluation, care and/or treatment, as available. 
 
Intervention Arm: Participants in the intervention arm will be provided 
integrated health services delivered in the mobile unit and peer navigation 
for 26 weeks. The integrated health services in the mobile unit will include:  
• 
MOUD and harm reduction services for OUD 
• 
HIV testing 
• 
HIV treatment for people living with HIV not already in care 
• 
PrEP for people without HIV 
• 
Testing and referral for vaccination or treatment for HAV and 
HBV 
• 
Testing and referral for treatment for HCV 
• 
STI testing and treatment  
• 
Primary care 
• 
Harm reduction services 
 
Peer navigation in the intervention arm will coordinate and facilitate 
integrated care in the mobile unit through 26 weeks. As participants 
become established in care, navigation will help transition participants to 
community-based services by 26 weeks after randomization. 
 
Active Control Arm: Participants in the active control arm will be provided 
26 weeks of peer navigation to connect them to health services available at 
community-based agencies.  
 
All participants (both arms) will have study visits at 26 and 52 weeks for 
evaluation of study endpoints. 
 
Primary 
Objective: 
 
To evaluate whether 26 weeks of “one stop” integrated health services 
delivered in a mobile unit, supported by peer navigation, improves use of 
MOUD and increases use of PrEP among people without HIV, as 
measured at 26 weeks, when compared to 26 weeks of peer navigation to 
similar health services available at community-based agencies. 
 
Secondary 
Objectives: 
 
1) To evaluate whether 26 weeks of “one stop” integrated health services 
delivered in a mobile unit, supported by peer navigation, compared to 
26 weeks of peer navigation to similar health services available at 
community-based agencies: 
a) improves use of MOUD at 52 weeks  
b) increases rates of viral suppression among people living with 
HIV at 52 weeks 
c) increases use of PrEP among people without HIV at 26 and 52 
weeks 
d) decreases opioid and polysubstance use at 26 and 52 weeks  
e) decreases prevalence of bacterial STIs at 26 and 52 weeks 
f) decreases fatal and non-fatal overdose events by 26 and 52 
weeks 

 
 
 
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g) increases the proportion of participants with undetectable HCV 
RNA at 26 and 52 weeks among those with chronic HCV 
infection at enrollment  
h) decreases HCV incidence at 52 weeks, for those who are HCV 
negative at enrollment 
i) increases rates of viral suppression among people living with 
HIV as measured at 26 weeks 
 
2) To evaluate whether 26 weeks of “one stop” integrated health 
services delivered in a mobile unit, supported by peer navigation, 
increases MOUD use, viral suppression, and PrEP use at 26 and 52 
weeks compared to Enrollment 
 
3) To evaluate whether 26 weeks of peer navigation to similar health 
services available at community-based agencies increases MOUD 
use, viral suppression, and PrEP use at 26 and 52 weeks compared to 
Enrollment 
 
4) To document the prevalence of seropositivity for SARS-CoV-2 at 
baseline, 26 and 52 weeks 
 
5) To document the impact of the COVID-19 epidemic on participants’ 
experiences of seeking, obtaining and/or maintaining health services, 
housing, food security and drugs 
    
6) To evaluate implementation of “one-stop” integrated health services 
using a mobile unit, supported by peer navigation, across study sites 
to identify mechanisms at multiple levels to: 
a) Guide real-time improvements and refinements in the 
conduct of the study to ensure primary and secondary 
outcomes are met with fidelity 
b) Examine the quality and process of services delivered in each 
study arm, particularly as these affect primary and 
secondary outcomes 
c) Develop evidence-based guidance for policymakers on the 
uptake and implementation of integrated health services 
using peer navigation and mobile health units in urban US 
regions to address HIV prevention in PWID 
d) Identify factors that enhance or impede the delivery of 
integrated health services using a mobile unit, supported by 
peer navigation, on primary and secondary outcomes, 
including responding to the impact of COVID-19 on service 
delivery  
 
7) To use mathematical modeling methods to:  
a) Estimate the effect of integrated health services delivered in a 
mobile unit, supported by peer navigation, on reducing HIV 
incidence in PWID and their sexual and injection partners 
b) Estimate the cost-effectiveness of the integrated health services 
provided in a mobile unit and supported by peer navigation 
 

 
 
 
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Process 
Objectives: 
For participants in the intervention arm, assess: 
 
1) Time to provide MOUD treatment, ART (among those who are living 
with HIV and not on ART at Enrollment) and PrEP (among those who 
are without HIV at Enrollment)  
2) The proportion of participants linked to community-based MOUD, 
ART and PrEP services at 26 weeks 
 
Exploratory 
Objectives: 
 
Stored samples may be used to analyze HIV subtypes/strains, HIV drug 
resistance, and the duration of HIV infection. Phylogenetic methods may 
be used to evaluate behavioral, demographic, and clinical factors associated 
with viral clusters and transmission dynamics. Stored samples may also be 
used to characterize HCV strains and the relationship between HIV and 
HCV infections, and to explore issues related to COVID-19. 

 
 
 
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Figure 1- Overview of Study Design 
 
 
 
HPTN 094 
INTEGRA: A Vanguard Study of Health Service Delivery in a Mobile Health Delivery Unit to Link Persons who Inject 
Drugs to Integrated Care and Prevention for Addiction, HIV, HCV and Primary Care 
 
 

 
 
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1. 
INTRODUCTION 
 
1.1 
Background and Rationale 
 
Drug overdose is the leading cause of accidental death in the United States (US), with over 
67,000 fatalities in 2018.1 Efforts to address the opioid overdose epidemic are reducing rates of 
death due to prescription opioids, though the rate of overdose related to fentanyl use continued to 
rise through 2018.1  The opioid epidemic remains North America’s most widespread behavioral 
public health problem, with a higher number of deaths due to drug overdose in 2016 compared to 
deaths due to HIV at the peak of the AIDS epidemic in the US.2 The growing epidemic now 
significantly involves Black and Latino individuals in urban areas such as New York City, where 
opioid overdose rates among Blacks surpassed Whites for the first time in 2019.3-5 Progression 
from prescription opioid use to injection heroin use is common, though the increase has slowed.6-8 
Fentanyl and its analogues represent the “third wave” of the US opioid epidemic and are major 
contributors to the ongoing and massive increase in drug overdose deaths.1,7 Injection drug use is 
the primary driver for doubling hepatitis C (HCV) incidence in the US, with several recent HCV 
outbreaks among people who inject drugs (PWID).9-13 Moreover, unsafe injection practices that 
drive HCV incidence often foreshadow increases in HIV incidence, and most PWID living with 
HIV have also acquired HCV.14 The latest surveillance reports continue to show increases in 
methamphetamine and cocaine involvement in drug overdose deaths.1 
 
Health risks for persons with OUD and living with or at risk for HIV in the US include multiple 
and overlapping problems that interfere with consistent access to health care, particularly when 
the substance use disorder is active.15 Throughout this document we interchangeably use the 
terms “addiction” and "substance use disorder” within the definition as written in the NIAID HIV 
Language Guide: “Addiction is defined as a pattern of compulsive substance use—marked by a 
change in behavior caused by biochemical changes in the brain—despite negative consequences 
related to that substance use. Addiction is not a diagnostic term but is considered synonymous 
with moderate to severe substance use disorder.” The behaviorally disorganizing aspects of 
substance use disorder can interfere with traveling to existing services (lack of transportation), 
with willingness to tolerate judgements and attitudes from personnel in health care settings 
(stigma) and with foregoing pleasure in lieu of healthcare (addiction). Consequently, persons with 
active addiction spend large amounts of time hanging out together in “hot spots” near jails, 
criminal justice community supervision programs, syringe exchange programs (SEPs), parks and 
tourist areas. The location and size of these hot spots can vary within regions.  
 
This calls for an HIV prevention response that meets people living with or at-risk for HIV who 
also live with OUD where they are, with the aim to reduce barriers at each step in the process of 
accessing and sustaining medication for opioid use disorder (MOUD) treatment and HIV care and 
prevention. Moreover, there is a need to examine barriers that interfere with entry and retention in 
MOUD and with sustaining relevant HIV outcomes. This is particularly true among this 
population, many of whom face additional stigma, barriers and health disparities related to their 
multi-dimensional identities (e.g., as sex workers, men who have sex with men (MSM) and 
polysubstance users).15  
 
The rationale for this study is based on this premise: HIV outbreaks in the US among PWID 
occur when simultaneous factors—lack of access to health care (including MOUD), poverty, 
prevalent poly-substance use, and mental health disorders and others—combine to exacerbate 
HIV transmission and acquisition. PWID living with or at risk of HIV who are not engaged in 
MOUD face the nearly impossible task of getting care from bricks and mortar clinics that provide 
separate, siloed care for opioid addiction (methadone, buprenorphine), HIV (antiretroviral therapy 

 
 
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[ART] and pre-exposure prophylaxis [PrEP]) and primary care (sexually transmitted infections 
[STI] testing and treatment, hepatitis testing and treatment, diagnosis and treatment for chronic 
and other conditions) with limited or no financial resources. Health services to address these 
diverse problems, when they exist, are often located far away from each other and from the PWID 
who need them, presenting serious distance/travel barriers to access. The challenge of finding and 
sustaining HIV care and prevention in the setting of untreated OUD in persons with multiple 
additional health threats contributed to multiple HIV outbreaks in the US (in Indiana, 
Massachusetts, Washington, West Virginia).16-18 The use of a mobile venue that meets out-of-
treatment PWID wherever they might be in their communities and links them to care systems 
and/or harm reduction is innovative, is likely to save lives and, if efficacious, could be efficiently 
scaled-up in the US, especially as the US health system responds to dramatic new pressures 
imposed by the COVID-19 pandemic. 
 
The initial COVID-19 outbreak in early 2020 changed the world in innumerable ways, including 
general disruption of daily life, implementation of social distancing policies, and prioritization of 
healthcare systems to address the coronavirus. These changes exacerbated challenges PWID 
already faced to initiating or maintaining treatment/prophylaxis regimens for OUD and HIV and 
to obtaining other health care. Creative new strategies by the healthcare system in response to the 
COVID-19 epidemic included use of medical consultations by telephone or video (telehealth), 
and relaxing restrictions on how medications could be prescribed and dispensed (particularly 
buprenorphine/naloxone); these strategies have the potential to help PWID receive healthcare and 
maintain adherence. It is not clear what the healthcare environment will look like at the time this 
study begins, or how it will change during study implementation. To that end, this protocol 
includes research objectives that address the effect of COVID-19 on the lives and healthcare of 
PWID. We describe adaptations that we anticipate will be necessary to implement this study and 
this intervention successfully in the context of an ongoing or resurgent COVID-19 epidemic. We 
will also consider incorporating additional healthcare delivery activities during the study, such as 
COVID-19 diagnostic testing, based on feasibility, availability, and other factors. 
 
1.2 
Rationale for Study Design 
 
This vanguard study addresses the current and overlapping health challenges to engaging and 
retaining people who are living with HIV or at-risk persons in HIV care and prevention at a time 
when OUD has re-emerged as a potential driver for HIV infections in the US. It does this by 
integrating engagement and retention for HIV care and prevention with the parallel effort to 
engage and retain PWID with OUD in treatment using MOUD19,20 (i.e., buprenorphine, 
methadone and extended-release naltrexone). For persons with OUD, MOUD functions as a key 
harm reduction and treatment strategy by reducing the disruptive and dysregulating behaviors of 
addiction and by lowering the likelihood of overdose and death. In this way, MOUD enables 
increased uptake and adherence to ART among people living with both HIV and OUD 21,22 
including PWID. To date, however, only 15% of those with OUD in the US are receiving 
MOUD.9,23 This vanguard study will test the efficacy and the impact of an integrated strategy that 
provides integrated care services including provision of ART and PrEP, MOUD treatment, STI 
testing and treatment, primary health care, and harm reduction from a mobile health delivery unit 
(“mobile unit”) and supported by peer navigation compared with an active control arm that 
receives peer navigation to similar health services available at community-based agencies. 
Primary outcomes are centered on HIV and OUD: viral suppression, PrEP use, and uptake and 
use of MOUD. This study will also offer an unparalleled opportunity to document the prevalence 
of SARS-CoV-2 seropositivity in this population at baseline and over time, and to investigate the 

 
 
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impact of the COVID-19 epidemic on the lives of people with opioid addiction and living with or 
at risk for HIV.24,25       
 
Fit with the Network. The INTEGRA integrated strategy accomplishes two important objectives 
of the HIV Prevention Trials Network (HPTN): (1) To conduct HIV research in at-risk PWID 
with OUD and measure linked MOUD and HIV outcomes in the US; and (2) to address the 
multiplicity of challenges and barriers to primary care, HIV and HCV prevention and care, and 
MOUD/harm reduction programs. This study is well suited to make use of the resources of the 
HPTN to conduct high impact HIV prevention work in PWID with OUD, a key priority 
population for the HPTN. The availability of research sites in diverse geographic locations and 
the statistical and laboratory capacities of the HPTN are other key advantages of network 
engagement. The INTEGRA integrated strategy also addresses in real time and in full measure 
the call for integrated strategies to respond to the ongoing dual epidemics of HIV and opioid use 
disorder,26 and to respond to a novel third epidemic, COVID-19. 
 
Rationale for use of Mobile Health Delivery Units. The literature on mobile health service 
provision includes low to moderate quality studies showing that mobile units improve care 
outcomes in multiple settings and for multiple health needs. Needle exchange programs delivered 
from mobile units have been successful in engaging PWID in services that are either unacceptable 
or unavailable in brick and mortar settings.27,28  These prior studies provide key support for the 
design of this study. This could raise the criticism that the outcome of this trial can be assumed to 
be favorable and does not require a randomized investigation. While there is hope and 
expectation the intervention will be efficacious, there are numerous reasons why this study is 
worthwhile even if one were to assume a positive outcome: 
 
• 
First, these would be the first data to inform the improvement in outcomes using a mobile 
health delivery system, above an energetic navigation condition, for improving rates of 
viral suppression and PrEP adherence among PWID and for engaging and retaining these 
individuals in MOUD for significant periods. This study will provide a unique 
opportunity to assess exposure to COVID-19 in this population over time and document 
the impact of COVID-19 on service delivery to PWID before and during the trial period.  
• 
Second, even if the intervention does improve outcomes, it may be that the improvement 
is negligible, or that it is not cost-effective. This is why the study has built-in 
comprehensive costing and cost-effectiveness analyses. The peer navigation provided in 
the active control arm is to equal what is provided in the intervention arm; this will allow 
us to evaluate the marginal effects of integrated care in the mobile unit supported by 
navigation compared to navigation to community-based services without direct provision 
of care. We may find that most of the benefit seen in the intervention arm is due to peer 
support and navigation alone; this would provide policy makers with useful cost-benefit 
data. Important data will also come from analysis of outcomes at 52 weeks, six months 
after the conclusion of the intervention. These data will inform policy makers about the 
durability (or lack thereof) of any gains seen in the intervention arm and/or control arm, 
particularly whether navigation and/or mobile unit-based care need to be provided long 
term, or whether these interventions can be effective by “jump-starting” long-term 
recovery with a transition to community-based services.  
• 
Last, if the mobile unit intervention proves to be successful, documentation of this effect 
in a randomized controlled trial (RCT) will be helpful for integrating this intervention 
into public health guidelines.  
 
 
 

 
 
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Ensuring High-Risk in the Sample. In order to enhance the sample for participants with greater 
risk of HIV acquisition and transmission, and to ensure that sub-groups of PWID who might 
otherwise be recruited at disproportionately low numbers are adequately represented in the 
sample, recruitment targets have been included for young and female participants.  
 
• 
Women. Approximately 30% of PWID with OUD diagnosis are women29,30 but studies of 
PWID show that women who inject opioids historically are younger than men, progress 
more rapidly to addiction, and access treatment at lower rates than men,31 largely because 
the services provided do not address their needs.31 Once provided appropriate services, 
however, women achieve treatment benefits at the same rates as men.32 To ensure that the 
efficacy and implementation science results of this study reflect the experiences of 
women (who might otherwise be enrolled in small numbers) this study will target 
enrollment of 25% women regardless of HIV status.  
• 
Younger PWID. The median age for PWID in the US30 is in the mid-40s, but those 18-29 
years engage in HIV risk behaviors (e.g., sharing injecting equipment or sex without 
condoms) at substantially higher rates than PWID in older groups.33 The group of people 
with OUD least likely to receive treatment are also young (under 26).34 To enrich our 
sample for persons at higher risk of acquiring or transmitting HIV and having untreated 
OUD, we will aim to enroll 25% of participants younger than 30 years (approximately 
20% of PWID are younger than thirty years) regardless of their HIV status.30   
 
The Importance of Documenting Study Processes and Procedures. There is increasing recognition 
that mobile care is an approach that policy makers should be considering. In a review of 51 
studies published in 2017, the conclusions regarding the effects of using mobile health clinics 
(MHCs) to deliver healthcare shows a consistent signal that: “…mobile health clinics are 
successful in reaching vulnerable populations, by delivering services directly at the curbside in 
communities of need and flexibly adapting their services based on the changing needs of the 
target community. As a link between clinical and community settings, MHCs address both 
medical and social determinants of health, tackling health issues on a community-wide level. 
Furthermore, evidence suggests that MHCs produce significant cost savings and represent a cost-
effective care delivery model that improves health outcomes in underserved groups.”35  
Convincing evidence from this trial would come at a time when policy makers are considering 
mobile clinics for public health practice. Moreover, data collected during the pre-implementation 
and implementation phases of the trial will be used to assess the impact of COVID-19 on 
availability and access to services delivered in the community and as delivered through the 
mobile units at study sites.  
 
This study will provide valuable information to policy makers in the four main areas that have 
been recognized as presenting substantial limitations to using mobile health clinics to deliver 
integrated care services: (1) fragmentation of care; (2) financial issues; (3) spatial and structural 
limits; and (4) logistical challenges. This project will directly address fragmentation of care by 
providing integrated health services. As well, findings from the implementation science portion of 
this work will advise financial issues necessary to mount and maintain using mobile medical 
units within a health jurisdiction. Mobile health clinics are, indeed, tight quarters. In preparing the 
mobile health units, it will be key to provide for spaces that can be allotted for medical purposes, 
while also providing some spaces for consultations. The project will identify the need for 
additional spaces and creative approaches that can be used to solve space issues (e.g., parking 
the mobile unit next to a facility that can provide quiet and private spaces for navigation 
sessions). The project will also advise methods for addressing logistical challenges, (e.g., 
portable generators to maintain refrigeration and other requirements, using WiFi “hot spots” for 
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Finally, the rationale for the study is that the use of a mobile unit is considered best practice for 
the seldom reached or unsuccessfully engaged population of PWID who are not in drug 
treatment. There are examples of these types of integrated care strategies, offered in mobile units, 
that are considered best practices in the recently published NASEM report, Opportunities to 
Improve Opioid Use Disorder and Infectious Disease Services: Integrating Responses to a Dual 
Epidemic.26 Perhaps providing most compelling evidence, best practices highlighted in this report 
developed and implemented integrated strategies for addressing HIV, addiction medicine, 
primary care, harm reduction, stigma, with two of the best practices (one in Lawrence, 
Massachusetts) using a mobile unit (see section 1-8 of the NASEM report).  
 
This evidence, both quantitative and qualitative, provides strong justification for using a mobile 
unit approach for HPTN 094. The extent to which reductions in barriers of distance and stigma 
will produce superior outcomes compared to an enhanced control condition that includes active 
navigation will inform policymakers in decisions about whether to adopt mobile health delivery 
systems in their jurisdictions. The implementation science aspect of the protocol will provide cost 
effectiveness data that will equip policymakers with cost data to advise implementing and 
maintaining a mobile health unit providing integrated care strategies in their jurisdiction.  
 
This integrated strategies approach recognizes the key link between rapid, coordinated and 
sustained engagement in both MOUD and HIV prevention and care to achieve relevant HIV and 
substance use outcomes.26 The study will use two dependent variables: MOUD use and use of 
antiretroviral (ARV) drug regimens for HIV treatment and prevention (ART for people living 
with HIV; PrEP for people without HIV). These outcomes will be documented by laboratory 
testing. 
 
Summary. The national opioid epidemic is a crisis that threatens to feed a renewed HIV epidemic. 
A threat of this nature requires that strategies to address the crisis have goals that are as ambitious 
as the threat is grave. To that end, the goal of this study is that this intervention will prove so 
efficacious that it will change policy in local, state and national jurisdictions responsible for 
addressing clinical practice for PWID with OUD in urban settings. Findings will document the 
prevalence of SARS-CoV-2 seropositivity in this population at baseline and over the course of the 
study and will provide insights about the impact of the COVID-19 epidemic on this group 
affected by intertwined HIV and opioid epidemics.  
 
Audacious Goals. The ambitious goals for this study are as follows: that 50% of participants in 
the intervention arm are on MOUD at 26 weeks, with 40% on MOUD at 52 weeks; that the death 
rate in the intervention arm is reduced by half, compared to the active control arm; and that twice 
as many participants in the intervention arm are virally suppressed or on PrEP compared to the 
active control arm.  
 
1.2.1 Implementation Science Framework 
 
The implementation science component of this study provides the opportunity to determine how 
to deliver this intervention successfully and with fidelity in different US settings (mid-Atlantic, 
South, West) that are affected differently by the opioid, HIV and COVID-19 epidemics. Attention 
to each of the elements of the integrated strategy is vital for the health of people living with OUD 
who have HIV or are at risk for HIV, and have STIs, hepatitis, and other chronic health 
conditions. However, implementing an integrated care delivery strategy is complex, especially 
in settings where there can be different levels of access to addiction treatment, HIV services, 
harm reduction, and primary care services for PWID. We will leverage a hybrid type 1 
implementation study design, where we will evaluate how factors affect the implementation of 

 
 
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the intervention, and the primary and secondary study outcomes; we will also develop a database 
that will inform a more rapid translation of study results into public health practice.36 
 
The Practical, Robust Implementation and Sustainability Model (PRISM) framework37 will 
guide the implementation evaluation in this study. PRISM integrates theory for new behavior 
adoption (Diffusion of Innovations model); for chronic disease processes like OUD and HIV (the 
Chronic Care model); and for continuous program improvement (the Model for Improvement). 
PRISM will allow evaluation of multi-level factors that influence the implementation process 
including, (i) how the interventions in both arms are perceived by providers and patients, (ii) 
characteristics that influence the delivery and receipt of the intervention in both arms, (iii) 
community-level factors in the external environment that may influence how the intervention is 
accessed, (iv) systems- and policy-level factors that affect the infrastructure and sustainability of 
the intervention, and (v) how COVID-19 affects access to the mix of integrated services of 
MOUD, HIV care (ART, PrEP), STI and hepatitis treatment, primary care, and harm reduction at 
the systemic and individual level. Finally, PRISM allows evaluation of the implementation 
outcomes of the intervention through the RE-AIM model (reach, effectiveness, adoption, 
implementation, maintenance).38 
 
This implementation science framework will use a mixed method approach leveraging data 
systematically captured from routine community engagement, fidelity monitoring, and efficacy 
evaluation procedures. These data will be augmented by qualitative data collected at each site 
from participants, providers of integrated health care in the mobile unit and key community 
stakeholders. 
 
2.0 
STUDY OBJECTIVES  
 
2.1 
Primary Objective 
 
To evaluate whether 26 weeks of “one stop” integrated health services delivered in a mobile unit, 
supported by peer navigation, improves use of MOUD, and increases use of PrEP among people 
without HIV, as measured at 26 weeks, when compared to 26 weeks of peer navigation to similar 
health services available at community-based agencies. 
 
2.2 
Secondary Objectives 
 
1) To evaluate whether 26 weeks of “one stop” integrated health services delivered in a mobile unit, 
supported by peer navigation, compared to 26 weeks of peer navigation to similar health services 
available at community-based agencies: 
a) improves use of MOUD at 52 weeks 
b) increases rates of viral suppression among people living with HIV at 52 weeks 
c) increases use of PrEP among people without HIV at 26 and 52 weeks 
d) decreases opioid and polysubstance use at 26 and 52 weeks  
e) decreases prevalence of bacterial STIs at 26 and 52 weeks 
f) decreases fatal and non-fatal overdose events by 26 and 52 weeks 
g) increases the proportion of participants with undetectable HCV RNA at 26 and 52 
weeks among those with chronic HCV infection at Enrollment  
h) decreases HCV incidence at 52 weeks, for those who are HCV negative at Enrollment 
i) increases rates of viral suppression among people living with HIV as measured at 26 
weeks 
 
 

 
 
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2) To evaluate whether 26 weeks of “one stop” integrated health services delivered in a mobile unit, 
supported by peer navigation, increases MOUD use, viral suppression, and PrEP use at 26 and 
52 weeks compared to enrollment 
 
3) To evaluate whether 26 weeks of peer navigation to similar health services available at 
community-based agencies increases MOUD use, viral suppression, and PrEP use at 26 and 52 
weeks compared to enrollment 
 
4) To assess the prevalence of SARS-CoV-2 seropositivity at baseline, 26 and 52 weeks 
 
5) To document the impact of the COVID-19 epidemic on participants’ experiences of seeking, 
obtaining and/or maintaining health services, housing, food security and drugs 
 
6) To evaluate implementation of “one-stop” integrated health services using a mobile unit, 
supported by peer navigation, across study sites to identify mechanisms at multiple levels to: 
a) Guide real-time improvements and refinements in the conduct of the study to ensure 
primary and secondary outcomes are met with fidelity 
b) Examine the quality and process of services delivered in each study arm, particularly as 
these affect primary and secondary outcomes 
c) Develop evidence-based guidance for policymakers on the uptake and implementation 
of integrated health services using peer navigation and mobile health units in urban US 
regions to address HIV prevention in PWID 
d) Identify factors that enhance or impede the delivery of integrated health services using a 
mobile unit, supported by peer navigation, on primary and secondary outcomes, 
including responding to the impact of COVID-19 on service delivery  
 
7) To use mathematical modeling methods to:  
a) estimate the effect of integrated health services delivered in a mobile unit, supported by 
peer navigation, on reducing HIV incidence in PWID and their sexual and injection 
partners 
b) estimate the cost-effectiveness of the integrated health services provided in a mobile unit 
and supported by peer navigation 
 
2.3 
Process Objectives 
 
To assess among participants in the intervention arm: 
 
1) time to provide MOUD treatment, ART (among those who are living with HIV and not on ART 
at enrollment) and PrEP (among those who are without HIV at Enrollment) 
2) the proportion of participants linked to community-based MOUD, ART and PrEP services at 26 
weeks 
 
2.4 
Exploratory Objectives  
 
Stored samples may be used to analyze HIV subtypes/strains, HIV drug resistance, and the duration 
of HIV infection. Phylogenetic methods may be used to evaluate behavioral, demographic, and 
clinical factors associated with viral clusters and transmission dynamics. Stored samples may also be 
used to characterize HCV strains and the relationship between HIV and HCV infections, and to 
explore issues related to COVID-19.  
 

