Integrated Treatment and Prevention for People Who Inject Drugs: A Vanguard Study for a Network-based Randomized HIV Prevention Trial Comparing an Integrated Intervention Including Supported Antiretroviral Therapy to the Standard of Care
Phase: NA
Conditions: HIV Positive
Sponsor: HIV Prevention Trials Network

HPTN074 
Integrated treatment and prevention for people who inject drugs: A vanguard study for a 
network-based randomized HIV prevention trial comparing an integrated intervention 
including supported antiretroviral therapy to the standard of care 
A Study of the HIV Prevention Trials Network 
Sponsored by: 
Division of AIDS, US National Institute of Allergy and Infectious Diseases 
US National Institute on Drug Abuse 
US National Institutes of Health 
Protocol Chair: 
William Miller, MD, PhD, MPH 
Protocol Co-Chair: 
Irving Hoffman, PA, MPH 
Final Version 2.0 
26 July 2017 
DAIDS Document ID: 11917 

HPTN074 
Integrated treatment and prevention for people who inject drugs: A vanguard study for a 
network-based randomized HIV prevention trial comparing an integrated intervention 
including supported antiretroviral therapy to the standard of care 
TABLE OF CONTENTS 
LIST OF ABBREVIATIONS AND ACRONYMS .................................................................... v 
PROTOCOL TEAM ROSTER ................................................................................................. vii 
PROTOCOL SIGNATURE PAGE ........................................................................................... xi 
SCHEMA ............................................................................................................................... ; .. xii 
Table 1. Estimated Sample Size .............................................................................................. xiii 
OVERVIEW OF STUDY DESIGN AND RANDOMIZATION SCHEME ............................ xv 
1.0 
INTRODUCTION ........................................................................................................ · ..... ! 
1.1 
Background ....................................................................................................................... 1 
1.2 
Rationale ........................................................................................................................... 2 
Figure 1: Conceptual Framework ................................................................................................ 5 
1.3 
Theoretical Basis for Intervention ..................................................................................... 6 
2.0 
STUDY OBJECTIVES AND DESIGN ........................................................................... 7 
2.1 
Primary Objectives ............................................................................................................ 7 
2.2 
Secondary Objectives ........................................................................................................ 8 
2.3 
Study Design ..................................................................................................................... 8 
Table 1. Estimated Sample Size ................................................................................................ 10 
3.0 
STUDY SETTING AND POPULATION ...................................................................... 10 
Table 2. Availability of substance use treatment and registration requirements for the most 
suitable sites ............................................................................................................................... 11 
3 .1 
Inclusion Criteria ............................................................................................................. 13 
3 .2 
Exclusion Criteria ........................................................................................................... 14 
3 .3 
Recruitment process for index participants ..................................................................... 14 
3 .4 
Identification of network injection partners .................................................................... 16 
3.5 
Co-Enrollment Guidelines .............................................................................................. 17 
3.6 
Participant Retention ....................................................................................................... 18 
3. 7 
Participant Withdrawal ................................................................................................... 18 
4.0 
STUDY INTERVENTION PACKAGE ........................................................................ 19 
Table 3. Summary of intervention and standard packages of services by study arm ................ 19 
4.1 
Standard package of services (standard care arm) .......................................................... 20 
4.2 
Intervention package of services (intervention arm) ....................................................... 20 
4.2.1 
Systems navigators .................................................................................................. 21 
4.2.2 
Psychosocial counseling .......................................................................................... 22 
4.2.3 
Systems navigator and psychosocial counseling personnel. .................................... 23 
4.2.4 
Initiation of ART ..................................................................................................... 23 
5.0 
STUDY PROCEDURES ................. .-............................................................................... 23 
5.1 
Study Intervention Package ............................................................................................ 24 
5.1.1 
Systems Navigation ................................................................................................. 24 
5 .1.2 
Psychosocial Counseling ......................................................................................... 24 
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5.2 
Behavioral measurements - index participants and network injection partners .............. 24 
5.2.1 
Sexual behavior, substance use, substance use treatment and ART experience 
interviews (for Index Participant only) .................................................................................. 24 
5.2.2 
Social Network Interviews ...................................................................................... 25 
5 .2.3 
Social Impact Assessments ...................................................................................... 25 
5.2.4 
Assessment of barriers and facilitators to ART (Index only) and substance use 
treatment ................................................................................................................................ 25 
5 .3 
Laboratory Assessments ................................................................................................. 26 
5.3.1 
Laboratory Assessments for HIV-infected Index Participants ................................ 26 
5.3.2 
Laboratory Assessments for HIV-uninfected Network Injection Partners .............. 26 
5.3.3 
Additional Laboratory Assessments for Network Injection Partners Who Acquire 
HIV During the Study ............................................................................................................ 27 
5.3.4 
Laboratory Assessments for Ineligible HIV-infected Network Injection Partners .27 
5.4 
Visit Procedures for Index Participants .......................................................................... 28 
5.4.1 
Screening Visit for Index Participants ..................................................................... 28 
5.4.2 
Enrollment Visit for Index Participants ................................................................... 29 
5.4.3 
Follow-up visits for Index Participants .................................................................... 29 
5.4.3.1 
Week 4 visits for Index Participants ................................................................. 30 
5.4.3.2 
Quarterly Visits for Index Participants ............................................................. 30 
5.4.3.3 
Exit Visit for Index Participants ....................................................................... 31 
5.5 
Visit Procedures for Network Injection Partners ............................................................ 32 
5.5.1 
Screening visit for Network Injection Partners ....................................................... 32 
5.5.2 
Enrollment visit for Network Injection Partners ..................................................... 32 
5.5.3 
Follow-up visits for Network Injection Partners ..................................................... 33 
5.5.3.1 
Week 4 Visit for Network Injection Partners ................................................... 34 
5.5.3.2 
Quarterly visits for network injection partners ................................................. 34 
5.5.3.3 
Exit visit for Network Injection Partners .......................................................... 35 
5.6 
Additional procedures for network injection partners who have a reactive or positive 
HIV test at any visit after Enrollment (See Appendix III) ......................................................... 36 
5.6.1 
HIV Confirmation Visit Following a Reactive or Positive HIV Result .................. 36 
5.6.2 
Weeks 26, 52, 78 and 104 (if HIV infection has been confirmed) .......................... 36 
5.7 
Data collection procedures for systems navigators and psychosocial counselors ......... .36 
5.7.1 
Systems Navigators ................................................................................................. 36 
5.7.2 
Psychosocial Counselors ......................................................................................... 37 
5.8 
Data Collection Procedures for Semi-Structured Interviews .......................................... 37 
6.0 
SAFETY MONITORING AND ADVERSE EVENT REPORTING ......................... 38 
6.1 
Safety Monitoring ...................................................................................................... : .... 38 
6.2 
Clinical Data Safety Review ........................................................................................... 39 
6.3 
Adverse Events ............................................................................................................... 39 
6.3.1 
Non-Serious Adverse Events ................................................................................... 39 
6.3.2 
Serious Adverse Events ........................................................................................... 39 
6.3.3 
AE Reporting to DAIDS .......................................................................................... 40 
6.3 .4 
Grading severity of adverse events ......................................................................... .40 
6.3.5 
Toxicity Management .............................................................................................. 40 
6.4 
Concomitant Medications ............................................................................................... 40 
6.5 
Regulatory Requirements ................................................................................................ 40 
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6.6 
Social Impacts Reporting ................................................................................................ 41 
6.7 
Clinical Management of Pregnancy ............................................................................... .42 
7.0 
STATISTICAL CONSIDERATIONS ........................................................................... 42 
7 .1 
Review of Study Design ................................................................................................. 42 
7.1.1 
Primary Endpoints ................................................................................................... 42 
7 .1.2 
Secondary Endpoints ................................................................................................ 44 
7.2 
Accrual, Follow-up, and Sample Size ............................................................................ .46 
7.2.1 
Primary endpoints .................................................................................................... 46 
Table 4. Exact Poisson Confidence Intervals for Annual Standard of Care Arm Incidence 
Rates .......................................................................................................................................... 47 
Table 5. Intervention Uptake ..................................................................................................... 47 
Table 6: Effect sizes for the HPTN074 intervention with 90% power ..................................... .48 
7 .2.2 
Secondary endpoints ......................... , ...................................................................... 49 
Table 6. Power for detecting Odds Ratios for comparison between arms ................................. 50 
7.3 
Random Assignment/ Study Arm Assignment .............................................................. 50 
7.4 
Data Analysis .................................................................................................................. 50 
7.4.1 
Primary Analyses ..................................................................................................... 50 
7.4.2 
Secondary Analyses ................................................................................................. 51 
8.0 
HUMAN SUBJECTS CONSIDERATIONS ................................................................. 51 
8.1 
Ethical Review ................................................................................................................ 51 
8.2 
Informed Consent ............................................................................................................ 52 
8.3 
Risks ................................................................................................................................ 52 
8.4 
Benefits ........................................................................................................................... 52 
8.5 
Incentives ........................................................................................................................ 53 
8.6 
Confidentiality ................................................................................................................ 53 
8.7 
Communicable Disease Reporting Requirements ........................................................... 54 
8.8 
Study Discontinuation ..................................................................................................... 54 
9.0 
LABORATORY SPECIMENS AND BIOHAZARD CONTAINMENT ................... 54 
9.1 
Local Laboratory (LL) Specimens .................................................................................. 54 
9.2 
HPTN Laboratory Center (LC) Specimens ..................................................................... 54 
9.3 
Quality Control and Quality Assurance Procedures ....................................................... 55 
9.3.1 
QC for HIV diagnostic testing ................................................................................. 55 
9.3.2 
QC for HIV viral load .............................................................................................. 55 
9.3.3 
QC for CD4 cell count determination ...................................................................... 56 
9.4 
Specimen Storage and Possible Future Research Testing .............................................. 56 
9 .5 
Bio hazard Containment. .................................................................................................. 56 
10.0 
ADMINISTRATIVE PROCEDURES ........................................................................... 56 
IO.I 
Protocol Registration ................................................................................................... 56 
10.2 
Study Activation .......................................................................................................... 57 
10.3 
Study Coordination ...................................................................................................... 57 
10.4 
Study Monitoring ........................................................................................................ 58 
10.5 
Protocol Compliance ................................................................................................... 58 
10.6 
Investigator's Records .................................................................................................. 58 
10.7 
Use oflnformation and Publications ........................................................................... 59 
REFERENCES .......................................................................................................................... 60 
Appendix I. Schedule of Procedures and Evaluations - Index .................................................. 65 
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Appendix II. Schedule of Procedures and Evaluations -Network injection partners ............... 66 
Appendix III. Additional procedures for network injection partners who have a reactive or 
positive HIV test result at any visit after Enrollment* .............................................................. 67 
Appendix IV A. Sample Screening Consent ............................................................................. 69 
Appendix IV-B. Sample Enrollment Consent for Index ........................................................... 77 
Appendix IV-C. Sample Enrollment Consent for Network Injection Partners ......................... 87 
Appendix IV -D. Sample Key Informant Interview Informed Consent for Selected Study Index 
Participants, Navigators, Counselors or Key Clinic Personnel at the HIV Care and Substance 
Use Treatment Sites ........................................................ , .......................................................... 95 
Appendix IV-E. Sample Re-Enrollment Consent for Index Extension (up to 12 additional 
months) ...................................................................................................................................... 99 
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26 July 2017 

HPTN074 
Integrated treatment and prevention for people who inject drugs: A vanguard study for a 
network-based randomized HIV prevention trial comparing an integrated intervention 
including supported antiretroviral therapy to the standard of care 
LIST OF ABBREVIATIONS AND ACRONYMS 
AE 
AIDS 
ART 
ARTAS 
CBT 
CDC 
CFR 
CMC 
DAERS 
DAIDS PRO 
DAIDS 
DAIDS-ES 
EAE 
EC 
EQA 
EWG 
FDA 
GCP 
HBV 
HCV 
HEART 
HIV RNA 
HIV 
HPTN 
ICF 
ICH 
IQA 
IRB 
LC 
LDMS 
LL 
LOC 
MAPS 
MoH 
NIAID 
NIDA 
NIH 
PWID 
HPTN 074, Final Version 2.0 
Adverse Event 
Acquired Immunodeficiency Syndrome 
Antiretroviral Therapy 
Antiretroviral Treatment and Access to Services 
Cognitive Behavioral Therapy 
Centers for Disease Control and Prevention 
Code of Federal Regulations 
Clinical Management Committee 
Division of AIDS Adverse Experience Reporting System 
Division of AIDS Protocol Registration Office 
Division of AIDS 
Division of AIDS-Enterprise System 
Expe.dited Adverse Event 
Ethics Committee 
External Quality Assurance 
Ethics Working Group 
(United States) Food and Drug Administration 
Good Clinical Practices 
Hepatitis B Virus 
Hepatitis C Virus 
Helping Enhance Adherence to Antiretroviral Therapy 
Human Immunodeficiency Virus Ribonucleic Acid 
Human Immunodeficiency Virus 
HIV Prevention Trials Network 
Informed Consent Form 
International Conference on Harmonisation 
Immunology Quality Assessment 
Institutional Review Board 
(HPTN) Laboratory Center 
Laboratory Data Management System 
Local Laboratory 
(HPTN) Leadership and Operations Center 
Managed Problem Solving 
Ministry of Health 
(United States) National Institute of Allergy and Infectious Diseases 
(United States) National Institute on Drug Abuse 
(United States) National Institutes of Health 
People Who Inject Drugs 
Pagev 
26 July 2017 

QA 
QC 
RCT 
RE" 
ROC 
RSC 
SAE 
SBIRT 
SDMC 
SMART 
SMC 
SOP 
SSP 
STI 
SUSAR 
TB 
UKNEQAS 
VQA 
WHO 
HPTN 074, Final Version 2.0 
Quality Assurance 
Quality Control 
Randomized Controlled Trial 
Regulatory entity 
Regulatory Operations Center 
Regulatory Support Center, DAIDS 
Serious Adverse Event 
Screening, Brief Intervention, and Referral to Treatment 
(HPTN) Statistical and Data Management Center 
Sharing Medical Adherence Responsibilities Together 
Study Monitoring Committee 
Standard Operating Procedures 
Study Specific Procedures 
Sexually Transmitted Infection 
Suspected Unexpected Serious Adverse Reaction 
Tuberculosis 
United Kingdom National External Quality Assessment Service 
Virology Quality Assurance 
World Health Organization 
Page vi 
26 July 2017 

HPTN074 
Integrated treatment and prevention for people who inject drugs: A vanguard study for a 
network-based randomized HIV prevention trial comparing an integrated intervention 
including supported antiretroviral therapy to the standard of care 
PROTOCOL TEAM ROSTER 
Protocol Chair 
Protocol Co-Chair 
William C. Miller, MD, PhD, MPH 
Irving F. Hoffman, PA, MPH 
Associate Professor 
Associate Professor 
University of North Carolina Chapel Hill 
Director of International Operations 
School of Medicine, Department of Medicine 
University of North Carolina Chapel Hill 
Division of Infectious Diseases 
School of Medicine, Department of Medicine 
2146 Bioinformatics 
Division of Infectious Diseases 
Campus Box 7030 
2151 Bioinformatics 
Chapel Hill, NC 27599 USA 
Campus Box 7030 
Phone: 919 966 9407 
Chapel Hill, NC 27599 USA 
Email: bill miller@unc.edu 
Phone: 919 966 6324 
Email: hoffmani@med.unc.edu 
Michael G. Hudgens, PhD 
Carl Latkin, PhD 
Associate Professor, 
Johns Hopkins University 
Department of Biostatistics 
Bloomberg School of Public Health 
Director, Center for AIDS Research (CF AR) 
Department of Health Policy and 
University of North Carolina 
Management 
3107-E McGavran-Greenberg Hall 
624 North Broadway 
Chapel Hill, NC 27599 USA 
Baltimore, MD 21205 USA 
Phone: 919 966 7253 
Phone: 410 955 3972 
Email: mhudgens@bios.unc.edu 
Email: clatkin@jhs:gh.edu 
Vivian Go, PhD 
David Metzger, PhD 
University of North Carolina Chapel 
University of Pennsylvania 
Hill Gillings School of Global Public Health 
School of Medicine 
Department of Health Behavior 
HIV Prevention Research Division 
361 Rosenau Hall 
Department of Psychiatry 
Campus Box 7 440 
3535 Market Street, Suite 4000 
Chapel Hill, NC 27599-7440 USA 
Philadelphia, PA 19104 USA 
Phone: 919 966 3908 
Phone: 267 566 2483 
Email: vgo@live.unc.edu 
Email: dsm@mail.med.u:genn.edu 
HPTN 074, Final Version 2.0 
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26 July 2017 

Jeremy Sugarman, MD, MPH 
David Bums, MD, MPH 
Johns Hopkins University, Berman Institute 
DAIDS Medical Officer 
of Bioethics and Department of Medicine 
Division of AIDS/NIAID/NIH 
1809 Ashland Ave 
6700-B Rockledge Drive, 
Deering Hall, Room 203 
Room 5249 MSC 7628 
Baltimore, MD USA 
Bethesda, MD 20892 USA 
Phone: 410 614 5634 
Phone: 301 435 8896 
Email: jsugarman@jhu.edu 
Email: burnsda@niaid.nih.gov 
Steffanie Strathdee, PhD 
Susan Eshleman, MD, PhD 
University of California San Diego 
Johns Hopkins University School of Medicine 
School of Medicine 
720 Rutland A venue 
Division of Global Public Health 
Ross Bldg., Room 646 
Institute of the Americas 
Baltimore, MD 21205 USA 
10111 N. Torrey Pines Rd. 
Phone: 410 614 4734 
La Jolla, CA 92093 USA 
Email: seshlem@jhmi.edu 
Phone: 858 822 1952 
Email: sstrathdee@ucsd.edu 
William Clarke, PhD, MBA, DABCC 
Estelle M. Piwowar-Manning, BS, MT 
Johns Hopkins University School of Medicine (ASCP), SI 
600 N. Wolfe Street 
Johns Hopkins University 
Meyer B-125 
Pathology Bldg., Room 313 
Baltimore, MD 21287 USA 
600 North Wolfe Street 
Phone: 410 502 7692 
Baltimore MD 21287 USA 
Email: wclarke@jhmi.edu 
Phone: 410 614 6736 
Email: ~iwowa@jhmi.edu 
Paul Richardson, M.Sc., FIBMS 
Deborah Donnell, PhD 
Senior QA/QC Coordinator 
SDMC Biostatistician 
Johns Hopkins University 
SCHARP-FHCRC 
600 North Wolfe Street 
1100 Fairview Ave. North, LE-400 
Pathology 313 
PO Box 19024 
Baltimore, MD 21287 USA 
Seattle, WA 98109, USA 
Phone: 410 502 0435 
Phone: 206 667 5661 
Email: prichal 8@jhmi.edu 
Email: deborah@schill:J2.org 
Lynda Emel, PhD 
Laura McKinstry, MPH 
Research Program Manager 
Project Manager 
SCHARP-FHCRC 
SCHARP-FHCRC 
1100 Fairview Ave. North, E3-129 
1100 Fairview Ave. North, E3-129 
PO Box 19024 
PO Box 19024 
Seattle, WA 98109, USA 
Seattle, WA 98109, USA 
Phone: 206 667 5803 
Phone: 206 667 7322 
Email: lemel@schill:J2.org 
Email: lmckinst@sch!!IQ.org 
HPTN 074, Final Version 2.0 
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26 July 2017 

Greg Lucas, MD, PhD 
Nirupama Sista, PhD 
Johns Hopkins University School of Medicine Associate Director 
1830 E. Monument Street, Room 421 
FHI 360 
Baltimore, MD 21287 USA 
359 Blackwell St. 
Phone: 410 614 0560 
Suite 200 
Email: glucas@jhmi.edu 
Durham, NC 27701, USA 
Phone: 919 544 7040, Ext. 11590 
Email: nsista@fhi360.org 
Scott Mitchell Rose, BS 
Samsuridjal Djauzi, MD 
Sr. Clinical Research Manager 
Faculty of Medicine 
FHI 360 
University of Indonesia/Cipto 
359 Blackwell St. 
Mangunkusumo Hospital 
Suite 200 
Jalan Diponegoro No. 71 Kenari Senen 
Durham, NC 27701, USA 
Jakarta Pusat, 10310 
Phone: 919 405 1447 
Phone: 62 818 853 856 
Email: srose@fhi360.org 
Email: samsuridjal@yahoo.com 
Erica Hamilton, MPH 
Kathy Lancaster, MPH, PhD 
Clinical Research Manager 
University of North Carolina Chapel Hill 
FHI 360 
Department of Epidemiology 
359 Blackwell St. 
Campus Box 7435 
Suite 200 
Chapel Hill, NC 27599-7435, USA 
Durham NC 27701, USA 
Email: klanc@live.unc.edu 
Phone: 919 544 7040, Ext. 11295 
Email: ehamilton@fhi360.org 
Jonathan Paul Lucas, MPH 
Tran Viet Ha, MD 
Community Programs Manager 
University of North Carolina Chapel Hill 
FHI 360 
No. 6, Lane 76, Linh Lang Street 
359 Blackwell St. 
Ba Dinh District, Hanoi, Vietnam 
Suite 200 
Phone: 84 432 115 839 
Durham, NC 27701, USA 
Email: tranvietha@jhsph.vn 
Phone: 919 544 7040, Ext. 11458 
Email: jlucas@fhi360.org 
Nguyen Van Vuong, MD 
Sergii Dvoriak, MD, PhD 
Director, Pho yen Health District Center 
Ukrainian Institute on Public Health Policy 
Ba Hang Town, Pho Yen District 
4 Malopidvalna Str. Of. 6 
Thai Nguyen, Vietnam 
Kyiv 01001 Ukraine 
Phone: 84 987 984 887 
Phone: 38 044 279 3586 
Email: vuongttvtpy@gmail.com 
Email: dvoryak@uiphp.org.ua 
HPTN 074, Final Version 2.0 
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26 July 2017 

Konstantin Dumchev, MD, MPH 
Ukrainian Institute on Public Health Policy 
4 Malopidvalna Str. Of. 6 
Kyiv 01001 Ukraine 
Phone: 38 044 279 3586 
Email: k.dumchev@gmail.com 
HPTN 074, Final Version 2.0 
Pagex 
' Zubairi Djoerban, MD 
Faculty of Medicine 
University of lndonesia/Cipto 
Mangunkusumo Hospital 
Jalan Diponegoro No.71 Kenari Senen 
Jakarta Pusat, 10310 
Phone: 62 815 116 867 67 
Email: zubairi djoerban@yahoo.com 
26 July 2017 

HPTN 074 
Integrated treatment and prevention for people who inject drugs: A vanguard study for a 
network-based randomized HIV prevention trial comparing an integrated intervention 
including supported antiretroviral therapy to the standard of care 
Final Version 2.0 /26 July 2017 
A Study of the HIV Prevention Trials Network (HPTN) 
Sponsored by: 
U.S. National Institute of Allergy and Infectious Diseases and 
U.S. National Institute on Drug Abuse 
U.S. National Institutes of Health 
PROTOCOL SIGNATURE PAGE 
I will conduct the study in accordance with the provisions of this protocol and all applicable 
protocol-related documents. I agree to conduct this study in compliance with United States (US) 
Health and Human Service regulations ( 45 CFR 46); applicable U.S. Food and Drug 
Administration regulations; standards of the International Conference on Harmonization 
Guideline for Good Clinical Practice (E6); Institutional Review Board/Ethics Committee 
determinations; all applicable in-country, state, and local laws and regulations; and other 
applicable requirements (e.g., US National Institutes of Health, Division of AIDS) and 
institutional policies. 
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 Site Investigator of Record 
Signature of Site Investigator of Record 
Date 
HPTN 074, Final Version 2.0 
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26July2017 

HPTN074 
Integrated treatment and prevention for people who inject drugs: A vanguard study for a 
network-based randomized HIV prevention trial comparing an integrated intervention 
including supported antiretroviral therapy to the standard of care 
Purpose: 
Design: 
Study Population: 
Study Size: 
SCHEMA 
The purpose of this study is to determine the feasibility of a future trial that 
will assess whether an integrated intervention combining psychosocial 
counseling and supported referrals for antiretroviral therapy (ART) at any 
CD4 cell count and substance use treatment for HIV-infected people who 
inject drugs (PWID) will reduce HIV transmission to HIV-uninfected 
injection partners, as compared to routine care dictated by national 
guidelines for HIV-infected PWID. 
This is a multi-site, two-arm, randomized, vanguard study. Network units 
will consist of an HIV-infected index participant and his/her HIV-uninfected 
network injection partner(s). Network units will be randomized to the 
intervention or standard of care arms in a 1 :3 ratio, stratified by site. To 
assess feasibility of the intervention, additional interviews will be conducted 
with study staff (systems navigators and counselors) and clinic-based 
stakeholders at each study site. 
The study population will consist of the following participant types: 
Index participants: 
HIV-infected PWID who have an HIV viral load 2:1,000 copies/mL at 
Screening. This may include individuals who report that they are: (a) ART-
naive, (b) ART-exposed but currently off therapy, or (c) on ART. 
Network injection partners: 
HIV-uninfected injection partners of index participants (up to five active 
partners per index participant at a time). 
At least 500 network units, defined as one index participant and one network 
injection partner, will be recruited. The study will be performed at three 
study sites. 
Each site will enroll approximately 167 index participants and 250 network 
injection partners (up to five network injection partners per index 
participant). At least half of the index participants enrolled at each site are 
expected to report that they are ART-naive at study enrollment. Provision is 
made for replacement of network injection partners (late-entry HIV-
uninfected network injection partners) during the study. 
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26 July 2017 

Table 1. Estimated Sample Size 
All Sites 
Individual Sites 
Total, 
Intervention 
Standard 
Total, 
Intervention 
Standard 
All sites 
Care 
Per Site 
Care 
HIV-infected Index 
500 
125 
375 
167 
42 
125 
Participants 
HIV-uninfected 
Network Injection 
-750 
-188 
-563 
-250 
-62 
-188 
Partners 
Late-entry HIV-
uninfected Network 
-75 
-25 
Injection Partners 
--
--
--
--
(replacements) 
Treatment Regimen: 
Index participants will be randomized to one of two study anns at a ratio of 
1 :3 (intervention: standard of care). Index participants in the intervention 
ann will receive (in addition to the standard hann reduction package) an 
integrated intervention that includes supported ART regardless of CD4 cell 
count and facilitated systems navigation and counseling for substance use 
treatment. The integrated intervention is designed to improve engagement 
and retention in HIV care and substance use treatment, and includes 
systems navigation, counseling to encourage engagement in care and 
adherence, and social support. 
Study Duration: 
Index participants in the standard of care ann will receive referrals for the 
in-country standard of care for ART and substance use treatment and a 
standardized harm reduction package. 
Network injection partners in both anns will receive a standardized hann 
reduction package with referral for substance use treatment, consistent with 
national guidelines. 
Approximately 27 months at each site, with recruitment of index participants 
over 15 months and follow-up for a minimum of 12 months and a maximum 
of 24 months, regardless of study ann. All participants will end study 
participation when 27 months have passed since the first enrolled participant 
at the site. Network injection partners (including replacement partners) will 
be followed until the corresponding index participant reaches his/her Exit 
visit. After the originally scheduled Exit visit, Index participants will be 
offered the opportunity to re-enroll in the study for up to 12 additional 
months in order to further assess the durability of ART uptake and HIV viral 
suppression in the intervention. Should an effect of the intervention during 
the first phase of the study be realized during the additional 12 months of 
follow-up, participants in the standard of care ann will be offered all 
components of the intervention. 
HPTN 074, Final Version 2.0 
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26 July 2017 

Primary Objectives: 
• 
To assess the feasibility of a future randomized controlled trial by: 
a) estimating the HIV inddence among network injection partners of index participants in the 
standard of care arm in three distinct global settings with epidemics driven predominantly by 
injection drug use; 
b) evaluating enrollment and retention of HIV-infected PWID and their HIV-uninfected 
network injection partners over a period of 12-36 months for index participants and 12-24 
months for partners. 
c) assess the durability of ART uptake and viral suppression in the intervention arm 
• 
To assess the feasibility, barriers, and uptake of an integrated intervention for prevention of 
HIV transmission among HIV-infected index participants. 
Secondary Objectives: 
• 
To estimate HIV incidence among network injection partners of index participants in the 
intervention arm. 
• 
To explore the effect of the integrated intervention, as compared to standard of care, on 
engagement in HIV care, initiation of ART, retention on ART, ART adherence, and virologic 
suppression among ART-eligible index participants (index participants meeting national 
guidelines in the standard of care arm; all index participants in the intervention arm). If an 
effect is observed on ART uptake or HIV viral suppression in the intervention arm vs. 
standard of care arm, participants in the standard of care arm will be offered the intervention 
for the remainder of the study. 
• 
To assess the uptake and retention on ART over the short term (additional 12 months of 
follow-up) in the standard of care arm. 
• 
To explore the effect of the integrated intervention, as compared to standard of care, on the 
proportion of index participants and network injection partners engaged and retained in 
substance use treatment. 
• 
To estimate the size and stability of the injection network of the index participants and how 
this affects recruitment and retention of network injection partners. 
• 
To assess the social harms and benefits of research participation for PWID. 
• If feasible and if funding is identified, to use phylogenetic methods to characterize 
transmission dynamics in the study cohort. 
• 
To perform secondary laboratory assessments that may include evaluation of factors related 
to HIV infection; antiretroviral (ARV) drug use; substances of abuse; methadone and other 
treatments for substance abuse; cross-sectional HIV incidence estimation; characterization of 
HIV in infected participants, including phylogenetics and linkage; evaluation of the host 
response to HIV infection; and evaluation oflaboratory assays related to study objectives. 
Study Sites: 
• 
Research centers in Jakarta, Indonesia; Thai Nguyen, Vietnam; and Kiev, Ukraine. 
HPTN 074, Final Version 2.0 
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HPTN074 
Integrated treatment and prevention for people who inject drugs: A vanguard study for a 
network-based randomized HIV prevention trial comparing an integrated intervention 
including supported antiretroviral therapy to the standard of care 
OVERVIEW OF STUDY DESIGN AND RANDOMIZATION SCHEME 
Recruitment and screening 
ofPWID 
Eligible network units 
HIV-infected index regardless of CD4 count 
At least one HIV-uninfected network injection partner* 
Intervention 
HIV -infected index** 
N=I25 
HIV-uninfected 
network injection 
partners (enrolled at 
baseline)* 
N-188 
HIV-uninfected 
network injection 
partners 
(replacement)* 
N-75 
Standard of Care 
HIV-infected index** 
N=375 
HIV-uninfected 
network injection 
partners ( enrolled at 
baseline)* 
N-563 
*Confirmed network injection partner of the index participant: sharing needles/syringes 
at least once in the last month 
**Follow-up for all index participants is 12-24 months with an additional, optional 12 
month follow-uo period 
HPTN 074, Final Version 2.0 
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26 July 2017 

1.0 
INTRODUCTION 
This protocol describes research to assess the feasibility of a future trial that will determine 
whether an integrated intervention with supported referral for ART at any CD4 cell count 
for HIV-infected people who inject drugs (PWID) will reduce HIV transmission to HIV-
uninfected network injection partners, as compared to routine care dictated by national 
guidelines for care of HIV-infected PWID. The overall goal of this study is to ensure the 
feasibility of a future randomized trial by demonstrating sufficient HIV incidence among 
the standard of care arm and appropriate uptake of the integrated intervention. 
1.1 
Background 
Injection drug use is the predominant risk behavior for HIV transmission in several parts of 
the world.[1, 2] Nearly 150 countries report injection drug use epidemics; 120 countries 
have a concurrent HIV epidemic. Injection drug use is a major factor underlying the HIV 
epidemics in Eastern Europe, the Commonwealth of Independent States, and many parts of 
Asia. The largest estimated populations of PWID are in Russia, China, and the United 
States (US). Notably, Ukraine, Vietnam and Indonesia have estimated HIV prevalence 
among PWID above 30%.[3] The persistently high incidence of HIV infection among 
PWID in many locations with concentrated epidemics necessitates aggressive efforts to 
prevent HIV transmission. [3] 
HIV epidemics among PWID often result in rapid expansion of the epidemic. In the past 
decade, injection drug use has been responsible for a significant proportion of new HIV 
infections in Eastern Europe and East, Southeast, and Central Asia.[1, 2] Serial use and 
sharing of drug injection equipment, such as needles and syringes, create risks for 
acquiring and transmitting HIV, as well as viral hepatitis. Furthermore, preparing drugs 
for injection and collectively using shared drug solutions pose additional risks for HIV 
transmission. [ 4] 
HPTN 052 clearly demonstrated the potential benefit of ART to prevent sexual HIV 
transmission within serodiscordant couples in stable relationships,[5] presumably by ART-
induced reduction of HIV viral load in genital secretions.[6] HPTN 052 was the first 
randomized clinical trial to demonstrate that early initiation of ART in HIV-infected 
individuals reduces risk of sexual transmission of HIV to uninfected partners. This success 
provides a template for further HIV prevention efforts in other groups at high risk for HIV 
acquisition, including men who have sex with men and PWID. 
The findings ofHPTN 052, which excluded active PWID, have not been validated for 
prevention of parenteral transmission of HIV infection. In ecological and cohort studies, 
expanded ART to PWID appears to be effective. In Vancouver, expanded access to ART 
in an epidemic predominantly driven by injection drug use has led to reduced reporting of 
new HIV cases.[7, 8] However, these data are limited because (i) other interventions were 
previously introduced, confounding the association with ART, and (ii) new diagnoses were 
HPTN 074, Final Version 2.0 
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26 July 2017 