 
 
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3.0 
STUDY DESIGN 
 
INTEGRA will be a two-arm, individually randomized, unblinded longitudinal study. The study 
will be conducted in five US cities selected to represent the geographic diversity of the country’s 
opioid epidemic; for having an appropriate population in sufficient numbers for timely enrollment 
of the study; and for the ability to implement the study successfully. All potential participants will 
be screened and enrolled (if eligible) in a mobile unit. The mobile unit will be configured as a 
mobile clinic, staffed by clinicians licensed to provide MOUD and other care, and will travel to 
“hot spots” in the community frequented by PWID. Clinicians providing care in the mobile unit 
will do so under the auspices of the institution or clinical group with which the research site is 
affiliated, typically a university health system or medical school. Screening and enrollment 
procedures, which will take place over a minimum of two visits, will include providing informed 
consent, obtaining opioid use and treatment history, answering questions about current and past 
health, and obtaining urine, blood and swab samples for laboratory tests.  
 
All enrolled participants will be PWID with OUD (verified by diagnostic interview) who are not 
on MOUD. Following randomization, participants in the intervention arm will be offered peer 
navigation and treatment for OUD (MOUD) integrated with HIV services (ART for people living 
with HIV, PrEP for people without HIV) and additional health services in a mobile unit for 26 
weeks. In the active control arm, participants will receive peer navigation to community-based 
services for the same services as the intervention arm for 26 weeks. Approximately 450 
participants will be enrolled with about 225 participants per arm, with a target minimum 25% 
women, 25% participants under 30 years of age, and 10% people living with HIV at enrollment. 
 
The services that participants in both arms receive during the 26 weeks of the intervention will be 
provided on a schedule determined by the needs of the participant. At baseline, all participants 
will be seen in the mobile unit to complete the consent process and interview and to provide 
specimens for laboratory testing. Participants in the intervention arm will receive immediate 
MOUD, ART, PrEP, STI testing and treatment, hepatitis and pregnancy testing, and primary 
health services, and navigation to promote uptake of clinical services offered in the mobile unit. 
Before or at the start of a visit, participants will be assessed for COVID-19; if SARS-CoV-2 
infection is suspected, the visit will be deferred to a later date and the participant will be referred 
for further evaluation and/or care, as indicated and available.  
 
Intervention arm participants will also receive immediate navigation to health services or 
diagnostic tests not available in the mobile unit, and to successfully transfer all care to existing 
facilities in the community by 26 weeks. Participants in the active control arm will receive 
navigation through 26 weeks to community-based services for all health services, including 
MOUD, ART, PrEP, STI testing and treatment, HCV treatment, primary health services and 
COVID-19 evaluation, testing and care. Peer navigation will be delivered by a cadre of staff 
called peer navigators; these navigators may be true peers, i.e., have been in recovery for OUD 
for at least a year and will have been trained and certified to provide recovery coaching (support 
and assistance to help others initiate and adhere to MOUD) and health systems navigation. When 
true peers are not available, staff members can deliver navigation services in the absence of lived 
experience but should have completed at least one year of education, job experience or training in 
delivering navigation services to people living with OUD. 
 
Laboratory testing will be performed retrospectively to assess MOUD, ART and PrEP use using 
samples collected at 26 weeks (primary endpoint) and 52 weeks (secondary endpoint) to assess 
the initial and durable effects of the intervention. Laboratory testing will also be performed 
retrospectively to assess substance use, HIV incidence, HCV incidence (52 weeks), and 

 
 
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prevalence of SARS-CoV-2 seropositivity (baseline, 26 and 52 weeks). Results of retrospective 
testing will not be returned to the sites or participants. Results of point-of-care testing for MOUD 
and substance use testing at baseline, 26 and 52 weeks will be provided to participants. 
Prevalence of bacterial STIs will be analyzed from samples drawn at baseline, week 26 and week 
52, but are processed locally at time of draw. 
 
A graphical depiction of the study design and randomization scheme is provided in Figure 1 
above. See Appendix I for a schedule of study visits and procedures. 
 
3.1 
Participating Sites/Institutions 
 
The five sites participating in this study are all in US cities and are listed in the Study Specific 
Procedures (SSP) Manual.  
 
3.2 
Study Duration 
 
Study duration is approximately three and a half years. The study will be initiated at all sites over a 
six-month period. Accrual is anticipated to occur over two and a half years with individual 
participants followed on study for approximately one year (26 weeks receiving the intervention or 
peer navigation, followed by an evaluation for durability of effect at the end of 52 weeks). 
 
4.0 
STUDY POPULATION 
 
Approximately 450 PWID with OUD not in MOUD and either without HIV  or living with HIV 
will be included in this study, with a target of a minimum 25% women, 25% aged 18-29, and 
10% people living with HIV at enrollment. Participants will be selected for the study according to 
the criteria in Section 4.1 and 4.2 and the guidelines in Section 4.4.  Participants will be recruited, 
screened, and enrolled as described in Section 4.3 and assigned to intervention or active control 
group as described in Section 8.5. Requirements related to participant retention and withdrawal 
from the study are described in Sections 4.5 and 4.6, respectively.  
 
 
4.1 
Inclusion Criteria 
 
Adults who meet all of the following criteria are eligible for inclusion in this study: 
• 
At least 18 years of age  
• 
Urine test positive for recent opioid use and with evidence of recent injection drug use 
(“track marks”) 
• 
Diagnosed with OUD per Diagnostic and Statistical Manual of Mental Disorders 
(DSM)-5 
• 
Able and willing to give informed consent 
• 
Willing to start MOUD treatment 
• 
Able to successfully complete an Assessment of Understanding 
• 
For those who are without HIV: Self-reported sharing injection equipment and/or 
condomless sex in the last three months with partners who are  living with HIV or 
unknown status 
• 
Able to provide adequate locator information 
• 
Confirmed HIV status, as defined in the HPTN 094 SSP Manual 
See SSP Section 4 for further guidance on assessment of inclusion criteria. 
 

 
 
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4.2 
Exclusion Criteria 
 
Adults who meet any of the following criteria will be excluded from this study: 
• 
Urine testing that is not negative for methadone within 30 days prior to Enrollment is 
exclusionary, unless verified hospital records show methadone received as a medication 
for hospitalization only during the screening period. A volunteer may provide a sample 
for urine testing more than once during the screening period in order to achieve a 
negative result. If this criterion cannot be met within 30 days from the start of screening, 
the individual will be considered a screen failure and the volunteer has up to two more 
screening chances to successfully complete the screening process again. 
• 
Received MOUD in the 30 days prior to enrollment by self-report.  
• 
Co-enrollment in any other interventional study unless approved by the Clinical 
Management Committee (CMC) 
 
See SSP Section 4 for further guidance on assessment of exclusion criteria. 
Persons who are otherwise eligible to be enrolled will be deferred if they are suspected to have 
COVID-19; the period of deferral will be determined based on criteria for discontinuation of 
isolation per US Centers for Disease Control and Prevention (CDC) guidelines or applicable local 
guidelines. Depending on the length of deferral, screening procedures may have to be repeated to 
establish eligibility. 
Note: The CMC is a sub-group of the Protocol Team that includes physicians from sites, the 
Protocol Chair and Co-Chair and the DAIDS Medical Officer. Additional roles of the CMC are 
addressed in sections 7, 10 and 11 of this protocol and will be further described in the SSP and 
the CMC charter. 
4.3 
Recruitment Process 
 
Sites will be responsible for developing appropriate recruitment processes that are geared toward 
their respective local communities. All advertising materials must undergo approval by the 
Institutional Review Board (IRB). 
 
Recruitment of PWID with OUD  who are living with HIV or who are without HIV and at high-
risk will need attention at regular intervals to ensure adequate enrollment for the study in the time 
allotted. A recruitment plan will be developed at each site to guide outreach to and enrollment of 
participants. Outreach activities will be consistently conducted at “hot spots” - facilities and 
venues where PWID are commonly found and can be contacted for possible enrollment in the 
study.  
 
Hot spots will be identified and mapped at each site prior to the start of the project. Examples of 
locations that are common hot spots include venue-based areas (locations outside jails, criminal 
justice community supervision programs, syringe exchange sites, detox centers, emergency rooms 
and hospitals) and street-based areas (tourist areas, parks, strolling areas, skid row, public 
housing). Hot spots will change over the course of the study as groups of PWID who are not 
receiving MOUD migrate to new locations due to changes in the local environment (e.g., policing 
patterns, gentrification). Each site will therefore need to continually review their recruitment data 
and other information such as the productivity of hot spots in yielding enrollments.  
 
 
 

 
 
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Plans for recruitment at each site will be detailed (and revised) in the SOPs and/or recruitment 
plan. Sites will be expected to use local data (e.g., heat maps of overdoses) and consultation with 
local experts to develop their recruitment plan and keep it updated. Local experts consulted may 
include 1) public health department officials (especially those responsible for conducting 
National HIV Behavioral Surveillance [NHBS] and for managing publicly-funded MOUD), 2) 
law enforcement, 3) harm reduction leaders and advocates, 4) health care providers (particularly 
infectious disease clinicians, emergency room physicians and hospitalists), 5) medical 
examiners/coroner’s office, 6) scientists who are involved in studying PWID in the area and 7) 
community members.  As hot spots are identified, this information will be recorded and 
maintained through the life of the study to provide a running list of environmental features (e.g., 
parks, “broken windows,” cheap motels, convenience and liquor stores, marijuana dispensaries, 
gentlemen’s clubs, etc.) where PWID who are not receiving MOUD may congregate. 
 
Hot spots will serve not only as sites for outreach and recruitment, but also as sites where the 
mobile unit may be deployed to implement the study.  
 
In addition to recruiting from identified hot spots we will employ peer recruitment and referral 
strategies. Participants will be encouraged to recruit their peers from their social network, from 
other PWID and from their communities. We will also encourage referrals from providers such as 
emergency departments, alternative-to-incarceration programs, homeless shelters, harm reduction 
programs, public health departments, etc. 
 
As noted in Section 1.2 of this protocol, a minimum of 25% women are planned for enrollment in 
this study and a minimum of 25% under age 30 years. Sites may propose additional recruitment 
strategies needed to yield the expected minimums of women and youth for the study. 
 
4.4 
Co-Enrollment Guidelines 
 
In general, participants in this study will not be allowed to take part in other concurrent 
interventional research studies during their study participation, unless approved by the CMC. This 
is due in part to concerns about participant study burden and to avoid confounding in the 
interpretation of the study data. This concern is particularly relevant for co-enrollment in studies 
of long-acting HIV care and prevention products. Given this situation, the CMC should be 
consulted for any possible exceptions, including participation in observational studies.  
 
4.5 
Participant Retention 
 
It is expected that this population under study (PWID with OUD who are not in MOUD 
treatment) will present challenges exceeding those encountered in traditional HPTN protocols. As 
such, retention activities will require additional attention and resource to ensure that 90% 
retention targets at 26 and week 52 visits are met. The following activities, strategies and 
perspectives are required in some combination to ensure participants are found throughout the 
study period and especially at distal follow-up visits.  
 
Study site staff are responsible for developing and implementing local standard operating 
procedures (SOPs) to achieve the 90% retention goal. Components of such procedures may 
include: 
• 
Thorough explanation of the study visit schedule, the importance of keeping each study 
visit, procedural requirements during the informed consent process and re-emphasis of 
the importance of these visits and requirements at each study visit. 

 
 
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• 
Thorough explanation of the importance of both study treatment groups to the overall 
success of the study. 
• 
Collection of detailed and valid locator information at the study Screening Visit, with 
active review and updating of this information at each subsequent visit. 
• 
Providing a small incentive for regular locator information updates or high study 
retention. 
• 
Soliciting consent to contact providers, such as physicians, social workers or nurses, 
when trying to locate the participant. 
• 
Use of mapping techniques to establish the location of participant residences and other 
locator venues at Screening and at each visit to monitor changes in living situations. 
• 
Use of appropriate and timely visit reminder mechanisms. 
• 
Immediate (as soon as recognized), consistent (until a response is gotten) and 
multifaceted (all contacts reached) follow-up activities on missed visits. 
• 
Mobilization of trained outreach workers or “tracers” to complete in-person contact with 
participants at their homes and/or other community locations. 
• 
Regular communication with the study community at large to increase awareness about 
HIV/AIDS and explain the purpose of HIV prevention research and the importance of 
completing research study visits. 
In addition to the procedures described, which are standard for all HPTN studies, an important 
aspect that will facilitate retention of this population will be to ensure that all study staff, and 
particularly clinicians and peer navigators, display a non-judgmental, supportive attitude toward 
PWID in general and study participants specifically, and that they build genuine rapport with 
participants during study encounters in both arms.   
 
It will also be important for study staff to establish and maintain rapport and good will with the 
community of PWID and with those who work with PWID in the local setting. This will facilitate 
reconnecting with participants who have missed visits or become lost to follow up, an inevitable 
eventuality when working with this population.  
 
4.6 
Participant Withdrawal from Study 
 
Participants may voluntarily withdraw from the study for any reason at any time. The Investigator 
of Record (IoR) or designee also may withdraw participants from the study in order to protect 
their safety and/or if they are unwilling or unable to comply with required study procedures after 
consultation with the Protocol Chair, DAIDS Medical Officer, SDMC Protocol Statistician, and 
LOC Clinical Research Manager (CRM). 
 
Participants also may be withdrawn if the study sponsor, government or regulatory authorities, or 
IRB terminate the study prior to its planned end date. 
 
Every reasonable effort will be made to complete a final evaluation (as described in Section 6.5 
and Appendix I) of participants who terminate from the study prior to the Week 52 visit, and 
study staff will record the reason(s) for all withdrawals from the study in participants’ study 
records. 
 
 

 
 
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5.0 
STUDY INTERVENTIONS 
 
Participants in both study arms will receive initial medical assessment and services in the mobile 
unit during Screening and Enrollment (see Section 5.1 for details). Following enrollment and 
randomization: 
 
• 
Those assigned to the intervention arm will receive medical services for OUD (MOUD), 
HIV treatment or prevention (ART or PrEP), and other primary care conditions that can 
be managed in the mobile unit (see Table 2 below). They will also receive 26 weeks of 
peer navigation. Although medical services will initially be based in the mobile unit, a 
goal of peer navigation will be to successfully transition participants to services at 
existing facilities in the community by  26 weeks.  
• 
Those assigned to the active control arm will receive 26 weeks of peer navigation to the 
same medical services delivered at existing facilities in the community.  
 
At the end of 26 weeks, participants in both arms will have study visits for assessment of primary 
and secondary endpoints. At the end of 52 weeks, participants in both arms will have a final study 
visit for assessment of additional secondary endpoints. Table 1 (p.33 summarizes services that 
will be provided to participants in the two arms. Table 2 (p.37) provides details of the medical 
services that will be provided in the mobile unit to intervention arm participants. 
 
5.1 
Initial Assessment and Provision of Services in the Mobile Unit - All 
Participants 
 
Engagement with persons interested in participating in the study will begin with the informed 
consent process. To protect the safety of community members and staff, sites may implement a 
pre-screening assessment for COVID-19 before beginning study screening procedures. These 
procedures may take place remotely (e.g., over the telephone) or outside of the mobile unit, per 
guidelines. Those suspected to have COVID-19 will be deferred from screening and referred for 
testing and/or treatment, as appropriate and available. 
 
Once informed consent has been obtained, participants will begin screening procedures and, if 
appropriate, enrollment into the study. As part of Screening and Enrollment, all participants will 
receive assessment by a clinician in the mobile unit and point-of-care testing for OUD, HIV, and 
pregnancy (for those who can become pregnant). Samples will also be collected for laboratory 
testing for HIV, HCV, HBV, HAV, STIs, and hematology/chemistry at this time. Those who test 
HIV positive will receive additional testing as appropriate (CD4 cell count, viral load, resistance 
testing). At enrollment, basic medical services will be provided to all participants, including 
empiric treatment for STIs if symptoms are present, provision of harm reduction services 
(naloxone kits and, where possible, syringe/needle exchange services), and preparation of a 
treatment plan. All participants will be assessed for OUD diagnosis per the DSM-5 at either the 
Screening or Enrollment Visit. At the enrollment visit, participants will be asked about any 
MOUD treatment in the past 30 days and will meet with their peer navigators for the first time. 
Persons with suspected COVID-19 or recent exposure will be deferred from enrollment until they 
meet the criteria for discontinuation of isolation per CDC guidelines or applicable local 
guidelines and will be referred for COVID-19 testing and treatment services, as appropriate and 
available. The specific procedures for assessing participants for COVID-19 will be described in 
the SSP Manual. Following the Enrollment Visit, navigation, medical and counseling services 
will be provided by study arm as described below. 
 

 
 
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5.2 
Provision of Medical Services 
5.2.1 Medical Services - Intervention Arm 
 
For the 26 weeks of intervention following study enrollment and randomization, participants 
assigned to the intervention arm will receive medical services in the mobile unit from a clinician. 
First and foremost, participants will be provided immediate access to MOUD to control 
withdrawal symptoms quickly and thereby minimize the disorganizing behavioral effects of 
addiction that jeopardize adherence to HIV treatment or prophylaxis regimens. The MOUD 
regimen provided in the mobile unit will be influenced by the participant’s recent drug use and 
treatment history, the drug regimens used in local opioid treatment programs, and availability of 
medications on the mobile unit (i.e., a restricted range of medications will be available on the 
mobile unit; a wider range of MOUD options will be available via navigation/linkage to regularly 
available resources at local clinics). The clinician in the mobile unit will have the necessary 
medical waiver (Drug Addiction Treatment Act- 2000 “X” waiver) and clinical experience to 
provide MOUD to this population.  
 
For those identified as living with HIV during Screening and Enrollment (and not already 
established in ART elsewhere), and for those who acquire HIV during the intervention period, 
ART will be provided in the mobile unit. Those identified as being without HIV at Enrollment 
will be provided risk reduction counseling, assessed for PrEP and offered PrEP according to 
assessment; these participants will be tested for HIV infection during the intervention period. 
Clinical care including applicable laboratory test monitoring for participants living with HIV and 
those on PrEP will be provided per national clinical guidelines. Over time, these participants will 
be linked to appropriate long-term ART or PrEP service settings. 
 
Based upon the results of testing for HAV, HBV and HCV at Enrollment, participants will meet 
with their navigators to receive facilitated referral to the most appropriate community-based 
services in their area for vaccination and/or treatment, anticipated to be Federally-Qualified 
Health Centers (FQHCs) and clinics with experience in providing hepatitis services for PWID. 
An exception to this will be for HBV treatment, where ART or PrEP regimens provided in the 
mobile unit can also treat HBV infection, if determined to be appropriate by the medical provider.  
 
STI treatment (or referral for cases that cannot be addressed in the mobile unit) will be provided 
for those with laboratory-confirmed infection from samples collected at Enrollment (testing for 
GC/CT and syphilis); at all visits, participants with STI symptoms will be offered empiric 
treatment. Sites will use local guidelines for interpretation of test results for clinical management. 
To determine syphilis prevalence, syphilis results will also be evaluated retrospectively at the 
HPTN LC to differentiate active infection from past exposure.  
 
Assessment and/or treatment of other basic medical conditions will be provided in the mobile unit 
for participants in the intervention arm (see Table 2). Treatment or management of more complex 
conditions will require referral. In this population, it is expected that few participants will already 
be successfully engaged with health services providers in their community. However, if a 
participant does prefer to receive some or all of their care from community-based services instead 
of the mobile unit (for example, if they are already receiving HIV care from a clinic in the 
community), that will be allowed and supported by peer navigation. 
 
Clinicians on the mobile unit will assess participants in the intervention arm for COVID-19 
during the first 26 weeks. Participants with suspected COVID-19 or recent exposure will be 
referred for services in the community and facilitated in accessing those services.  
 

 
 
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Participants who also use stimulants (methamphetamine, cocaine) in addition to opioids, will be 
referred to 12-step meetings available locally such as crystal meth anonymous, narcotics 
anonymous and alcoholics anonymous. Participants will be assisted in finding counseling services 
for evidence-based behavioral treatment, where available.  
 
Harm reduction services (naloxone kits, and where possible, needle/syringe exchange) will be 
available on the mobile unit, as will condoms and lubricant. We will collaborate with local 
community-based organizations providing such services to augment what is offered in the mobile 
unit. Peer navigators will offer condoms and lubricants during their meeting with participants. 
 
5.2.2 Medical Services - Active Control Arm 
 
Except for the services described above in Section 5.1, medical services for participants in the 
active control arm will not be provided in the mobile unit but will be provided by the existing 
facilities in the local area (referred to in this protocol as “community-based services”) according 
to the local standard of care (SOC). Throughout the 26 weeks, linkage provided through peer 
navigation will assist participants in the active control arm to access, at local clinics and agencies, 
the full range of health services that intervention arm participants will be provided on the mobile 
unit or be navigated to. Peer navigators will offer condoms and lubricants during their meetings 
with participants. 
 
5.3 
Provision of Peer Navigation Services 
 
Peer navigation is intended to assist people who may not have ready access to services to 
overcome barriers and to enter care and remain in treatment. These services will be provided by a 
cadre of trained study staff designated as peer navigators who will act both as health system 
navigators (assisting participants to access care in a fractured health system) and as peer recovery 
coaches with lived OUD experience (assisting participants to initiate and sustain MOUD 
treatment). It is possible that peer recovery coaches may not be available to hire for this role. In 
such an instance, it is acceptable to hire a peer navigator who lacks lived experience, but who has 
at least one year of education, job experience or training in delivering navigation services to 
PWID. 
 
Peer navigators will motivate and assist participants to successfully enroll in and consistently use 
MOUD, ART, PrEP, as well as to receive STI testing and treatment, hepatitis vaccine or 
treatment, SARS-CoV-2 testing (if available), and referral for services, primary care and harm 
reduction services. It is anticipated that many participants will be eligible to receive medical 
insurance or other government support for their medical care and treatment. Peer navigators will 
help participants sign up for/access health insurance or other programs for which they are 
eligible, especially if no insurance is available. Depending on participant need, navigation 
services will include identifying appropriate health service providers in the community, 
arrangement of medical appointments, reminding participants of upcoming appointments, 
assisting with transport or accompaniment to appointments (whether in the mobile unit or at 
community-based services), and transfer of medical records. Although assistance with obtaining 
health care services and adhering to treatment/prophylaxis regimens will be the primary focus of 
peer navigation, peer navigators will also provide referrals to local resources for participants who 
have needs related to food security, housing and employment.  
 
Participants in both arms will work with a trained peer navigator for the first 26 weeks on study. 
It is expected that initial interactions between the peer navigator and a participant will be 
conducted in person, beginning with the Enrollment Visit in the mobile unit. For participants with 

 
 
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a phone, it is expected that the peer navigator will use messaging apps/texts to maintain regular 
contact with participant, confirm appointments, locate those who have missed scheduled visits, 
etc. throughout the 26 weeks of navigation. To the extent possible and depending on local 
availability, navigators will assist with temporary shelter placements for those who need them and 
will provide transport vouchers (e.g., bus tokens) to enable participants to access services and 
remain in care.  
 
The frequency and timing of navigation encounters will be measured for both arms in order to 
monitor dose by condition in number of sessions, minutes spent per encounter and types of 
activities, referrals and services completed by the navigator. The study staff supervisor will meet 
with the navigators on a weekly basis in both conditions and provide support for navigators as 
described in the SOP. Rather than set a required “dose” of navigation for each arm, monitoring 
implementation of navigation will document whether equipoise is maintained between conditions 
through the trial when evaluating efficacy of the mobile unit on primary and secondary outcomes, 
and when evaluating improvements in outcomes for both conditions compared to baseline. 
 
5.3.1 Navigation Services - Intervention Arm 
 
Peer navigators in the intervention arm will assist their participants to access medical services 
provided from the mobile unit. They will also assist their participants to obtain care from 
community-based services for those tests or services that cannot be addressed in the mobile unit. 
Initial visits between the participant and their navigator are expected to occur in person, 
beginning with introductions at the Enrollment Visit in the mobile unit. As the participant-
navigator relationship becomes more established, interactions can be expected to take place at 
locations other than the mobile unit and may occur by phone or by messaging app/text. The peer 
navigator will also be responsible for working with the participant during the intervention period 
to prepare them to transition to community-based services by 26 weeks.  
 
5.3.2 Navigation Services- Active Control Arm 
 
The role of the peer navigator for active control arm participants will be to link them to 
community-based services for the same types of medical services provided in the mobile unit in 
the intervention arm, i.e., MOUD, HIV treatment (ART) and prevention (PrEP), vaccination or 
treatment for hepatitis, STIs testing and treatment, SARS-CoV-2 testing (if available), and 
referral, primary care and harm reduction services.  As described for the intervention arm, initial 
meetings between the participant and the navigator will be in-person. As the participant-navigator 
relationship becomes more established, interactions can be expected to occur by phone or by 
messaging app/text.  
 
5.4 
Medication Considerations  
 
All of the drugs that will be provided as part of services in the mobile unit will be US Food and 
Drug Administration (FDA)-approved medications in common use for these conditions; this 
study does not involve any investigational products. Some medications provided from the mobile 
unit will be procured locally by the study teams and others provided centrally through the study. 
FTC/TDF, FTC/TAF and BIC/F/TAF provided by Gilead for PrEP and ART may also be referred 
to as study products. Because the MOUD medication expected to be used in this study will be 
buprenorphine, or combination buprenorphine/naloxone, both schedule III controlled substances, 
the study team will work with the US Drug Enforcement Administration at the national and local 
level to comply with policies for dispensation of buprenorphine or buprenorphine/naloxone to 

 
 
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participants. Study sites are responsible for procuring antibiotics locally for STI treatment and 
may choose to locally procure buprenorphine-containing regimens for MOUD.  
 
5.4.1  Medications for HIV and MOUD 
 
The following medications will be centrally supplied by the study to the sites, and will be offered 
to participants in the intervention arm, as appropriate, for HIV treatment or prevention (ART or 
PrEP) or MOUD. Centrally supplied medications must be stored in the pharmacy in the original 
bottles and in accordance with the manufacturer’s recommendations. 
 
PrEP 
• 
Emtricitabine/tenofovir disoproxil fumarate 200mg/300mg (FTC/TDF, Truvada®) 
FTC/TDF (Truvada®) is a fixed dose combination tablet containing 200 mg of  FTC and 
300 mg of TDF. FTC/TDF (Truvada®) must be stored at 25°C (77°F), with excursions 
permitted between 15°C-30°C (59°F-86°F) [see USP Controlled Room Temperature]. 
FTC/TDF tablets must be stored and dispensed in the original container. Refer to the 
relevant Package Insert for further information. 
 