used as a surrogate for HIV incidence. In a preliminary report of a cohort study in 
Baltimore, HIV incidence among PWID decreased with an increased frequency of ART 
use.[9] These studies support the concept of treatment as prevention in PWID, but clearly 
do not provide sufficient justification for widespread use of ART for prevention in this risk 
group. 
Treatment of PWID, whether for prevention of HIV transmission to others or for the 
person's own benefit, presents unique challenges. HIV transmission in PWID takes place 
in the context of risk networks, typically with the involvement of multiple injection 
partners, varied injection practices, and sexual risk behaviors.[10, 11] ART should be 
offered to PWID in conjunction with prevention and substance use treatment activities to 
maximize the potential for ART success.[3] For example, ART effectiveness can be 
compromised in PWID due to poor adherence, potentially leading to treatment failure and 
transmission of resistant strains.[12] PWID may also exhibit behavioral risk compensation 
after initiating ART. Finally, the infectious dose is typically higher during parenteral 
transmission, as demonstrated by a higher transmission probability.[13] Prior to 
widespread implementation of treatment as prevention in PWID, the efficacy and potential 
harms, such as development of resistance secondary to poor ART adherence, must be 
assessed. 
1.2 
Rationale 
HPTN 074 is a vanguard study designed to assess the feasibility of a proposed randomized 
clinical trial (RCT) assessing the effectiveness an integrated intervention to provide 
treatment as prevention to PWID. The intervention addresses the biological, behavioral, 
and social issues specific to this population. HPTN 074 also addresses the feasibility, 
barriers, and uptake of an integrated intervention to facilitate treatment as prevention. 
Designing this feasibility study and the future RCT presents several challenges unique to 
working with PWID. 
Potential low incidence of HIV in PWID: PWID who are provided with risk reduction 
counseling and access to medication-assisted substance use treatment in HIV prevention 
trials have experienced very low HIV incidence. In particular, two HPTN trials, HPTN 
037 and HPTN 058, were unable to address the impact of interventions on HIV incidence 
because the incidence in both intervention and control arms was low, less than 1 case/100 
person-years in both studies.[14, 15] Thus, a critical question is whether any large RCT of 
HIV prevention in PWID can be conducted with HIV incidence as an outcome given the 
observed low incidence in previous studies. 
Given the low incidence in HPTN 037 and HPTN 058, new network sites for HPTN 074 
were identified (see Section 3.0). These sites were chosen based on demonstration of 
research capacity, HIV prevalence, and when available, HIV incidence. Given the 
previous experience with prevention trials among PWID, the first objective ofHPTN 074 -
to assess the incidence among HIV-uninfected PWID network injection partners - is 
critical. If incidence is low in HPTN 074, future randomized controlled prevention trials 
with PWID are unlikely to be successful and alternative designs will be necessary. 
HPTN 074, Final Version 2.0 
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To ensure that an adequate estimate of the HIV incidence is obtained, the index 
participants will be allocated to the intervention and standard of care with an allocation 
ratio of 1 :3 (intervention: standard of care). The larger number of participants randomized 
to the standard of care arm is intended to improve the precision of the HIV incidence 
estimate among the HIV-uninfected network injection partners under standard of care 
conditions. To evaluate the second primary objective, a smaller number of participants are 
randomized to the intervention arm to evaluate feasibility, barriers and uptake of the 
integrated intervention. 
"Real-world" focus on HIV-infected PWID (Prevention for Positives): Fundamentally, 
HPTN 074 and the proposed future RCT, and their interventions, are focused on the HIV-
infected PWID. In most settings, HIV-infected PWID will present alone for HIV testing or 
medical care (without an injection or sexual partner). The goal of this study is to develop 
and subsequently provide an integrated intervention that can be administered to HIV-
infected PWID to interrupt future transmission events. The intervention is limited in scope 
to be feasible and sustainable, given the challenges in clinical settings. 
This real-world focus on the HIV-infected PWID is evident in several design features of 
HPTN074: 
1) ART and substance use treatment are provided by existing health care facilities at each 
site and are not provided or directed by the study. This approach is critical to replicate 
the challenges faced by PWID in navigating the health care system, a common barrier 
to receipt of appropriate care. 
2) Real-time in-country laboratory testing will be performed using locally-available test 
kits and methods; where necessary, testing will be repeated retrospectively at the 
HPTN LC using a single method to provide a consistent set of data for key analyses, 
and to evaluate the quality of locally-obtained test results. 
3) The intervention is designed to be flexible to meet the needs of individual PWID. A 
principal focus is on facilitating entry into and retention in the HIV care and substance 
use treatment systems. At recruitment, PWID are likely to be at different stages of 
readiness for engagement in HIV care and substance use treatment. The PWID are also 
likely to face different types of problems with engagement and adherence. Thus, the 
flexibility of the intervention allows tailoring of the intensity of the intervention for 
different PWID. Identification of the key elements of the integrated intervention that 
will be feasible, effective, and scalable at the programmatic level is a critical goal of 
this study, and the future RCT. 
4) The ultimate goal of this approach is to prevent transmission from HIV-infected PWID 
to their injection partners. Persons with higher viral loads are at increased risk for 
transmission. The eligibility criterion that index participants must have an HIV viral 
load ~_1,000 copies/mL is designed to include persons with higher transmission 
potential. Recruitment of ART-na"ive, HIV-infected participants is given emphasis to . 
reflect the potential implementation of this approach with diagnosis and/or initial 
engagement in care. 
5) HIV-uninfected network injection partners are enrolled specifically for the purpose of 
measuring transmission events (i.e., HIV incidence). The HIV-uninfected network 
HPTN 074, Final Version 2.0 
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injection partners in both arms receive standard of care risk reduction counseling and 
referral for substance use treatment. 
6) HIV-infected network injection partners are not enrolled. The study team considered 
enrolling all members of a network unit and providing the study interventions to all 
members of the component. However, in many settings, PWID are unlikely to be 
asked formally to recruit other network members to receive an intervention together, 
but instead, will face the challenges of engaging in care alone or with a support person. 
Integrated intervention: The integrated intervention focuses on engaging HIV-infected 
PWID in HIV care and substance use treatment. The intervention is based on the 
following premises: 
1) Achieving sustained virologic suppression will be an effective means to reduce HIV 
transmission from HIV-infected PWID to their injection partners; 
2) PWID experience unique barriers to engaging and remaining in HIV care, preventing 
many PWID from receiving and remaining adherent to ART; 
3) Overcoming these barriers requires a flexible intervention that addresses the specific 
needs of the PWID to engage in HIV care and substance use treatment, initiate and 
adhere to ART, and sustain these behaviors for the long-term. 
The components of the integrated intervention are adapted from interventions that have 
been successful in facilitating engagement in health care. The components are 
intentionally limited in scope to ensure that implementation at scale would be feasible and 
sustainable. The theoretical basis for the non-biomedical intervention components are 
described in Section 1.4. 
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Precursors/moderators 
HPTN 074, Final Version 2.0 
Figure l: Conceptual Framework 
Sodal·Environmenfal 
Factors 
· Individual Fadol's 
Inte;rvention FOc:used 
Outcomes 
Page 5 of 108 
Distal QutcoD1es 
26 July 2017 

1.3 
Theoretical Basis for Intervention 
This HIV prevention intervention integrates systems navigation to overcome structural 
barriers to engagement in care with psychosocial counseling to provide the support and 
skills necessary to initiate and sustain HIV care and substance use treatment. 
The proposed integrated intervention is based on maintenance theory, social cognitive and 
diffusion of innovation meta-theories of behavior change, as well as theories of cognitive 
dissonance, role theory, social norms, and social identity that overlap and expand on those 
meta-theories.[16-21] According to maintenance theory, decisions regarding behavioral 
initiation are dependent on favorable expectations regarding future outcomes, whereas 
decisions regarding behavioral maintenance are predicted to depend on perceived 
satisfaction with received outcomes. [ 16] Social identity theory suggests that common 
experiences and knowledge frameworks are more likely in relationships in which 
individuals are invested and have mutual trust which facilitates interpersonal 
communication, knowledge transfer, and shared understanding.[19] 
Our multidimensional framework (Figure 1) highlights the role of psychosocial, social 
networks, and structural processes on behavior change and maintenance. Recent 
recommendations for improving entry into care, retention, and ART adherence include 
"multidisciplinary education and counseling intervention approaches", "one-on-one 
adherence support to patients through one or more adherence counseling approaches", and 
"brief, strengths-based case management for individuals with a new HIV diagnosis". The 
recommendations also include the potential use of paraprofessional patient navigators.[22] 
The intervention in HPTN 074 integrates systems navigation and counseling to facilitate 
entry into HIV care and substance use treatment, initiation of ART, and sustain adherence 
to ART and substance use treatment. Systems navigation is relatively low intensity, short 
term case management, designed to be feasible and sustainable. The systems navigator 
approach is based on the literature of best evidence in case management, including the 
Antiretroviral Treatment and Access to Services (ARTAS) study and recent work in 
Russia.[23-27] System navigators identify barriers to treatment that reside outside the 
individual or are a function of an interaction between the individual and the health care 
system. For example, lack of familiarity with a health care organization and how to enroll 
in HIV medical care may be due to both system and individual factors. A systems 
navigator will help to identify these barriers as well as overcome the barriers. Case 
management services are now common in HIV medical care programs.[23] These 
approaches are based on findings that system and structural barriers to HIV care and 
substance use treatment are major impediments for entering and staying in medical care. 
As barriers to entry and retention in HIV care and substance use treatment are diverse and 
often context specific, a systems navigator approach provides sufficient flexibility to help 
people address the myriad of systems and structural barriers to health care. [23, 28, 29] 
The systems navigation approach will be integrated with psychosocial counseling focusing 
on entry into HIV care and substance use treatment and adherence to ART. The counseling 
sessions to increase entry into HIV care and drug treatment will be based on brief 
HPTN 074, Final Version 2.0 
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motivational interviewing techniques [30-37]; Screening, Brieflntervention, and Referral 
to Treatment (SBIRT) approaches; and Cognitive Behavioral Therapy (CBT) exercises for 
retention into drug treatment developed in HPTN 058. The HIV medication adherence 
intervention is based on the Managed Problem Solving (MAPS) intervention [38]. For 
index participants who choose to engage their medical care and adherence supporters in the 
counseling sessions, these optional dyad sessions will be based on the Sharing Medical 
Adherence Responsibilities Together (SMART) couples study, which included two dyad 
sessions [39], and Project Helping Enhance Adherence to Antiretroviral Therapy (HEART) 
[ 40]. Index participants in the intervention arm will be encouraged to recruit a support 
person to maintain engagement in care and adherence long-term. The positive role of 
social support on HIV medication adherence and substance use treatment outcomes is well 
documented.[41-43] The emotional social support promotes entry and retention into 
substance use treatment and HIV medical care as well as supports HIV medication 
adherence.[44] In HPTN 074, it is anticipated that supportive others can cue the behavior 
of taking medications, provide verbal reminders, reward timely and consistent taking of 
HIV medication as well as buffer stress which may lead to depression, as depression has 
been demonstrated to have a potentially negative effect on HIV medication adherence.[45, 
46] In the field of substance use treatment, it is also well established that supportive 
behaviors by supporters that promote and reward non drug activities and encourage 
abstinence are linked to successful substance use treatment outcomes.[47] 
A wide range of methods of psychosocial counseling have been found to be effective in 
substance use treatment programs. Generally, no one approach to psychosocial counseling 
has been clearly demonstrated to be superior to other approaches. It is likely that there are 
overlapping techniques in different psychosocial counseling programs. Many psychosocial 
counseling programs include techniques of goal setting, avoiding cue to use, reducing and 
coping with stress, developing activities that are alternatives to substance use, as well as 
increasing motivation for cessation of substance use. These techniques for behavior 
change have also been successfully applied to numerous behaviors including medication 
adherence.[48] In the proposed study the team will integrate motivational interviewing 
with brief intervention and cognitive behavioral counseling techniques. 
2.0 
STUDY OBJECTIVES AND DESIGN 
2.1 
Primary Objectives 
The primary objectives of this study are: 
• 
To assess the feasibility of a future randomized controlled trial by: 
a) estimating the HIV incidence among network injection partners of 
index participants in the standard of care arm in three distinct global 
settings with epidemics driven predominantly by injection drug use; 
b) evaluating enrollment and retention of HIV-infected PWID and their 
HIV-uninfected network injection partners over a period of 12-36 months 
for index participants and 12-24 months for partners. 
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c) assess the durability of ART uptake and viral suppression in the 
intervention arm 
• 
To assess the feasibility, barriers, and uptake of an integrated 
intervention for prevention of HIV transmission among HIV -
infected index participants. 
2.2 
Secondary Objectives 
The secondary objectives of this study are to: 
• 
To estimate HIV incidence among network injection partners of index 
participants in the intervention arm. 
• 
To explore the effect of the integrated intervention, as compared to 
standard of care, on engagement in HIV care, initiation of ART, retention 
on ART, ART adherence, and virologic suppression among ART-eligible 
index participants (index participants meeting national guidelines in the 
standard of care arm; all index participants in the intervention arm). ). If 
an effect is observed on ART uptake or HIV viral suppression in the 
intervention arm vs. standard of care arm, participants in the standard of 
care arm will be offered the intervention for the remainder of the study. 
• 
To assess the uptake and retention on ART over the short term (additional 
12 months of follow-up) in the standard of care arm. 
• 
To explore the effect of the integrated intervention, as compared to 
standard of care, on the proportion of index participants and network 
injection partners engaged and retained in substance use treatment. 
• 
To estimate the size and stability of the injection network of the index 
participants and how this affects recruitment and retention of network 
injection partners. 
• 
To assess the social harms and benefits of research participation for 
PWID. 
• If feasible and if funding is identified, to use phylogenetic methods to 
characterize transmission dynamics in the study cohort. 
• 
To perform secondary laboratory assessments that may include evaluation 
of factors related to HIV infection; antiretroviral (ARV) drug use; 
substances of abuse; methadone and other treatments for substance abuse; 
cross-sectional HIV incidence estimation; characterization of HIV in 
infected participants, including phylogenetics and linkage; evaluation of 
the host response to HIV infection; and evaluation of laboratory assays 
related to study objectives. 
2.3 
Study Design 
This vanguard study is designed to assess the feasibility of a future trial by estimating 
HIV incidence among HIV-uninfected network injection partners of HIV-infected PWID 
(index participants), and evaluating enrollment and retention of HIV-infected PWID and 
their HIV-uninfected network injection partners. The study is also designed to assess the 
feasibility, barriers and uptake of an integrated intervention to prevent HIV transmission 
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by HIV-infected PWID. The study will also collect data on the success of both standard 
of care and supported ART at any CD4 cell count in engagement in HIV care; ART 
treatment; adherence to ART; retention on ART; incidence of treatment failure; and 
engagement and retention in substance use treatment for both index participants and their 
HIV-uninfected network injection partners. 
This is a multi-site, two-arm, randomized feasibility study. Network units of an HIV-
infected participant (index) and his/her HIV-uninfected network injection partner(s) will be 
randomized to the intervention or standard of care arms in a 1 :3 ratio. 
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Table 1. Estimated Sample Size 
All Sites 
Individual Sites 
Total, 
Intervention 
Standard 
Total, 
Intervention 
Standard 
All sites 
Care 
Per Site 
Care 
HIV-infected 
Index 
500 
125 
375 
167 
42 
125 
Participants 
HIV-
uninfected 
Network 
-750 
-188 
-563 
-250 
-62 
-188 
Injection 
Partners 
Late-entry 
HIV-
uninfected 
Network 
-75 
--
--
-25 
--
--
Injection 
Partners 
(replacements) 
The team has chosen an allocation ratio of 1 :3 to improve precision of the estimate of 
HIV incidence in the standard of care arms. This information will inform sample size 
determination for a future RCT, while simultaneously assessing the feasibility and 
logistical challenges of implementing the intervention package for the larger trial. 
3.0 
STUDY SETTING AND POPULATION 
This vanguard study will be conducted in three geographically-diverse sites. The sites 
will be determined based on several key parameters reflecting the status of the HIV 
epidemic in PWID at the site, site capabilities, and potential capacity to conduct a future, 
network-level RCT (e.g., laboratory, data, and clinical infrastructure; leadership; 
expertise). Specific criteria for site selection include: (1) proportion of HIV-infected 
population using injection drugs (2:30%); (2) expected annual HIV incidence (>3%) or 
HIV prevalence (2:25%) among PWID; (3) evidence of injection-sharing behavior among 
PWID; (4) access to ART, including agreement to provide ART for use during and after 
the study should a positive effect be observed (antiretroviral drugs will not be supplied by 
the study); (5) ability to enroll 167 HIV-infected PWID within 15 months; (6) access to 
evidence-based substance use treatment; and (7) previous or existing NIDA funded 
research. 
Site selection was based on leadership, staffing, country import (e.g., for External Quality 
Assurance [EQA] samples) and export regulations (e.g., for study specimens), experience 
with network recruitment, and participant retention. Prior to initiation of the study, each 
study site will develop the necessary infrastructure to implement the study including 
personnel, clinical infrastructure (including the ART initiation and maintenance system), 
laboratory capacity, and data management capacity. 
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Three sites have been identified through the HPTN site selection process. These sites are 
research centers in Jakarta, Indonesia; Thai Nguyen, Vietnam; and Kiev, Ukraine. 
The availability of substance use treatment for each proposed research center is outlined 
in Table 2 below as well as registration requirements for PWID. 
Table 2. Availability of substance use treatment and registration requirements for the 
most suitable sites 
Ukraine 
Detoxification with symptomatic treatment followed by: 
• Methadone - zero cost to those willing and registered as PWID 
• Buprenorphine - zero cost to those willing and registered as PWID however, 
extremely limited amounts ofbuprenorphine are available (very limited slots 
for treatment) 
• Registration is required for PWID 
Indonesia 
Detoxification when necessary with symptomatic treatment followed by: 
• Methadone - zero cost to those willing and registered as PWID 
• Buprenorphine, which is paid for by the patient 
• No registration is required for PWID 
Vietnam 
Detoxification with symptomatic treatment followed by: 
• Methadone - free to those willing and registered as PWID 
• Registration is required for PWID 
Index participants will be HIV-infected PWID (men and women who report injecting 
drugs at least 12 times the past three months and six times in the past month and report 
sharing needles, syringes or drug solutions) who have an HIV viral load ~1,000 
copies/mL at Screening. This may include individuals who report that they are: (a) ART-
nai"ve, (b) ART-exposed but currently off therapy, or (c) on ART. The index participants 
may be recruited using a variety of methods, including referral from HIV-testing sites, 
community outreach, and personal referrals. Five hundred index participants (167 per 
site) will be enrolled. The goal for each site is to enroll at least half ART-nai"ve index 
participants. A screening ratio of more than 4: 1 will likely be needed to consent and 
enroll 167 HIV-infected index participants at each site. 
Each index participant will recruit one to five HIV-uninfected network injection partners 
using referral identification cards; at least one partner must be enrolled before the index 
and his/her partner(s) are randomized to the intervention or standard of care arm. The 
first network injection partner enrollment must occur within 60 days after the screening 
blood draw for the index participant. If the first injection network partner is not enrolled 
within 60 days after the index participant's screening blood draw, both the index 
participant and partner will be asked to return for another Screening visit. However, it 
will not be necessary to repeat HIV testing repeat for any participant whose HIV positive 
infection status was previously confirmed using two separate samples collected on 
different days. 
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Referred network injection partners who have one or more reactive/positive HIV test(s) at 
study entry (Screening and/or Enrollment) will not be eligible for enrollment as network 
injection partners. However, with appropriate consent, these individuals may screen as 
potential index participants if the initial referring index does not enroll. 
At Screening, all partners will be asked to complete a brief behavioral risk and HIV care 
questionnaire and provide a blood sample for storage. If the partner has one or more 
reactive/positive HIV tests and is therefore ineligible to be a partner, and if the participant 
agreed to specimen storage, then the stored specimen will be saved for possible use in 
phylogenetic analyses. Ineligible partners who do not screen as potential index 
participants will be referred to local care centers for confirmation of HIV diagnosis (if the 
diagnosis is not established during the Screening and/or Enrollment visits), as well as 
HIV care (if HIV-infected) and substance use treatment; referrals to HIV care and 
substance use treatment will be made in the same manner as the standard of care group, 
as described in site-specific SOPs. 
Index participants will be asked to identify members of their risk networks - individuals 
with whom they engage in HIV-risk related injection activities, interact with at least once 
a week, and have known for at least one month. The index participants will be asked to 
prioritize recruitment of the network injection partners with whom they have the most 
HIV-risk-related exposures, as assessed by sharing needles, syringes, or injection 
solution. Index cases will receive compensation (amount to be determined locally) for 
successful enrollment of network injection partners. The team will evaluate each partner 
referral to minimize the probability that a referral is being made for economic benefit 
only without actual injection exposure to the index case. 
The network injection partner cohort will be dynamic to accommodate the duration of 
relationships within injection partnerships, recognizing that the partnerships of an index 
participant may change over time. Network injection partners will begin contributing 
person-time at the time of their enrollment. Person-time contribution will discontinue at 
the HIV test of a confirmed HIV seroconversion or at the HIV test following the reported 
discontinuation of the partnership. When a network injection partnership ends, the 
partner will continue to be followed, as it is likely that the injection relationship may 
continue at a later point in time. As the network injection partnership ends, person-time 
contribution will end at the HIV test visit following the reported end of the partnership. 
If the partnership is renewed, person-time contribution will start again at the visit 
following the reported renewal of the partnership. In these cases, the index participant 
will be asked to recruit a new partner to replace the ending partnership, if an alternative 
partner is available and willing to enroll. In addition, the index participant may recruit a 
new partner during the course of the study if the index participant develops a new 
relationship and has fewer than five partners enrolled in the study. If a new partner is 
enrolled, he/she will begin contributing person-time at the time of his/her enrollment and 
will discontinue contributing person-time at the visit following the reported end of the 
partnership. Follow-up of all partners will end when the corresponding index participant 
completes his/her last study visit. 
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3.1 
Inclusion Criteria 
Men and women who meet all of the following criteria are eligible for inclusion in this 
study as index participants: 
• 
Age 18-60 years at the Screening visit (age verification procedures will be 
defined in the Study Specific Procedures [SSP] Manual) 
• 
Able to provide informed consent 
• 
Active injection drug user, defined as self-report of: a) injecting drugs at 
least 12 times in the past three months and at least 6 times in the past 
month; and b) a PWID in the opinion of site staff 
• 
Reports sharing needles/syringes or drug solutions at least once in the last 
month 
• 
HIV-infected based on a study-defined testing algorithm (defined in the 
SSP Manual) 
• 
Viral load 2:1,000 copies/mL at Screening 
• 
CD4 >50 cells/mm3 at Screening 
• 
Willing and able to identify, recruit, and have enrolled at least one HIV-
uninfected network injection partner who is eligible for study participation 
according to the criteria below 
• 
Have no plans to move outside the study area for at least one year after 
study enrollment 
• 
Willing to participate in intervention activities, including regular phone 
contact 
Men and women who meet all of the following criteria are eligible for inclusion in this 
study as HIV-uninfected network injection partner: 
• 
Age 18-60 years at the Screening visit (age verification procedures will be 
defined in the SSP Manual) 
• 
Able to provide informed consent 
• 
Active injection drug user, defined as: a) self-report of injecting drugs at 
least 12 times in the past three months and at least 6 times in the past 
month; and b) PWID in the opinion of site staff 
• 
Confirmed injection partner, using referral identification cards, or other 
means of identification from the index participant 
• 
HIV-uninfected based on the study-defined testing algorithm* (defined in 
the Study SSP Manual) 
• 
Have no plans to move outside the study area for at least one year after 
study enrollment 
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*Individuals will not be eligible for enrollment as a partner if any of the HIV tests performed 
at Screening or Enrollment is reactive or positive, even if they are subsequently confirmed to 
be HIV-uninfected. 
3.2 
Exclusion Criteria 
Men or women who meet any of the following criteria will be excluded from this study as 
an index participant: 
• 
Current participation in any HIV prevention study 
• 
Previous or current participation in an HIV vaccine trial 
• 
Appearance of psychological disturbance or cognitive impairment that would 
limit the ability to understand study procedures, as determined by the 
investigators 
• 
Any other condition that, in the opinion of the investigators, would make 
participation in the study unsafe, or otherwise interfere with the study 
activities 
• 
Prior screening as a potential network member of a enrolled index participant 
in this study (NOTE: Screened partners who fail screening because they have 
one or more reactive/positive HIV test(s) may screen as an Index participant 
only if the original referring Index participant does not enroll). 
• 
Currently or previously a partner of an index participant 
Men or women who meet any of the following criteria will be excluded from this study as 
network injection partner: 
• 
Current participation in any HIV prevention study 
• 
Previous or current participation in an HIV vaccine trial 
• 
Any reactive or positive HIV test at Screening or Enrollment, even if the 
individual is confirmed to be HIV-uninfected 
• 
Appearance of psychological disturbance or cognitive impairment or any 
other condition that in the opinion of the investigator would limit the ability to 
understand study procedures, would make participation in the study unsafe, or 
otherwise interfere with the study activities 
• 
Previously named and enrolled as a partner of another index participant 
3.3 
Recruitment process for index participants 
Approximately 167 index participants will be recruited at each study site (N=500 
minimum across all sites). This may include individuals who report that they are: (a) ART-
naYve, (b) ART-exposed but currently off therapy, or (c) on ART; it is expected about half 
of the index participants will be ART-naYve. Participants who fail screening may re-
screen only once. HIV testing will not be necessary during a re-screening visit for 
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participants previously confirmed as HIV infected using two separate samples collected on 
different days. 
Screening of index participants will take place for approximately 15 months. A variety of 
methods will be used for recruitment, including referral from HIV-testing sites, 
community outreach, identification of substance treatment program failures, and injection 
network referrals. Sites will be able to use their previously established systems for 
recruiting participants. Trained outreach workers will identify geographic areas, HIV 
testing sites, or other settings and organizations that are frequented by PWID. Outreach 
workers will disseminate information about the study, will provide oral and written 
descriptions of the studies to prospective participants, and will encourage index 
participants to participate in screening activities at a local study site. Potential Index 
participants will also be informed that they should pass the information on to other 
individuals if the study does not apply to them. 
Outreach workers will be trained to not pre-select individuals who fit their description of 
"drug users"; instead, they will provide information to a range of individuals and 
encourage those individuals to pass information about the study to others in the 
community. Outreach workers will be selected from the community and must be 
knowledgeable about the community's dynamics and trained on basic methods of rapid 
assessment procedures in order to target areas of high drug use. They will also be trained, 
as part of the study, in methods of approaching and communicating with potential 
participants, personal safety, and confidentiality. 
Potential index participants who present at the study site will be offered HIV counseling 
and testing and receive a brief introduction to the study. Those who are interested in 
participating will be asked to provide informed consent for Screening. A sample of the 
consent forms can be found in Appendix IV. After providing informed consent for 
screening, volunteers will undergo an eligibility screening survey. If at any time during 
screening, they are found to be ineligible, screening will be discontinued; however, HIV 