• 
Emtricitabine/tenofovir alafenamide 200mg/25mg (FTC/TAF, Descovy®) 
FTC/TAF (Descovy®) is a fixed dose combination tablet containing 200 mg of FTC and 
25 mg of TAF. FTC/TAF (Descovy®) must be stored in the original bottle below 30°C 
(86°F) and dispensed in the original container. Refer to the relevant Package Insert for 
further information. 
 
ART 
• 
Bictegravir/emtricitabine/tenofovir alafenamide 50mg/200mg/25mg (BIC/F/TAF, 
Biktarvy®) 
BIC/F/TAF (Biktarvy®) is a fixed dose combination tablet containing 50 mg of 
bictegravir, 200 mg of emtricitabine, and 25 mg of tenofovir alafenamide. BIC/F/TAF 
(Biktarvy®) must be stored in the original bottle below 30°C and dispensed in the 
original container. Refer to the relevant Package Insert for further information. 
 
MOUD 
• 
Buprenorphine/naloxone 2mg/0.5mg sublingual tablets 
• 
Buprenorphine/naloxone 8mg/2mg sublingual tablets 
 
Both buprenorphine/naloxone 2mg/0.5mg and buprenorphine/naloxone 8mg/2mg sublingual 
tablets must be stored in the original bottle at 20° to 25°C (see USP Controlled Room 
Temperature) and dispensed in a tight, light-resistant container with a child-resistant closure. 
Refer to the relevant Package Insert for further information. 
 
5.4.2  Centrally Supplied Medication Acquisition and Accountability 
 
FTC/TDF 200 mg/300 mg tablets (Truvada®), FTC/TAF 200 mg/25 mg tablets (Descovy®), and 
BIC/F/TAF 50mg/200mg/25mg tablets (Biktarvy®) are manufactured and provided by Gilead 
Sciences, Inc.  
 

 
 
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Buprenorphine/naloxone 2mg/0.5mg and buprenorphine/naloxone 8mg/2mg sublingual tablets 
are purchased with funding support from the HPTN Leadership and Operations Center 
(LOC).  
 
FTC/TDF 200mg/300mg tablets, FTC/TAF 200mg/25mg tablets, BIC/F/TAF 50mg/200mg/25mg 
tablets, buprenorphine/naloxone 2mg/0.5 sublingual tablets, and buprenorphine/naloxone 
8mg/2mg sublingual tablets will be available through the National Institute of Allergy and 
Infectious Diseases (NIAID) Clinical Research Products Management Center (CRPMC). The 
study site pharmacist can obtain the above listed medications through the CRPMC by following 
the instructions in the Pharmacy Guidelines and Instructions for DAIDS Clinical Trial Networks, 
and instructions in the SSP Manual. Sites may alternatively choose to locally procure 
buprenorphine/naloxone per the site’s standard operating procedures.  
 
5.4.3 Accountability for Centrally Supplied Medications 
 
A written prescription must be provided to the site pharmacist when a participant initiates 
FTC/TDF, FTC/TAF, BIC/F/TAF and/or buprenorphine/naloxone. All local pharmacy laws and 
regulations must be followed regarding prescription requirements and dispensation procedures. 
All centrally supplied medications must be dispensed per a written prescription and labeled with a 
participant-specific label that is in accordance with local pharmacy laws and regulations along 
with the instructions in the Pharmacy Guideline and Instructions for DAIDS Clinical Trial 
Networks.  
 
The site pharmacist is required to maintain complete records of all centrally supplied medications 
received from the CRPMC and subsequently dispensed to study participants. All centrally 
supplied medications received from the CRPMC must be stored in the pharmacy. All unused  
centrally supplied medications that were received from the CRPMC must be returned to the 
CRPMC after the study is completed or terminated or otherwise instructed by the study sponsor. 
The procedures to be followed are provided in the Pharmacy Guidelines and Instructions for 
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Table 1- Summary of Services Provided to the Intervention and Active Control Arms 
 
Service 
Summary 
Diagnostic 
Testing 
Screening/ 
Enrollment 
Screening and Enrollment will occur on the mobile unit for all participants.  
Screening Visit:  
• 
HIV rapid testing  
• 
Urine testing for substances of abuse and MOUD.  
• 
Collection of blood for local laboratory testing for HIV. Laboratory results will not be immediately 
available. 
Enrollment Visit:  
In both arms,  
• 
HIV rapid testing, if not previously confirmed   
• 
Rapid pregnancy testing, as appropriate 
• 
Collection of blood, urine and swab specimens for local laboratory testing for HIV, STIs, 
HAV/HBV/HCV, and hematology/chemistry assessments. Laboratory results will not be immediately 
available.  
In the intervention arm, laboratory results should be provided at the next mobile unit care visit, within days of 
enrollment. If this is not possible, laboratory results will be conveyed by a navigator, clinician or trained staff 
member, as appropriate, in person or by phone, medical app, or letter.  
In the active control arm, laboratory results will be conveyed by navigator, clinician or trained staff member, 
as appropriate, in person or by phone, medical app, or letter.  
After 
Enrollment 
Between Enrollment and week 26 
In the intervention arm,  
• 
As needed, further/repeat testing for clinical care related to MOUD, HIV, STIs, hepatitis or pregnancy.  
In the active control arm, no diagnostics will be performed in the mobile unit or as part of the study during 
this time (all care & diagnostics will need to be provided from community-based services). 
 
At week 26 and 52 Visits 
In both arms,  
• 
HIV rapid testing (for those not previously confirmed to be living with HIV)  
• 
Rapid pregnancy testing (as appropriate)  
• 
Urine testing performed for substances of abuse and MOUD.  
• 
Collection of blood and swabs for laboratory testing for HIV (for those not previously confirmed to be 
living with HIV), STIs and (week 52 only) incident HCV infection in those who were HCV negative at 
study entry. Those with chronic HCV will receive HCV RNA testing at week 26 and 52.  

 
 
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Laboratory results will not be available until after the visit; clinically-relevant results will be conveyed by 
navigator, clinician or trained staff member, as appropriate, in person or by phone, medical app, or letter.  
Medical 
Care and 
Treatment  
Enrollment 
Enrollment Visit:  
In both arms in the mobile unit,  
• 
Assessment for COVID-19 
• 
Assessment for OUD and confirmation of HIV status.  
• 
HIV and MOUD counseling and a basic physical exam.  
• 
Assessment for mental health needs by standardized questionnaires 
• 
Obtaining a targeted medical history.  
• 
Assessment of STI symptoms and provision of empiric treatment as indicated.  
• 
Staff will provide information about MOUD therapy, ART and PrEP, and viral hepatitis treatment and 
vaccination.  
• 
Clinician and participant will develop a preliminary care plan.  
• 
Condoms, lube and harm reduction will be offered. 
For those in the intervention arm,  
• 
The participant will be given instructions on how to prepare for initiating MOUD therapy. In some 
instances, it may be appropriate to dispense medication to begin MOUD, ART or PrEP at this visit, but it 
is expected that this will be rare. 
For those in the active control arm, no additional procedures.  
After 
Enrollment 
Between Enrollment and week 26 
Condoms, lubricant and harm reduction will be available to all participants 
In the intervention arm, the participant will have visits in the mobile unit as indicated for limited primary care. 
Results from enrollment tests will be provided. Test results will inform updates to the clinical plan. 
• 
Assessment for COVID-19 
• 
Establish participant on MOUD, ART (if living with HIV), PrEP (if living without HIV) 
• 
Treat bacterial STIs  
• 
Refer for treatment or vaccination for hepatitis infection.  
For additional details on medical care in the mobile unit, see Table 2. 
In the active control arm, the clinician or other appropriate site staff will provide results from enrollment tests 
to the participant, typically over the phone, though in-person delivery at a peer navigation visit may also be 
common. Test results will inform updates to the clinical plan.  
• 
The clinician and peer navigator will identify appropriate referrals to community-based services and will 
provide test results to these services with participant consent.  
 
At week 26 and 52 Visits 

 
 
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Limited medical services will be provided to participants at the week 26 and 52 visits, which may take place in 
the mobile unit or another location such as a community clinic or CRS.  
• 
Assess for COVID-19 
• 
HIV testing and counseling will be provided to those who were not previously confirmed to be living with 
HIV  
• 
Rapid pregnancy testing (as appropriate) and results provided during the visit.  
• 
Provision of condoms, lubricant and harm reduction.  
The results of tests for HIV viral load, STIs, and HCV Ab/viral load, performed on samples obtained at the visit 
will be provided to participants when available, with appropriate referral to community-based services. 
Peer 
Recovery 
Coaching 
and 
Navigation 
At 
Enrollment 
• 
All participants will be assigned and introduced to a peer navigator at the Enrollment Visit and together 
will identify preliminary goals and plans.  
• 
The dosage of peer navigation will be titrated to the level necessary to keep the participant engaged in the 
study, engaged in the medical care and treatment to achieve the goals prioritized in the clinical plan, and 
able to be located for 26 and 52 week follow-up visits.  
• 
Protocol team leaders will provide supervision and guidance to monitor peer navigator use by condition 
and to provide feedback to navigators to ensure relatively similar levels of navigator session use by 
condition.  
• 
Obtaining insurance or enrollment in other programs to pay for health services will be a top priority.  
• 
Once laboratory results from testing of samples collected at Enrollment are available, the preliminary 
clinical plan will be updated and confirmed. 
After 
Enrollment 
Between Enrollment and week 26 
Intervention Arm:  
Peer navigators will 
• 
Help the participant obtain (or confirm) health insurance 
• 
Identify an appropriate provider and accompany the participant to visits until the participant feels 
confident in doing this on their own, and provide assistance for transportation costs (e.g., vouchers, bus 
passes) for any health need that cannot be addressed on the mobile unit  
• 
Remind participants of appointments at the mobile unit or other providers, follow-up when appointments 
are missed, and motivate the participant to follow through on goals  
• 
Help the participant fill prescriptions at the pharmacy   
• 
Provide encouragement, practical advice and understanding, as a person with MOUD experience, as the 
participant engages in recovery 
• 
Help the participant in the weeks before the end of the intervention, transition from receiving care in the 
mobile unit by establishing care at community-based services so that when the intervention stops, the 
participant is already comfortable with the new provider 

 
 
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Active Control Arm: The services provided by the peer navigator in the active control arm will be the same as 
for the intervention arm except that from the start, the peer navigator will be connecting the participant to 
services available in the community rather than the mobile unit.  
 
 

 
 
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Table 2- Overview of Medical Care Provided in the Mobile Unit for Intervention 
Arm Participants 
 
This table describes the scope of clinical services provided in the integrated strategies approach on 
the mobile unit. Details of the timing of tests and activities are provided in Appendices IA-IB.  
 
This is not a comprehensive list of services provided by clinicians in the mobile unit, as clinicians 
may encounter and respond to many conditions in the course of providing care for addiction, 
infectious diseases and primary care. The descriptions below set expectations for how primary care 
clinicians can function in the mobile unit with consistency from site to site, with limits on what will 
be provided, while enabling them to provide needed attention to the conditions most common to 
primary care. Referrals will be provided for diagnosis and maintenance of care of most chronic 
primary care conditions. Referrals will also be provided for conditions that will routinely be 
managed in the mobile unit (e.g. STI infection) if they require more specialized care (e.g. 
neurosyphilis). 
Condition 
Notes 
OUD 
MOUD will be managed on the mobile unit. Will include dispensation of drugs  to 
include: 
• 
Buprenorphine-based medicine (sublingual and possibly injectable regimens) 
Participants who prefer methadone will be referred to community-based services if 
available 
Stimulant Use 
Participants who also use stimulants (methamphetamine, cocaine) will be referred 
to 12-step meetings such as crystal meth anonymous, narcotics anonymous and 
alcoholics anonymous, and evidence-based behavioral treatment, where available. 
HIV-ART 
ART will be managed from the mobile unit for those not already in HIV care, 
including: 
• 
Dispensation of one first-line, single-pill regimen to participants for whom 
this is indicated 
• 
Prescription provided for fulfillment at a pharmacy if a different regimen is 
indicated   
HIV-PrEP 
PrEP will be managed from the mobile unit including: 
• 
Dispensation of single pill regimens for PrEP 
• 
Prescription provided for fulfillment at a pharmacy if a different regimen is 
indicated   
HCV Treatment 
 
• 
Testing will be performed as part of study procedures.  
• 
Those who test positive will be referred for treatment. 
STI 
Bacterial STIs will be managed from the mobile unit including: 
• 
Provision of antibiotics for treatment of bacterial STIs tested for as part of 
the protocol (CT, GC and syphilis)  
• 
Providing a prescription for fulfillment at a pharmacy, or a referral to 
community-available services, for any conditions not able to be treated on 
the mobile unit  
HAV  
• 
Testing will be performed as part of study procedures.  
• 
Those without evidence of immunity will be referred for vaccination. 
HBV 
• 
Testing will be performed as part of study procedures.  
• 
Those without evidence of immunity will be referred for vaccination.  
• 
Those with evidence of chronic infection who are living with HIV  may be 
co-treated by an appropriate ART regimen dispensed on the mobile unit or 
through a prescription fulfilled at a local pharmacy.  

 
 
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• 
Those with HBV who are without HIV will be counseled on the 
risks/benefits of PrEP. 
Mental Health 
Clinicians will screen for symptoms of mental health disorders during visits on the 
mobile unit.  
• 
For any issues identified, participants will be referred for further evaluation 
and/or care at community-based services, facilitated by peer navigation.  
• 
If a person appears to be at risk of harming themselves or others, 911 will be 
called 
Pregnancy 
Pregnant participants may utilize the mobile unit. 
• 
Participants who are pregnant will continue to be seen for MOUD, ART, 
PrEP and other services on the mobile unit. All pregnant participants will be 
referred for obstetric care with an OB/GYN provider comfortable treating 
pregnant people who inject drugs treated with MOUD. Study clinicians will 
endeavor to coordinate with the obstetric care provider to optimize care.  
Reproductive 
Health 
Limited reproductive health services will be provided in the mobile unit 
• 
Prescriptions for oral contraception  
• 
Condoms/lube 
Basic Primary 
Care 
Basic primary care that will be provided on the mobile unit will include: 
• 
Diagnosis and management of minor acute illnesses and infections such as 
upper respiratory tract infections, colds, flu, diarrheal illness 
• 
Providing prescriptions for pharmacy fulfillment for such conditions if 
indicated.  
• 
Identifying more complex care needs and referring for further diagnostics 
and care from community-available services 
COVID-19 
Clinicians will assess participants for COVID-19 at each encounter. Those with 
suspected COVID-19 or recent exposure will be referred for further evaluation, 
care and treatment, as appropriate and available. CDC and local guidelines for 
discontinuation of isolation will direct when participants with suspected COVID-
19 or recent exposure can resume in-person visits. Distance procedures to collect 
data and monitor health will be implemented to the extent possible. 
More Complex 
Care Needs & 
Chronic 
Conditions 
• 
Management of complex care needs or chronic conditions will be referred to 
community-available services, such as FQHCs or other clinics  
• 
Clinicians on the mobile unit may provide prescriptions for medications for 
chronic conditions that have been lost or stolen or are needed for continuity 
of care, including communication and coordination, as possible, with the 
provider managing the care of the chronic condition. 
 
 

 
 
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6.0 
STUDY PROCEDURES 
 
An overview of the study visits and procedures is presented in Appendix I. Presented below is 
additional information about specific-study procedures. Additional detailed instructions to guide 
and standardize all study procedures across sites will be provided in the SSP Manual. Visit 
windows and visit coding are described in the SSP Manual. 
 
Routine laboratory test results will be provided to participants in a timely fashion. The clinical 
teams will attempt to report results to participants in the following time frames: routine normal 
laboratory results will be reported to patients within two weeks, routine abnormal results within 
two days, and critical abnormal results the same day. Depending on the circumstance and 
urgency, results may be provided to participants via phone call, medical app, in person or via 
letter (if participant has an address). The personnel who provide results (both normal and 
abnormal) will be clinical staff and non-clinical staff (as permitted by local regulations), who 
have received appropriate training.  
 
We will respond flexibly and in accord with federal and local health policies and guidelines to the 
challenges presented by an ongoing or recurrent COVID-19 epidemic throughout the study. The 
accommodations to study procedures listed below reflect our best estimate of the scenarios we 
might face and what approaches might be possible under such conditions. Any modifications to 
protocol conduct or pausing of screening, enrollment or follow-up undertaken to address the 
threat of SARS-CoV-2 infection will be carefully considered by the protocol team in consultation 
with the sponsor to minimize threats to the integrity of the study and the safety of study 
participants and staff. As well, we will create a study specific protocol for outlining management 
of conducting research on HIV and opioid addiction in the context of COVID-19. 
 
6.1 
Screening Visit  
 
It is the responsibility of the local site to determine the best approach to screening. For each 
participant, independent written informed consent will be obtained before any study procedures 
are initiated. Screening procedures may occur over one or more visits. Enrollment must occur 
within 30 days of initiation of screening, defined as the date the participant signs the informed 
consent form. Screening and Enrollment may not occur on the same day. 
 
Sites will follow the HIV testing algorithm for screening included in the SSP Manual. Individuals 
deemed not eligible will be informed that they do not meet the eligibility criteria for the study and 
will be referred for appropriate medical care, if necessary.   
 
Potential participants may be rescreened up to two times (three screening attempts total) at the 
discretion of the IoR or their designee.   
 
To protect community members and staff, it is expected that sites will implement pre-screening 
procedures to identify persons with symptomatic COVID-19 among those presenting for 
screening.  Those with suspected COVID-19 or recent exposure will be deferred from screening 
and referred for community-available services/care/treatment. 
 
6.2 
Enrollment Visit 
 
Potential participants determined to be eligible at screening will be invited to join the study. Not 
everyone who is screened eligible may be offered enrollment depending on the need to achieve 

 
 
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enrollment targets by sex, age and HIV status. Participants will be considered enrolled once they 
have been randomized to either the intervention or active control arm. For those in the 
intervention arm, the activities of the Enrollment Visit will include the beginning of their clinical 
care in the mobile unit and will be more extensive. For participants randomized to the active 
control arm, the Enrollment Visit procedures will be fewer but will include the significant step of 
initiation of peer navigation, the primary benefit they will receive during the intervention period.  
 
When creating a clinical plan for an intervention arm participant, staff will prioritize initiating 
MOUD to reduce the disruptive effects of addiction as a first step. For the buprenorphine 
regimens we anticipate using for MOUD in this study, induction requires the participant to be in a 
state of withdrawal before treatment can begin. It is therefore expected that in the majority of 
cases, participants will not be ready to begin MOUD until at least one day after Enrollment. But 
there may be cases in which a participant will be ready to be induced at Enrollment and MOUD 
will begin that day. This flexibility-- to start MOUD either at Enrollment or aa later clinical care 
visit-- is reflected in the schedule of evaluations (Appendix I).  
 
Similarly, it is expected that most participants in the intervention arm will not initiate ART or 
PrEP until after they are initiated on MOUD, at a later clinical care visit . However, there may be 
instances where initiating ART or PrEP immediately is a high priority for a participant and is 
supported by the clinician. In such cases ART or PrEP may be started at the Enrollment Visit. 
This flexibility in when to start ART or PrEP is reflected in the schedule of evaluations 
(Appendix I). We also anticipate that some participants may already be on ART, in which case 
peer navigation will support continuation of ART and HIV care at their existing provider.  
 
As part of enrollment procedures, staff will assess potential participants for COVID-19. Persons 
who are otherwise eligible to be enrolled will have enrollment deferred if they are suspected to 
have COVID-19, until they meet the criteria for discontinuation of isolation per CDC guidelines 
or applicable local guidelines. Depending on the length of deferral, screening procedures may 
have to be repeated to establish eligibility. Enrollment may need to be paused if COVID-19 
conditions dictate responses such as shelter-in-place in the cities where the study is being 
implemented. 
 
6.3 
Clinical Care and Navigation Visits Between Enrollment and Week 26 
 
Between the Enrollment Visit and the week 26 visit, participants in both arms will engage with 
study staff regularly for peer navigation. Expectations for the frequency of visits between 
participants and navigators will be spelled out in the SSP manual, but the actual timing, length 
and content of navigation visits for any given participant will be determined by participant needs 
rather than a fixed study visit schedule. 
 
In the intervention arm, participants will be seen in the mobile unit as needed to provide 
medication and to manage adherence to MOUD and ART or PrEP, and to address other 
participant health needs. These will be considered “care visits.”   
 
Intervention arm participants who have a reactive/positive test at a clinical care visit and are 
confirmed to have HIV based on testing at the Confirmatory visit will follow the Schedule of 
Events for participants who are living with HIV (see Appendix IA) at all future visits.  
 
If a participant has a documented positive HIV status outside of the study (hospital record, for 
example) after enrollment and before the week 26 visit, confirmatory testing should occur at a 
clinical care visit (see Section 6.6). 

 
 
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Control arm participants who are first diagnosed with HIV outside of the study will be allowed to 
come to the mobile unit before week 26 for an interim visit for HIV testing and/or Confirmatory 
visit (see Section 6.6). If HIV infection is confirmed at that study visit, these participants will 
follow the Schedule of Events for participants who are living with HIV (Appendix IA) at all 
future visits. 
 
These same procedures will be followed for participants who seroconvert between the week 26 
and week 52 visits. Please refer to Section 6.6 and the SSP Manual for further information.  
 
For navigation visits, the timing, length, frequency and care provided during clinical visits will be 
determined by the needs of the participant and not by a fixed study schedule. As intervention arm 
participants near the end of the 26 weeks, their peer navigator will facilitate their transition to 
community-based services. 
 
Select data will be captured into the study database from peer navigation and clinical care visits to 
document and describe the intervention as delivered (particularly the “dose” of navigation 
delivered in each arm, to assist with interpretation of primary and secondary outcomes), to assist 
the study team in monitoring fidelity and comparability of delivery of the intervention during the 
period of study conduct and to enable the study team to make real-time improvements to 
intervention delivery during execution of the trial. 
 
It is anticipated that the COVID-19 pandemic will require accommodations to how participant 
visits with peer navigators or on the mobile unit can be conducted. Enhanced infection control 
procedures such as wearing of personal protective equipment (PPE), reduced density of persons 
allowed in and around the unit, and thorough disinfection of the unit between participants will be 
undertaken. Participants will be assessed for COVID-19 before beginning a visit and deferred 
from continuing if COVID-19 is suspected. Guidelines for resumption of in-person visits will be 
per CDC and/or local guidelines for discontinuation of isolation. CDC and local guidelines will 
be followed regarding quarantine of staff with potential exposure to persons with known or 
suspected COVID-19. If the intensification of the COVID-19 pandemic prevents routine in-
person clinical care or navigation visits between staff and participants, the study team will use 
available tools and approaches to continue to provide services to participants, as possible.  
 
As of the time of the writing of this protocol, DEA regulations allow participants to be prescribed 
buprenorphine over the telephone with home induction. If participants have mobile phones, sites 
may provide peer navigation and clinical care via telemedicine, with appropriate training of peer 
navigators and clinicians in these approaches. Uninterrupted provision of medications for 
MOUD, ART and PrEP may be instituted through in-person delivery that maintains social 
distancing while insuring delivery to the prescribed recipient. Measures will be taken to ensure 
that participants taking ART or PrEP are receiving appropriate clinical follow-up, including 
periodic laboratory testing.  
 
6.4 
Week 26 Visit 
 
The week 26 visit marks the end of the intervention period for both arms of the study.  Biological 
samples obtained at this visit will be used for assessment of primary and secondary objectives.  
For participants in both arms, peer navigation will end at 26 weeks; from this point forward, 
participants will be responsible for obtaining care from community-based services without further 
assistance from study staff.   
 

 
 
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Blood, urine and swabs will be collected from participants for laboratory assessment of HIV 
infection (in those not previously confirmed to have HIV), ART adherence or PrEP use, STIs, 
SARS-CoV-2 infection, substance use and, for those with a positive HCV antibody test at 
enrollment, HCV RNA.  Results from point-of-care testing (e.g., for HIV and pregnancy) will be 
provided to the participant at the visit. For all other medical diagnoses or conditions identified 
during or after the visit, referral to community-based services will be provided.  The site will 
attempt to provide any laboratory results obtained after the visit to the participant and to refer the 
participant to obtain any medical care/treatment indicated by these results from community-based 
services. 
 
Although the mobile unit will be prioritized for Screening, Enrollment and provision of 
intervention services, this research visit may take place in the mobile unit, or at a community 
clinic or CRS. Conduct of these visits may take place at appropriate locations in the community 
where participants will feel comfortable, such as the CRS or an affiliated clinic or community 
space. Should concerns about the COVID-19 epidemic make conduct of in-person visits 
impossible, week 26 visits may be conducted using telephone/internet visits as scheduled, with 
collection of biospecimens at a different date. The study team would make every effort in such a 
situation to minimize the disruption to the study schedule, to collect as much data as possible 
while prioritizing the health of participants and staff. 
 
6.5 
Week 52 Visit 
 
The week 52 visit marks the end of the period on study for all participants.  Samples obtained at 
this visit will be used for assessment of secondary objectives.  Blood, urine and swabs will be 
collected from all participants for laboratory assessment of HIV (in those not previously 
confirmed to have HIV), ART adherence or PrEP use, STIs, SARS-CoV-2, HCV (for those 
negative at Enrollment), substance use and HCV RNA (for those with a prior positive HCV 
antibody test).  Test results available during the visit will be provided to the participant. The site 
will attempt to provide any clinically important laboratory results obtained after the visit to the 
participant (e.g., confirmed HIV, STIs, HCV; results of HIV drug restistance testing) with referral 
to community-based services.  As with the week 26 visit, this research visit may take place in the 
mobile unit, community clinic or CRS.  
 
As described for the week 26 visit, week 52 visits need to be in-person visits. Also as described 
for week 26 visits, concerns related to the COVID-19 epidemic might necessitate making 
accommodations to complete the week 52 visits using on-line and distance procedures to protect 
the health of participants and staff, with every attempt to minimize the effects of deferred visits 
on study data and subsequent interpretation of endpoints. 
  
6.6 
Procedures for participants who do not have HIV at Enrollment and have a 
reactive or positive HIV test after study enrollment 
 
A participant who has a reactive or positive HIV test at a clinical care visit, interim visit, week 
26, or week 52 visit must have a Confirmatory visit (see Appendix IB). A Confirmatory visit 
must also be performed if the participant or a health care provider provides written documentation 
of HIV test results from testing performed outside of the study that indicate a positive HIV status 
(see SSP Manual for documentation requirements). Prior to documentation of HIV positive status 
at an in-study Confirmatory visit, participants should continue to be followed using the Schedule 
of Events for participants who were without HIV at Enrollment. Procedures at these visits 

 
 
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(described in Appendix IA) may be combined with procedures for the in-study Confirmatory visit 
(described in Appendix IB) in the following three scenarios: 
(1) Written documentation of positive HIV status obtained outside of the study was first 
provided to study staff at an interim or clinical care visit, but the participant did not return for 
the in-study Confirmatory visit before the Week 26 or Week 52 visit, or 
(2) Written documentation of positive HIV status obtained outside of the study is first 
provided to study staff at the time of the Week 26 or Week 52 visit, or 
(3) The participant tested positive for HIV in the study at an interim or clinical care visit but 
did not return for the in-study Confirmatory visit before the Week 26 or Week 52 visit 
 
Participants who report that they were diagnosed with HIV outside of the study but cannot 
provide written documentation of that testing will follow standard study procedures and will have 
HIV testing performed in the study at two study visits conducted on separate dates. 
 
In all cases, Confirmatory visits must follow procedures shown in Appendix IB. 
 
If the testing from the Confirmatory visit indicates a positive HIV status, participants will follow 
the Schedule of Study Visits and Procedures for participants who are living with HIV at all future 
visits (see Appendix IA). If the testing performed at the Confirmatory visit does not confirm the 
HIV positive result, notify the Site PI and HPTN LC and schedule the participant for another visit 
for HIV testing and HIV counseling. Please refer to the SSP Manual for further information. 
 
6.7 
Implementation Evaluation and Cost-Effectiveness Data Collection 
Procedures 
 
Implementation Evaluation Procedures. We will use a mixed methods, theory-driven (PRISM)  
conceptual model to determine factors that affect delivery of integrated care using a mobile unit, 
supported by peer navigation, successfully and with fidelity in different US settings co-affected 
by opioid and HIV epidemics. Quantitative and qualitative data will identify with depth and 
precision the multi-level factors (i.e. patient, healthcare organization and personnel, community 
environment, structural) that correspond with the fidelity of implementation, effectiveness, and 
dissemination of integrated health care delivered in a mobile unit including responding to the 
impact on service delivery imposed by COVID-19. To achieve the implementation evaluation 
objectives, site-level data will be collected across three timepoints: (a) the pre-implementation 
phase of the study to document baseline status of the local opioid epidemic, the local HIV 
epidemic, the policies and agencies aligned to address these epidemics through landscape data 
collection of the site, and to identify factors that may influence the delivery of integrated health 
services via mobile unit and peer navigation (e.g. site-level access to quality addiction, HIV, and 
primary care for PWID), (b) the implementation phase of the study to collect data on factors that 
promote or impede the implementation of the intervention (in the mobile unit and for peer 
navigation) to inform site-level refinements and processes that may influence primary and 
secondary outcomes, and (c) we will use the findings in the data analytical plan to understand 
what influence implementation factors may have had on the primary and secondary outcomes.  
 
Data sources.  
Data for implementation evaluation will be collected at each study site over the course of the 
study, and reviewed monthly by the implementation evaluation team as part of an iterative 
analysis process. Data will be drawn from three primary sources: 
 
1. Protocol activities involved in the conduct of the study (i.e., routine meetings, fidelity 
monitoring, and efficacy evaluation procedures). These data will be routinely collected by 

 
 
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study staff involved with documenting (i) the process and outcomes of study-related 
meetings, (ii) capturing participant data, and (iii) documenting the conduct of the study.  
• 
A standing agenda item or specific prompts related to the implementation evaluation will 
be added to existing community engagement meetings and protocol site and cross-site 
meetings with study staff. Relevant responses will be flagged in meeting minutes or 
transcripts and field notes from these meetings for analysis. 
• 
Participant records and encounter forms, quality assurance and quality control (QA/QC) 
activities conducted by staff, and standardized checklists for assessing fidelity metrics in 
clinical encounters with providers and linkage to services by peer navigators will be 
reviewed and summarized at the site level for analysis. 
• 
Sociodemographic data (e.g. age, gender, race) on PWID at each site will be obtained 
from published reports or service records from regularly-available services (i.e. MOUD, 
ART, PrEP, and harm reduction) and for PWID who are screened and enrolled into the 
study protocol. 
 
2. In-depth interviews with PWID, as well as providers of integrated health care in the mobile 
unit and key community stakeholders. Interviews will be conducted by field staff trained in 
qualitative methods either in-person or over the telephone/internet and will be recorded. We 
anticipate our qualitative sampling framework (see Table 3) will generate ~39 in-depth 
interviews per study site (195 interviews total) to be conducted approximately 6 months after 
the start of the study implementation phase while the study is still in the field. 
 
Table 3- Sampling frame for in-depth qualitative interviews 
 
Source 
Selection strategy 
Sample size per site 
PWID 
~20% of PWID enrolled at each study site will be 
purposefully sampled. Sampling criteria will aim to select 
PWID enrolled in the study who are demographically 
representative of the local injection community in terms of 
age, gender, race, and HIV status. 
n=17 
Mobile Unit 
staff 
Staff who support integrated healthcare delivered in the 
mobile unit at each site will be sampled. This includes 
clinicians delivering MOUD and ARV treatment (n=2), 
peer navigators (n=3), and frontline staff routinely engaged 
with PWID recruitment and tracking activities (n=2) 
n=7 
Community 
stakeholders 
Key community stakeholders will be identified through the 
study’s formative landscape analysis to map community 
assets and gaps in the pre-implementation phase. This 
process will identify regularly available MOUD, HIV, 
harm reduction, and primary care services at each study 
site. Through this process we will invite up to 3 
stakeholders from each of the following service domains 
who would be involved in the coordination and future 
sustainability of integrated health care and peer navigation: 
HIV services (n=3), MOUD services (n=3), harm reduction 
services (n=3), primary care (n=3), and public health 
officials (n=3). 
n=15 

 
 
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3. Ethnographic observations of the surrounding environment and delivery of integrated 
healthcare and peer navigation at each study site. These data will be captured by experienced 
staff trained in the conduct of qualitative methods. 
• 
Landscape analysis conducted in the pre-implementation phase of the study will 
document the availability of MOUD, HIV, harm reduction, and primary care services 
regularly available at local clinics at each study site, how these services were impacted by 
COVID-19, as well as structural determinants of existing service delivery (e.g. policy 
regulating the distribution of unused needles, public health infrastructure) to ensure 
participant recruitment and intervention delivery occur in the local areas with the greatest 
need. 
• 
Ecological assessments will document factors in the community and mobile care-delivery 
environments that may affect recruitment, retention and delivery of services in both arms. 
These brief assessments will be routinely conducted throughout the implementation phase 
to guide real-time improvements and refinements in the conduct of the study and to 
document process-oriented factors that may affect primary and secondary outcomes. 
 
Cost-Effectiveness Procedures  
No participant-oriented procedures are required to complete the planned cost-effectiveness 
analyses (CEA). Data sources for CEA will include estimates of effectiveness from modeling, 
and estimates of costs to include (1) costs of all commodities used in the intervention; (2) labor 
costs for intervention workers; (3) intervention startup costs; (4) average time participants spent 
with intervention including transportation / staff time / time for referrals; (6) local wages of target 
population; (5) rent; (6) maintenance; (7) volunteer activities; (8) user fees; (9) value of donated 
goods and services; and (10) other relevant costs, including training of providers and mobile unit 
fuel costs.   
 
Cost estimates will incorporate data from time-and-motion (TAM) studies. These studies will be 
conducted at each study site during the implemenation phase at two timepoints: soon after study 
initiation and again when the participants have begun to transition from integrated health care 
delivered on the mobile unit to community-based services. These data will document the number 
of staff and number of staff hours involved in delivering the intervention to participants receiving 
(i) integrated healthcare on the mobile unit, and (ii) transitioning PWID from the mobile unit to 
community-based care via peer navigation. TAM studies will collect data during staff interactions 
with participants, but will not entail collection of participant-specific data. 
 
6.8 
Study Visit Windows 
 
For each required study visit, there is an allowable visit window specifying on which study days 
(post-enrollment) the visit is "allowed" to be completed. The allowable visit windows are 
contiguous between week 26 and week 52 and do not overlap. Within each allowable visit 
window, there is a target visit window and study visits should ideally be conducted within this 
window. These windows are outlined in Table 4 below. If more than one visit is necessary to 
complete all visit procedures, these could be completed during multiple days within the allowable 
visit window. For the enrollment visit, the date of randomization is day 0. If necessary, 
enrollment visit procedures may take place at more than one visit (a “split visit”). Sites are 
strongly encouraged to complete a split enrollment visit within 10 days of the first enrollment 
visit encounter, but all procedures and randomization must be completed by 30 days after 
screening (as defined in the SSP). If the potential participant is not randomized within 30 days of 
screening, they will be an enrollment failure and will need to be re-screened if the site wishes to 
enroll them. Potential participants will only be randomized once all procedures expected for the 
day of enrollment (see SSP) have been completed.  

 
 
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Table 4: Study Visit Windows 
Visit 
Target 
Visit Day 
Target Visit 
Window 
Allowable Visit Window 
Screening 
 
 
Up to 30 days before enrollment 
Enrollment 
Day 0 
Split visit 
completed 
within 10 days 
Randomization within 30 days of 
screening 
Week 26 
Day 182 
Day 168 - 210 
Day 126 - 308 
Week 52 
Day 365 
Day 351 - 393 
Day 309 – until the study is closed 
at the site 
 
7.0 
SAFETY MONITORING AND SERIOUS ADVERSE EVENT REPORTING 
 
7.1 
Adverse Event Definition and Reporting 
 
In this study, the only drugs that will be dispensed or prescribed will be US FDA-approved 
medications for treatment or prevention of OUD, HIV, and STIs and prescriptions for 
contraceptives, primary care concerns, and chronic conditions, if indicated. There are no 
investigational products in this protocol. Therefore, monitoring and reporting of unanticipated 
treatment-related risks will be limited to the following: Suspected Unexpected Serious Adverse 
Reactions (SUSARs) to study products (those drugs provided centrally by the study for ART or 
PrEP)will be collected and reported in an expedited manner to the DAIDS Adverse Event 
Reporting System (DAERS) (https://rsc.niaid.nih.gov/clinical-research-sites/manual-expedited-
reporting-adverse-events-daids). 
 
Adverse events (AEs) that study staff become aware of will be recorded in source documentation 
and will be assessed for seriousness. Non-serious AEs will not be reported in the study database 
and referrals for care will be provided as necessary. Serious adverse events (SAEs) are those AEs 
that result in one or more of the following outcomes: 
• 
Death 
• 
A life-threatening (i.e., an immediate threat to life) event 
• 
Requires in-patient hospitalization or prolongation of an existing hospitalization 
• 
A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• 
A congenital anomaly/birth defect 
• 
A medically important 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 
 
Examples of SAEs that can be expected to occur during this study include deaths (e.g., fatal 
overdoses or other addiction-related deaths) and life-threatening events requiring intervention 
(e.g. overdoses/overdose reversals). Study participants will be provided contact information and 
instructed to contact the study clinician to report any SAEs they may experience. For life-
threatening events, they will also be instructed to seek immediate emergency care.  
 
All SAEs will be entered into the study data base, with appropriate levels of documentation and 
notification of the IRB and sponsors. SAEs will be assessed for relatedness to study product(s) 
(centrally-supplied ART or PrEP) by the site study clinician. SAEs are included in reports to the 
Study Monitoring Committee (SMC) for review.  

 
 
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In addition to expedited reporting of SUSARs to DAIDS, it will be important that site teams 
routinely review clinical events that occur among their participants and alert study leadership if 
any individual incidents or trends raise concern about conduct of the study at that site or raise the 
possibility of serious or unanticipated risks to study participants posed by the trial. If such a risk 
is identified, by either site staff or other study team members, it will be reported and responded to 
as described below in Section 7.4. 
  
7.1.1 Grading Severity of Events 
 
The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, 
Corrected Version 2.1, July 2017, will be used for determining and reporting the severity of 
adverse events. The DAIDS grading table is available on the DAIDS Regulatory Support Center 
(RSC) website at https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-
tables. 
 
7.1.2 Reporting Timeframe 
 
The reporting period for all participants is from the time of enrollment through when a participant 
exits the study. However, any SAEs that come to the attention of the investigator after a 
participant has exited the study, but before the database has been locked, will also be reported in 
the same manner as when the participant was on study. 
 
7.1.3 SUSAR Assessment 
 
An SAE with onset after exposure to study product(s) (centrally-supplied ART or PrEP) will be 
reported as a SUSAR if the SAE is deemed both related and unexpected. Assessments for 
relatedness and unexpectedness shall be made by a site study clinician. SUSAR assessment will 
be as specified in Version 2.0, January 2010 (or most current version) of the Manual for 
Expedited Reporting of Adverse Events (EAE) Reporting to DAIDS.  
 
7.1.4 AE Reporting to DAIDS 
 
For all SUSARs as defined above, DAERS, an internet-based reporting system, must be used for 
EAE reporting to DAIDS. In the event of system outages or technical difficulties, EAEs may be 
submitted via the DAIDS EAE form. This form is available on the RSC website:  
https://rsc.niaid.nih.gov/clinical-research-sites/paper-eae-reporting.  For questions about DAERS, 
please contact DAIDS-ES at DAIDS-ESSupport@niaid.nih.gov. Site queries may also be sent 
with the DAERS application itself. For questions about EAE reporting, please contact the RSC at 
DAIDSRSCSafetyOffice@tech-res.com. 
 
7.1.5 EAE Reporting to DAIDS 
Requirements, definitions and methods for expedited reporting of adverse events are outlined in 
Version 2.0 of the DAIDS EAE Manual, which is available on the DAIDS RSC website at 
https://rsc.niaid.nih.gov/clinical-research-sites/manual-expedited-reporting-adverse-events-daids. 
The DAIDS Adverse Experience Reporting System (DAERS), an internet-based reporting 
system, must be used for EAE reporting to DAIDS. In the event of system outages or technical 

 
 
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difficulties, EAEs may be submitted using the DAIDS EAE Form. This form is available on the 
DAIDS RSC website at https://rsc.niaid.nih.gov/clinical-research-sites/paper-eae-reporting. 
For questions about DAERS, please contact NIAID CRMS Support at 
CRMSSupport@niaid.nih.gov. Please note that site queries may also be sent from within the 
DAERS application itself. 
For questions about expedited reporting, please contact the DAIDS RSC Safety Office at 
(DAIDSRSCSafetyOffice@tech-res.com). 
7.1.5.1 EAE Reporting Requirements for the Study 
The SUSAR Reporting Category, as defined in Version 2.0 of the DAIDS EAE Manual, will be 
used for this study. 
The study products for which expedited reporting are required are centrally-supplied PrEP or 
ART: 
PrEP 
• 
Emtricitabine/tenofovir disoproxil fumarate 200mg/300mg (FTC/TDF, Truvada®) 
• 
Emtricitabine/tenofovir alafenamide 200mg/25mg (FTC/TAF, Descovy®) 
ART 
• 
Bictegravir/emtricitabine/tenofovir alafenamide 50mg/200mg/25mg (BIC/F/TAF, 
Biktarvy®) 
In addition to the SUSAR Reporting Category identified above, other adverse events that must be 
reported in an expedited manner are abnormal pregnancy outcomes. 
7.1.5.2 Grading Severity of EAEs 
The most current Division of AIDS Table for Grading the Severity of Adult and Pediatric 
Adverse Events (DAIDS AE Grading Table) is used and is available on the DAIDS RSC website 
at https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables.  
7.1.5.3 EAE Reporting Period 
The EAE reporting period for this study is as per the DAIDS EAE Manual.  
After the protocol-defined EAE reporting period, unless otherwise noted, only SUSARs as 
defined in Version 2.0 of the DAIDS EAE Manual will be reported to DAIDS if the study staff 
become aware of the events on a passive basis (from publicly available information).· Abnormal 
pregnancy outcomes should be followed until the final outcome can be determined. even after the 
participant is off study, up until the point that the study database is closed. 
7.2 
Social Impact Reporting 
 
It is possible that participants' involvement in the study could become known to others, and that a 
social impact may result (participants could be perceived as having HIV or at high risk for 
acquiring HIV or could be subject to stigma related to their HIV status or their use of injection 

 
 
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drugs). For example, participants could be treated unfairly, or could have problems accessing 
work or social benefits or being accepted by their families and/or communities. A social impact 
that is reported by the participant and judged by the IoR/designee to be serious or unexpected will 
be reported to the IRB at least annually, or according to the IRB’s requirements. Social impacts 
will be collected and submitted to the study database during regular visits. In the event that a 
participant reports a social impact, every effort will be made by study staff to provide appropriate 
responses and counseling to the participant as necessary, and/or referral to appropriate resources 
for the safety of the participant. Each site will provide such responses and counseling in 
accordance with standardized guidance in the SSP Manual. While maintaining participant 
confidentiality, study sites may engage their community advisory board (CAB) in exploring the 
social context surrounding instances of social impacts, to minimize the potential occurrence of 
such an impact. 
 
It will be important that site teams routinely review social impacts that occur among their 
participants and alert the CMC, including the DAIDS Medical Officer, if any individual impacts 
or trends in impacts raise concern about conduct of the study at that site or raise the possibility of 
serious or unanticipated risks to study participants posed by the trial. See Section 7.4 below for 
further information about how possible serious or unanticipated risks will be reported and 
addressed.  
 
Prior to study initiation, each site will conduct a “landscape analysis” of the local environment, 
including local laws, policies and practices affecting PWID. As part of this analysis, the site team 
will determine the degree of risk (of arrest, incarceration, physical harm, unwanted disclosure of 
drug use, of other harms) facing PWID in that location and whether study participation may put 
PWID at greater risk for harm. Each site will also enact a strategy to mitigate these risks and 
build support for the study prior to implementation and during study conduct. A key component 
of this work will be engagement of local stakeholders such as government officials, law 
enforcement personnel, public health departments, local medical providers, and community 
leaders to explain the study and obtain support for the work.  
 
7.3 
Other Unanticipated Problems 
 
In addition to SAEs, SUSARs and social impacts, other unanticipated problems may arise in the 
conduct of this research. An unanticipated problem is any incident, experience, or outcome that 
meets all of the following criteria: 
 
• 
Unexpected (in terms of nature, severity, or frequency) given (a) the research procedures 
that are described in the protocol-related documents, such as the IRB-approved research 
protocol and informed consent document; and (b) the characteristics of the subject 
population being studied; 
• 
Related or possibly related to participation in the research (possibly related means there is 
a reasonable possibility that the incident, experience, or outcome may have been caused 
by the procedures involved in the research); and 
• 
Suggests that the research places study participants or others at a greater risk of harm 
(including physical, psychological, economic, or social harm) than was previously known 
or recognized.  
All unanticipated problems that meet the three criteria above will be reported to the IRB and to 
the CMC as described in Section 7.44 below. 
 
 
 

 
 
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7.4 
Safety Monitoring and Clinical Data Review 
 
A multi-tiered safety review process will be followed for the duration of this study. The study site 
investigators are responsible for the initial identification, evaluation and reporting of safety 
concerns at the participant or site level. Sites are required to have detailed SOPs describing 
methods for identifying, reporting and managing serious or unanticipated safety concerns raised 
by SAEs, social impacts or other unanticipated problems.  
 
When sites identify a potentially serious or unexpected risk or problem, they will report it to the 
CMC. The CMC will work together with appropriate entities such as the site investigators, LOC 
CRM, SDMC Biostatistician, SDMC Clinical Coding and Safety Staff, HPTN LC, DAIDS 
personnel (in addition to the Medical Officer on the CMC) and other study team members  
as appropriate to evaluate the risk or problem and determine an appropriate response. The 
timelines and mechanisms for reporting and responding to such events will be described in the 
SSP. 
 
The study team will use regularly scheduled conference calls during the period of study 
implementation to address safety concerns or unanticipated problems that have been identified. 
Additional ad hoc calls will be convened if required. 
 
Participant safety data is also monitored by the SDMC Clinical Safety staff, who review 
incoming safety data for completeness and consistency on an ongoing basis. Events identified as 
questionable, inconsistent, or unexplained will be queried for verification.  
 
This study also will be monitored by an HPTN SMC, which will meet at least annually to review 
safety and efficacy data. More frequent or ad hoc reviews of safety data may be conducted by the 
SMC as needed. The SMC may make recommendations based on review of safety and efficacy 
data. 
 
7.5 
Pregnancy 
 
The CMC must be notified of any pregnancies identified at Enrollment or that occur among 
participants on study.  
 
All pregnancies should be followed until the final outcome can be determined. The appropriate 
case report form for pregnancy outcome and obstetric medical complications at the end of the 
pregnancy may be completed, even after the participant is off study, up until the point that the 
study database is closed. As noted in Section 7.1.5.1, all abnormal pregnancies outcomes will be 
reported to DAIDS in an expedited manner.  
 
Participants should be advised that not all contraceptive choices can prevent HIV transmission. 
Study participants who are sexually active with partners who are living with HIV or whose HIV 
status is unknown should be advised that they need to consider effective strategies for reducing 
the risk of HIV transmission. Participants should be instructed to discuss contraceptive choices 
and HIV risk reduction methods with their health care provider.  
 
Pregnancies that occur on study among participants taking ART or PrEP should be reported to 
The Antiretroviral Pregnancy Registry. More information is available at www.apregistry.com. 
Phone: 800-258-4263; Fax: 800-800-1052. Intrapartum complications and/or pregnancy outcome 

 
 
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will be recorded to The Antiretroviral Pregnancy Registry as well as on study case report forms, 
if possible. 
 
8.0 
STATISTICAL CONSIDERATIONS 
 
8.1 
Review of Study Design 
 
This is a two-arm, controlled, individually randomized, open label study that will include PWID 
living with HIV and PWID without HIV from five major cities in the US. The purpose of this 
study is to determine whether providing 26 weeks of peer navigation with “one stop” integrated 
services in a mobile unit – particularly MOUD for OUD and HIV treatment and prevention 
medications -- to PWID with OUD will improve uptake and adherence to MOUD and uptake and 
adherence to ART or PrEP, compared to 26 weeks of peer navigation to community-based 
services. This trial will likely be conducted in the context of a significant COVID-19 epidemic 
which may reach peak levels in the five study cities at different times and may have varying 
levels of impact in each city. The individually randomized design used in this study (as compared 
to a cluster-randomized design) will protect against confounding that could arise if cities in one 
arm of the trial were by chance more affected by the epidemic than cities in the other arm. 
 
8.2 
Endpoints 
8.2.1 Primary Endpoints 
 
Consistent with the primary study objective to evaluate whether the intervention improves use of 
MOUD, and increases use of PrEP among people without HIV, as measured at 26 weeks, the 
following endpoints will be assessed: 
• 
Documented current use of MOUD. At the Week 26 visit: 
1.  Alive 
2. Retained 
3. Biological evidence of MOUD (any detectable medications) 
4.  A MOUD prescription current at the week 26 visit or proof of current receipt of 
MOUD from a clinic that does not provide individual MOUD prescriptions (e.g., 
methadone clinics) 
• 
Among participants who were without HIV at enrollment: alive, retained, without HIV, 
with detectable PrEP drugs in dried blood spot (DBS) samples at the week 26 visit 
 
8.2.2 Secondary Endpoints 
 
Consistent with secondary study objectives (1a-c), to evaluate whether the intervention improves 
use of MOUD, increases rates of viral suppression among people living with HIV, and increases 
use of PrEP among those without HIV, compared to the active control condition, the following 
endpoint(s) will be assessed: 
• 
Documented current use of MOUD: alive, retained, with biological evidence of MOUD 
(any detectable medications) at the week 52 visit and a MOUD prescription current at 52 
weeks after enrollment or proof of current receipt of MOUD from a clinic that does not 
provide individual MOUD prescriptions (e.g., methadone clinics) at the week 52 visit 
• 
Documented use of MOUD during the study: a MOUD prescription documented during 
the 52 weeks of study follow-up or proof of current receipt of MOUD from a clinic that 
does not provide individual MOUD prescriptions (e.g., methadone clinics) during the 52 
weeks of study follow-up 

 
 
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• 
Among participants living with HIV at enrollment: alive, retained, and virally suppressed 
(VL <200 copies/mL) at the week 52 visit 
• 
Among participants without HIV at enrollment: alive, retained, HIV negative, with 
detectable PrEP drugs in DBS at the week 52 visit 
• 
Among participants without HIV at enrollment: alive, retained, HIV negative, with 
protective levels of PrEP drugs in DBS samples at the week 26 and 52 visits 
 
Consistent with secondary endpoint (1d) to evaluate whether the intervention reduces opioid and 
polysubstance use at 26 and 52 weeks, compared to the active control condition, the following 
endpoint(s) will be assessed: 
• 
Alive, retained, and no opioids (natural or synthetic), stimulants (methamphetamine, 
cocaine) or benzodiazepines detected in urine samples at the week 26 and 52 visits 
 
Consistent with secondary study objective (1e) to evaluate whether the intervention reduces 
prevalence of bacterial STIs, compared to the active control condition, the following endpoint(s) 
will be assessed: 
• 
Alive, retained and no evidence of gonorrhea, chlamydia, or new or recurrent syphilis 
infection detected at the week 26 and 52 visits 
 
Consistent with secondary study objective (1f) to evaluate whether the intervention reduces the 
rate of fatal and non-fatal overdose events by 26 and 52 weeks, compared to the active control 
condition, the following endpoint(s) will be assessed: 
• 
Death, with overdose as cause 
• 
Self-report of non-fatal overdose, collected at week 26 and 52 visits 
 
Consistent with secondary study objective (1g) to assess whether the intervention increases the 
proportion of participants with undetectable HCV RNA among those with chronic HCV infection at 
enrollment, compared to the active control condition, the following endpoint(s) will be assessed: 
• 
Undetectable HCV RNA at the week 26 and 52 visits among participants with chronic 
HCV at enrollment 
 
Consistent with secondary study objective (1h) to evaluate whether the intervention reduces HCV 
incidence, compared to the active control condition, the following endpoint(s) will be assessed: 
• 
HCV antibody positive at the week 52 visit among participants who are HCV antibody 
negative at enrollment 
 
Consistent with secondary study objective (1i) to evaluate participants living with HIV at 
enrollment, the following endpoints will be assessed: 
• 
Alive, retained, and virally suppressed (VL<200 copies/mL) at the week 26 visit  
 
Consistent with secondary study objective (2) to evaluate whether 26 weeks of “one stop” 
integrated health services delivered in a mobile health delivery unit, supported by peer 
navigation, increases MOUD use, viral suppression, and PrEP use at 26 and 52 weeks compared 
to enrollment, the following endpoint(s) will be assessed: 
• 
In the intervention arm, change over time in the use of MOUD during the study, 
comparing documented use of MOUD (biological evidence of MOUD - any detectable 
medications - and a current MOUD prescription or proof of current receipt of MOUD 
from a clinic that does not provide individual MOUD prescriptions (e.g., methadone 
clinics)) at 26 and 52 weeks to documented use of MOUD at enrollment.  MOUD use is 

 
 
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assumed to be zero at enrollment due to study exclusion criteria. Follow-up endpoints 
will be defined as alive, retained, and having documented MOUD use. 
• 
Among participants living with HIV at enrollment: change over time in the proportion of 
people with viral suppression (VL<200 copies/mL), comparing 26 and 52 weeks to 
enrollment. Follow-up endpoints will be defined as alive, retained, and virally 
suppressed. 
• 
Among participants who were without HIV at enrollment: change over time in the 
proportion of people with detectable PrEP drugs in DBS at 26 and 52 weeks compared to 
enrollment. Follow-up endpoints will be defined as alive, retained, and having detectable 
PrEP. 
 