counseling and testing will be offered to all persons who present for screening. 
Participants who meet initial study screening eligibility criteria will undergo pre- and post-
test counseling. HIV-infected individuals who have an HIV viral load ~1,000 copies/mL 
and are otherwise eligible for enrollment will be asked to provide study consent. These 
individuals may report that they are: (a) ART-narve, (b) ART-exposed but currently off 
therapy, or (c) on ART. Participants who are found to be eligible will be asked to provide 
informed consent for enrollment. 
Index participants who are confirmed to be HIV-infected will not be randomized to a 
study arm until their first HIV-uninfected network injection partner is enrolled. The 
effective point of enrollment is randomization of the index participant. After confirmation 
of eligibility of their first HIV-uninfected network injection partner, the index participant 
will return to the study site for randomization and will initiate study activities, as 
appropriate. Study site staff members are responsible for developing and implementing 
local SOPs to help ensure index participants return for randomization. These procedures 
will be similar to the participant retention procedures (as described in Section 3.6). 
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The index participant will be informed that his/her HIV status will be disclosed to network 
injection partners who are referred for study screening. The index participant will be 
counseled at the time of consent to disclose his/her HIV status prior to referring the 
partner for the study. Brief counseling by study staff will be provided to support this 
disclosure. If the index participant prefers, he/she may opt to bring the partner to the 
study site for screening and undergo a joint disclosure session with the study staff. Care 
will be taken to prevent inadvertent HIV disclosure in individual networks. Finally, the 
index participant may opt not to have his/her HIV status directly disclosed to the injection 
partner. In this case, the network injection partner will be able to deduce the HIV status of 
the index through the screening consent process. The informed consent of the index will 
clearly address the need for disclosure and the options for disclosure. 
3.4 
Identification of network injection partners 
After confirmation of HIV status, HIV-infected index participants will be asked to 
identify members of their injection network with whom they engage in HIV-risk related 
activities. Index participants will be asked to prioritize recruitment of the partners with 
whom they have the most HIV-related injection exposures; network injection partners 
must have injected with the index partner in the past month. Sexual partners will not be 
recruited unless he/she is an active injection partner. Up to five concurrent HIV-
uninfected network injection partners per index participant, designated as network 
injection partners, may be enrolled in the study. If partners withdraw from the study, 
additional replacement partners may be added. Whether an enrolled partner continues to 
be an injection partner of the index may change over time, and will be recorded 
longitudinally throughout the study. Index participants will be provided with referral 
identification cards marked with their study identification number to facilitate the 
recruitment of their network members. There will be no identifying information on the 
cards to indicate participation in an HIV or substance use study. Eligible index 
participants will be asked to give the cards to injection drug use partners and will 
encourage the partner(s) to bring the cards to the local study site to serve as their 
identification for participation in screening. Index participants will receive compensation 
for successful enrollment of partners. Partners also will be compensated for their time 
and participation. The amount and form of compensation will vary by site. Each 
site/country will be encouraged to include fair and ethical compensation in their site 
specific Informed Consent Forms which will be reviewed and approved at the local level. 
Sites will review partner referrals for validity to ensure that partner referrals are not based 
solely for economic benefit. HIV disclosure by index participants to partners will be 
recommended and facilitated. 
For HIV-uninfected injection partners to participate in the screening process, they must 
either present at a local study site with a card bearing their index participant's 
identification (ID) number, or match the description provided by the index during his or 
her screening survey according to site-specific procedures. Such partners will then be 
asked to provide study informed consent for enrollment. Individuals who provide study 
consent will complete social network interview, the baseline sexual and drug behavior 
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data collection, and will participate in HIV risk reduction counseling and testing. 
Injection partners who are confirmed to be HIV-infected at Screening will not be enrolled 
as network injection partners. Once an HIV-uninfected injection partner is enrolled in the 
study as a network injection partner, he/she will be unable to enroll as an index 
participant (i.e., if he/she acquires HIV infection during the study), or in as other index 
participant's network injection partner ( each network injection partner will be associated 
with a single index participant throughout the study). The frequency with which HIV-
uninfected partners are referred by more than one index participant will be documented 
and assessed as part of the network structure. 
The network injection partner cohort will be dynamic, to accommodate the variable 
duration of relationships within risk networks. The partnerships of an index participant 
may change over time. If an index participant has fewer than five partners enrolled in the 
study, the index participant may recruit new HIV-uninfected partners at any time prior to 
the penultimate study visit (last routine study visit prior to the termination visit). If a 
network injection partnership ends, the index participant will be asked to recruit a new 
injection partner to replace the ending partnership, if an additional partner is available 
and willing. An index participant will be actively encouraged to recruit another HIV -
uninfected partner to the study if he/she has zero or one active partners in the study. 
Although the number of replacement partners is not limited, the team expects each site 
may enroll approximately 25 replacement partners. Index participants who have no 
partners on follow up will not be terminated. New partners cannot be recruited after the 
index's penultimate or termination visits. Additionally, if an index participant terminates 
participation in the study after randomization, network injection partners will also 
terminate early. Partners will terminate follow-up at the next scheduled visit after their 
index participant's termination visit. 
All partners will begin contributing person-time at the time of their enrollment and will 
discontinue contributing person-time at the HIV test following the reported 
discontinuation of the partnership or confirmed HIV seroconversion. However, in the 
case ofreported discontinuation of the partnership the network injection partner will 
continue to be followed, as it is likely that the injection relationship may continue at a 
later point in time. If the partnership is renewed, person-time contribution will start again 
at the visit following the reported renewal of the partnership. Template tracking systems 
of index participants and network injection partners will be developed in collaboration 
with the sites and will be described in the SSP Manual and in site specific SOPs. 
3.5 
Co-Enrollment Guidelines 
Participants should not be currently participating in any HIV prevention study and may 
not enroll in any HIV prevention trial during this study; these guidelines are needed to 
reduce participant burden with study visits, to facilitate high levels of retention, and to 
avoid confounding in the interpretation of the primary and secondary endpoint data. 
Also, participants may not enroll if they have been or are currently enrolled in an HIV 
vaccine trial, since vaccination could complicate interpretation of HIV test results. 
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3.6 
Participant Retention 
Once an index participant enrolls in this study, the study site will make every effort to 
retain him/her for 12-24 months (plus a potential additional 12 months for willing and re-
consenting index participants) of follow-up to minimize possible bias associated with 
loss-to-follow-up. The sites will also make every effort to retain network injection 
partners through the exit interview of the index participant. Study site staff members are 
responsible for developing and implementing site-specific procedures and local SOPs to 
reach this goal. A basic philosophy of the retention strategy is that follow-up begins at 
recruitment and is a priority at every visit. Components of such procedures include: 
• 
Thorough explanation of the study visit schedule and procedural requirements 
during the informed consent process, with re-emphasis at each study visit. 
• 
Thorough explanation of the importance of both study arms (intervention and 
standard of care) to the overall success of the study. 
• 
Collection of detailed locator information at the Screening visit, with active 
review and updating of this information at each subsequent visit. 
• 
Use of mapping techniques to establish the location of participant residences 
and other venues that participants frequent. This information wiH be used 
only for participant retention. No study procedures will be conducted at 
participants' homes. 
• 
Use of appropriate and timely visit reminder mechanisms. 
• 
Visit calendars, flyers or other handouts will be offered at enrollment to assist 
with retention. 
• 
Immediate and multifaceted follow-up on missed visits, including 
outreach/locator efforts such as phone calls, text messages, or home contacts. 
(The timing and number of contacts will be outlined in site-specific 
procedures.) 
• 
Mobilization of trained outreach workers or "tracers" to complete in-person 
contact with participants at their homes and/or other community locations. 
• 
Regular review of follow-up procedures and current status by site leadership 
and staff. 
• 
Regular communication with the study community at large to build trust and 
increase awareness about substance use treatment and HIV/AIDS. 
3. 7 
Participant Withdrawal 
Regardless of the participant retention methods just described, participants may 
voluntarily withdraw from the study for any reason at any time. The investigators 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, Statistical and Data Management Center 
(SDMC) Protocol Statistician, and LOC Protocol Specialist. Participant non-adherence to 
the intervention is not a reason for participant withdrawal from the study. 
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Participants also may be withdrawn if the study sponsor, government or regulatory 
authorities, or site institutional review boards (IRBs) or ethics committees (ECs) 
terminate the study prior to its planned end date. 
Participants will not be considered withdrawn unless the participant actively withdraws 
or dies, or the investigators withdraw the participant for the reasons given above. 
Every reasonable effort will be made to complete a final evaluation (as described in 
Sections 5.4.3.3 and 5.5.3.3) of participants who terminate from the study early, and 
study staff will record the reason(s) for all withdrawals from the study in participants' 
study records. 
4.0 STUDY INTERVENTION PACKAGE 
All participants in both intervention and standard of care arms will receive a 
comprehensive set of integrated harm reduction services intended to reduce HIV 
incidence through effective behavioral, biological and social interventions. The basic 
package, provided to all participants (intervention, standard of care, index, network 
injection partner), is described below. 
Table 3. Summary of intervention and standard packa2es of services by study arm 
HIV-infected index 
HIV-uninfected network 
injection partner 
Control 
Intervention 
Control 
Intervention 
Harm reduction services 
Referral for treatment of substance 
X 
X 
X 
X 
use/ addiction 
Referral to needle and syringe 
X 
X 
X 
X 
exchange programs, if legal and 
available 
Injection risk reduction counseling 
X 
X 
X 
X 
Sexual risk reduction counseling 
X 
X 
X 
X 
including access to condoms 
HIV counseling and testing 
X 
X 
X 
X 
Referral for ART according to national 
X 
X 
guidelines 
Referral for diagnosis and treatment of 
X 
X 
X 
X 
sexually transmitted infections (STis), 
hepatitis B and C virus (HBV, HCV), 
and tuberculosis (TB) as appropriate 
Systems Navigator 
X 
Psychosocial Counseling and Social 
X 
x· 
Network support 
ART at any CD4 count 
X 
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'Psychosocial counseling and social network support for HIV uninfected partners of intervention 
arm index participants may be available at the request of the index participant. 
4.1 
Standard package of services (standard care arm) 
All index participants will receive, as a minimum, the in-country standard of care, based 
on current national guidelines for PWID that are largely based on the WHO 
comprehensive package of care for PWID.[49, 50] This standard of care typically 
includes: 
• 
Harm reduction services 
o Referral for treatment of substance use / addiction 
o Referral to needle and syringe exchange programs, if legal and available 
o Injection risk reduction counseling 
o Sexual risk reduction counseling including access to condoms 
• 
HIV counseling and testing 
• 
Referral for ART according to national guidelines 
• 
Referral for diagnosis and treatment of sexually transmitted infections (STis), 
hepatitis Band C virus (HBV, HCV), and tuberculosis (TB) as appropriate 
All index participants in the standard of care arm will receive a standardized counseling 
session that will include referral to programs for needle and syringe exchange (where 
available), referral for medication assisted substance use treatment and/or detoxification 
(where available), risk reduction counseling for injection drug use, sexual risk reduction 
counseling, and referral for STI, hepatitis, and TB diagnosis and treatment. All 
participants eligible for ART according to the national guidelines will be referred to local 
centers for ART initiation. 
Standard care network i"njection partners: Network injection partners in the standard of 
care arm will receive the applicable national guidelines, as described above, with 
exception of referral for ART. Based on site information, pre-exposure prophylaxis is 
not currently available and is not expected to become available in any of the sites under 
consideration. 
4.2 
Intervention package of services (intervention arm) 
The integrated intervention draws upon multiple successful psychosocial and structural 
interventions with PWID. The focus of the intervention is the index participants.[51-53] 
The intervention includes the following components: a) systems navigators to facilitate 
engagement, retention, and adherence in substance use treatment and HIV care; b) 
psychosocial counseling using motivational interviewing, problem solving, skills 
building, and goal setting to facilitate substance use treatment and HIV care and 
medication adherence; optional sessions involving supporters will be offered; and c) 
ART at any CD4 count. The intervention is rooted in cognitive-behavioral theory, 
motivational interviewing, and diffusion of behavioral change.[16, 17] This intervention 
is designed to be flexible and appropriate across a range of cultures. The program will be 
adapted to individual contexts and cultures, while remaining comparable across sites and 
cultures. 
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Prior to study implementation, a limited number of in-depth interviews will be conducted 
in a subset of the study sites to explore barriers and facilitators for uptake of substance 
use treatment, HIV care, ART use, and adherence. Interviews will be conducted with 
PWID, support persons, and health care providers. These interviews will be used to 
refine the intervention manual and inform the final questionnaires. 
Intervention arm network injection partners: Network injection partners in the 
intervention arm will receive the applicable national guidelines, as described above, with 
exception ofreferral for ART. Partners will not have access to the systems navigators or 
psychosocial counseling provided to index participants except at the request of the index 
participant as noted in Section 5. 
4.2.1 Systems navigators 
Each index participant in the intervention arm will be assigned a systems 
navigator who will work with the index participant to identify the primary 
obstacles to engaging in both substance use treatment and HIV care. A systems 
navigator is defined as a staff member who is knowledgeable about local HIV 
care and substance use treatment services and possesses the skills to facilitate 
initiation and retention in care. Systems navigators may also serve as counselors 
at the discretion of the sites. Systems navigators will emphasize entry into 
substance use treatment, HIV care, ART initiation, retention in care, and ART 
adherence. During contact with the index, the systems navigator will assess the 
progress of the index through each stage of engagement in HIV care and 
substance use treatment using a standardized checklist. Barriers to progress will 
be identified and the systems navigator and index will formulate specific plans to 
overcome those barriers. Such plans may include, for example, facilitation of 
appointments by the systems navigator, assistance recruiting support persons, or 
identification of the need for additional counseling sessions. 
The systems navigator and index participant will have two initial sessions held in 
conjunction with psychosocial counseling sessions (section 4.2.2). Subsequently, 
contacts will be made in person, or with telephone calls or text messages to 
maintain regular contact with the index participants. Home contacts will be used 
as a last resort if repeated calls and text messages are unsuccessful. The systems 
navigator will communicate weekly for the first eight weeks, then monthly for the 
duration of the study. Additional contact may be made to remind participants of 
scheduled appointments. Contact frequency may be increased during any crisis 
period, such as resuming active drug use after initial discontinuation, withdrawal 
from HIV care, discontinuation of ART, or withdrawal from substance use 
treatment. 
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4.2.2 Psychosocial counseling 
Index participants in the intervention arm will receive a minimum of two 
psychosocial counseling sessions. The counselor will use a standardized 
inventory to assess the participants' need for counseling on risk reduction, drug 
treatment entry and retention, HIV medical care, and medication adherence. 
Based on this assessment, additional optional individual sessions will be 
conducted. Common circumstances where additional sessions would be added 
would be supplemental adherence counseling, failure to engage in care, 
withdrawal from substance use treatment, or if the index participant has a specific 
request. 
To enhance ART adherence and adherence to drugs used for substance use 
treatment, index participants in the intervention arm will be asked to identify 
adherence supporters, persons identified by the index participants within their 
broader social network to provide support for ART and substance use treatment 
adherence. The supporter may be any person close to the index participant, such 
as a parent, sibling, or friend, whom the index participant trusts to take an active 
role in encouraging adherence to ART. The psychosocial counselor and/or 
systems navigator will facilitate the identification of an appropriate person. The 
index participant and the supporter may participate in up to two optional 
counseling sessions together to practice adherence communication skills, enhance 
the HIV literacy of their supporters, and the development of a medication 
adherence plan. If the supporter is also a sexual or injection partner the 
counseling session will also address risk reduction. If an index participant is 
unable to identify a support person, he/she remains eligible to participate in all 
other components of the study intervention. 
Prior to facilitating entry into substance use treatment and HIV care, the systems 
navigator and counselor will identify level of interest in substance use treatment. 
For participants who are ambivalent about entering substance use treatment, the 
counselors will use motivational interview techniques to enhance interest in 
enrolling in substance use treatment programs.[54] For those participants who are 
interested in substance use treatment, the counselor will identify barriers to 
substance use treatment entry and retention. This same approach will be used for 
individuals who are ambivalent about entering HIV care. Using motivational 
interviewing, problem solving, skills building, and goal setting, the counselors 
will work with the index participants to overcome barriers to enrollment and 
retention in substance use and HIV treatment, adherence, and risk reduction.[53, 
55] Once the participants are prescribed ART, based on a problem solving and 
goal setting approach, the counselors will work with them on issues of medication 
adherence, including addressing side effects, developing a routine for taking 
medications, developing a plan to obtain medication refills, and for obtaining 
ART adherence social support from their network. 
Participants will be offered the opportunity for two additional booster sessions 
approximately one month and three months after Enrollment. For individuals 
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who have low levels of adherence to ART or substance use treatment, additional 
counseling sessions will be available through self-referral or referral by the 
systems navigator. 
4.2.3 
Systems navigator and psychosocial counseling personnel 
At the discretion of the study sites, systems navigators and psychosocial 
counselors may either be the same staff members or two distinct groups 
(navigators and counselors). The study is designed to be low cost and require 
minimal staff expertise so that it could be readily disseminated and translated into 
the community. The staff will have previous experience in harm reduction and 
working with PWID. The staff must also be familiar with the HIV and substance 
use treatment systems and will typically have two years of experience for those 
designated as counselors. Prior to study initiation, each counselor will receive 
training including role plays, conducting tasks such as addressing participants' 
interest in substance use treatment, identification of barriers, entry and retention 
in those programs. This training will address prioritization and suitability of 
programs for the individual participant, but also the priority of risk reduction for 
HIV, including needle/syringe exchange, oral versus injectable opiate replacement 
treatment besides all other common measures such as social stabilization, partner 
frequency reduction and condom counseling. Systems navigators and counselors 
will not be used for data collection such as behavioral risk assessments. 
4.2.4 Initiation of ART 
All index participants in the intervention arm will be referred for ART, regardless 
of CD4 cell count. The systems navigator will support the initial referral to and 
engagement in care. This support will be developed and targeted within each 
country. ART adherence will be a focal point of psychosocial counseling and 
social network support. 
ART will be provided through the local authorities. As part of the site selection 
process, each potential site was required to obtain an official approval from local 
authorities stating specifically that ART would be provided to all willing study 
_ participants regardless of CD4 count. This would continue as appropriate post 
study. The participants will be provided with a letter describing participation in 
the study and stating approval from the appropriate regulatory agencies. Prior to 
study initiation, ART clinics will be alerted to the study procedures and the 
authenticity of these letters. The letters will be personalized and appropriately 
authorized to minimize the potential for forgery. 
5.0 
STUDY PROCEDURES 
An overview of study visits and procedures is presented in Appendices I, II, and III. 
Additional information on visit-specific study procedures is presented below. Detailed 
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instructions to guide and standardize study procedures across sites are provided in the 
SSP Manual. 
5.1 
Study Intervention Package 
As noted in Section 4.0, all participants will receive a comprehensive set of 
integrated harm reduction services aimed at reducing HIV risk behavior. Index 
participants in the intervention arm will also be offered systems navigation and 
psychosocial counseling, as described below. These may be scheduled in 
conjunction with or separate from the standard biological and behavioral 