Consistent with secondary study objective (3) to evaluate whether 26 weeks of peer navigation to 
similar health services available at community-based agencies increases MOUD use, viral 
suppression, and PrEP use at 26 and 52 weeks compared to enrollment, the following endpoint(s) 
will be assessed: 
• 
In the active control arm, change over time in the use of MOUD during the study, 
comparing documented use of MOUD (biological evidence of MOUD - any detectable 
medications - and a current MOUD prescription or proof of current receipt of MOUD 
from a clinic that does not provide individual MOUD prescriptions (e.g., methadone 
clinics)) at 26 and 52 weeks to documented MOUD use at enrollment.  MOUD use is 
assumed to be zero at enrollment due to study exclusion criteria. Follow-up endpoints 
will be defined as alive, retained, and having documented MOUD use. 
• 
In the active control arm among participants living with HIV at enrollment: change over 
time in the proportion of people with viral suppression (VL<200 copies/mL), comparing 
26 and 52 weeks to enrollment. Follow-up endpoints will be defined as alive, retained, 
and virally suppressed. 
• 
In the active control arm among participants who were without HIV at enrollment: 
change over time in the proportion of people with detectable PrEP drugs in DBS at 26 
and 52 weeks compared to enrollment. Follow-up endpoints will be defined as alive, 
retained, and having detectable PrEP. 
 
Consistent with secondary study objective (4) to assess the prevalence of SARS-CoV-2 
seropositivity at baseline, 26 and 52 weeks, the following endpoint will be assessed: 
• 
Laboratory evidence of antibodies to SARS-CoV-2  
 
Consistent with secondary study objective (5) to document the impact of the COVID-19 epidemic 
on participants’ experiences of seeking, obtaining and/or maintaining health services, housing, 
food security and drugs, the team will: 
• 
Document self-reported subjective experiences linked to COVID-19 when seeking 
MOUD, HIV care (ART, PrEP), STI testing and treatment, hepatitis screening and 
treatment, primary care, and harm reduction counseling. 
 
Consistent with implementation objectives to evaluate implementation of “one-stop” integrated 
health services using a mobile unit, supported by peer navigation, across study sites to identify 
mechanisms at multiple levels to: 
 
(6a) Guide real-time improvements and refinement in the conduct of the study to ensure primary 
and secondary outcomes are met with fidelity, the team will: 

 
 
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• 
Describe the local opioid and HIV epidemics and contextual facilitators and barriers that 
influenced the delivery of integrated services at each study site, and site-specific 
refinements used to maintain fidelity to service delivery. 
 
(6b) Examine the quality and process of services delivered in each study arm, particularly as these 
affect primary and secondary outcomes, the team will:  
• 
Describe contextual factors that may have influenced the quality and process of 
delivering services in each study arm, including the initiation into and transition out of 
mobile service delivery. 
 
(6c) Develop evidence-based guidance for policymakers on the uptake and implementation of 
integrated health services using peer navigation and mobile health units in urban US regions to 
address HIV in PWID, the team will: 
• 
Describe policies and other external environmental factors that affected the uptake and 
implementation of integrated health services and peer navigation via mobile unit at each 
study site; informing how these services may be best implemented in other settings. 
 
(6d) identify factors that enhance or impede the delivery of integrated health services using a 
mobile unit, supported by peer navigation, on primary and secondary outcomes, including 
responding to the impact of COVID-19 on service delivery, the team will: 
• 
Characterize outcomes of implementing integrated health services via mobile unit across 
study sties that may affect the impact of the intervention arm on co-occurring treatment 
outcomes (MOUD, ART, PrEP) and how service delivery and outcomes may be impacted 
by COVID-19 outbreaks.  
 
Consistent with the secondary study objective (7a) to use mathematical modeling to estimate the 
effect of integrated health services delivered in a mobile unit, supported by peer navigation, on 
reducing HIV incidence in PWID and their sexual and injection partners, the following endpoints 
will be assessed: 
• 
Cumulative HIV incidence over one year for PWID with OUD without HIV in the 
intervention arm and the active control arm. This will be compared to HIV incidence 
under SOC informed by background markers via NHBS and other datasets where 
available. 
• 
Cumulative HIV transmission over one year from PWID with OUD in intervention arm 
and active control arm. This will be compared to estimated HIV transmission under SOC 
informed by background markers via NHBS and other datasets where available. 
• 
Number of HIV-related deaths averted in the intervention arm and the active control arm 
in comparison to the background HIV-related deaths from county death indices at 
baseline through week 52. 
• 
Changes in hepatitis and STI acquisition for PWID with OUD in the intervention arm 
and active control arm in comparison to the background rates of hepatitis and STI 
acquisition taken from departments of public health records at baseline through week 52 
• 
Quality-adjusted life years (QALYs) gained with the integrated strategy including non-
HIV benefits such as treatment and prevention of STIs, HAV, HBV, HCV, 
improvements in health, employment, overdose and criminal justice factors linked with 
improved retention in MOUD. 
 
Consistent with the secondary study objective (7b) to use mathematical modeling to estimate the 
cost-effectiveness of integrated health services provided in a mobile unit and supported by peer 
navigation, the following endpoints will be assessed: 

 
 
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• 
Estimated per-person incremental costs to provide the integrated strategy (intervention 
arm) and the limited intervention (active control arm) compared to SOC  
• 
Estimated treatment costs incurred (and averted, by preventing HIV) due to the 
integrated strategy and the limited intervention  
• 
Incremental cost effectiveness ratio (ICER) estimate  
o per incident HIV case 
o per HIV-associated death, and   
o per QALY gained comparing the intervention arm to the active control arm 
 
8.2.3 Process Endpoints 
 
Consistent with process objective (1) to assess the time to provide MOUD treatment, ART and 
PrEP in the intervention arm, the following endpoints will be assessed in the intervention arm: 
• 
Proportion of participants for whom MOUD was provided within 1 week of enrollment 
• 
Proportion of people living with HIV who were ART naïve or not currently on ART 
provided ART within 2 weeks of enrollment 
• 
Proportion of people without HIV who were provided with PrEP within 2 weeks of 
enrollment 
 
Consistent with process objective (2) to assess the proportion of participants in the intervention 
arm linked to community-based MOUD, ART and PrEP services at 26 weeks, the following 
endpoints will be assessed in the intervention arm: 
• 
Proportion of participants linked to MOUD at community-based services by the week 26 
visit 
• 
Proportion of people living with HIV linked to care for HIV at community-based services 
by the week 26 visit 
• 
Proportion of people without HIV linked to care for PrEP at community-based services 
by the week 26 visit 
 
8.3 
Sample Size 
 
Sample sizes are chosen to provide sufficient power for both the HIV-related and MOUD-related 
primary outcomes. By computing sample sizes based on each individual outcome separately and 
choosing the largest sample size needed for either outcome, high power is achieved for both 
individual outcomes. Prior work in PWID populations suggests that uptake of MOUD, ART, and 
PrEP in the control condition will likely be modest;39,40 we anticipate 25% uptake of MOUD, 
42.5% achieving viral suppression, and 5% uptake of PrEP in the control arm.  Sample sizes are 
computed to provide 90% power to detect a fifteen percentage point difference in the proportion 
of participants achieving success, assuming a 5% type-I error rate (two-sided). A sample of 400 
participants is needed to detect a 15-point difference in MOUD use (25% vs. 40%) between the 
active control and intervention arm at 26 weeks. Approximately 216 people without HIV would 
be needed to see a 15-point difference in PrEP uptake (5% vs. 20%). To cover both HIV and 
MOUD outcomes, 400 people without HIV will be needed. Approximately 10% of the study 
population is expected to be living with HIV – insufficient to accommodate a fully powered 
subgroup - but because this subgroup is expected to have very different rates of HIV-related 
success than the people without HIV subgroup, it will be important to analyze these participants 
separately. To assure 400 people without HIV, the target sample size will be augmented by 50 for 
a combined total of 450 participants, where 40-50 of those are expected to be people living with 
HIV.  
 

 
 
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8.4 
Accrual and Retention 
 
The study cohort (n=450) will be enrolled over the course of approximately 2.5 years and 
followed for 52 weeks each. This corresponds to a rate of approximately 15 new enrollees per 
month, or, approximately 3 new enrollees per month at each of the five sites.  
 
8.5 
Random Assignment/Study Arm Assignment 
 
Random treatment-arm allocation will occur at a 1:1 ratio, stratified by study site and by HIV 
status. Permuted-block randomization will be used to assure balanced groups within each study 
site and HIV-status subgroup. 
 
8.6 
Blinding 
 
This study is unblinded. 
 
8.7 
Data and Safety Monitoring Oversight 
 
HPTN SMC oversight is planned for this study. The SMC will conduct interim reviews of study 
progress, including rates of participant accrual, visit retention, completion of primary and 
secondary endpoint collection, and, in a closed report, safety data by arm. The frequency and 
content of SMC reviews will be determined prior to the start of the study and outlined in the SSP 
Manual. 
 
8.8 
Statistical Analysis 
 
This section briefly describes the final study analyses. Detailed technical specifications of the 
statistical analyses will be described in a separate Statistical Analysis Plan. 
 
8.8.1 Primary Analyses 
 
All primary endpoint proportions will be compared across study arms using simple linear-
binomial regression models (estimating risk differences) adjusted for site (strata variable), with 
separate models for the people living with HIV and people without HIV subgroups. Planned 
sample sizes should allow for Normal-based confidence intervals. No interim analyses are 
planned. 
 
8.8.2 Secondary Analyses 
 
Secondary analysis endpoint proportions will be compared using the identical method described 
for the comparison of proportions among primary endpoints with the exception of within-cohort 
change over time. Within-cohort change over time will be estimated using correlated-data 
binomial regression (a random-effects model estimating risk differences) adjusted for city. 
Incidence rates will be computed as the number of incident events (including recurrent events 
where applicable) divided by total number of accrued person-years in each study arm, where 
person time is computed for each person as the difference between enrollment date and the last 
available sample-collection date for which the corresponding STI test was performed. Person-
time for participants with new HIV infection will be calculated as the difference between 
enrollment date and date of first detection of HIV infection.  
 

 
 
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Implementation Evaluation Analysis 
The analysis for each objective will be iterative, whereby the implementation team meets monthly 
to review the incoming data for ideas, themes, and patterns that emerge from the data pertaining 
to the PRISM framework’s multi-level factors that influence the implementation process that will 
be used to define a set of analytic coding categories. Trained staff will iteratively code the 
qualitative data and employ qualitative analysis techniques. Quantitative data will be 
descriptively summarized. The implementation evaluation analysis for each implementation 
objective will be achieved via parallel mixed method data analysis, integrating qualitative and 
quantitative results to triangulate and interpret overall findings. 
  
Results from pre-implementation analyses will inform the implementation of the intervention 
across study sites; implementation results will be used to systematically document site-specific 
refinements and document fidelity to the “one-stop” integrated strategies delivered in the mobile 
unit and supported by peer navigation. Ultimately, it is hoped that results from the analysis phase 
can inform implementation of the study’s integrated healthcare services approach as a public 
health program to benefit PWID and to reduce drug-associated HIV transmission in cities across 
the US. 
 
Modeling and Cost-Effectiveness Analysis 
The modelling analysis will be conducted in two distinct phases. First, a stochastic individual-
based model will be developed to simulate HIV acquisition among people without HIV and HIV 
transmission from people living with HIV for cohorts of PWID with OUD representative of the 
trial populations in the settings where HPTN 094 is conducted. This model will be used to help 
interpret the trial results by providing an estimate of the intervention impact on the HIV 
acquisition risk among participants without HIV and HIV transmission rate from participants 
living with HIV. Second, a cost-effectiveness analysis of the integrated intervention will be 
performed that will take into account the costs of the full (integrated strategy) and limited (active 
control arm) interventions, the treatment costs incurred (and averted) in preventing new HIV 
infections, and modeled effectiveness. Effectiveness and cost-effectiveness results will be 
reported for the intervention compared to SOC. 
 
9.0 
HUMAN SUBJECTS CONSIDERATIONS 
 
9.1 
Ethical Review  
 
This protocol and the sample informed consent forms (ICFs) contained in Appendices II and III 
will be reviewed and approved by the HPTN Scientific Review Committee and NIAID 
Prevention Science Review Committee with respect to scientific content and compliance with 
applicable research and human subjects regulations.  
 
The protocol, site-specific ICFs, participant education and recruitment materials, and other 
requested documents — and any subsequent modifications — also will be reviewed and approved 
by the IRB responsible for oversight of this research study.  
 
Subsequent to initial review and approval, the IRB will review the protocol at least annually. The 
investigators will make safety and progress reports to the IRB 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 must comply with the requirements of 45 CFR 46.108(a)(4) 
and 21 CFR 56.108b for promptly reporting the following: all unanticipated problems involving 
risks to human subjects or others;; serious or continuing noncompliance with applicable 

 
 
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regulations or the requirements or determinations of their IRBs/ECs; and any suspension or 
termination of IRB approval. In addition, all open SMC reports will be provided to the IRB. 
Study sites will submit documentation of continuing review to the DAIDS Protocol Registration 
Office, in accordance with the current DAIDS Protocol Registration Policy and Procedure 
Manual. 
 
9.2 
Informed Consent 
 
Written informed consent will be obtained from each study participant. Each study site is 
responsible for developing a study ICF for local use, based on the templates in Appendices II and 
III, which describe the purpose of the study, the procedures to be followed, and the risks and 
benefits of participation, in accordance with all applicable regulations. If applicable, the study site 
also is responsible for translating the template form into languages other than English and 
verifying the accuracy of the translation by performing an independent back-translation. Sites 
may have additional consent requirements based upon local requirements, e.g., for clinical care, 
privacy protection, etc.  
 
Literate participants will document their provision of informed consent by signing their informed 
consent forms. Non-literate participants will be asked to document their informed consent by 
marking their ICFs (e.g., with an X, thumbprint, or other mark) in the presence of a literate third-
party witness. (Further details regarding DAIDS requirements for documenting the informed 
consent process with both literate and non-literate participants are provided in the DAIDS 
Standard Operating Procedure for Source Documentation.) Any other IRB requirements for 
obtaining informed consent from non-literate persons also will be followed.  
 
Participants will be provided with copies of their ICFs if they are willing to receive them.  
 
9.3 
Risks 
 
Taking blood samples may cause participants some pain, bruise their arm, or cause them to feel 
lightheaded. In rare cases they may faint. There is a slight chance of infection when blood is 
drawn. Participants may experience pain or discomfort in their throat, rectum or vagina from the 
swab. In some cases, they may have some bleeding. 
 
We will make every effort to protect participants’ confidentiality during the study, however, it is 
possible that others may learn of a person’s participation in this study and may think that the 
participant is living with HIV or at high risk for acquiring HIV or may make assumptions about 
the participant’s use of drugs. If participants communicate with a peer navigator using texting or 
messaging apps and others are able to access their phone, this could be a confidentiality risk. This 
will be highlighted in the consent process. The participant could face stigma related to HIV or 
drug use. Participants may be nervous while waiting for HIV or other test results. If the tests 
show that a participant has HIV or another infection, they may worry about their health and 
future. The questions we will ask participants about sexual behavior, medical history, drug use 
and drug treatment history, history of being incarcerated, and experiences of depression, anxiety 
or trauma may make them feel uneasy. Trained counselors will be available to help participants 
deal with these feelings. 
 
There are no risks related to investigational products in this study because no investigational 
products will be used. 
 

 
 
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For participants assigned to the group that WILL NOT receive medical care in the mobile health 
delivery unit, medications to treat STIs will be provided by the study staff at the Enrollment Visit, 
if they have STI symptoms, and they will be offered naloxone kits during study participation that 
can be used to treat an overdose. Participants may also be given or prescribed other commonly-
used medications at the Enrollment Visit to treat things like a cough or infection. The clinician 
will explain to the participant any side effects associated with any of those medications. After the 
Enrollment Visit, the peer navigator will help the participant receive care from community-based 
services.  
 
Participants assigned to the group that WILL receive medical care in the mobile unit will receive 
or be prescribed medications by the study staff during the first six months of their participation in 
the study. The medications that a participant might be dispensed in the mobile unit include those 
to treat or prevent: STIs or other bacterial infections, HIV, opioid use disorder and overdose. 
Participants may also be prescribed other medications as part of primary care provided in the 
mobile health delivery unit. The clinician will explain to the participant any side effects of the 
specific medications they are prescribed or given. 
 
9.4 
Benefits 
 
Participants in this study will receive many health services at no charge. Participants will be 
tested for HIV, HAV, HBV, HCV, and other STIs. Participants will receive treatment or referral 
for treatment, as appropriate, for these infections. The counseling participants receive during this 
study may help them avoid HIV, HAV, HBV, HCV, and other STIs. For participants with HIV, 
counseling may help them learn how to better care for themselves and avoid passing HIV to 
sexual partners (or their fetus, if pregnant). People without HIV will be offered PrEP or referral 
for PrEP to help avoid HIV infection. Peer navigators will work to link participants to health 
services, including treatment for OUD and HIV care or prevention services. Participants will 
receive free condoms and naloxone kits for overdose reversal. Participants in the group that 
receives medical services in the mobile unit will be provided with medical care and medication in 
a single convenient location.  
 
Participants may receive indirect benefits from this study. The information gathered during this 
study may show how medical services can be provided more successfully to people who inject 
drugs, particularly services for OUD and HIV. This could influence how medical services are 
provided in the future and may be beneficial to participants and their community.  
 
9.5 
Population-Specific Considerations 
 
As noted in Section 1.1, persons with OUD and living with or at risk for HIV in the US typically 
face multiple and overlapping problems that can include criminal justice involvement. In 
HPTN 094, prisoners will not be recruited or enrolled from jail or prison settings (persons with 
parole status will be recruited and enrolled), nor will study-related visits with study participants 
be conducted in prisons or jails. Participants who become incarcerated during their time on study 
will be scheduled for study activities for which they are eligible upon release.  
 
As noted in Sections 1.2 and 4.3 of this protocol, approximately 25% of the participants in this 
study will be women. It is expected that some number of these participants will be or will become 
pregnant while enrolled in the study. The “Common Rule” for conduct of human research studies 
funded by the US Government stipulates additional consideration for pregnant people as study 
participants, particularly regarding benefits and risks to both the pregnant individual and their 
fetus. 

 
 
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In considering the risks and benefits presented by the participation of pregnant people in this 
study, the intervention being investigated is the combination of therapies commonly prescribed 
for people with OUD and people with (or at risk for) HIV, in a mobile health delivery unit, with 
peer navigation. The medications that will be prescribed and provided are not investigational but 
will be US FDA-approved medicines commonly used to treat or prevent these conditions. 
Providing these standard therapies, in a manner that we expect will improve their uptake and 
adherence (i.e., in an accessible mobile health delivery unit, with supportive navigation), will not 
increase risks to either a pregnant individual or to the fetus greater than would be encountered if 
they were to obtain them in a standard clinic setting.  
 
The therapies that are the focus of this intervention are all commonly prescribed for pregnant 
people because of their acknowledged beneficial risk-benefit profile for both the pregnant person 
and the fetus. For ART, treatment in a pregnant person is highly effective at preventing 
transmission of HIV to the fetus and treatment has health benefits for the pregnant individual 
(current guidelines recommend treatment for all adults living with HIV for their own health), with 
very low risk presented to either pregnant person or fetus by currently used regimens. For PrEP, 
both the pregnant person and the fetus benefit from avoiding potential HIV infection, and the 
currently approved PrEP regimen (Truvada) has a very well-studied and minimal risk profile. For 
MOUD, there are substantial benefits to treatment for both the pregnant person and the fetus 
compared with the harms from untreated opioid use disorder. A pregnant person on treatment 
spares themselves and the developing fetus the fluctuating levels of opioid exposure and 
injection-related risks that occur from cycles of use and withdrawal of street-acquired opioids. 
MOUD reduces the dysregulated behavior of addiction, allowing the person to improve nutrition, 
sleep, situational stability, attend pre-natal care visits, etc., with corresponding benefits for the 
fetus. Recommendations for treatment will always be based on the clinician’s assessment of the 
individual participant’s needs; if a particular therapy (i.e., methadone, buprenorphine, naltrexone) 
is deemed not appropriate for a particular participant (pregnant or otherwise), it will not be 
prescribed.  
 
In the risk-to-benefit analysis, benefits of offering this intervention to pregnant people far 
outweigh potential risks for both the pregnant person and the fetus. Excluding pregnant people 
would present ethical challenges, principal among them violating the principle of beneficence by 
excluding the opportunity for pregnant participants to benefit from the interventions provided 
(including medications) in this study in the face of no more than minimal risks to pregnant people 
and their fetuses treated using these medications. As well, including pregnant people allows the 
study population to be more representative of the population of PWID with OUD, and therefore 
allows our findings to be more generalizable. 
 
9.6 
Incentives 
 
Pending IRB approval, 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. As well, some 
participants may be offered additional compensation for referring other PWID who enroll in the 
study. Site-specific reimbursement amounts will be specified in the study ICFs. 
 
9.7 
Confidentiality 
 
All study-related information will be stored securely. All participant information will be stored in 
locked file cabinets in areas with access limited to study staff. All laboratory specimens, reports, 
study data collection, process, and administrative forms will be identified by a coded number only 
to maintain participant confidentiality. All databases will be secured with password-protected 

 
 
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access systems. Forms, lists, logbooks, appointment books, and any other listings that link 
participant ID numbers to other identifying information will be stored in a separate, locked file in 
an area with limited access. 
 
Interviews will be transcribed by qualified personnel and all identifiable information will be 
removed from the transcripts. All reports and publications will be carefully redacted to ensure 
that identification of interview or focus group participants is not possible. 
 
Participants’ study information will not be released without the written permission of the 
participant, except as necessary for monitoring by the NIAID, National Institute on Drug Abuse 
(NIDA) and/or their contractors; representatives of the HPTN LOC, SDMC, and/or LC; other 
government and regulatory authorities, and/or IRB.  
 
The HPTN will obtain a Certificate of Confidentiality from the US Department of Health and 
Human Services that will be applicable for this study. Sites may register under the Certificate 
through the HPTN LOC once they have obtained IRB approval for the study. This Certificate 
protects study staff from being compelled to disclose study-related information by any Federal, 
State or local civil, criminal, administrative, legislative, or other body. 
 
9.8 
Communicable Disease Reporting Requirements 
 
Study staff will comply with all applicable local requirements to report communicable diseases 
identified among study participants to local health authorities. Participants will be made aware of 
all reporting requirements during the study informed consent process. 
 
9.9 
Study Discontinuation 
 
The study also may be discontinued at any time by NIDA, NIAID, the HPTN, other government 
or regulatory authorities, and/or the IRB.  
 
10.0 
LABORATORY SPECIMENS AND BIOHAZARD CONTAINMENT 
 
Laboratory procedures are described below (See Appendix IA), and Section 6.0; additional 
laboratory procedures are required at a subsequent visit for participants who have a reactive or 
positive HIV test result after enrollment (See Appendix IB). 
 
10.1 
Local Laboratory Specimens 
 
As described in Section 6.0, the following types of specimens will be collected:  
• 
Blood 
• 
Urine 
• 
Swabs (oropharyngeal, rectal, vaginal)  
As described in Section 6.0, the following types of testing will be performed in the mobile unit or 
at the local laboratory:    
• 
HIV testing – see SSP Manual 
• 
CD4 cell count and HIV viral load testing (if HIV positive) 
• 
Hepatitis testing, including HBsAg, HBsAb, HBcAb, HCV Ab, HAV Ab, HCV RNA (if 
HCV positive), and HBV DNA (if needed for clinical management)   

 
 
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• 
Syphilis testing and GC/CT by NAAT: oropharyngeal swab and rectal swab (all), 
vaginal/neo-vaginal swab, urine (men and women as a less preferred alternative to 
vaginal/neo-vaginal swab) 
• 
The schedule of GC/CT testing by NAAT may be adjusted or prioritized at the discretion 
of the site investigator if there is a potential for shortage of supplies for collection and/or 
testing. Please see CDC recommendation September 8, 2020 
https://www.cdc.gov/std/general/DCL-Diagnostic-Test-Shortage.pdf 
• 
Urine substance use testing (must include opioid, cocaine, amphetamines, 
benzodiazepines) 
• 
Urine fentanyl testing 
• 
Urine MOUD testing (must include buprenorphine and methadone) 
• 
Urine pregnancy testing 
• 
Chemistry testing for creatinine, ALT, AST, total bilirubin 
• 
Hemoglobin  
• 
HIV drug resistance testing, if needed for clinical management 
Notes: Some tests will be performed in mobile units and some will be performed in local 
laboratories (see SSP Manual). Other testing related to HIV and HCV infection may be 
performed for clinical management (see Appendix 1A). 
Each study site (mobile health delivery unit, clinic, laboratory, etc.) must adhere to standards of 
Good Clinical Laboratory Practice (GCLP) 
(https://www.niaid.nih.gov/sites/default/files/gclp.pdf) referenced in the HPTN Manual of 
Operations (MOP), the SSP Manual and local SOPs for proper collection, processing, labeling, 
transport, and storage of specimens to the local laboratory. In addition, each study site must 
adhere to the Requirements for DAIDS Funded and or Sponsored Laboratories in Clinical Trials 
Policy (https://www.niaid.nih.gov/sites/default/files/Lab-Appendix-I-US-Labs.pdf). Specimen 
collection, testing, and storage at the local laboratory will be documented using the HPTN 
Laboratory Data Management System (LDMS) as described in the SSP Manual. 
 
10.2 
HPTN Laboratory Center Specimens 
 
The following types of specimens will be collected/prepared for testing at the HPTN LC. 
 
• 
Plasma 
• 
Serum 
• 
Urine 
• 
DBS 
 
10.2.1 Stored Specimens 
 
Plasma, serum, urine, and DBS specimens will be stored at the local site throughout the study. 
Study specimens will be maintained at the site until at least one year after publication of the 
primary findings of the study and all protocol-related testing has been performed. A subset of the 
stored samples will be shipped to the HPTN LC (located in the US) for QA and other 
assessments. Stored samples may be used to evaluate the performance of laboratory methods 
relevant to protocol objectives. As indicated below, testing on stored samples will be performed 
by the HPTN LC or another laboratory selected by the HPTN LC. These samples may not be used 
for local laboratory testing without written approval by the HPTN LC prior to use.  
 

 
 
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10.2.2 Virology 
 
For participants with HIV infection, HPTN LC testing will include HIV viral load, and analysis 
of viral subtypes/strains, drug resistance, and duration of infection; other tests may be performed 
to characterize the host response to HIV infection. Results will not be returned to the sites or 
study participants, with the exception of HIV testing (if results obtained at the HPTN LC do not 
agree with site results).  
For participants with HCV infection, HPTN LC testing may include HCV viral load, and analysis 
of HCV strains, drug resistance, and duration of infection; other tests may be performed to 
characterize the host response to HCV infection. Results will not be returned to the sites or study 
participants.  
HIV resistance testing will be performed at the HPTN LC or a laboratory designated by the  
HPTN LC. This testing will be performed retrospectively at the end of the study. Results of this 
testing will not be returned to study sites. Because real-time resistance testing may be needed for 
clinical management in the event of HIV infection, each site will have an SOP as to how they will 
accomplish real-time local or regional resistance testing to assist with clinical decision making; 
separate specimens should be collected for that testing.  
 
Phylogenetic analysis may also be performed to evaluate the genetic relationships between HIV 
strains. This may include analysis of clustered/linked HIV infections, transmission dynamics, and 
the association of behavioral, demographic, and clinical factors with HIV 
transmission/acquisition. This analysis may also include evaluation of the multiplicity of infection 
and HIV superinfection. Similar analysis may also be performed to characterize HCV infections 
and the relationship between HIV and HCV infections. 
 
Laboratory testing will be performed to assess the prevalence of SARS-CoV-2 seropositivity. 
Testing may also be performed to characterize the host response to infection and factors 
associated with SARS-CoV-2 seropositivity. 
 
10.2.3 Pharmacology and Toxicology Testing 
 
Plasma, urine, and DBS samples will be processed and frozen locally for subsequent shipment to 
the HPTN LC following procedures outlined in the SSP Manual.  
 
Plasma and DBS samples for Pharmacology testing will be collected throughout the study for 
analysis of PrEP use and adherence. Analysis at the HPTN LC may be limited to a subset of the 
samples. Pharmacology testing will be performed at the HPTN LC or at an outside laboratory 
designated by the HPTN LC. The primary pharmacologic assessments will be performed using 
assays that have been validated and approved by the Clinical Pharmacology Quality Assurance 
(CPQA) Committee. Results will not be returned to the study participants. 
 
Stored plasma may also be tested for the presence of other drugs, including ARV drugs used for 
HIV treatment or other reasons and drugs used for hepatitis treatment. Stored samples may be 
tested for the presence of medications used to treat substance use, other concomitant medications, 
and substances of abuse. 
 
 
 

 
 
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10.3 
Quality Control and Quality Assurance Procedures 
 
The clinical sites will document that their clinical laboratories (including clinic laboratories, 
mobile units, or other locations where processing and testing are performed) have either a 
Clinical Laboratory Improvement Amendments of 1988 (CLIA)-waiver or are CLIA-certified 
under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-certified) and/or 
participate in DAIDS sponsored external quality assurance programs. Laboratories must also 
follow the DAIDS requirements (link to policy on DAIDS website 
https://www.niaid.nih.gov/research/daids-clinical-research-laboratory-specimens-management).  
 
LC staff will conduct periodic visits to each site to review the implementation of on-site 
laboratory QC procedures, including proper maintenance of laboratory equipment and use of 
appropriate supplies and reagents. LC staff will follow up directly with site staff to resolve any 
QC or QA problems identified through proficiency testing or on-site visit reviews. Throughout 
the course of the study, the HPTN LC will select a random sample of stored specimens to test for 
QA purposes. LC staff will follow-up directly with site staff to resolve any QA problems 
identified through this process.  
 
HIV diagnostic tests will be listed on the US lab information sheet and will be subject to review 
and acceptance by DAIDS and the HPTN LC.  
 
Throughout the course of the study, the SDMC will work with the HPTN LC to determine and 
select random sample of stored specimens to test for QA purposes, and to assist with and/or 
confirm HIV seroconversion cases.  
 
The SDMC and/or the LC will inform site staff of the samples selected for QA testing, and site 
staff will ship the selected specimens to the LC. The LC will perform HIV diagnostic testing for 
QC, endpoint confirmation, end of study confirmation, and will work with the SDMC to compare 
the results of their tests with the results obtained by the local labs. LC staff will follow-up directly 
with site staff to resolve any QA problems identified through this process. 
 
10.4 
QC for HIV Diagnostic Testing 
 
The local laboratories will perform testing for HIV diagnosis at Screening, Enrollment, and other 
scheduled visits as described in the SSP Manual. HIV status will be confirmed at study sites using 
local HIV testing guidelines or following the advice from the CMC/HPTN LC. In addition, if a 
participant has signs or symptoms consistent with acute HIV infection, or expresses a concern 
about recent HIV acquisition, testing will be performed using an RNA test such as the Aptima 
HIV-1 Qualitative Assay. Regardless of whether HIV RNA testing is used for diagnostic testing, 
incident HIV infection (seroconversion events) must be confirmed in all cases using two 
independent samples collected on different days. HIV algorithms for HIV diagnostic testing are 
provided in the SSP Manual. The HPTN LC will perform QC testing to confirm seroconversion 
events and evaluate the accuracy of site test results. 
 
10.5 
HIV RNA Monitoring 
 
Quantitative HIV RNA (viral load) testing will be performed at local clinical laboratories to 
monitor HIV infection in any subject with confirmed HIV infection. Viral load testing will be 
performed in people living with HIV at the visit when HIV infection is confirmed, and at 

 
 
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subsequent study visits. Note that this is distinct from use of qualitative HIV RNA testing that is 
performed to determine HIV infection status.  
 
10.6 
CD4 Cell Count Determination 
 
CD4 cell count testing will be performed for participants who are living with HIV at enrollment 
and for participants who acquire HIV during the study.  
 
10.7 
Specimen Storage and Possible Future Research Testing 
 
Study site staff will store urine, plasma, serum, and DBS collected in this study at least through 
the end of the study (this includes completion of all protocol-related testing, including testing at 
the HPTN LC). Sample destruction requires approval in writing from the LC to the site and will 
not occur until at least one year has passed after publication of the primary manuscript. In 
addition, study participants will be asked to provide written informed consent for their specimens 
to be stored after testing for all protocol-related testing has been completed (including testing for 
primary, secondary, and exploratory objectives) for possible future testing. The specimens of 
participants who do not consent to long-term storage and additional testing will be destroyed at 
the end of the study after the protocol-related testing has been completed, at least one year after 
completion of the primary manuscript. A list of samples to be destroyed will be provided by the 
SDMC, to be reviewed and reconciled by the site. Final approval for sample destruction will be 
provided in writing to the site by the LC. 
 
10.8 
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 specimens will be 
shipped using packaging that meets requirements specified by the International Air Transport 
Association Dangerous Goods Regulations for UN 3373, Biological Substance, Category B, and 
Packing Instruction 650.  
 
11.0 
ADMINISTRATIVE PROCEDURES 
 
11.1 
Protocol Registration  
 
Initial Registration of the protocol by the DAIDS Protocol Registration Office (PRO) is required 
prior to implementation of this protocol. As part of this process, each site must have the protocol 
and protocol ICF(s) approved, as appropriate, by the IRB. Upon receiving final approval, sites 
will submit all required protocol registration documents to the DAIDS PRO at the RSC. The 
DAIDS PRO will review the submitted protocol registration packet to ensure that all of the 
required documents have been received. In the case of Initial Registration, site-specific ICFs will 
be reviewed and approved by the DAIDS PRO. Sites will receive an Initial Registration 
Notification from the DAIDS PRO that indicates successful completion of the protocol 
registration process. A copy of the Initial Registration Notification should be retained in the site's 
regulatory files. 
 
Upon receiving final IRB/EC and any other applicable RE approval(s) for an amendment, sites 
should implement the amendment immediately. Sites are required to submit an amendment 

 
 
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registration packet to the DAIDS PRO at the RSC. The DAIDS PRO will review the submitted 
protocol registration packet to ensure that all the required documents have been received. Site-
specific ICF(s) WILL NOT be reviewed and approved by the DAIDS PRO and sites will receive 
an Amendment Registration Notification when the DAIDS PRO receives a complete registration 
packet. A copy of the Amendment Registration Notification should be retained in the site's 
regulatory files. 
 
For additional information on the protocol registration process and specific documents required 
for initial and amendment registrations, refer to the current version of the DAIDS Protocol 
Registration Manual, which can be found at https://rsc.niaid.nih.gov/clinical-research-sites/daids-
protocol-registration-policy-and-procedures-manual. 
 
11.2 
Study Activation 
 
Pending successful protocol registration and submission of all required documents, the HPTN 
LOC staff will “activate” a site to begin study operations. Study implementation may not be 
initiated until a study activation notice is provided to the site by the HPTN LOC. In addition, if 
study activation is determined to be necessary for any subsequent amendments, study 
implementation may not be initiated until a study activation notice is provided to the site by the 
HPTN LOC. 
 
11.3 
Study Coordination 
 
Study implementation will be directed by this protocol as well as the SSP Manual. The SSP 
Manual will contain links to the Requirements for Source Documentation in DAIDS Funded 
and/or Sponsored Clinical Trials, as well as the DAIDS Toxicity Tables. This manual will outline 
procedures for conducting study visits; data and forms processing; SAE assessment, management 
and reporting; dispensing medications and documenting product accountability; and other study 
operations. 
   
Study CRFs and other study instruments will be developed by the protocol team and HPTN 
SDMC. Data will be submitted to the HPTN SDMC for cleaning, reporting and analysis. Quality 
control data queries will be generated on a routine schedule for verification and resolution by site 
data management staff.  
 
Close coordination between protocol team members will be necessary to track study progress, 
respond to queries about proper study implementation, and address other issues in a timely 
manner. Rates of accrual, adherence, follow-up, and SAE incidence will be monitored closely by 
the team as well as the HPTN SMC. The CMC will address issues related to study eligibility and 
SAE management and reporting as needed to assure consistent case management, documentation, 
and information-sharing across sites. 
 
11.4 
Study Monitoring 
 
Monitoring will be performed in accordance with DAIDS policies. Study monitors will visit the 
site 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 

 
 
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• 
Confirm the quality and accuracy of information collected at the study site and entered 
into the study database. 
 
Site investigators will allow study monitors to inspect study facilities and documentation (e.g., 
ICFs, clinic and laboratory records, other source documents, paper or electronic CRFs), as well as 
observe the performance of study procedures. Investigators also will allow inspection of all study-
related documentation by authorized representatives of the HPTN LOC, HPTN SDMC, HPTN 
LC, NIAID, NIDA, IRB, and US regulatory authorities (Office for Human Research Protections 
(OHRP) and other regulatory agencies). A site visit log will be maintained at each study site to 
document all visits. 
 
Monitoring visits may be conducted on-site or remotely. Remote visits may include 
remote source document verification using methods specified for this purpose by 
NIAID. Remote monitoring visits may be performed in place of, or in addition to onsite 
visits to ensure the safety of study participants and data integrity41 . The site must make 
available study documents for site monitors to review utilizing a secure platform that is 
HIPAA and 21 CFR Part 11 compliant. The Data Management Center will configure 
Medidata Remote Source Review (RSR) and make it available to all sites. We encourage 
Sites to use the DMC provided Medidata RSR platform but other potential platform 
options include: Veeva SiteVault, site-controlled SharePoint or cloud-based portal, and 
direct access to Electronic Medical Record (EMR). Other secure platforms that are 21 
CFR Part 11 compliant may be utilized, as allowed by the DAIDS Office of Clinical Site 
Oversight (OCSO). 
 
11.5 
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 Protocol Chair and DAIDS Medical Officer. All 
protocol amendments must be submitted to and approved by the IRB and the RSC prior to 
implementing the amendment. 
 
11.6 
Investigator’s Records 
 
The Investigator will maintain, and store in a secure manner, complete, accurate, and current 
study records throughout the study. Under the US Department of Health and Human Services 
(DHHS) regulations, the Investigator is required to retain all study records relating to research for 
at least three years after completion of the research, or longer if needed to comply with local 
regulations.  
 
Completion of a clinical research study occurs when the following activities have been 
completed: 
 
• 
All research-related interventions or interactions with human subjects (e.g. when all 
participants are off study);  
• 
All protocol-required data collection of identifiable private information described in the 
IRB-approved research plan;  
• 
All analysis of identifiable private information described in the IRB-approved research 
plan;  
• 
Primary analysis of either identifiable private or de-identified information.  
 

 
 
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Study records include administrative documentation — including protocol registration documents 
and all reports and correspondence relating to the study — as well as documentation related to 
each participant screened and/or enrolled in the study — including ICFs, locator forms, CRFs, 
notations of all contacts with the participant, and all other source documents. 
 
11.7 
Use of Information and Publications 
 
Publication of the results of this study will be governed by the HPTN Manual of Operations. Any 
presentation, abstract, or manuscript will undergo review by the HPTN Manuscript Review 
Committee and DAIDS, prior to submission. 
 

 
 
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Hedegaard H, Minino AM, Warner M. Drug overdose deaths in the United States, 1999-
2018. 2020. 
2. 
Centers for Disease Control and Prevention (CDC). Drug Overdose Death Data. 2017 
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3. 
Nolan M, Tuazon E, Blachman-Forshay J, Paone D. Unintentional Drug Poisoning 
(Overdose) Deaths in New York City, 2000-2017. New York City Department of Health and 
Mental Hygiene: Epi Data Brief (104) 2018. 
4. 
Nicholson HL, Vincent J. Gender Differences in Prescription Opioid Misuse Among U.S. 
Black Adults. Subst Use Misuse 2019; 54(4): 639-50. 
5. 
Allen B, Nolan ML, Kunins HV, Paone D. Racial Differences in Opioid Overdose Deaths 
in New York City, 2017. JAMA Intern Med 2019; 179(4): 576-8. 
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Hedegaard H, Minino AM, Warner M. Drug Overdose Deaths in the United States, 1999-
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7. 
Ciccarone D. Fentanyl in the US heroin supply: A rapidly changing risk environment. 
International Journal of Drug Policy 2017; 46: 107-11. 
8. 
Ciccarone D. The triple wave epidemic: Supply and demand drivers of the US opioid 
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9. 
Volkow N, Frieden T, Hyde P, Cha S. Medication-assisted therapies--tackling the opioid-
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Kolodny A, Courtwright D, Hwang C, et al. The prescription opioid and heroin crisis: a 
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Compton W, Jones C, Baldwin G. Relationship between Nonmedical Prescription-Opioid 
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Compton W, Volkow N, Throckmorton D, Lurie P. Expanded access to opioid overdose 
intervention: research, practice, and policy needs. Annals of Internal Medicine 2013; 158(1): 65-
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Strathdee S, Beyrer C. Threading the Needle - How to Stop the HIV Outbreak in Rural 
Indiana. New England Journal of Medicine 2015; 373(5): 397. 
14. 
Platt L, Easterbrook, P., Gower, E., McDonald, B., Sabin, K., McGowan, C., Yanny, I., 
Razavi, H., Vickerman, P. Prevalence and burden of HCV co-infection in people living with HIV: 
a global systematic review and meta-analysis. . Lancet Infect Diseases 2016; 16(7): 797-808. 
15. 
Blanco C, Volkow ND. Management of opioid use disorder in the USA: present status 
and future directions. Lancet 2019; 393(10182): 1760-72. 
16. 
Peters PJ, Pontones P, Hoover KW, et al. HIV Infection Linked to Injection Use of 
Oxymorphone in Indiana, 2014–2015. New England Journal of Medicine 2016; 375(3): 229-39. 
17. 
Cranston K, Alpren C, John B, et al. Notes from the Field: HIV Diagnoses Among 
Persons Who Inject Drugs - Northeastern Massachusetts, 2015-2018. MMWR Morbidity and 
mortality weekly report 2019; 68(10): 253-4. 
18. 
Golden MR, Lechtenberg R, Glick SN, et al. Outbreak of Human Immunodeficiency 
Virus Infection Among Heterosexual Persons Who Are Living Homeless and Inject Drugs - 
Seattle, Washington, 2018. MMWR Morbidity and mortality weekly report 2019; 68(15): 344-9. 
19. 
El-Bassel N, Marotta P, Gilbert L, et al. Integrating treatment for opioid use disorders and 
HIV services into primary care: Solutions for the 21st Century. In: Crosby R, DiClemente R, eds. 
Preventing HIV Transmission and Improving HIV Care through the Use of Structural-Level 
Approaches: Global Insights from Successful Approaches. Cambridge, UK: Oxford University 
Press; In Press. 
20. 
Williams A, Nunes E, Bisaga A, et al. Developing an opioid use disorder treatment 
cascade: A review of quality measures. Journal of Substance Abuse Treatment 2018; 91: 57-68. 

 
 
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21. 
Malta M, Magnanini MMF, Strathdee SA, Bastos FI. Adherence to Antiretroviral 
Therapy Among HIV-Infected Drug Users: A Meta-Analysis. AIDS and Behavior 2010; 14(4): 
731-47. 
22. 
Malta M, Ralil da Costa M, Bastos FI. The Paradigm of Universal Access to HIV-
Treatment and Human Rights Violation: How Do We Treat HIV-Positive People Who Use 
Drugs? Current HIV/AIDS Reports 2014; 11(1): 52-62. 
23. 
Volkow ND, Wargo EM. OVerdose prevention through medical treatment of opioid use 
disorders. Annals of Internal Medicine 2018; 169(3): 190-2. 
24. 
Shoptaw S, Goodman-Meza D, Landovitz RJ. Collective Call to Action for HIV/AIDS 
Community-Based Collaborative Science in the Era of COVID-19. AIDS Behav 2020. 
25. 
Green TC, Bratberg J, Finnell DS. Opioid use disorder and the COVID 19 pandemic: A 
call to sustain regulatory easements and further expand access to treatment. Subst Abus 2020; 
41(2): 147-9. 
26. 
The National Academies of Sciences Engi (Washington District of Columbia). 
Opportunities to improve opioid use disorder and infectious disease services : integrating 
responses to a dual epidemic. Washington: The National Academies Press; 2020. 
27. 
Iyengar S, Kravietz A, Bartholomew TS, Forrest D, Tookes HE. Baseline differences in 
characteristics and risk behaviors among people who inject drugs by syringe exchange program 
modality: an analysis of the Miami IDEA syringe exchange. Harm Reduct J 2019; 16(1): 7. 
28. 
Allen ST, Ruiz MS, Jones J. Assessing Syringe Exchange Program Access among 
Persons Who Inject Drugs (PWID) in the District of Columbia. J Urban Health 2016; 93(1): 131-
40. 
29. 
Degenhardt L, Peacock A, Colledge S, et al. Global prevalence of injecting drug use and 
sociodemographic characteristics and prevalence of HIV, HBV, and HCV in people who inject 
drugs: a multistage systematic review. Lancet Glob Health 2017; 5(12): e1192-e207. 
30. 
Centers for Disease and Prevention. HIV Infection, Risk, Prevention, and Testing 
Behaviors among Persons Who Inject Drugs—National HIV Behavioral Surveillance: Injection 
Drug Use, 20 U.S. Cities, 2015. HIV Surveillance Special Report 18 2018. 
31. 
Ait-Daoud N, Blevins D, Khanna S, Sharma S, Holstege CP, Amin P. Women and 
Addiction: An Update. Med Clin North Am 2019; 103(4): 699-711. 
32. 
Palis H, Marchand K, Guh D, et al. Men's and women's response to treatment and 
perceptions of outcomes in a randomized controlled trial of injectable opioid assisted treatment 
for severe opioid use disorder. Subst Abuse Treat Prev Policy 2017; 12(1): 25. 
33. 
Wejnert C, Hess KL, Hall HI, et al. Vital Signs: Trends in HIV Diagnoses, Risk 
Behaviors, and Prevention Among Persons Who Inject Drugs - United States. MMWR Morb 
Mortal Wkly Rep 2016; 65(47): 1336-42. 
34. 
Lapham G, Boudreau DM, Johnson EA, et al. Prevalence and treatment of opioid use 
disorders among primary care patients in six health systems. Drug Alcohol Depend 2020; 207: 
107732. 
35. 
Yu SWY, Hill C, Ricks ML, Bennet J, Oriol NE. The scope and impact of mobile health 
clinics in the United States: a literature review. Int J Equity Health 2017; 16(1): 178. 
36. 
Curran GM, Bauer M, Mittman B, Pyne JM, Stetler C. Effectiveness-implementation 
hybrid designs: combining elements of clinical effectiveness and implementation research to 
enhance public health impact. Med Care 2012; 50(3): 217-26. 
37. 
Feldstein AC, Glasgow RE. A Practical, Robust Implementation and Sustainability 
Model (PRISM) for Integrating Research Findings into Practice. The Joint Commission Journal 
on Quality and Patient Safety 2008; 34(4): 228-43. 
38. 
Glasgow RE, Vogt TM, Boles SM. Evaluating the public health impact of health 
promotion interventions: the RE-AIM framework. Am J Public Health 1999; 89(9): 1322-7. 

 
 
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39. 
Miller WC, Hoffman IF, Hanscom BS, et al. A scalable, integrated intervention to engage 
people who inject drugs in HIV care and medication-assisted treatment (HPTN 074): a 
randomised, controlled phase 3 feasibility and efficacy study. Lancet 2018; 392(10149): 747-59. 
40. 
Morgan JR, Schackman BR, Leff JA, Linas BP, Walley AY. Injectable naltrexone, oral 
naltrexone, and buprenorphine utilization and discontinuation among individuals treated for 
opioid use disorder in a United States commercially insured population. J Subst Abuse Treat 
2018; 85: 90-6. 
41. 
Food and Drug Administration. Conduct of Clinical Trials of Medical Products During 
the COVID-19 Public Health Emergency: Guidance for Industry, Investigators, and Institutional 
Review Boards. January 27, 2021 2020. https://www.fda.gov/media/136238/download2023). 
 
 
 

 
 
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APPENDIX IA: SCHEDULE OF STUDY VISITS AND PROCEDURES  
  
Screening 
Enrollment 
Care 
visit(s)1 
26 Weeks 
52 Weeks 
Administrative and Behavioral Procedures 
Informed consent 
X 
 
 
 
 
Locator information 
X 
X 
X 
X 
X 
MOUD counseling 
X 
X 
X 
X 
X 
HIV risk reduction counseling 
and test results 
X 
X 
X 
X 
X 
Offer condoms and lubricant  
X 
X 
X 
X 
X 
Provide/facilitate access to harm 
reduction 
X 
X 
X 
X 
X 
Demographic information 
X 
 
 
 
 
Randomization 
 
X 
 
 
 
Behavioral data collection 
 
X 
 
X 
X 
Introduction to peer navigator 
 
X 
 
 
 
Conclusion of peer navigation 
 
 
 
X 
 
Clinical Evaluations/Procedures  
Assessment for COVID-192 
X 
X 
X 
X 
X 
Assessment for OUD3, recent 
injection drug use (track marks)4 
X 
X 
 
 
 
Targeted medical history to 
include MOUD treatment 
history, HIV risk behaviors, 
participation in other research 
studies5 
X 
X 
(X) 
X6 
X6 
Basic physical exam7 
 
X 
(X) 
 
 
Screen for mental health needs 
and refer for services as 
indicated 
 
X 
(X) 
X 
X 
Initiate (intervention arm) or 
refer (active control arm) for 
HIV treatment or PrEP 
 
(X8) 
(X8) 
 
 
COWS assessment and initiate 
mobile unit-based MOUD 
treatment program (intervention 
arm only) 
 
(X9) 
(X9) 
 
 
Provide clinical management of 
MOUD and HIV infection or 
PrEP, including medication or 
prescription dispensation, as 
indicated 
 
 
X 
 
 
HAV vaccination referral  
 
 
X10 
 
 
HBV vaccination referral 
 
 
X10 
 
 
HBV treatment/treatment referral 
 
 
X10,11 
 
 
HCV treatment referral 
 
 
X10 
 
X 

 
 
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Development of a clinical plan 
 
X 
 
 
 
Empiric treatment of STIs (if 
symptomatic) 
 
(X) 
(X) 
(X) 
(X) 
Provide lab-based STI results 
and, if indicated, treatment 
(intervention arm) or referral 
(active control arm) 
 
 
X12 
 
 
Provide lab-based STI results, 
and, if indicated, referral 
 
 
 
X12 
X12 
Provide clinical assessment and 
management or referral for other 
medical conditions 
 
 
X 
 
 
Blood collection 
X 
X 
(X) 
X 
X 
Urine collection 
X 
X 
(X) 
X 
X 
Swabs for STI testing13 
  
X 
(X) 
X 
X 
Laboratory Evaluations/Procedures  
HIV rapid testing 
X 
X14 
(X)15 
X15 
X15 
Laboratory-based HIV testing 
(see SSP Manual) 
X16 
X15 
(X)15 
X15 
X15 
HIV viral load (people living 
with HIV only) 
 
X 
(X) 
X 
X 
CD4 cell count (people living 
with HIV only) 
 
X 
(X) 
 
 
MOUD testing (urine)17 
X 
X 
 
X 
X 
Substance use testing (urine)18 
X 
X 
(X) 
X 
X 
Fentanyl testing (urine) 
X 
X 
(X) 
X 
X 
Pregnancy testing (urine)19 
 
X 
(X) 
(X) 
(X) 
STI testing (syphilis, GC/CT 
NAAT) 
 
X 
(X) 
X 
X 
HCV Ab testing20 
 
X 
(X) 
 
X 
HCV RNA (viral load)21 
 
X 
(X) 
X 
X 
HBV testing (HBsAg, HbsAb, 
HbcAb) 
 
X 
(X) 
 
 
Other HBV-related testing22 
 
(X) 
(X) 
 
 
HAV Ab testing 
 
X 
(X) 
 
 
Heme/Chem testing23 
 
X 
 
 
 
Plasma storage24 
X 
X 
 
X 
X 
Urine storage25 
 
X 
 
X 
X 
DBS storage (people without 
HIV only) 26 
 
X 
 
X 
X 
Serum storage for SARS-CoV-2 
testing27 
 
X 
 
X 
X 
 
 
 

 
 
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Footnotes for Appendix IA 
 
Parentheses around an X indicate that this procedure will be done as needed. 
 