assessment visits described in Sections 5.2 and 5.3. At the discretion of the study 
sites, systems navigators and psychosocial counselors may either be the same staff 
members or two distinct groups (navigators and counselors). 
5.1.1 Systems Navigation 
At enrollment, index participants in the intervention arm will meet with a systems 
navigator (see Section 4.2.1 ). The systems navigator will communicate with 
participants weekly for the first eight weeks, then monthly for the duration of the 
study. Contact frequency may be increased during any crisis period, such as 
resuming active drug use after initial discontinuation, withdrawal from HIV care, 
or withdrawal from substance use treatment. Contacts with study participants will 
be recorded on an encounter form. 
5.1.2 
Psychosocial Counseling 
Sites will be expected to offer index participants in the intervention arm a 
minimum of two psychosocial counseling sessions (see Section 4.2.2) during their 
study participation. Optional additional individual sessions should be offered at 
the discretion of the counselor based on identified needs. Participants will be 
offered the opportunity for two additional booster sessions, approximately one 
month and three months after enrollment. For individuals who report low levels 
of adherence to ART or substance use treatment, additional counseling sessions 
will be available. Counselors can also offer a group session with the index 
participant and their identified support person, at the request of the index 
participant. 
5.2 
Behavioral measurements - index participants and network injection 
partners 
5.2.1 
Sexual behavior, substance use, substance use treatment and ART 
experience interviews (for Index Participant only) 
At Enrollment, an interview will be conducted for all participants including: 
substance use history, HIV status, HIV testing history, previous substance use 
treatment, injection risk behaviors, sexual risk behaviors, and the impact of 
perceived stigma on engagement in substance use treatment. Additionally, for 
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index participants, the interview will include previous ART exposure, ART 
adherence, and perceived stigma on engagement in ART. This interview is 
anticipated to take about 30 minutes. 
At Week 4 and each subsequent quarterly visit, as appropriate (based on timing of 
partner enrollment), shorter 20-minute interviews will be conducted with all 
participants to evaluate: (1) injection behaviors since the previous visit, (2) use of 
non-injectable drugs, including alcohol, (3) enrollment in substance use treatment 
and the use of methadone, buprenorphine, or naltrexone, ( 4) adherence to 
substance use treatment, and (5) injection partner turnover among all injection 
partners, as described below. Index participants on ART will also be asked about: 
(6) ART adherence, and (7) side effects of ART. Note that the index participant 
and network injection partner(s) may have visits on different days. 
At study Exit, an approximately 30-minute interview will be conducted to address 
those items in the quarterly visit interviews, plus additional information regarding 
perceived stigma on engagement in HIV care (index only) and substance use 
treatment. 
5.2.2 Social Network Interviews 
At Enrollment, Week 4 and all quarterly visits, all participants will also be asked 
about: (1) current injection partners, including terminated and new relationships, 
and (2) social network measures, including turnover of all injection network 
members, network density, network support for adherence to ART (index only) 
and/or substance use treatment, and (3) frequency of injection and sexual risk 
behaviors with each identified injection network member (including persons 
enrolled and not enrolled in the study). At all subsequent visits, all participants 
will be prompted to update any possible changes to their social networks. 
5.2.3 Social Impact Assessments 
At all study visits after Screening, participants will be asked to report any social 
harms or benefits experienced due to study participation. Both harms and benefits 
will be recorded using a short standardized assessment tool based on previous 
experience with PWID participation in research. 
5.2.4 Assessment of barriers and facilitators to ART (Index only) and 
substance use treatment 
At Enrollment, Week 4 and all quarterly visits (including the Exit visit), the 
barriers and facilitators to the receipt of ART for HIV-infected participants and 
substance use treatment for all participants will be assessed. This brief 
assessment will address likely barriers and facilitators derived from previous 
research and will include will include an open ended "and other, specify" option 
for the participant to report any barrier not included in the given responses. 
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5.3 
Laboratory Assessments 
5.3.1 Laboratory Assessments for HIV-infected Index Participants 
HIV testing will be performed using testing algorithms described in the SSP 
Manual. These testing algorithms may vary across sites. The HPTN LC will 
perform extended QA testing for HIV diagnosis using a single testing algorithm. 
Index participants will only be emolled if HIV infection is confirmed on site 
according to the SSP Manual. In all cases, confirmation of HIV infection will be 
based on results obtained from samples collected at both the Screening and 
Emollment visits; these visits must be performed on different dates. 
HIV viral load testing will be performed in real time at study sites for all index 
participants at Screening (after an initial reactive or positive HIV test result is 
obtained). Viral load testing will be performed retrospectively at the HPTN LC 
for quality assurance and to obtain additional data for the assessment of adherence 
to ART. 
CD4 cell count testing will be performed for all index participants at Screening 
(after an initial reactive or positive HIV test result is obtained). CD4 cell count 
testing will also be performed at Weeks 26, 52, 78, 104, 130 and 156. 
Plasma samples will be stored for other assessments at the HPTN LC, as 
described in Section 9 and Appendix I. This will include retrospective ARV drug 
testing at the HPTN LC; these data will be analyzed as part of the ART adherence 
assessment. Results of this testing will not be reported to study sites or 
participants. 
Urine testing for substances of abuse will be performed in real-time at all study 
visits except the Screening visit, using locally-available test kits. Plasma and 
urine samples, including dried urine samples, will be stored for retrospective 
testing for substances of abuse and medications used for substance use treatment. 
This testing will be performed at the HPTN LC. Results of this testing will not be 
reported to study sites or participants. 
5.3.2 Laboratory Assessments for HIV-uninfected Network Injection 
Partners 
Injection partners of enrolled index participants will be tested for HIV infection at 
the Screening visit and at the Emollment visit according to the SSP Manual; if 
this testing indicates that the individual is HIV uninfected, the individual will be 
considered for emollment in the study as a network injection partner. Injection 
partners who have one or more reactive/positive HIV test(s) at the Screening or 
Emollment visits will not be eligible for emollment as network injection partners, 
even if they are confirmed to be uninfected. 
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Emolled network injection partners will be tested for HIV infection at each study 
visit using testing algorithms described in the SSP Manual. Note that these 
algorithms may vary from site to site. The HPTN LC will perform extended QA 
testing for HIV diagnosis using a single HIV testing algorithm. In all cases, 
confirmation of HIV seroconversion will be based on results obtained from 
samples collected on two different dates. 
Plasma samples will be stored for testing at the HPTN LC, as described in Section 
9 and Appendix II. 
Urine testing for substances of abuse will be performed in real-time at all study 
visits except the Screening visit, using locally-available test kits. Plasma and 
urine samples, including dried urine samples from a subset of participants, will be 
stored for retrospective testing for substances of abuse and medications used for 
substance use treatment. This testing will be performed retrospectively at the 
HPTN LC. A subset of dried urine samples will be tested. Results of this testing 
will not be reported to study sites or participants. 
5.3.3 Additional Laboratory Assessments for Network Injection Partners 
Who Acquire HIV During the Study 
Some network injection partners may become HIV infected during the study 
period. These network injection partners will continue to be followed according 
to their existing schedule of visits, including the collection of behavioral data. 
Site-specific HIV testing algorithms, including tests required to confirm HIV 
acquisition, are described in the SSP Manual. All possible HIV seroconversion 
events will be confirmed retrospectively at the HPTN LC (see Section 9.3.1). HIV 
testing will not be performed on site at subsequent visits after HIV infection is 
confirmed (see SSP Manual). CD4 cell count testing will be performed at the 
HIV confirmatory visit (see Appendix III) and at Weeks 26, 52, 78, and 104 (if 
HIV infection is confirmed prior to those visits). 
5.3.4 
Laboratory Assessments for Ineligible HIV-infected Network 
Injection Partners 
Network injection partners who have one or more positive/reactive HIV test 
results at Screening or Emollment will not be emolled as Partners. These 
individuals will be referred tfor further HIV confirmatory testing according to 
national guidelines. These individuals may continue screening as a potential 
index participant (provided that the original index does not emoll). For these 
individuals, if they agree, plasma obtained during the initial "Partner" screening 
process will be stored for possible phylogenetic analysis. 
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5.4 
Visit Procedures for Index Participants 
5.4.1 
Screening Visit for Index Participants 
It is the responsibility of the local site to determine the best approach to screening 
which will be documented in a site specific standard operating procedure (SOP). 
For each participant, independent written informed consent for Screening will be 
obtained before Screening procedures are initiated. For each index participant, 
Enrollment must occur on a separate date within 60 days of the date of blood 
collection at the Screening visit. See Section 3 .3 for important screening 
information. Note that all Screening procedures (including completion of the HIV 
testing algorithm for the Screening visit) must be completed before a participant is 
enrolled. HIV test results from both the Screening and Enrollment visit will be 
used to determine study eligibility. In addition to testing for HIV infection at the 
Screening visit using local testing guidelines, at least one HIV test ( e.g. HIV rapid 
test) must be positive/reactive at the Enrollment visit for the index participant to 
be considered eligible for the study. 
Administrative, Behavioral and Regulatory Procedures 
• 
Informed consent 
• 
Demographic information 
• 
Locator information 
• 
HIV pre-test, risk reduction, and post-test counseling 
• 
Brief assessment of injection risk behavior, substance use, substance use 
treatment, and ART use for eligibility 
• 
Referral to needle and syringe exchange programs (if legal and available) 
• 
Referral to substance use treatment 
• 
Referral for diagnosis and treatment of STis, HBV, HCV and TB (as 
appropriate )Brief, standardized injection and sexual transmission risk 
reduction counseling 
Clinical Procedures 
• 
Blood collection 
Laboratory Procedures - Local Laboratory 
• 
HIV testing (see SSP Manual)* 
• 
CD4 cell count (if an HIV test is reactive or positive) 
• 
HIV viral load (if an HIV test is reactive or positive) 
• 
Plasma storage 
*HIV test results from both the Screening and Enrollment visit will be used to 
determine study eligibility (two different blood draws collected on different days 
are required for confirmation of HIV infection). If this is a re-screening visit for a 
participant who has not previously been confirmed to be HIV-infected based on 
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testing performed using specimens collected on two separate dates (index or 
partner screening), HIV testing will be required at re-screening. 
5.4.2 Enrollment Visit for Index Participants 
The effective point of emollment is randomization. 
Administrative, Behavioral and Regulatory Procedures 
• 
Informed Consent 
• 
Update locator information 
• 
Randomization 
• 
Baseline sexual behavior, injection risk behaviors, substance use, substance 
use treatment and ART use and adherence interviews 
• 
Assessment of barriers and facilitators to HIV care and substance use 
treatment, mediators and moderators of key outcomes. 
• 
Social network interview 
• 
Social impact assessment 
• 
HIV pre-test, risk reduction, and post-test counseling 
• 
Referral for ART (If clinically indicated according to national guidelines 
and/or participant is randomized to the intervention group) 
• 
Brief, standardized injection and sexual transmission risk reduction 
counseling 
• 
Referral for diagnosis and treatment of STis, HBV, HCV and TB (as 
appropriate) 
Clinical Procedures 
• 
Blood collection 
• 
Urine collection 
Laboratory Procedures - Local Laboratory 
• 
HIV testing (see SSP Manual)* 
• 
Urine testing for substances of abuse will be performed in real-time at study 
sites using locally-available methods 
• 
Plasma storage 
• 
Urine storage 
• 
Dried urine storage 
*HIV test results from both the Screening and Emollment visit will be used to 
determine study eligibility. 
5.4.3 Follow-up visits for Index Participants 
Index participants will have a visit at week 4 and followed quarterly a minimum of 
52 weeks, up to a maximum of 156 weeks. If possible, an Exit visit will be 
conducted for all index participants. 
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Index participants will only be considered terminated from the study if the 
participant actively withdraws or dies during the course of the study. Incarcerated 
participants will be able to resume study participation on release from 
incarceration. 
5.4.3.1 Week 4 visits for Index Participants 
Administrative, Behavioral and Regulatory Procedures 
• 
Update locator information 
• 
Assessment of barriers and facilitators to HIV care and substance use 
treatment, mediators and moderators of key outcomes. 
• 
Social network interview 
• 
Social impact assessment 
• 
Brief, standardized injection and sexual transmission risk reduction 
counseling 
• 
Follow up sexual behavior, substance use, substance use treatment and 
ART experience interviews 
• 
Referral for diagnosis and treatment of STis, HBV, HCV and TB (as 
needed) 
• 
Referral for ART (If clinically indicated according to national 
guidelines and/or participant is randomized to the intervention group) 
Clinical Procedures 
• 
Blood collection 
• 
Urine collection 
• 
Adverse Event Assessment 
Laboratory Procedures 
• 
Urine testing for substances of abuse 
• 
Plasma storage 
• 
Urine storage 
5.4.3.2 Quarterly Visits for Index Participants 
*Quarterly visits will occur at Weeks 13, 26, 39, 52, 65, 78, 91, and 104. 
Note that Weeks 52, 65, 78, 91, 104, 117, 130, 143 or 156 may be an Exit 
visit for some participants, depending on the timing of the participant's 
enrollment relative to the enrollment period at the site. For Exit visit 
procedures, refer to Section 5.4.3.3. 
Administrative, Behavioral and Regulatory Procedures 
• 
Update locator information 
• 
Follow up sexual behavior, substance use, substance use treatment and 
ART experience interviews 
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• 
Referral for ART (If clinically indicated according to national 
guidelines and/or participant is randomized to the intervention group) 
• 
Assessment of barriers and facilitators to HIV care and substance use 
treatment, mediators and moderators of key outcomes. 
• 
Social network interview 
• 
Social impact assessment 
• 
Brief, standardized injection and sexual transmission risk reduction 
counseling 
• 
Referral for diagnosis and treatment ofSTls, HBV, HCV and TB (as 
needed) 
Clinical Procedures 
• 
Blood collection 
• 
Urine collection 
• 
Adverse Event Assessment 
Laboratory Procedures - Local Laboratory 
• 
Urine testing for substances of abuse 
• 
CD4 cell count (Weeks 26, 52, 78, 104, 130 and 156 only) 
• 
Plasma storage 
• 
Urine storage 
• 
Dried urine storage as supplies permit (Weeks 26, 52 and Exit) 
5.4.3.3 Exit Visit for Index Participants 
* Weeks 52, 65, 78, 91 104, 117, 130, 143 or 156 may be an Exit visit for some 
participants, depending on the timing of the participant's enrollment relative to 
the enrollment period at the site. 
Administrative, Behavioral and Regulatory Procedures 
• 
Update locator information 
• 
Exit sexual behavior, substance use, substance use treatment and ART 
experience interviews 
• 
Social network interview 
• 
Social impact assessment 
• 
Brief, standardized injection and sexual transmission risk reduction 
counseling 
• 
Assessment of barriers and facilitators to HIV care and substance use 
treatment, mediators and moderators of key outcomes. 
• 
Referral for diagnosis and treatment of STis, HBV, HCV and TB (as 
appropriate) 
Clinical and Laboratory Procedures are the same as those performed at quarterly 
visits. 
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5.5 
Visit Procedures for Network Injection Partners 
5.5.1 Screening visit for Network Injection Partners 
It is the responsibility of the local site to determine the best approach to Screening. 
For each participant, independent written informed consent for Screening will be 
obtained before Screening procedures are initiated. For each network partner 
participant, Enrollment must occur on a separate date within 60 days of the blood 
collection for the Index Screening visit. See Section 3.3 for important screening 
information. Note that all Screening procedures (including completion of the HIV 
testing algorithm for the Screening visit) must be completed before a participant is 
enrolled. HIV test results from both the Screening and Enrollment visit will be 
used to determine study eligibility. 
Administrative, Behavioral and Regulatory Procedures 
• 
Informed consent 
• 
Demographic information 
• 
Locator information 
• 
HIV pre-test, risk reduction, and post-test counseling 
• 
Brief assessment of injection risk behavior, substance use, and substance use 
treatment for eligibility 
• 
Confirmation via local procedures of relationship to an index participant 
(network association) 
• 
Referral to needle and syringe exchange programs (if legal and available) 
• 
Referral to substance use treatment 
• 
Brief, standardized injection and sexual transmission risk reduction 
counseling 
• 
Referral for diagnosis and treatment of STis, HBV, HCV and TB (as 
appropriate) 
Clinical Procedures 
• 
Blood collection 
Laboratory Procedures 
• 
HIV testing (see SSP Manual)* 
• 
Plasma storage 
*HIV test results from both the Screening and Enrollment visit will be used to 
determine study eligibility. 
5.5.2 Enrollment visit for Network Injection Partners 
The effective point of enrollment is randomization. 
Administrative, Behavioral and Regulatory Procedures 
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• 
Informed Consent 
• 
Update locator information 
• 
HIV pre-test, risk reduction, and post-test counseling 
• 
Baseline sexual behavior, injection risk behaviors, substance use and 
substance use treatment interviews 
• 
Assessment of barriers and facilitators to substance use treatment, mediators 
and moderators of key outcomes 
• 
Social network interview 
• 
Social impact assessment 
• 
Brief, standardized injection and sexual transmission risk reduction 
counseling 
• 
Referral for diagnosis and treatment of STis, HBV, HCV and TB (as 
appropriate) 
Clinical Procedures 
• 
Blood collection 
• 
Urine collection 
Laboratory Procedures 
• 
HIV testing (see SSP Manual)* 
• 
Urine testing for substances of abuse 
• 
Plasma storage 
• 
Urine storage 
• 
Dried urine storage 
*HIV test results from both the Screening and Enrollment visit will be used to 
determine study eligibility. 
5.5.3 Follow-up visits for Network Injection Partners 
Network injection partners (including replacement partners) will be followed until 
the index participant's Exit visit. If a network injection partner ends his/her 
relationship with the index participant, this network injection partner will continue 
to be followed and will have all follow-up assessments performed, even if the 
index participant recruits a new, active network injection partner. 
Network injection partners will only be considered terminated from the study if the 
participant actively withdraws or dies during the course of the study. Incarcerated 
participants will be able to resume study participation on release from 
incarceration. 
All replacement ( or late enrolling) partners will have a Week 4 visit before 
assuming the visit schedule of the corresponding Index. 
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5.5.3.1 Week 4 Visit for Network Injection Partners 
Administrative, Behavioral and Regulatory Procedures 
• 
Update locator information 
• 
HIV pre-test, risk reduction, and post-test counseling 
• 
Follow up sexual behavior, substance use, substance use treatment and 
ART experience interviews 
• 
Assessment of barriers and facilitators to substance use treatment, 
mediators and moderators of key outcomes 
• 
Social network interview 
• 
Social impact assessment 
• 
Brief, standardized injection and sexual transmission risk reduction 
counseling 
• 
Referral for diagnosis and treatment of STis, HBV, HCV and TB (as 
appropriate) 
Clinical Procedures 
• 
Blood collection 
• 
Urine collection 
• 
Adverse Event Assessment 
Laboratory Procedures 
• 
HIV testing (see SSP Manual)* 
• 
Urine testing for substances of abuse (may be performed in the clinic 
or the local laboratory) 
• 
Plasma storage 
• 
Urine storage 
5. 5. 3. 2 Quarterly visits for network injection partners 
Quarterly visits will occur at Weeks 13, 26, 39, 52, 65, 78, 91, and 104. 
Note that Weeks 52, 65, 78, 91, or 104 may be an Exit visit for some 
participants, depending on the timing of the participant's enrollment 
relative to the enrollment period at the site. For Exit visit procedures, 
refer to Section 5.5.3.3. 
Administrative, Behavioral and Regulatory Procedures 
• 
Update locator information 
• 
Follow up sexual behavior, substance use and substance use treatment 
interviews 
• 
Assessment of barriers and facilitators to substance use treatment, 
mediators and moderators of key outcomes 
• 
Social network interview 
• 
Social impact assessment 
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• 
HIV pre-test, risk reduction, and post-test counseling 
• 
Brief, standardized injection risk reduction counseling 
• 
Referral for diagnosis and treatment of STis, HBV, HCV and TB (as 
appropriate) 
Clinical Procedures 
• 
Blood collection 
• 
Urine collection 
• 
Adverse Event assessment 
Laboratory Procedures 
• 
HIV testing (see SSP Manual) 
• 
Urine testing for substances of abuse (may be performed in the clinic or 
the local laboratory) 
• 
Plasma storage 
• 
Urine storage 
• 
Dried urine storage as supplies permit (Weeks 26,52 and Exit only) 
5. 5. 3. 3 Exit visit for Network Injection Partners 
Weeks 52, 65, 78, 91 or 104 may be an Exit visit for some participants, depending 
on the timing of the participant's enrollment relative to the enrollment period at 
the site. 
Administrative, Behavioral and Regulatory Procedures 
• 
Update locator information 
• 
Exit sexual behavior, substance use, and substance use treatment 
experience interviews 
• 
Social network interview 
• 
Social impact assessment 
• 
HIV pre-test, risk reduction, and post-test counseling 
• 
Brief, standardized injection and sexual transmission risk reduction 
counseling 
• 
Assessment of barriers and facilitators to substance use treatment, 
mediators and moderators of key outcomes 
• 
Referral for diagnosis and treatment of STis, HB.V, HCV and TB (as 
appropriate) 
Clinical and Laboratory Procedures are the same as those performed at Quarterly 
Visits 
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5.6 
Additional procedures for network injection partners who have a reactive or 
positive HIV test at any visit after Enrollment (See Appendix III). 
5.6.1 HIV Confirmation Visit Following a Reactive or Positive HIV Result 
This visit should occur within 14 days of the first reactive/positive HIV test) and 
must occur on a different date than the date at which the first reactive/positive HIV 
test result was obtained. Referrals will be made for standard of care treatment as 
indicated. Referrals for expanded access to ART will not be provided to network 
injection partners who become HIV infected while on follow up. 
Clinical Procedures 
• 
Blood collection 
Laboratory Procedures - Local Laboratory 
• 
HIV testing (see SSP Manual)* 
• 
CD4 cell count 
• 
Additional plasma storage 
* Sites may contact the HPTN LC to see if these procedures may be waived for 
individuals who have a single assay result that is near the assay cutoff and 