1  Between the Enrollment Visit and the 26-week visit, participants in the intervention arm will engage with study 
staff for clinical care in the mobile unit at a frequency determined by clinical need. These are considered care 
visits. Specimen collection and testing at care visits will be as needed for clinical care. Active control arm 
participants will not have these visits. 
2  Assessment for COVID-19 will consist of a symptom screen and temperature. Details included in the SSP 
Manual. 
3  Assessment for OUD will be performed using a tool provided in Section 9 of the SSP Manual. Sites may assess 
for OUD at either the Screening or Enrollment Visit. If OUD is confirmed at screening, it does not need to be 
reassessed (confirmed) at enrollment.  
4 See SSP Section 4 for further guidance about eligibility assessment related to evidence of recent injection drug use 
and sharing of injection equipment. 
5 See SSP Section 4 for further guidance about eligibility assessment related to MOUD history and HIV risk 
behaviors. 
6  Targeted medical history to include participation in other interventional studies, overdose events, and follow-up of 
unresolved AEs/SAEs identified previously. 
7   Physical exam at enrollment to include vital signs, height, weight, general appearance, mouth and throat, neck, 
chest, abdomen, extremities and skin. Additional elements at clinician’s discretion for patient care. 
8  HIV treatment (or referral) will be offered at the first visit where HIV infection is confirmed, for those participants 
not already in treatment. Intervention arm participants will be offered HIV treatment in the mobile unit if the 
available regimen is appropriate for them. Intervention arm participants who require a different regimen and 
active control arm participants will be referred for treatment. Initiation of MOUD treatment will be the clinical 
priority, so people living with HIV may defer initiating HIV treatment until established on MOUD. 
9  The exact timing of COWS assessment and MOUD initiation will depend on clinician judgment, the readiness of 
the participant to begin treatment and other factors. See Section 6.2. 
10  Vaccination referral or treatment/treatment referral will be offered at the first visit where results from testing are 
available. 
11  For participants in the intervention arm receiving care in the mobile health delivery unit, ART regimens can be 
selected by study clinicians that treat HIV as well as HBV. Active control arm participants will receive referrals 
indicating their dual infection with HIV and HBV so that they may also receive appropriate treatment.  
12 STI results and referrals provided on a date after results are available, coded as a “split visit”.  
13 The types of samples collected (oropharyngeal, rectal, vaginal) are specified in the SSP Manual.  
14  See SSP Manual for instances when the HIV rapid test at Enrollment may be waived. 
15 HIV testing required for participants who were not previously confirmed to be living with HIV. See SSP Manual. 
16 Other HIV-related testing may be performed for clinical care. This may include HIV drug resistance testing and/or 
HLA-B5701 testing. If indicated, this testing should be performed at a local laboratory; these results will not be 
reported to the HPTN SDMC. 
17 Testing for medications used to treat substance use (see SSP Manual).  
18 Testing for substances of abuse. See SSP Manual Section 4 for guidance about eligibility related to detection of 
opioids in urine. 
19 Testing for pregnancy (urine human chorionic gonadotropin [HCG] testing) for any participant who could 
potentially be pregnant at that visit (unless already known to be pregnant). 
20 Perform HCV Ab testing at enrollment for all participants; perform HCV Ab testing at week 52 for participants 
who tested HCV negative at enrollment.  
21 Perform HCV viral load testing at enrollment, 26 weeks, and 52 weeks for participants who have a positive HCV 
Ab test. HCV RNA viral load testing may be performed on a date after HCV Ab results are available. 
 Perform HBV viral load testing for participants with chronic HBV infection (HBsAg+) or isolated HBcAb 
positive for clinical care management (intervention arm only). 
23 The following tests are required: hemoglobin, creatinine, ALT, AST and total bilirubin. Sites may obtain these 
values by ordering a complete blood count and comprehensive metabolic panel if that is standard practice or less 
costly than performing individual tests. 
24 Plasma will be stored at Screening, Enrollment, 26 and 52 week visits, and at any visits where laboratory-based 
HIV testing is performed. Stored plasma will be used for testing at the HPTN LC, as described in Section 10. 

 
 
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25 Stored urine will be used for testing at the HPTN LC, as described in Section 10. 
26 Stored DBS will be used for testing at the HPTN LC, as described in Section 10. 
27 Stored serum will be used for retrospective testing at the HPTN LC to determine the prevalence of SARS-CoV-2 
seropositivity at baseline, 26 and 52 weeks; stored samples may also be used for specialized testing related to 
COVID-19 (see Section 10 and SSP Manual). 
 
Abbreviations: Ab: antibody; ART: antiretroviral treatment; aPTT: activated partial thromboplastin time; 
COWS: Clinical Opiate Withdrawal Scale; DBS: dried blood spot; GC/CT: gonorrhea/chlamydia; HAV: 
hepatitis A virus; HBV: hepatitis B virus; HBcAb: HBV core antibody; HBsAb: HBV surface antibody; 
HBsAg: hepatitis B surface antigen; HCV: hepatitis C virus; HLA: Human Leukocyte Antigen; MOUD: 
medications for opioid use disorder; NAAT: nucleic acid amplification test; OUD: opioid use disorder; PT: 
prothrombin time; SDMC: Statistical and Data Management Center; SSP: Study specific protocol; STI: 
sexually transmitted infection. 
 
 
 
 
 

 
 
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APPENDIX IB: ADDITIONAL PROCEDURES FOR PARTICIPANTS WHO 
HAVE A REACTIVE OR POSITIVE HIV TEST AFTER ENROLLMENT 
  
Confirmatory visit 
Administrative and Behavioral Procedures 
HIV counseling and test results 
X 
Clinical Evaluations/Procedures 
Initiate or refer for HIV 
treatment1 
X 
Blood collection 
X 
Laboratory Evaluations/Procedures  
HIV testing (see SSP Manual)2 
X 
HIV viral load 
X 
CD4 cell count 
X 
Other HIV related testing3 
X 
Plasma storage4 
X 
DBS storage5 
X 
 
 
1  For participants with documentation of confirmed HIV infection (see SSP Manual).  
2 Site should also ensure that local guidelines for HIV confirmatory testing are followed. 
3Other HIV testing may be performed for clinical care. This may include HIV drug resistance testing and/or HLA-
B5701 testing. If indicated, this testing should be performed at a local laboratory; these results will not be reported 
to the HPTN SDMC. 
4Stored plasma will be used for testing at the HPTN LC, as described in Section 10.  
5  Stored DBS will be used for testing at the HPTN LC, as described in Section 10.  
 

 
 
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APPENDIX II: SAMPLE INFORMED CONSENT FORM - MAIN STUDY 
 
HPTN 094 
INTEGRA: A Vanguard Study of Health Service Delivery in a Mobile Health Delivery Unit 
to Link Persons who Inject Drugs to Integrated Care and Prevention for Addiction, HIV, 
HCV and Primary Care 
 
 
Version 2.0 
20 February 2023 
DAIDS Document ID: 38715 
 
Sponsored by: Division of AIDS, US National Institute of Allergy and Infectious Diseases, US 
National Institutes of Health.  
 
PRINCIPAL INVESTIGATOR: [Insert Name] 
 
PHONE: [Insert Number] 
 
Key Information: 
 
The first two pages of this document include summary information about this study that 
will help you decide whether or not you should participate. More detailed information is 
provided after this summary section. 
 
About this research  
You are being asked to join a research study. Scientists do research to answer important questions 
which might help change or improve the way we do things in the future. This form explains the 
research study and your part in the study. Please read it carefully and take as much time as you 
need. Ask your study doctor or the study team to explain any words or information that you do 
not understand. You may take this description home and discuss it with your family or friends to 
help you decide.  
  
Taking part in this research study is voluntary 
You may choose not to take part in the study or may choose to leave the study at any time. 
Deciding not to participate, or deciding to leave the study later, will not result in any penalty or 
loss of benefits to which you are entitled and will not affect your relationship with the study site. 
 
Important Information  
This information gives you an overview of the research. More information about these topics may 
be found in the pages that follow.  
 
1. Why is this research being done? 
This research study will help us see whether providing medical services in a mobile unit will help 
people who inject drugs (PWID) start and stay on anti-HIV medicines and medicines for opioid 
use disorder better.  
 

 
 
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2. What will happen to me during the study? 
You will either receive health care services at visits conducted from a mobile unit or you will be 
guided to regular clinics in the area for your health care. All participants at Screening and Enrollment 
will receive laboratory testing to evaluate opiate use, HIV, hepatitis and sexually transmitted diseases. 
Participants will also receive a physical exam, counseling and develop a clinical plan with the health 
care providers. All participants will be assigned a peer health navigator to work with them during the 
study. 
  
3. How long will I participate in the study? 
If you decide to join the study, participation will last about 1 year with two visits after enrollment. 
 
4. Will I benefit from the study? 
It is possible that you may benefit from taking part in this study; however, there is no guarantee that it 
will help you. You will get information about your health and the results of the tests, as well as 
treatment for sexually transmitted infections. The counseling you get during this study may help you 
avoid HIV and other sexually transmitted infections. For more information, please see below.  
 
5. Will taking part in the study expose me to risks? 
Taking part in this research may expose you to risks. We may not know or understand all the risks at 
this time. It is very important that you understand the risks in this research study before you decide 
whether you will participate. For details and a list of risks you should know about, please see below. 
 
6. Will I be paid to participate? 
Payment for your time or travel is available if you decide that you will take part in this study. For 
more information, please see below.  
 
7. Will it cost me anything to participate? 
There is no cost to you for taking part in this study. 
  
Please review the rest of this document for details about these topics and additional things 
you should know before making a decision about whether you will participate in this 
research.  
 
 
INTRODUCTION 
 
You are being asked to take part in a research study for people who inject drugs (PWID) with 
opioid use disorder (OUD) who are either without human immunodeficiency virus (HIV) or who 
are living with HIV which means you may either be at risk for getting HIV or could pass HIV on 
to others. HIV is the virus which causes acquired immunodeficiency syndrome (AIDS). This 
research study will help us see whether providing medical services in a mobile unit will help 
PWID start and stay on anti-HIV medicines and medicines for opioid use disorder better.  
 
Before you decide whether to join the study, we will explain the purpose of the study, the risks 
and benefits to you, and what is expected of you if you decide to participate. 
 
A research team member will talk with you about the study, tell you what will happen if you 
decide to participate in this study and give you this consent form to read. If you do not understand 
what you are reading please ask the study staff to explain anything you do not understand, 
including any language contained in this form. You may ask to have this form read to you.  
 

 
 
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After the study is explained to you and all your questions have been answered, you can decide 
whether or not you want to join the study. You do not have to make a decision now; you can take 
the consent document home and share it with family, friends, and your health care provider. 
Taking part in the study is voluntary which means you can choose whether or not to participate. If 
you join the study, you can then choose to leave at any time and it will not affect your eligibility 
to receive regularly-provided health services. 
 
If you decide to join the study, you will be asked to sign this consent form and a copy of this form 
will be given to you. Keep this form; in it you will find contact information for the research staff 
and answers to questions about the study. If you choose not to take a copy of this form, we will 
give you a card with the research staff contact information. 
1. You should know key information about this study before you join.  
 
Here is a summary of important information about the study:  
 
• 
This is a research study. Research is not the same as routine treatment or medical care. The 
purpose of a research study is to answer scientific questions. These answers can help find better 
ways to deliver treatment and improve knowledge of human behavior. 
• 
Your participation in this study is voluntary. You may refuse to join, or you may withdraw your 
consent to be in the study, at any time, for any reason.  
• 
We are doing this study to see whether providing medical services in a mobile unit will help 
PWID start and stay on opioid use treatment medications and anti-HIV medications. 
• 
About 450 PWID either without HIV or who are living with HIV will participate in this study 
from cities in the United States. Participants will be in the study for about one year. 
• 
We will collect blood, urine, and swabs from you at study visits to test for sexually transmitted 
infections (STIs). Collecting blood samples may cause pain, bruise your arm or make you feel 
lightheaded.  
• 
We will test you for HIV, hepatitis A, B, and C and STIs during the study. You will receive 
treatment or referral for treatment as appropriate. The STIs we will test for are Chlamydia, 
gonorrhea, and syphilis. There are other STIs, but we will not test for them as part of this study. 
• 
Before a study visit or at the start of a visit, we will assess you for COVID-19. If you are 
suspected to have COVID-19, you will need to wait until it is safe for you to be seen by study 
staff before we can conduct the visit. 
• 
You may be provided medication for opioid use disorder (MOUD) and anti-HIV medications for 
HIV treatment or prevention, or you will be referred to places where you can get these 
medications. 
• 
There may be some social risks. You may feel embarrassed or uncomfortable with some of the 
questions you will be asked, some of the procedures that will be done, or some of the test results 
that you will receive.  
• 
We will make every effort to protect your confidentiality during the study. However, it is possible 
that others may learn that you are part of this study.  
• 
The counseling you receive during this study may help you to avoid HIV, hepatitis A, B, and C 
and other STIs.  
• 
If you join this study you will receive many health services at no charge while you are 
participating in the research. As well, the information gathered during this study may help to 
develop ways to prevent HIV and other STIs and to increase use of treatment for OUD among 
PWID and their partners in your community.  
 

 
 
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More information is given in this form about the study. You should feel that you understand the 
study before deciding whether you will participate. 
 
ABOUT THE STUDY 
 
The HIV Prevention Trials Network (HPTN) and [insert site name] are doing this study to see whether 
providing medical services in a mobile unit will help PWID start and stay on medications. The 
medications we mean here are for treatment of OUD as well as for treatment or prevention of HIV. About 
450 PWID will participate in this study from cities in the United States. Participants will be in the study 
for about one year.  
 
2. The study is testing a program to provide care for HIV and opioid use disorder to PWID in a 
mobile health delivery unit (“mobile unit”). 
 
Opioid use is the leading cause of accidental death in the United States. Injecting drugs can put people at 
high risk for getting HIV or passing HIV on to others. It can be difficult for people who inject opioids to 
start or stay on medication treatment offered at clinics. These clinics can be hard to get to and sometimes 
people have to go to multiple clinics to get all the services they need. We want to see whether providing 
multiple services in one location—the mobile unit—in a convenient place will make it easier to get 
treatment for OUD and HIV prevention and treatment. Medications offered in the mobile unit will be the 
same medications used in the regular clinics in this city. The only difference will be that they are provided 
in the mobile unit. This study may show a new way to improve the health of PWID.  
 
3. Participants will be placed in 1 of 2 groups. 
 
All participants will be assigned to one of two groups by random chance (the equivalent of flipping a 
coin). The difference between the groups is that the first group will receive health care services delivered 
on a mobile unit. These services include MOUD, HIV testing, HIV treatment for people living with HIV 
and not in care, pre-exposure prophylaxis (PrEP) for people who do not have HIV, and STI testing and 
treatment. The second group will have their initial Screening and Enrollment Visits in the mobile unit, but 
all other visits will occur in regular clinics in the area.  
 
Participants in both groups will be assigned a peer navigator for 26 weeks who will assist participants in 
accessing and remaining in medical care.  
 
All participants will come in for study assessments at approximately six and 12 months after starting the 
study and will be in the study for about a year total.  
 
JOINING THE STUDY 
 
4. It is your decision whether to participate in the study. 
 
This consent form gives information about the study that will be discussed with you. We will help 
you understand the form and answer your questions before you sign this form. Once you 
understand the study, and if you agree to take part, you will be asked to sign your name or make 
your mark on this form. You will be offered a copy of this form to keep.  
 
Before you learn about the study, it is important that you know the following: 
 
• 
Your participation is voluntary.  You do not have to take part in any of the tests or procedures in 
the study. 

 
 
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• 
You may decide not to take part in the study, or you may decide to leave the study at any time. 
Your decision will not affect your eligibility for continuing to receive health care at community-
based services.  
• 
If you decide not to take part in the study, you can still join another study at a later time if there is 
one available and you qualify. 
• 
You cannot join this study if you are taking part in another research study, without special 
permission.  You are asked to tell the study staff about any other studies you are taking part in or 
thinking of taking part in.   
 
5. You must qualify before you can join the study. 
 
If you decide to join this study, we will first do some tests and collect some information from you to find 
out if you qualify. These tests and the information collected are described in #6 below. If you do not 
qualify, you cannot join the study.  
 
6. We will ask you questions, examine you, and test your blood. 
 
To find out if you qualify, we will first conduct a “Screening Visit.” Your Screening Visit will happen 
after you read, discuss, understand, and sign this form. The Screening Visit will take about X hours [sites 
to fill in the amount of time]. 
 
At the Screening Visit, we will:  
 
• 
Ask you about symptoms of COVID-19 and take your temperature. 
• 
Ask you some questions about yourself, like your age, and your ethnic group. 
• 
Ask where you live and how to contact you 
• 
Provide drug use and HIV risk reduction counseling 
• 
Collect ~XX mL (about x teaspoons) [sites to complete] of blood for HIV testing  
• 
Collect urine to test for drug use and drug treatment 
• 
Ask you questions about your sexual and drug use behaviors and drug use history including an 
assessment for Opioid Use Disorder (OUD) and recent injection drug use (track marks)  
• 
Offer you condoms and lubricant and counsel you on how to use them safely   
• 
Provide you with unused needles and dispose of any used needles you have [sites to include if 
they are allowed to provide in their location] 
• 
Offer you a naloxone kit that can be used to treat an overdose, and show you how to use it 
 
We may assess you before or at the start of the visit for COVID-19. If you are suspected to have 
COVID-19, you will need to wait until it is safe for you to be seen by study staff before 
continuing with screening for the study.  
 
The initial results of the HIV test will be available immediately. If your initial test results indicate 
that you have HIV, we will perform additional testing in a laboratory to confirm these results and 
these will be available [site to insert timeframe of testing]. A small amount of blood will be stored 
from this visit. No other samples collected at the time of screening will be kept or used for any 
other tests other than those listed above. 
 

 
 
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7. We will confirm if you qualify for the study.  
 
If the information you provide and the test results from the Screening Visit indicate that you may be 
eligible for the study, you will be asked to return for an “Enrollment Visit”.  This visit will last about X 
hours [sites to fill in the amount of time].   
 
During the Enrollment Visit, we will first determine if you are eligible to enroll in the study. If you are 
enrolled, you will complete additional activities. We expect all Enrollment Visit activities to be completed 
on the same day. If they cannot be completed on the same day, you will need to come back to finish the 
procedures on another day. 
At the Enrollment Visit, before you’re enrolled in the study, we will: 
 
• 
Ask you questions to assess for COVID-19 infection and take your temperature.  If you are 
suspected to have COVID-19, you will need to wait until it is safe for you to be seen by study 
staff before continuing with the visit. 
• 
Confirm where you live and how to contact you. 
• 
Collect urine to test for drug use and drug treatment, STIs,, and, if you are enrolled, to check for 
pregnancy (if you are someone who can become pregnant)  
• 
Collect ~XX mL (about x teaspoons) [sites to complete] of blood for HIV testing and STIs.  If you 
are enrolled, we will then also test your blood for hepatitis (a liver disease) and to assess the 
health of your blood and liver. 
• 
Provide you with HIV test results and HIV counseling.   
• 
Ask you about your sexual practices and medical history, about your history of drug use and drug 
treatment..  We will also ask you about other research studies you are participating in. 
• 
We will ask you to show us the places on your body where you’ve most recently injected drugs. 
• 
Ask you questions about your medical history including MOUD treatment, HIV risk behaviors, 
and participation in other research studies.  We will also ask you about your history of being in 
jail or prison, and about experiences of depression, anxiety or trauma, and your use of tobacco, 
alcohol and other drugs.  
• 
Collect swabs from you to test for STIs.  These swabs may be taken from the throat, rectum and 
vagina. 
• 
Give you a physical exam, that includes measuring your height, weight, heart rate, temperature 
and blood pressure; looking into your mouth and throat; listening to your heart and lungs, feeling 
your neck and abdomen, looking at your skin, arms and legs, additional procedures if indicated 
for your care and asking you about any medicines you are taking.   
• 
Give you the results of tests that are available during the visit and discuss your health needs.   
 
8. If you qualify, you will enter the study 
 
If you are eligible to participate in the study, you will be enrolled during the Enrollment Visit. You will 
then be placed by random chance into either the group that will receive medical care in the mobile health 
delivery unit, or the group that will not. After that, the Enrollment Visit will continue and we will: 
• 
participationadditionalcareStore blood and urine samples for other testing related to this study.  
This may include tests for drugs, medications used to treat HIV, and medications to treat 
substance use. Tests may also be performed to characterize HIV and the body’s response to HIV. 
Similar testing may be performed for hepatitis viruses.  The stored blood samples may also be 
used to learn more about how HIV is spread throughout the community. Blood samples will also 
be used to test for possible exposure to the virus that causes COVID-19 and to learn more about 
how the body responds to COVID-19. Results from testing using stored samples will not be 
returned to you or the study site. 

 
 
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• 
Introduce you to a peer navigator, someone who has been trained to help you get medical services 
and be successful in getting treatment for OUD. 
• 
If you have symptoms of an STI at the time of the visit, we will provide you with treatment right 
away.  If laboratory testing of the samples collected at this visit show you have an STI, we will let 
you know, however these results will not be available until after this visit. 
• 
Make a plan for treating your opioid use disorder and for starting anti-HIV medications to treat or 
prevent HIV.   
• 
Offer you condoms and lubricant and counsel you on how to use them safely. 
• 
Provide you with unused needles and dispose of any used needles you have. [sites to include if 
they are allowed to provide in their location] 
• 
Offer you a naloxone kit that can be used to treat an overdose and show you how to use it 
 
BEING IN THE STUDY 
9. You will have two study visits over a year. In addition to this you will work with your peer 
navigator several times over the first six months of the study. If you are in the group that will 
receive medical care in the mobile unit, you will also have medical visits in the mobile unit at 
various times over the first six months of the study.  
 
Study Visits 
If you join the study you will have at least two additional study visits after your Enrollment Visit. These 
visits will be approximately six months (26 weeks) and 12 months (52 weeks) after the Enrollment Visit. 
Participants who become incarcerated during the Study will be scheduled for study activities for which 
they are eligible upon release.  
 
During the week 26 and 52 study visits, we will: 
 
• 
Ask you questions to assess for COVID-19 infection and take your temperature.  If you are 
suspected to have COVID-19, you will need to wait until it is safe for you to be seen by study 
staff before continuing with the visit. 
• 
Confirm where you live and how to contact you. 
• 
Ask you questions about your sexual practices and medical history, about your history of drug use 
and drug treatment, about your history of being in jail or prison, and about experiences of 
depression, anxiety or trauma. 
• 
Talk with you about HIV and ways to protect yourself from getting it if you do not have HIV.  
• 
Collect ~XX mL (about x teaspoons) [sites to complete] of blood for HIV testing if you are not 
already known to be living with HIV and to test your blood for STIs and hepatitis (a liver 
disease). We will test the level of HIV virus in your blood (viral load) if you have HIV. 
• 
Collect urine to test for drug use and drug treatment, and to check for pregnancy (if you are 
someone who can become pregnant)  
• 
Collect swabs from you to test for STIs.  These swabs may be taken from the throat, rectum and 
vagina. 
• 
We will store blood and urine samples for other testing related to this study.  This may include 
testing for drugs, medications used to treat HIV and substance use, and other tests related to HIV 
and HCV infection.  The stored blood samples may also be used to learn more about how HIV 
and HCV are spread throughout the community. Blood samples will also be used to test for 
possible exposure to the virus that causes COVID-19 and to learn more about how the body 
responds to COVID-19. Results from testing using stored samples will not be returned to you or 
the study site. 
• 
Provide treatment if you have symptoms of an STI. 

 
 
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• 
Give you the results of tests when they are available. 
• 
If your laboratory testing shows that you have an STI, we will refer you for treatment. 
• 
Offer you condoms and lubricant and counsel you on how to use them safely. 
• 
Provide you with unused needles and dispose of any used needles you have. [sites to include if 
they are allowed to provide in their location] 
• 
Offer you a naloxone kit that can be used to treat an overdose and show you how to use it 
 
Each of these visits will last about X hours [site staff to insert amount of time]. At your final study visit 
(week 52 visit), we will talk with you about what will happen when the study is over, including when the 
results of the study will be available.  
 
Visits with Your Peer navigator 
You will work with a peer navigator during the first six months of the study. Your peer navigator will 
help you address issues that may have made it hard for you to get care in the past. They will act as a coach 
to help you stay motivated in treatment for opioid use disorder and HIV care or prevention. They will 
remind you of medical appointments you have and help you find medical and other resources available to 
you in your community. 
 
You will mostly work with your navigator in-person at the start of the six months. Over time you may 
work together more over the phone/through messaging apps. If you are in the group that receives medical 
care in the mobile unit, your navigator will help you transition your medical care to a clinic or clinics in 
your community before the six months is over. If you are in the group that does not get medical care in 
the mobile unit, your navigator will work with you to get medical care at a clinic or clinics in your 
community right from the start. 
 
How often you interact with your navigator and how long these interactions last will depend on your 
needs. We expect you will be in contact with your navigator multiple times per month.  
 
Medical Care Visits in the Mobile Unit 
If you are put in the group that will receive medical care in the mobile unit, you will have multiple visits 
to the mobile unit over the first six months of the study. How often you have visits and how long they last 
will depend on your medical needs. This may change over time. 
 
Note that if you already receive medical care from providers in the community and are happy with this 
care, you do not have to switch to care in the mobile unit. You can also choose to get some care in the 
mobile unit and other care from regular clinics in the community. 
 
A primary goal of the care you receive in the mobile unit will be to provide you with medical treatment 
for opioid use disorder. The medications expected to be used in this Study will be buprenorphine or 
combination buprenorphine/naloxone. The Study Team will work with the U.S. Drug Enforcement 
Administration at national and local levels to comply with policies for dispensation of buprenorphine and 
buprenorphine/naloxone to participants. Another primary goal is to provide you with HIV treatment 
(ART) if you are living with HIV or to provide you with HIV prevention (PrEP) if you are not living with 
HIV. 
 
What happens at a medical care visit will depend on your medical needs at the time. We would expect 
that they would include at least some of the following: 
 

 
 
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• 
Ask you questions to assess for COVID-19 infection and take your temperature.  If you are 
suspected to have COVID-19, you will need to wait until it is safe for you to be seen by study 
staff before continuing with the visit. 
• 
Confirm where you live and how to contact you. 
• 
Ask you questions about your sexual practices, medical history, drug use and drug treatment 
history and how you feel about how your life is going. 
• 
Talk with you about HIV and ways to protect yourself from getting it if you do not have HIV 
• 
Give you a physical exam that may include measuring your weight, temperature, blood pressure, 
looking into your mouth and throat, listening to your heart and lungs, feeling your abdomen 
(stomach and liver), additional procedures if indicated for your care and asking you about any 
medicines you are taking.   
• 
Begin HIV treatment if you are living with HIV. Offer PrEP if you are without HIV. 
• 
Provide medications to treat opioid use disorder. 
• 
Provide referral for vaccinations for hepatitis A and B. 
• 
Provide referral for treatment, if you have hepatitis B or C. 
• 
Collect ~XX mL (about x teaspoons) [sites to complete] of blood for HIV testing if you are not 
already known to be living with HIV and to test your blood for STIs. We will test the level of 
HIV virus in your blood (viral load) and the health of your blood (CD4 cell count) if you have 
HIV. 
• 
Collect urine to test for drug use, and to check for pregnancy (if you are someone who can 
become pregnant).  
• 
Collect swabs from you to test for STIs.  These swabs may be taken from the throat, rectum and 
vagina. 
• 
We will store blood samples for other testing related to this study at any visit where HIV testing 
is done.  This may include testing for medications used to treat HIV and other tests related to HIV 
and HCV infection.  The stored blood samples may also be used to learn more about how HIV 
and HCV are spread throughout the community. Results from testing using stored samples will 
not be returned to you or the study site. 
• 
Provide treatment if you have symptoms or laboratory results indicating an STI. 
• 
Give you the results of tests when they are available. 
• 
Offer you condoms and counsel you on how to use them safely. 
• 
[Sites to include if allowed at their location: “Provide you with unused needles and dispose of any 
used needles you have.”]  
• 
Offer you a naloxone kit that can be used to treat an overdose and show you how to use it 
 
10. If you stop participating in peer navigation, or stop receiving OUD or HIV care or 
prevention, we will ask you to stay in the study. 
 
We hope that if you join this study, you will work with your peer navigator for the full six 
months. We also hope that you will start and stay on treatment for OUD and receive HIV 
treatment or prevention for the full six months (in the mobile unit if that is your group). But if 
you stop these activities for any reason, we still ask you to continue to come for the study visits at 
26 and 52 weeks. The data you provide at these study visits will still be important to the outcome 
of this study. You always have the right to stop participating in the study completely at any time. 
 
11. If you acquire HIV during the study, we will help you get care and support.  
 
We will test your blood for HIV during this study. If you are without HIV when you join the study and 
test positive for HIV while you are in the study you will stop taking PrEP if you started PrEP. You will be 
asked to come back to provide an additional ~XX mL (about x teaspoons) [sites to complete] blood to 

 
 
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confirm the HIV result and to provide additional samples for other assessments. You will also be asked to 
complete the remaining study visits (26 and/or 52 weeks). We will provide or help you find the care and 
support you need. You will still continue to receive peer navigation through six months and will continue 
to receive medical care in the mobile unit, if you are in the group that receives care in the mobile unit. 
 
12. We will test you for pregnancy during the study if you are someone who can become 
pregnant.  
 
We will collect urine to test for pregnancy and will give you these results each time. If you become 
pregnant during the study, you will be able to stay in the study as originally planned. If you are pregnant 
at the last study visit, we will contact you after that to find out the outcome of the pregnancy. 
 
Even if you are in the group to receive medical care in the mobile unit, the study cannot provide all the 
medical care you will need for a pregnancy or delivery of a baby. The baby will not be in the study. 
Therefore, it is important to receive medical care for a pregnancy outside the study. We will tell you 
where you can go for the care you need. 
 
If you are taking ART or PrEP and become pregnant, we will  provide some basic information about your 
pregnancy, such as what medications you took while pregnant, what prenatal care you received, and the 
outcome of your pregnancy, to the Antiretroviral Pregnancy Registry. None of your personal information, 
such as your name or address, will be provided to the registry. You can learn more about this registry at 
www.apregistry.com. 
 
13. Some of your blood and urine may be left over at the end of the study and may be used for 
future research, if you provide consent. 
  
Some of your blood and urine collected for this study may be left over after all of the study tests are 
completed. If you agree, these stored samples may also be used for future research related to HIV 
infection, hepatitis infection, COVID-19, and other infections, and to better understand laboratory tests 
related to this study. This research will not include whole genome sequencing also known as WGS. 
 
You will be asked to sign this consent form to give permission to use your stored samples for future 
research. Even if you do not give permission to store your blood for possible future research, you can still 
be in this study. If you give permission, you will not be asked to give permission again during the study. 
However, you may withdraw your consent to use your stored samples for future research at any time. We 
will then destroy your samples after all of the study-related testing has been completed. If you agree to 
have your stored samples used for future research, there is no time limit on how long your samples will be 
stored. The stored samples will be labeled only with your study number and will be tested at the HPTN 
Laboratory Center (LC) or laboratories designated by the HPTN LC. We will not share the key that says 
which study number is yours so the laboratory doing the testing will not know who you are. Only 
approved researchers will have access to your samples. Results from this testing will not be returned to 
the study site or you. Your samples will not be sold or directly used to produce commercial products or 
for commercial gain. All proposed research studies using your samples will be reviewed by the National 
Institutes of Health (NIH).  
 
RISKS OF THE STUDY  
 
14. There may be risks to being in this study.  
 
STUDY PROCEDURES 
 

 
 
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Taking blood samples may cause some pain, bruise your arm, or make you feel lightheaded. In rare cases 
you may faint. There is also a slight chance of infection when blood is drawn. You may be nervous while 
you are waiting for your HIV or other test results. If the tests show that you have HIV or another 
infection, you may worry about your health and future. You will receive counseling before and after the 
test to help address your concerns.  
 
You may experience pain or discomfort in your throat, rectum or vagina from the swab. In some cases, 
you may have some bleeding. 
 
You will be tested for gonorrhea, chlamydia, syphilis, and hepatitis. [Note to sites:  Insert here any 
reporting responsibilities for your state or local jurisdictions or reporting of these infections to public 
health authorities. Also include whether if a participant tests positive, the results will become part of 
public health records, or any other record (medical file, etc.)]. 
 
DISCLOSURE OF PERSONAL INFORMATION 
 
We will make every effort to protect your confidentiality during the study. However, it is possible that 
others may learn that you are part of this study and they may think that you are living with HIV or are at 
high risk for acquiring HIV. They could make assumptions about your use of drugs. Because of this, you 
could face stigma related to HIV or drug use. This could cause you trouble finding or keeping a job. You 
could also have problems with your family, friends and community. If you work with a peer navigator, 
you may choose to communicate with your navigator by text or messaging apps. If others have access to 
your phone, they may be able to see these communications. You should consider carefully what kind of 
information you want to share in this way. We can tell you more about how we will protect your 
information.  
 
SENSITIVE QUESTIONS 
 
The questions we will ask you like about your sexual practices, medical history, drug use, 
history of being in jail or prison, experiences of depression, anxiety or trauma may make 
you feel uneasy. However, you do not have to answer any question that you do not want to and 
you can stop answering the questions at any time.  
 
SIDE EFFECTS OF MEDICATIONS 
 
If you are assigned to the group that will NOT receive medical care in the mobile health delivery unit, 
you may receive medications from the study staff at the Enrollment Visit. These will be medications to 
treat STIs, if you have STI symptoms at the Enrollment Visit. The clinician will explain to you any side 
effects associated with those medications. After the Enrollment Visit, your peer navigator will help you 
receive care at the regularly available clinics in your community. The staff at those facilities can explain 
to you the side effects of any medications they give to you or prescribe for you. You will also be offered 
naloxone kits during your study participation that can be used to treat an overdose. The side effects of 
naloxone will be explained to you. 
 
If you are assigned to the group that WILL receive medical care in the mobile unit, you will receive or 
be prescribed medications by the study staff during the first six months of your participation in the study. 
The drugs you could be given on the mobile unit include medications to treat or prevent STIs or other 
bacterial infections, hepatitis, HIV, opioid use disorder or overdose. You may also be prescribed 
medications that you will need to pick up at a pharmacy. The clinician will explain to you the side effects 
of the specific medications you are prescribed or given. 
 

 
 
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IF YOU ARE PREGNANT OR BECOME PREGNANT WHILE PARTICIPATING IN THE STUDY 
The medications provided in this study are the same types of drugs that would be provided as part of 
regular care at clinics in your community and are commonly provided to pregnant people. There is no 
greater risk to you by receiving them as part of this study. If you are in the group that receives medical 
care in the mobile unit, your clinician will tell you if the medications you are taking have any risks or 
side effects that apply to pregnant people. If you are in the group that does not receive medical care in the 
mobile unit, you should tell your clinician that you are pregnant so that they can explain to you any risks 
or side effects of your treatment that apply to pregnant people. 
 
BENEFITS OF THE STUDY 
 
15. There may be direct and indirect benefits to you from participating in the study.  
 
If you participate in this study, you will receive many health services at no charge. You will be 
tested for HIV, hepatitis A, B, and C, and other STIs. You will receive treatment or referral for 
treatment, as appropriate, if you have these infections. The counseling you get during this study 
may help you to avoid HIV, hepatitis A, B, and C, and other STIs. If you have or get HIV, this 
counseling may help you to learn how to better care for yourself and avoid passing HIV to your 
sexual partners (or fetus, if you are or become pregnant). If you do not have HIV, you will be 
offered PrEP or referral for PrEP to help you avoid getting HIV. Your peer navigator will work to 
link you to health services, including treatment for OUD and HIV care or prevention services. 
You will receive free condoms and lubricant, and naloxone kits for overdose reversal. If you are 
put in the group that receives medical services in the mobile unit, you will be provided with 
medical care and medication in a single convenient location.  
 
If you are pregnant or become pregnant while participating in the study, there may be benefits to 
your fetus from participating in this study. Being on medical treatment for OUD may let you take 
better care of yourself, which will benefit your fetus. Taking OUD medication may decrease your 
use of street drugs, which can also benefit your fetus. Taking medication to either treat or prevent 
HIV while you are pregnant can help you prevent passing HIV on to your fetus. 
 
You may receive indirect benefits from this study. The information gathered during this study 
may show how medical services can be provided more successfully to people who inject drugs, 
particularly services for OUD and HIV. This could influence how medical services are provided 
in the future and may be beneficial to you and your community.  
 
OTHER INFORMATION ABOUT THE STUDY 
 
16. Some of the information we collect from you for this study may be used for other research. 
 
Information collected from this study may be used for other studies carried out by this team or by 
other researchers. The information we share with other researchers would never include your 
name or any other information that could identify you.  
 
17. We will tell you any new information that may affect your decision to be in the study.  
 
You will be told any new information learned during this study that might affect your willingness 
to stay in the study. You will also be told when the results of the study may be available, and how 
to learn about them.  
 
18. You may be withdrawn from the study without your consent.  

 
 
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We may take you out of the study at any time without your consent. This may happen if:  
 
• 
You are unable or unwilling to follow all of the study procedures or instructions.   
• 
The study is stopped or canceled. 
• 
The study staff feels that staying in the study would be harmful to you. 
• 
Other reasons, as decided by the study staff.  
 
If we take you out of the study, we may ask you to come back to the clinic one last time to collect a blood 
sample and ask you questions.  
 
19. You have other choices if you choose not to be in this study.  
 
[Sites to include/amend the following if applicable] There may be other studies going on here or 
in the community that you may be eligible for. If you wish, we will tell you about other studies 
that we know about. There also may be other places where you can go for HIV counseling and 
testing, HIV treatment or PrEP, and medication for OUD. We will tell you about those places if 
you wish. 
 
20. There is no cost to you to be in this study.  
 
There will be no cost to you for study related visits, physical examinations, laboratory tests, or 
other procedures or medications you receive in the mobile health unit.  
 
The study will not pay for any medications or health services you receive outside of the mobile 
unit. This is true even if you are given a prescription or a referral for these by the staff in the 
mobile unit. However, study staff will help connect you to health services in the community that 
may be free or low-cost and will help you to sign up for health insurance that you are eligible for. 
 
21. We will give you [site to insert amount] for each study visit. 
 
You will receive [$xx] for your time, effort, and travel to and from the clinic at each scheduled visit. We 
may invite you to refer people you know to enroll in this study and offer to pay you if those people enroll. 
If so, you will receive [$xx] for each of these referrals. [Sites to insert information about local 
reimbursement for the study.]   
 
22. We will do our best to protect your private information.  
 
Every effort will be made to keep your personal information confidential, but we cannot guarantee 
absolute confidentiality. To keep your information private, the samples of your blood and urine that are 
used for research purposes will be labeled with a code that can only be traced back to your study 
clinic. Your name, where you live, and other personal information will be protected by the study 
clinic. The results of any tests done on these research samples will not be included in your 
health records. You will be identified by a code, and personal information from your records will not 
be released without your written permission. Any publication of this study will not use your name 
or identify you personally. Your personal information may be disclosed if required by law. 
 
Clinic staff will have access to your study records. Your records may also be reviewed, under guidelines 
of the US Federal Privacy Act, by: 
 

 
 
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• 
The [insert name(s) of Single Institutional Review Board (IRB)] 
• 
The sponsor of the study (US National Institutes of Health [NIH]), its contractors, and its study 
monitors 
• 
the National Institute on Drug Abuse (NIDA) and/or their contractors 
• 
The US Office for Human Research Protections (OHRP) 
• 
other local, US, and international regulatory entities 
• 
Personnel of the HPTN research network that is conducting this study 
• 
And (insert any other applicable local authorities] 
 
In addition to the efforts made by the study staff to help keep your personal information 
confidential, we have obtained a Certificate of Confidentiality from the US Federal Government. 
This Certificate protects researchers from being forced to tell people who are not connected with 
this study, such as the court system, about your participation. The Certificate of Confidentiality 
does not prevent you from releasing information about yourself and your participation in the 
study. The Certificate cannot be used to resist a demand for information from personnel of the US 
Government that is used for auditing or evaluation of federally funded projects or for information 
that must be disclosed in order to meet the requirements of the US FDA. Even with the Certificate 
of Confidentiality, if the study staff learns of possible child abuse and/or neglect or a risk of harm 
to you or others, we will tell the proper authorities. 
 
The study staff will also use your personal information, if needed, to verify that you are not 
taking part in any other research studies. This includes other studies conducted by [site name] and 
studies conducted by other researchers that study staff know about. 
 
[Sites to include/amend the following if applicable:] [Local/state/national] regulations require 
study staff to report the names of people who test positive for [HIV and other infections] passed 
during sex to the [local health authority]. Outreach workers from the [health authority] may then 
contact you about informing your partners, since they also should be tested. If you do not want to 
inform your partners yourself, the outreach workers will contact them, according to the 
confidentiality guidelines of the [health authority]. 
 
The virus in one person with HIV is slightly different from the viruses in other people. If you give 
us permission to save your samples for future testing, and you are living with HIV, we may use 
special laboratory tests to compare the virus in your blood to the virus from other people with 
HIV. This can help us understand how HIV is spread throughout communities. The samples used 
for this testing will not include any information that would identify you, like your name. This is 
to prevent anyone from being able to connect any information we learn about your HIV to you. 
The results of this analysis will only be used for research.  
 
23. If you get sick or injured during the study, contact us immediately.  
 
[Sites to specify institutional policy:] It is unlikely that you will be injured as a result of study 
participation. If you are injured, the [institution] will give you immediate necessary treatment for 
your injuries. You [will/will not] have to pay for this treatment. You will be told where you can 
get additional treatment for your injuries. There is no program to pay money or give other forms 
of compensation for such injuries either through this institution or the US NIH. You do not give 
up any legal rights by signing this consent form. 
 
24. Contact us at any time if you have questions or problems. 
 

 
 
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If you ever have any questions about the study, or if you have a research-related injury, you 
should contact [insert name of the investigator or other study staff] at [insert telephone number 
and/or physical address]. 
 
An institutional review board (IRB) is an independent committee established to help 
protect the rights of research participants. If you have any questions about your rights as a 
research participant, and/or concerns or complaints regarding this research study, contact: 
 
• By mail: 
Study Subject Adviser 
Advarra IRB 
6100 Merriweather Drive 
Suite 600 
Columbia, MD 21044 
• or call toll free:    877-992-4724 
• or by email:          adviser@advarra.com 
 
If you have questions about who to contact at the research site, you should contact [insert name of 
the investigator or community educator or CAB member] at [insert physical address and 
telephone number] 
 
 

 
 
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SIGNATURE PAGE 
 
HPTN 094 
INTEGRA: A Vanguard Study of Health Service Delivery in a Mobile Health Delivery Unit 
to Link Persons who Inject Drugs to Integrated Care and Prevention for Addiction, HIV, 
HCV and Primary Care 
 
Version 2.0   
20 February 2023 
 
(Modify as needed per protocol requirements) 
Insert signature blocks as required by the local IRB:] If you have read this consent form, or had it 
read and explained to you, and you understand the information, and you voluntarily agree to join 
the study, please sign your name or make your mark below. Also, please indicate by providing 
your initials in the spaces below if you agree to long-term storage and future testing of your samples. 
 
________ 
I agree to take part in this study. 
 
________ 
I agree to have samples of my blood stored for future testing related to HIV infection, 
HCV infection, COVID-19, other infections, and other goals of this study. 
 
________ 
I agree to have samples of my urine stored for future testing related to HIV infection, 
HCV infection, COVID-19, other infections, and other goals of this study   
 
________ 
I do not agree to have samples of my blood stored and used for future testing. 
 
________ 
I do not agree to have samples of my urine stored and used for future testing. 
 
 
 
 
 
 
 
____________________________________ 
Participant Name (print) 
 
 
Participant Signature and Date 
 
 
 
 
 
 
____________________________________ 
Study Staff Conducting  
 
 
Study Staff Signature and Date 
Consent Discussion (print) 
 
 
 
 
 
____________________________________ 
Witness Name (print) 
 
 
 
Witness Signature and Date 
(As appropriate) 
 
 
 

 
 
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APPENDIX III: SAMPLE INFORMED CONSENT FORM- QUALITATIVE 
INTERVIEWS 
HPTN 094 
INTEGRA: A Vanguard Study of Health Service Delivery in a Mobile Health Delivery Unit 
to Link Persons who Inject Drugs to Integrated Care and Prevention for Addiction, HIV, 
HCV and Primary Care 
 
Final Version 2.0 
20 February 2023 
DAIDS Document ID: 38715 
 
Sponsored by: Division of AIDS, US National Institute of Allergy and Infectious Diseases, US 
National Institutes of Health.  
 
PRINCIPAL INVESTIGATOR: [Insert Name] 
 
PHONE: [Insert Number] 
KEY INFORMATION 
• 
Participation in this research study is entirely voluntary.  
• 
This study is part of a larger research project focused on people who inject drugs with 
opioid use disorder. That project is testing whether providing medical services in a 
mobile unit can help people who inject drugs stay on anti-HIV medicines and on 
medicines for opioid use disorder. 
• 
This research study will involve conducting interviews with different kinds of people to 
better understand what makes it easier or harder to successfully offer medical services in 
a mobile unit to people who inject drugs. Your participation will consist of a one-time, 
audio-recorded interview, conducted in-person or via phone/internet, and is expected to 
last 30-60 minutes. 
• 
Risks or discomforts associated with participating in this research study include potential 
feelings of discomfort due to the interview questions, as well as potential breaches of 
confidentiality and privacy. 
• 
It is unlikely that you will receive any direct benefit from participating in this research 
study. We hope that the information gathered from these interviews lead to better health 
options in the future for people who inject drugs. 
 
INTRODUCTION  
You are being asked to participate in an interview to help us understand what makes it 
easier or harder to successfully offer medical services in a mobile unit to people who 
inject drugs. We will interview different kinds of people to answer this question, 
potentially including leaders in the community, health care providers, people who inject 

 
 
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drugs and people who work with people who inject drugs, law enforcement, harm 
reduction leaders and advocates, medical examiners/coroner’s office, and scientists who 
are involved in studying PWID in the area.  
VOLUNTARY PARTICIPATION  
Your participation in this study is voluntary. You may refuse to join, or you may 
withdraw your consent to be in the study, at any time, for any reason. [For potential 
interviewees who are participants in the main study: “If you decide not to take part in 
this study, or if you join this study and then decide to leave, it will not alter the medical 
care you are eligible to receive. It also will not affect your ability to participate in the 
main study.”] [For potential interviewees who are staff members at a site: “If you decide 
not to take part in this study, or if you join this study and then decide to leave, it will not 
have any effect on your employment. You have the same right to decide whether to 
participate as main study participants do and will not be viewed as “uncooperative” if you 
choose not to participate.”] Although we hope that you will be comfortable answering all 
of the questions openly and honestly, please remember that you may refuse to answer any 
of the questions, or stop participating in the interview completely, at any time.  
Before you decide whether to join the study, we would like to explain the purpose of the 
study, the risks and benefits to you, and what is expected of you.  
This consent form gives information about the study that will be discussed with you. We 
will help you understand the form and answer your questions before you sign this form. 
Once you understand the study, and if you agree to take part, you will be asked to sign 
your name or make your mark on this form. You will be offered a copy of this form to 
keep.  
PURPOSE OF THE STUDY 
The purpose of this study is to learn what makes it easier or harder to successfully offer 
medical services in a mobile unit to people who inject drugs. The information you give in 
this interview will be combined with information collected during the main research 
study. We expect to interview approximately 195 people (39 people total in this city) 
from the cities where the main research study is being conducted. We hope that in the 
future the information collected in this study will allow medical care to better meet the 
needs of people who inject drugs. 
STUDY PROCEDURES 
If you decide to participate in this study, you will have one interview. The interview will 
be conducted by a member of the research team either in person or via phone. They will 
ask you where you live and how to contact you. They will ask you specific interview 
questions to address the overall question   
 
[for local public health officials: “what public health infrastructures would be needed to 
deliver medical services in a mobile unit to persons who inject drugs in the absence of 
this study?”] 
[for staff at existing community-based services: “in what ways does delivery of 
medical services in a mobile unit affect how people who inject drugs are served in this 
community?”] 

 
 
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[for staff on the moble mobile unit: “what are the resource and personnel needs you 
have had to address to deliver medical services to people who inject drugs on a mobile 
unit?”] 
[for study participants: “in what ways can having medical services in a mobile unit 
affect the health of people who inject drugs in this city?”] 
 
To help make sure that we fully understand your answers, the interviews will be audio-
recorded. The information on the audio-recording will then be turned into a transcript (a 
written record of the conversation) by an individual who works with the research team. 
Your name will not be included in that written record.  
• 
The interview requires only one study visit and will take 30-60 minutes to complete. 
• 
There will be no cost to you to participate in the interview. 
• 
You will receive [site to fill-in] for your time and effort.  
RISKS AND/OR DISCOMFORTS 
The risk to you in participating in this interview is that some of the questions may be 
uncomfortable or make you feel uneasy. However, you do not have to answer any 
question that you do not want to and you can stop answering the questions at any time. 
You will also be provided with contact and referral information if any of the questions 
raise issues that you would like to address at this or some later time. Other possible risks 
associated with this study may include breaches of confidentiality. Although study sites 
will make every effort to protect your privacy and confidentiality, it is possible that your 
involvement in the study could become known to others, and that social harms (e.g., 
unfair or discriminatory treatment) may result. To reduce the likelihood of these risks, all 
interviews will be conducted in a private setting, and names/identifying information will 
be removed from transcriptions to protect confidentiality.  
BENEFITS 
It is unlikely that you will receive any direct benefit from being in this study; however, 
information gathered during this study may lead to better health options in the future for 
people who inject drugs.  
STUDY RESULTS 
You will be told when the results of the study may be available, and how to learn about 
them. 
WHY YOU MAY BE WITHDRAWN FROM THE STUDY WITHOUT YOUR 
CONSENT 
You may be withdrawn from the study without your consent if any of the following 
occur:  
You are unable or unwilling to follow all of the study procedures or instructions.   
The study is stopped or canceled. 
The study staff feels that staying in the study would be harmful to you. 
You are not able to complete all study procedures. 

 
 
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Other reasons, as decided by the study staff.  
CONFIDENTIALITY 
The research team will protect your confidentiality by not putting your name on 
any audio files or interview transcripts. These items will be labeled with a code 
that can only be traced back to your study clinic and these items will be kept in a 
secure location that can only be accessed by the study staff. Your name and other 
personal information will be protected by the study clinic. Your information collected as 
part of this research study will not be used or distributed for future studies even if 
identifiers are removed. 
Efforts will be made to keep your study records and test results confidential to the extent 
permitted by law. However, we cannot guarantee absolute confidentiality. Your personal 
information may be disclosed if required by law. You will be identified by a code, and 
personal information from your records will not be released without your written 
permission. Any publication of this study will not use your name or identify you 
personally. However, your records may be reviewed, under guidelines of the US Federal 
Privacy Act, by the sponsor of the study (US National Institutes of Health [NIH]) and/or 
its authorized representatives, the Institutional Review Board (IRB), study staff, study 
monitors, [insert applicable local authorities] and other local, US or international 
regulatory authorities.  
In addition to the efforts made by the study staff to help keep your personal information 
confidential, we have obtained a Certificate of Confidentiality from the US Federal 
Government. This Certificate protects researchers from being forced to tell people who 
are not connected with this study, such as the court system, about your participation. The 
Certificate of Confidentiality does not prevent you from releasing information about 
yourself and your participation in the study. The Certificate cannot be used to resist a 
demand for information from personnel of the US Government that is used for auditing or 
evaluation of federally funded projects or for information that must be disclosed in order 
to meet the requirements of the US FDA. Even with the Certificate of Confidentiality, if 
the study staff learns of possible child abuse and/or neglect or a risk of harm to you or 
others, we will tell the proper authorities. 
Your records may be reviewed by: 
the US NIH 
the US Department of Heath and Human Services (DHHS), Office for Human Research 
Protection (OHRP) 
the National Institute on Drug Abuse (NIDA) and/or their contractors 
[insert name of IRB] 
US, local or international regulatory authorities/entities 
study staff 
study monitors 
Other regulatory agencies 
RESEARCH-RELATED INJURY 

 
 
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[Sites to specify institutional policy:] It is unlikely that you will be injured as a result of 
study participation. If you are injured, the [institution] will give you immediate necessary 
treatment for your injuries. You [will/will not] have to pay for this treatment. You will be 
told where you can get additional treatment for your injuries. There is no program to pay 
money or give other forms of compensation for such injuries either through this 
institution or the US NIH. You do not give up any legal rights by signing this consent 
form. 
PROBLEMS OR QUESTIONS 
If you have any questions about the study, or if you have a research-related injury, you 
should contact [insert name of the investigator or other study staff] at [insert telephone 
number and/or physical address]. 
If you have questions about your rights as a research participant, you should contact 
[insert name or title of person on the IRB or other organization appropriate for the site] 
at [insert physical address and telephone number]. 
If you have questions about who to contact at the research site, you should contact [insert 
name of the investigator or community educator or CAB member] at [insert physical 
address and telephone number]. 
 

 
 
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SIGNATURE PAGE 
 
HPTN 094 
INTEGRA: A Vanguard Study of Health Service Delivery in a Mobile Health Delivery Unit 
to Link Persons who Inject Drugs to Integrated Care and Prevention for Addiction, HIV, 
HCV and Primary Care 
 
Final Version 2.0 
20 February 2023 
 
 
If you have read this consent form, or had it read and explained to you, and you understand the 
information, and you voluntarily agree to join the study, please sign your name or make your 
mark below.  
 
 
 
 
 
 
____________________________________ 
Participant Name (print) 
 
 
Participant Signature and Date 
 
 
 
 
____________________________________ 
Study Staff Conducting  
 
 
Study Staff Signature and Date 
Consent Discussion (print) 
 
 
 
 
____________________________________ 
Witness Name (print) 
 
 
 
Witness Signature and Date 
(As appropriate)