likely to be a false-positive result based on other HIV test results obtained at 
the regularly scheduled study visit. 
5.6.2 Weeks 26, 52, 78 and 104 (if HIV infection has been confirmed) 
If HIV infection was confirmed at a prior visit, a CD4 cell count should be 
obtained (in addition to other study procedures and tests) at these visits. HIV pre-
test, post-test and risk reduction counseling as well as HIV testing will not be 
completed at these visits. 
5. 7 
Data collection procedures for systems navigators and psychosocial counselors 
5. 7.1 . Systems Navigators 
Systems navigators' contacts with index participants will be recorded with a 
standard encounter form. The encounter form will address the duration and 
content of the interaction with the participant, including the relationship to HIV 
care or substance use treatment, barriers addressed, and outcome. 
Systems navigators will also maintain a log book of contacts with health care 
settings or agencies. The log book will document the purpose of the contact, 
outcome/plan, and participants served by the interaction. 
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At the conclusion of follow-up, semi-structured interviews will be conducted with 
the systems navigators to address feasibility of and barriers to the intervention 
following the procedures outlined in Section 5.8. 
5. 7.2 Psychosocial Counselors 
Psychosocial counselors will record encounters with participants on a standard 
encounter form. The form will identify the type of encounter (individual or 
group), topics addressed, barriers identified, duration of encounter, an.d planned 
actions. 
At the conclusion of follow-up, the counselors will complete individual semi-
structured interviews addressing feasibility of and barriers to the intervention 
following the procedures outlined in Section 5.8. 
5.8 
Data Collection Procedures for Semi-Structured Interviews 
To assess the feasibility of the intervention, individual semi-structured interviews will be 
conducted with 4-10 stakeholders (minimum=12, maximum=30 across all sites) at each 
study site during the initial stages of enrollment and the final stages of follow-up 
(minimum= 24, maximum =60 interviews across all sites). The stakeholders will include 
navigators and counselors at the research sites as well as key clinic personnel at the HIV 
care and substance use treatment sites. The clinic (non-study) personnel will include HIV 
care and substance use treatment providers and supervisors. 
Sites will also have the option to conduct individual semi-structured interviews with a 
subset of index particpants randomized to the intervention arm. For each site that opts to 
conduct these interviews, a total of 4-15 intervention index participants (maximum=45 
intervention index participants across all sites) will be conducted during the initial stages 
of enrollment and a total of 4-20 intervention index participants (maximum=60 
intervention index participants across all sites) during the final stages of follow-up 
(maximum=105 interviews across all sites). 
Participation of stakeholders and index participants will be entirely voluntary. If a 
stakeholder/participant chooses not to participate, he/she will experience no penalty or 
loss of benefits. Furthermore for stakeholders, procedures will be undertaken to ensure 
that supervisors are not informed of a stakeholders decision regarding participation. If an 
index participant chooses not to participate, this decision will not affect his/her 
participation in the trial. Specific measures to handle and ensure protection of 
stakeholders and index participant refusal and participation will be outlined in a 
Qualitative Methods Handbook (included in the SSP). The informed consent process and 
interviews will be conducted in a location that assures adequate privacy and 
confidentiality, such as a non-study related office. 
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No personal identifiers will be retained on the collected data to assure privacy and 
confidentiality for stakeholders and index participants. Reports and publications will be 
carefully redacted to ensure that identities cannot be discerned. 
Semi-structured interviews will be conducted using a standard guide that includes site-
specific probes and a combination of client- and provider-centered queries. The 
interviews will explore the heterogeneity of treatment services available for clients. This 
will include objective measures such as hours of clinic operations, differences in rules for 
termination of substance use treatment, and any costs to participants. Additionally, the 
interviews will elicit what the clinic personnel believe are the common barriers and/or 
facilitators for them as providers - as well as their clients - to the intervention outcomes 
of: 
• 
the uptake of HIV testing 
• 
initiation of HIV care and substance use treatment 
• 
medication adherence 
The interviews will also explore the sustainability, strengths and weaknesses of the 
intervention in addressing the barriers and/or enhancing the facilitators. An example of a 
client-centered query is stakeholders' perception of why participants may not be able or 
willing to initiate HIV or substance use care. An example of a provider-centered query is 
staffing at methadone maintenance therapy and ART sites and scalability of the 
intervention. Interviews will last approximately one hour. All interviews will be audio-
taped, transcribed and translated by qualified personnel. All participant identifiers will be 
removed from transcripts. Coding will be approached with a two-phase analytic method 
(fully detailed in Section 7.2.1.3.) including topical and interpretive analyses. 
6.0 
SAFETY MONITORING AND ADVERSE EVENT REPORTING 
6.1 
Safety Monitoring 
Close cooperation between the Protocol Chair(s), study site Investigator(s), NIAID 
Medical/Program Officer, LOC Protocol Coordinator, SDMC Biostatistician, HPTN LC, 
and other study team members will be necessary in order to monitor participant safety 
and to respond to occurrences of toxicity in a timely manner. 
A sub-group of the Protocol Team, including the Protocol Chair and Co-Chair, DAIDS 
Medical Officer, one or more site clinicians, and the SDMC Clinical Affairs Safety 
Associate will serve as the Clinical Management Committee (CMC). The CMC is a 
resource for site clinicians in the management of individual participants which will meet 
if there is a particular participant situation that merits discussion. 
The study site Investigators are responsible for continuous close monitoring of reportable 
AEs (refer to Section 6.3.3) that occur among study participants from enrollment until the 
participant exits the study, and for alerting the CMC if unexpected concerns arise. 
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6.2 
Clinical Data Safety 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 evaluation and reporting of safety 
information at the participant level, and for alerting the CMC if unexpected concerns 
arise. The Study Monitoring Committee (SMC) will conduct periodic detailed reviews of 
reports of safety data ( e.g., SAEs, Social Harms). Additional reviews may be conducted 
at each of these levels as dictated by the occurrence of certain events. 
Events identified as questionable, inconsistent, or unexplained will be queried for 
verification. AE reports submitted in an expedited manner to the DAIDS Safety Office 
will be forwarded to the DAIDS Medical Officer for review. 
If at any time a decision is made to discontinue the study, DAIDS will notify the site 
Investigators of Record who will in tum notify the responsible IRBs/ECs/ Ministries of 
Health (MoH) expeditiously. 
6.3 
Adverse Events 
6.3.1 Non-Serious Adverse Events 
Non-serious adverse events will be collected and recorded in the source 
documentation with referrals as necessary, but not reported in the database as part 
of this research protocol for all study participants. 
6.3.2 Serious Adverse Events 
Serious AEs (SAEs) are defined per International Conference on Harmonisation 
(ICH) guidance, as specified in Version 2.0 of the Manual for Expedited Adverse 
Events to DAIDS, dated January 2010 (Section 2.1) and will be collected and 
reported on Case Report Forms (CRFs) for all study participants. However, only 
Suspected Unexpected Serious Adverse Reactions (SUSAR) will be collected 
and reported in an expedited manner to the DAIDS Adverse Event Reporting 
System (DAERS) (http://rsc.tech-res.com/docs/default-
source/safety/manual for expedited reporting aes to daids v2.pdf?sfvrsn=10). 
The reporting period for all participants is from the time of enrollment through 
when a participant exits the study. 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. 
Relatedness is an assessment made by a study clinician of whether or not the 
event is related to the study agent defined as the participant's current or last 
known ART and/or opiate substitution therapy. The relationship of all SAEs to 
study product will be assessed as specified in Version 2.0, January 2010 (or most 
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current version) of the DAIDS Expedited Adverse Event (EAE) Reporting 
Manual. 
6.3.3 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. For 
questions about DAERS, please contact NIAID CRMS Support at 
CRMSSupport@niaid.nih.gov. Site queries may also be sent with the DAERS 
application itself. 
For questions about EAE reporting, please contact the DAIDS RSC Safety Office 
at DAIDSRSCSafetyOffice@tech-res.com. 
6.3.4 Grading severity of adverse events 
The severity of all AEs will be graded according to the current Division of AIDS 
Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 
1.0, dated December 2004 (with Clarification dated August 2009), or most current 
version, which is available on the RSC website at 
http ://rsc. tech-res. com/ safetyandpharmacovigilance/. 
6.3.5 
Toxicity Management 
Toxicity associated with ART or substitution therapy will be managed by the host 
country medical authorities, given that ART will be administered under their 
authority. Toxicity associated with medication-assisted substance use treatment 
will also be managed by host country medical authorities. The CMC exists as an 
additional resource to site clinicians should questions arise. 
6.4 
Concomitant Medications 
Concomitant medications are permitted at the discretion of the local medical authorities. 
6.5 
Regulatory Requirements 
Information on hospitalizations and deaths occurring among all study participants will be 
recorded on case report forms and included in reports to applicable government and 
regulatory authorities. The site IoR/designee will submit this information in accordance 
with local regulatory agencies' or other local authorities' requirements. The site 
IoR/designee also will submit any other relevant safety information to the !RB/Ethics 
Committee (EC) in accordance with IRB/EC requirements. 
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6.6 
Social Impacts Reporting 
Social Impacts will be monitored closely throughout the study. At each follow-up visit, a 
series of structured questions will be used to probe for interpersonal, legal, housing and 
healthcare problems that have occurred as a result of study participation. All subjects 
will also be reminded of the importance of reporting problems to study staff between 
regularly scheduled visits and instructed on how to contact study staff should problems 
occur during intervals between visits. Additionally, Social Impacts reported by anyone 
other than study participants, e.g., family or staff members, will also be monitored and 
documented in site source records and monitored by study staff. When these events are 
serious, including incarceration, physical abuse, suicidal behavior, or homicidal behavior, 
they will be reported on case report forms. Whenever problems are identified, additional 
data regarding the severity and resolution will be described and recorded on a case report 
form and will include a description of actions taken by the participant, the site staff, and 
others to resolve or respond to the problem. The nature and frequency of these social 
impact reports will be monitored by the SMC as they occur. 
Given the status of illegal drug use, the associated social stigma and perceptions of drug 
users held by many members of the communities in which the study will be conducted, 
social harms could occur purely as a result of participation in a study targeting drug users. 
These could include discriminatory treatment and violence associated with possible 
disclosure of participants' drug or sex-related behaviors or of their HIV serostatus. 
Prior to site activation, a review of local and national policies and practice affecting 
injection drug users will be conducted. The purpose of this review will be to verify that 
laws, policies and enforcement strategies do not place participants in the research at 
significantly elevated risk of arrest, incarceration, physical harm, unwanted disclosure of 
drug use, or loss of access to health care relative to injection drug users not participating 
in the research. 
The assessment will consist of two components. The first component will review and 
analyze the laws relevant to injection drug use by examining laws concerning drug 
control, drug use, access to health care and privacy of medical information in each study 
country. This review will identify and collate constitutions and any treaties that have the 
force oflaw, statutes passed by the national, regional or local legislature, administrative 
regulations with the force of law and relevant court decisions interpreting these laws or 
regulations. This review of the legal and social risks will roughly follow the recently 
released Legal Assessment Tool (LAT), which is endorsed by the American Bar 
Association and the United States Agency for International Development (American Bar 
Association). Details on the use of the LAT are available in the LAT methodology 
manual.[56] This review will be conducted with the close involvement of independent 
legal experts in each study country. 
The second component will assess how these laws are put into practice and what possible 
influence they have on the risks and benefits of PWID participation in the study. 
Qualitative data regarding the effects of law on PWID will be gathered, along with data 
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on stigma, social risk, and social attitudes as they apply to PWID. These data will be 
collected via interviews with key informants in the legal and public health fields as well 
as current and former injection drug users. Data will be collected via standardized 
interview forms by independent researchers at each site. 
The review will provide a narrative summary and analysis of the law and its likely effects 
on study participants. As these laws, policies and practice strategies can be expected to 
change over time, site staff will continue to monitor relevant laws and policies for the 
duration ofHPTN 074. 
To the extent possible, activities involving participants will be conducted in venues that 
mask the criteria for study participation. It is impossible and unwise to think that the 
primary purpose of the study can be kept secret (i.e., a prevention study for PWID) from 
the community, including the police. An appropriate working relationship with the local 
law enforcement agency at each site, which recognizes the urgent need to prevent HIV in 
this population, will be established. Such relationships are believed to assist outreach 
staff whose presence in the community is understood and respected. Site staff will not 
disclose the names of participants to anyone other than members of the field research 
staff and have strict policies regarding the situations in which discussions of participants 
can take place, such as staff meetings on topics of recruitment and follow-up. All 
interview and laboratory data are securely stored in a confidential manner. 
6. 7 
Clinical Management of Pregnancy 
Participants who identify as pregnant, either index participants or network injection 
partners, will remain in the study. For HIV-infected pregnant women, ART will be 
managed according to national guidelines for prevention of mother-to-child transmission 
of HIV and treatment of the mother's HIV infection. 
7.0 
STATISTICAL CONSIDERATIONS 
7.1 
Review of Study Design 
This is a multisite, two-arm, randomized vanguard study. Network units consisting of an HIV-
infected index participant and his/her HIV-uninfected network injection partner(s) will be 
randomized to the intervention or standard of care arms in a 1 :3 ratio, stratified by site. 
7.1.1 Primary Endpoints 
Consistent with the primary study objective to assess the feasibility of a future 
randomized controlled trial by: 
a) estimating the HIV incidence among network injection partners of 
index participants in the standard of care arm in three distinct global 
settings with epidemics driven predominantly by injection drug use; 
b) evaluating enrollment and retention of HIV-infected PWID and their 
HIV-uninfected network injection partners over a period of 12-24 
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months plus an additional 12 months for those index participants 
willing to continue and re-consent. 
The following endpoints will be assessed: 
HIV incidence 
1) Overall and by site HIV seroconversion rates of network injection partners in 
the standard of care arm 
Enrollment and retention 
1) Calendar time to emoll and allocate to study arm 500 eligible HIV-
infected PWID overall and 167 eligible HIV-infected PWID by study site 
2) Number of eligible HIV-uninfected network injection partners overall and 
at each site 
3) Proportion of index participants retained at each visit overall and at each 
site 
4) Proportion of network injection partners, emolled at index participant's 
allocation to study arm, retained at each visit overall and at each site 
5) Mean (SE) person years at risk accumulated per index participant overall 
and at each site 
Consistent with the primary study objective to assess the feasibility, barriers, and 
uptake of an integrated intervention for prevention of HIV transmission among 
HIV-infected index participants, the following endpoints will be assessed overall 
and by site among participants in the intervention group only: 
Uptake measures 
Intervention component: Systems navigators 
1) Overall: Proportion of index participants using systems navigators at least 
once. 
2) Overall: Mean (standard error) number of contacts (text, email, telephone 
call, home visit, other) with index participants made with systems 
navigators (mean contacts per index participant) 
3) Use of navigators for ART: Mean (SE) number of contacts with HIV care 
sites made by systems navigators per index initiating ART. 
4) Use of navigators for uptake of substance use treatment: Mean (SE) 
number of contacts with medication-assisted substance use treatment 
centers made by systems navigators per index initiating substance use 
treatment. 
Intervention component: Psychosocial counseling 
1) Proportion of index participants completing two counseling sessions 
within four weeks of emollment 
Intervention component: Social network support 
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1) Proportion of index participants with an identified social support person 
within 13 and 52 weeks of enrollment 
2) Proportion of index participants completing a joint counseling session 
with an identified HIV medical care social support person within 13 and 
52 weeks of enrollment 
Intervention component: Substance use treatment 
1) Proportion of index participants self-reporting substance use treatment by 
4 and 13 weeks 
2) Proportion of index participants with detectable methadone or 
buprenorphine at selected study visits 
Intervention component: Supported ART (all intervention index participants 
ART-eligible) 
1) Proportion of index participants self-reporting initiating ART by 4 and 13 
weeks 
2) Proportion of index participants on ART with detectable antiretroviral 
drugs at selected study visits 
3) Proportion of index participants who achieve virologic suppression by 26 
and 52 weeks 
Feasibility and Barriers 
Analyses for feasibility of and barriers to the intervention will be exploratory. 
Feasibility of the intervention will be assessed through individual semi-structured 
interviews with the systems navigators, counselors, additional stakeholders, and a 
subset of index particpants randomized to the intervention arm . Barriers will be 
assessed through the barrier questionnaire with the participants, systems 
navigators' and counselors' data forms/log books, and interviews with additional 
stakeholders. 
7.1.2 Secondary Endpoints 
Consistent with the following secondary study objectives, the following 
endpoint(s) will be assessed: 
• 
To estimate HIV incidence among network injection partners of index 
participants in the intervention arm. 
1) Overall HIV seroconversion rates of network injection partners in the 
intervention arm 
• 
To explore the effect of the integrated intervention, as compared to standard 
of care, on engagement in HIV care, initiation of ART, retention on ART, 
ART adherence, and virologic suppression among ART-eligible index 
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participants (index participants meeting national guidelines in the standard of 
care arm; all index participants in the intervention arm). 
1) Number of HIV medical visits reported at 26 weeks and 52 weeks by index 
participants (self-report) 
2) Proportion of baseline ART-eligible index participants self-reporting ART 
initiation by 4 and 13 weeks 
3) Proportion of baseline ART-eligible index participants self-reporting current 
use of ART at 26 and 52 weeks 
4) Proportion of index participants on ART self-reporting high adherence to 
ART at 26 and 52 weeks 
5) Proportion of ART-eligible index participants with virologic suppression, at 
26 and 52 weeks 
6) Proportion of index participants on ART for at least 3 months with virologic 
suppression at 26 and 52 weeks 
• 
To explore the effect of the integrated intervention, as compared to standard 
of care, on the proportion of index participants and network injection partners 
engaged and retained in substance use treatment. 
1) Proportion of index participants and network injection partners initiating 
substance use treatment within 4 and 13 weeks 
2) Proportion of index participants and network injection partners in substance 
use treatment at 26 and 52 weeks 
3) Proportion of index participants and network injection partners in methadone 
treatment at 26 weeks 
• 
To estimate the size and stability of injection networks of the index participants 
and how this affects recruitment and retention of network injection partners. 
1) Number of reported network injection partners (size of injection network) at 
Enrollment, 13, 26, 39 and 52 weeks 
2) Number of new network injection partners reported over 13, 26, 39, and 52 
weeks 
3) Number of new network injection partners reported and recruited into the study 
over 26 and 52 weeks 
4) Number of "discontinued" network injection partners over 26 and 52 weeks 
5) Number of referred network injection partners who were HIV-infected at 
Screening or Enrollment 
• 
To assess the social harms and benefits of research participation for PWID. 
6) Benefits will be assessed in exploratory analyses to address improvement of 
physical health, mental health, quality of life, relationships, financial, or 
employment. Additional benefits to be explored include reduced drug use, 
reduced cravings, reduce HIV stigma, and gained knowledge. 
7) Harms will be assessed in exploratory analyses. 
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• 
If feasible and if funding is identified, to use phylogenetic methods to 
characterize transmission dynamics in the study cohort. 
1) Overall and by site HIV seroconversion rates of network injection partners in 
the standard of care arm, including phylogenetically confirmed transmission 
events only 
2) Overall HIV and by site seroconversion rates of network injection partners in 
the intervention arm, including phylogenetically confirmed transmission events 
only 
3) Proportion of all HIV seroconversions among network injection partners in 
both the standard of care and intervention arm that are phylogenetically 
confirmed. 
• 
Evaluation of factors related to HIV infection, antiretroviral (ARV) drug use; 
substances of abuse; methadone and other treatments for substance abuse; 
cross-sectional HIV incidence estimation; characterization of HIV in infected 
participants, including phylogenetics and linkage; evaluation of the host 
response to HIV infection; and evaluation of laboratory assays related to study 
objectives. 
7.2 
Accrual, Follow-up, and Sample Size 
7.2.1 Primary endpoints 
HIV incidence 
The sample size represents a balance between obtaining an estimate of HIV 
incidence among network injection partners in the standard of care group and the 
need to assess feasibility of the intervention components. 
The overall sample size of HIV-infected index participants is 500 persons. Given 
the allocation ratio of 1 :3, 375 index participants will be randomized to the 
standard of care arm. Assuming recruitment of 1.5 network injection partners per 
index, the standard of care group will include approximately 563 network 
injection partners for estimation of HIV incidence. The team also assumes 10% 
annual loss to follow-up. PWID who die or are incarcerated are not considered 
lost to follow-up. 
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Table 4. Exact Poisson Confidence Intervals for Annual Standard of Care Arm Incidence Rates 
Standard 
1.5 partners/index; 90% annual retention 
1.5 partners/index; 80% annual retention1 
Overall 
Three sites 
Overall 
Three sites 
of Care 
(N indexes= 375) 
(N indexes= 125) 
(N indexes= 375) 
(N indexes = 125) 
Arm 
N partners = 563, 
N partners = 188, 
N partners= 563, 
N partners = 188, 
incidence 
Person Years = 715 
Person Years = 23 8 
Person Years= 594 
Person Years = 198 
N 
95%CI 
N 
95%CI 
N 
95%CI 
N 
95%CI 
events 
events 
events 
events 
2% 
14 
1.07-3.29 
5 
0.68-4.90 
12 
0.79-3.26 
4 
0.00-4.54 
3% 
21 
1.82-4.49 
7 
1.18-6.06 
18 
1.58-4.48 
6 
0.20-5.86 
5% 
36 
3.53-6.97 
12 
2.61-8.81 
30 
3.24-6.86 
10 
1.71-8.39 
8% 
57 
6.04-10.33 
19 
4.81-12.47 
48 
5.86-10.30 
16 
4.11-12.05 
10% 
71 
7.76-10.33 
24 
6.46-15.00 
59 
7.50-12.36 
20 
5.78-14.42 
1 The same number of person years (and therefore the same confidence intervals) would apply with 1.25 partners per index and 
90% annual retention. 
The estimates provide reasonable precision for estimating the sample size in a 
future study. 
Note: These are estimated under the assumption of independence. While 
outcomes of HIV -infected partners of the same index will be correlated, because 
HIV incidence is expected to be a rare event and the networks are small, the 
impact of this correlation on the confidence limits is likely to be small. 
Intervention uptake 
The most critical endpoints for intervention uptake ( defined in 7 .1.1) are 
substance use treatment, support ART initiation and viral load suppression among 
the index participants assigned to the intervention arm. The targeted proportion 
achieving each of these is 75-95% of participants in the intervention arm. Table 5 
gives the 95% confidence intervals for proportions observed. 
Table 5. Intervention Uptake 
Intervention 
N Indexes = 125 
N Observed 
Proportion 
95% confidence 
bounds 
94 
75.2% 
(66.7, 82.5) 
100 
80.0% 
(71.9, 86.6) 
106 
84.8% 
(77.1, 90.6) 
112 
89.6% 
(82.9, 94.4) 
119 
95.2% 
(89.9, 98.2) 
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Table 6: Effect sizes for the HPTN074 intervention with 90% power. 
Total 
Control 
Intervention 
Minimum 
(N indexes = 500) 
(N indexes= 375) 
(N indexes= 125) 
Standard of 
N partners= 750, 
N partners= 563, 
N partners= 167 
alternative HR 
for which trial 
Care Arm 
PYears = 953 
PYears = 715 
PYears = 238 
has 90% 
incidence 
Total number of 
Expected number 
Expected number of 
of events under 
events under alternative 
power. 
events 
alternative HR 
HR 
2% 
14 
14 
0 
0.135 
3% 
22 
21 
1 
0.203 
5% 
39 
36 
3 
0.306 
8% 
64 
57 
7 
0.392 
10% 
81 
71 
10 
0.435 
Intervention feasibility and barriers 
Analyses of feasibility and barriers will have both exploratory quantitative and 
qualitative components. The exploratory quantitative components will involve 
descriptions of the frequencies of identified barriers, assessed over time during 
follow-up. Planned stratifications include gender and study site. Separate 
analyses will be conducted for index participants and network partners. 
Qualitative analyses: Semi-structured interviews with systems navigators, 
counselors, stakeholders (minimum= 12, maximum= 30 across all sites), and a 
sub-set of index participants randomized to the intervention arm (maximum =60 
across all sites) will be based on a standard field guide that will be used at all 
sites. All interviews will be audiotaped, transcribed and translated into English at 
each study site by qualified personnel. All participant identifiers will be removed 
from transcripts. Transcripts will be analyzed in two phases: topical and 
interpretive. 
In the first phase, topical analyses will identify content categories a priori and will 
cull data into units that reflect core content categories for summary. A codebook 
consisting of main topics of interest ( e.g., utilization of systems navigators and 
counselors, uptake of ART, pill-taking patterns, uptake of substance use 
treatment, and provider burden) will be developed by a centralized team. A 
standardized workshop will train local staff in the codebook, the application of 
codes and the use of Atlas ti.[57] Interviews will be indexed by pre-determined 
topics through the application of topical codes by trained teams of 2-3 site-level 
coders.[58] Specifically, coders will review transcript content for references to 
barriers and facilitators of both the intervention ( engagement in counseling and 
utilization of systems navigators) and uptake of HIV and drug treatment services 
from both patient and provider perspectives. Each identified barrier and 
facilitator will be further coded for content that is motivational, behavioral skills 
related, or informational. To maintain coding quality, each coder will complete a 
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certification exercise prior to initiating the work, qualitative supervisors will 
regularly review coded transcripts and senior data analysts will spot check coded 
transcripts from each site. The team anticipates that these data will provide 
nuanced information about the feasibility of and barriers to the various 
components of the intervention as well as HIV and drug treatment services. Data 
that are topically coded will be used to generate code reports for each of the 
feasibility endpoints across sites at the central level. Based on these code reports, 
detailed summary reports will note insights, key themes and patterns that emerge 
from the data. 
The second phase of analyses is interpretative and will occur at the central level. 
The team will use an iterative, inductive process of reviewing content and 
identifying themes within, across and outside of topical codes that characterize, 
qualify or define the phenomenon ofinterest.[59] This phase of analyses will 
begin with an iterative review of site-specific topical code reports by senior data 
analysts familiar with the phenomenon of interest to ensure an adequate level of 
sensitivity in the development of coding schemes. In addition to descriptions of 
the phenomenon identified through topical coding, the team will explore the 
context in which it occurs, specific conditions in which it occurs, activities done 
in response to the phenomenon and outcomes of the activities. This process will 
produce a set of general categories that describe the characteristics and patterns 
both within and across sites and topical codes. Given the interview objectives, the 
team anticipates that a priori phenomena would include utilization of systems 
navigators and counselors, uptake of ART, pill-taking patterns, uptake of 
substance use treatment, and provider burden. However, additional phenomena 
that may emerge from the interview data will also be included. Codes will then 
be consolidated into a final coding system that can be compared across sites. 
Through this process, critical aspects of intervention delivery as well as uptake of 
services along the HIV treatment cascade will be defined both a priori and 
through the identification of emerging phenomena that may not have been 
anticipated. 
7.2.2 Secondary endpoints 
The secondary endpoints primarily compare proportions of observed events 
across study arms. Proportions will be compared between study arms using odds 
ratios. Table 6 provides an indication of the differences the team has reasonable 
power to detect, both overall and at each site in indexes and network partners, 
assuming comparisons at specific time points. For comparisons with repeated 
observations at multiple study visits, the team would have considerably more 
power. 
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Table 6. Power for detecting Odds Ratios for comparison between arms 
Overall 
Three sites 
Odds 
N (Intervention: SOC) 
N (Intervention: SOC) 
Ratio 
N Indexes= 500 (125:375) 
N Indexes= 167 (42:125) 
N Partners= 750 (188:563) 
N Partners= 250 (62:188) 
Indexes 
Partners 
Indexes 
Partners 
1.50 
48.9% 
65.8% 
20.0% 
27.7% 
1.75 
74.9% 
89.7% 
33.0% 
46.1% 
2.00 
89.4% 
97.6% 
45.8% 
62.2% 
2.25 
95.8% 
99.5% 
56.9% 
74.3% 
2.50 
98.4% 
99.9% 
66.0% 
82.8% 
3.00 
99.7% 
100.0% 
78.5% 
92.0% 
7.3 
Random Assignment/ Study Arm Assignment 
HIV-infected index participants and their HIV-uninfected network injection partners will 
be randomized in a 1 :3 ratio to the intervention and standard of care arms. The 
randomization will be stratified by site. 
7 .4 
Data Analysis 
7.4.1 Primary Analyses 
HIV incidence 
The primary outcome of the study is the HIV incidence in the standard of care 
arm overall and by site. HIV incidence will be assessed using two approaches 
reflecting different assumptions about infections within a network: 
a. Treating all of the network injection partners of an index as representative 
of time exposed to the index participant (i.e., allowing for dependence 
between index participants' risk of infection). Poisson regression with GEE 
methods will be used fitting only an intercept term, for the overall rate (site 
as a covariate for site specific rates), with study time in an offset term using 
index as the cluster, and robust standard errors will be used. 
b. Assessing the rate of infection amongst all network injection partners 
enrolled in the study. Confidence intervals will be based on the Poisson 
distribution (assuming independent observations). 
Feasibility of and uptake of Integrated Intervention 
Descriptive statistics will be used to assess feasibility characteristics. The 
following methods will be used: for categorical variables, the number and percent 
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in each category; for continuous variables, the mean, median, standard deviation, 
quartiles and range (minimum, maximum); for time-to-event outcomes, estimate 
and confidence limits will be based on Kaplan-Meier curves. 
7.4.2 Secondary Analyses 
Statistical analyses for secondary objectives will be conducted as follows: 
Comparisons of proportions between arms will use odds ratios, stratified by site, 
adjusted for clustering by network. 
Comparison oftime to event data between arms (e.g., time to initiating ART) will 
use a log rank test stratified by site. Distributions of time to event data will be 
estimated using the Kaplan-Meier method. Interval censored and discrete time 
methods for time-to-event data will be used where appropriate, and analyses will 
account for clustering by network. 
Appropriate descriptive statistics will be used to summarize required study 
elements overall and by site (e.g., mean, standard error, median and interquartile 
ranges). Analyses will be adjusted for clustering by network as appropriate. 
8.0 
HUMAN SUBJECTS CONSIDERATIONS 
8.1 
Ethical Review 
This protocol and the template informed consent forms contained in Appendix IV -
and 
any subsequent modifications -
will be reviewed and approved by the HPTN Scientific 
Review Committee (SRC) and DAIDS Prevention Science Review Committee (PSRC) 
with respect to scientific content and compliance with applicable research and human 
subjects regulations. 
The protocol, site-specific informed consent form, participant education and recruitment 
materials, and other requested documents -
and any subsequent modifications -
also 
will be reviewed and approved by the ethical review bodies responsible for oversight of 
research conducted at the study sites. 
Subsequent to initial review and approval, the responsible IRBs/ECs will review the 
protocol at least annually. The Investigators will make safety and progress reports to the 
IRBs/ECs at least annually, and within three months of study termination or completion. 
These reports will include the total number of participants enrolled in the study, the 
number of participants who completed the study, all changes in the research activity, and 
all unanticipated problems involving risks to human subjects or others. 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. 
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8.2 
Informed Consent 
Written informed consent will be obtained from each study participant. Each study site is 
responsible for developing a study informed consent form for local use, based on the 
templates in Appendix IV, which describes the purpose of the study, the procedures to be 
followed, and the risks and benefits of participation, in accordance with all applicable 
regulations. The study site also is responsible for translating the template form into local 
languages, and verifying the accuracy of the translation by performing an independent 
back-translation. 
Literate participants will document their provision of informed consent by signing their 
informed consent forms. Non-literate participants will be asked to document their 
informed consent by marking their informed consent forms ( e.g., with an X, thumbprint, 
or other mark) in the presence of a literate third party witness. (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.) Participant literacy will be determined according to local 
site SOPs. Any other local IRB/EC requirements for obtaining informed consent from 
non-literate persons also will be followed. 
Participants will be provided with a copy of their informed consent forms if they are 
willing to receive them. 
8.3 
Risks 
By participating in the study, participants run the risk of social harm as described in 
Section 6.6. This could include discriminatory treatment and violence associated with 
possible disclosure of participants' drug or sex-related behaviors or of their HIV status. 
Participants also may become embarrassed, worried, or anxious when completing their 
HIV risk assessment and/or receiving HIV counseling. They also may become anxious 
while waiting for their HIV test results. Trained counselors will be available to help 
participants deal with these feelings. Although study sites will make every effort to 
protect participant privacy and confidentiality, it is possible that participants' involvement 
in the study could become known to others, and that social harms may result (i.e., 
because participants could become known as HIV-infected or at "high risk" for HIV 
infection). For example, participants could be treated unfairly or discriminated against, 
or could have problems being accepted by their families and/or communities." · 
Prisoners will not be recruited or enrolled in HPTN 074. Study-related visits will not be 
conducted in prisons or jails with study participants. Incarcerated participants will be 
eligible to resume study participation upon release. 
8.4 
Benefits 
Participants in this study will be offered free HIV testing and counseling for HIV risk 
reduction. HIV-infected individuals eligible for enrollment as an index participant will 
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be offered assistance in navigating disclosure of their status to people with whom they 
share drugs whom they believe to be HIV uninfected. 
As noted in Section 4.1, all participants will receive the in-country standard of care 
(including referral for harm reduction services, ART and treatment for noted infections) 
based on current national guidelines package of services for PWID. Index participants in 
the intervention arm will receive referral for expanded access to ART and a package of 
interventions designed to improve engagement and retention in care. 
Participants and others may benefit in the future from information learned from this 
study. Specifically, information learned in this study may lead to the development of a 
safe and effective intervention that helps prevent HIV infection by reducing high-risk 
behaviors where treatment options are very limited. 
8.5 
Incentives 
Pending IRB/EC 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. Site-
specific reimbursement amounts will be specified in the study informed consent forms for 
both Screening and Enrollment. 
8.6 
Confidentiality 
All study-related information will be stored securely at the study site. All participant 
information will be stored securely in areas with access limited to study staff. To 
maintain participant confidentiality, a coded number will identify all study specific 
laboratory specimens, reports, study data collection, process, and administrative forms. 
Study-specific laboratory specimens, case report forms or documents that are transferred 
or transmitted off-site for processing will be identified only by a coded number to 
maintain participant confidentiality. All local databases will be secured with password-
protected 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 area with limited access. The use of participant identifiers on study records 
will comply with the DAIDS SOPs for Source Documentation and Essential Documents. 
Individual semi-structured 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 discernment of individual 
stakeholders is not possible. 
Participant's study information will not be released without the written permission of the 
participant, except as necessary for monitoring by NIDA, NIAID and/or its contractors; 
representatives of the HPTN LOC, SDMC, and/or LC; other government and regulatory 
authorities; and/or local IRBs/ECs. 
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8. 7 
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. 
8.8 
Study Discontinuation 
The study may be discontinued at any time by the sponsor (US NIH), the HPTN, Office 
of Human Research Protection (OHRP), and/or local government or regulatory 
authorities, and/or site IRBs/ECs. 
9.0 
LABORATORY SPECIMENS AND BIOHAZARD CONTAINMENT 
9.1 
Local Laboratory (LL) Specimens 
As described in Section 5, specimens will be collected for the following tests and 
procedures at study sites (LL); note: this includes testing performed in the clinic: 
• 
HIV testing 
• 
CD4 cell count testing 
• 
HIV viral load testing 
• 
Urine test for substances of abuse 
• 
Plasma storage 
• 
Urine storage 
• 
Dried urine storage 
Each study site will adhere to standards of good clinical laboratory practice, and local 
SOPs for specimen management, including proper collection, processing, labeling, 
transport, and storage of specimens to the LL. Specimen collection, testing, and storage at 
the local laboratory will be documented using the Laboratory Data Management System 
(LDMS) as described in the SSP Manual. 
9.2 
HPTN Laboratory Center (LC) Specimens 
As described in Section 5, plasma, urine, and a subset of dried urine specimens will be 
stored for testing at the HPTN LC. At the discretion of the LC, some testing may be 
performed at another institution or at a commercial laboratory, designated by the HPTN 
LC. Results from testing performed at the HPTN LC ( or a HPTN LC-designated 
laboratory) will not be returned to study sites or study participants (with the possible 
exception of HIV diagnostic testing, if test results for HIV infection status differ from 
those obtained at study sites). This testing may include: 
• 
Extended QA for HIV diagnostic testing, including confirmation HIV acquisition 
• 
Viral load testing 
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• 
Testing for substances of abuse 
• 
Testing for antiretroviral drugs 
• 
Testing for methadone and other medications used to treat substance use 
• 
Testing related to cross-sectional assessment of HIV incidence 
• 
Phylogenetic and linkage analysis (if feasible) 
• 
Stored samples may also be used to characterize HIV viruses (e.g., for HIV 
subtyping, resistance testing, viral diversity analysis) and the host response to viral 
infection. 
9.3 
Quality Control and Quality Assurance Procedures 
The study sites will participate in locally-approved External Quality Assurance (EQA) 
programs. The HPTN LC staff will conduct periodic visits to each site to assess the 
implementation of on-site Quality Control (QC) procedures, including proper 
maintenance of laboratory testing equipment and use of appropriate reagents. 
The LC will inform site staff of the samples selected for QA testing, and site staff will 
ship the selected specimens to the LC. LC staff will follow-up directly with site staff to 
resolv~ any problems identified through this process. 
9.3.1 QC for HIV diagnostic testing 
Before performing HIV diagnostic testing, all sites must have validated the testing 
algorithm, and the validation must be reviewed by the HPTN LC. Local 
laboratories ( or clinics) will perform testing for HIV diagnosis at Screening, 
Enrollment, and other scheduled visits. Algorithms for HIV diagnostic testing are 
provided in the SSP Manual. These algorithms are expected to vary from site to 
site based on national guidelines and other factors. Laboratories are encouraged 
to participate in an EQA program for HIV testing that is approved by the HPTN 
LC. In addition, the HPTN LC will perform extended QA testing. Samples will 
be shipped to the HPTN for QA of HIV testing, approximately once every three 
months. 
If a participant has signs or symptoms consistent with acute HIV infection, or 
expresses a concern about recent HIV acquisition, additional testing may be 
performed using an HIV RNA test. Regardless of whether HIV RNA testing is 
used for diagnostic testing, HIV infection must be confirmed in all cases using 
two independent samples collected on different days. 
9.3.2 QC for HIV viral load 
Quantitative HIV RNA (viral load) testing will be performed at local laboratories 
at the Screening visit for potential index participants who have a reactive or 
positive HIV test result. Local laboratories must participate in the DAIDS 
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Virology QA (VQA) program, with EQA results that are deemed satisfactory by 
the HPTN LC. 
9.3.3 QC for CD4 cell count determination 
Local laboratories must be enrolled in the United Kingdom National External 
Quality Assessment Service (UK NEQAS) program through the DAIDS 
Immunology Quality Assessment (IQA) program, with EQA results that are 
deemed satisfactory by the HPTN LC. 
9.4 
Specimen Storage and Possible Future Research Testing 
Study sites will store all plasma, urine, and dried urine specimens collected in this study 
at least through the end of the study and until all HPTN LC assessments have been 
completed. In addition, study participants will be asked to provide written informed 
consent for their plasma, urine, and dried urine specimens to be stored after the end of the 
study for possible future testing. The specimens of participants who do not consent to 
long-term storage and additional testing will be destroyed after all QA and protocol-
related testing has been performed. 
9.5 
Biohazard Containment 
As the transmission of HIV and other blood-borne pathogens can occur through contact 
with contaminated needles, blood, blood products and body fluids, appropriate blood and 
secretion precautions will be employed by all personnel in the drawing of blood and 
shipping and handling of all specimens for this study, as currently recommended by the 
United States Centers for Disease Control and Prevention. All infectious specimens will 
be transported in accordance with United States regulations (42 CFR 72). 
10.0 ADMINISTRATIVE PROCEDURES 
10.1 Protocol Registration 
Prior to implementation of this protocol, and any subsequent full version amendments, 
each site must have the protocol and the protocol consent form(s) approved, as 
appropriate, by their local institutional review board (IRB)/ethics committee (EC) and 
any other applicable regulatory entity (RE). Upon receiving final approval, sites will 
submit all required protocol registration documents to the DAIDS Protocol Registration 
Office (DAIDS PRO) at the Regulatory Support Center (RSC). The DAIDS PRO will 
review the submitted protocol registration packet to ensure that all of the required 
documents have been received. 
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Site-specific informed consent forms (ICFs) will be reviewed and approved by the 
DAIDS PRO and 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 registration packet to the DAIDS PRO at the RSC. Site-specific ICF(s) will 
not be reviewed and approved by the DAIDS PRO and sites will receive an Amendment 
Registration Notification from the DAIDS PRO that approves the site specific ICFs and 
indicates successful completion of the amendment protocol registration process. A copy 
of the final amendment Registration Notification issued by the DAIDS PRO 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. 
10.2 Study Activation 
Pending successful protocol registration and submission of all required documents, LOC 
staff will "activate" the site to begin study operations. Study implementation may not be 
initiated until a study activation notice is provided to the site. 
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. 
10.3 Study Coordination 
Study implementation will be directed by this protocol as well as the SSP Manual. The 
SSP Manual-which will contain reference copies of the DAIDS SOPs for Source 
Documentation and Essential Documents, as well as the DAIDS Manual for Expedited 
Reporting of Adverse Events to DAIDS, Version 2.0, dated January 2010 and the DAIDS 
Toxicity Tables -
will outline procedures for conducting study visits, data and forms 
processing, AE assessment, management and other study operations. 
Study case report forms and other study instruments will be developed by the study team 
and HPTN SDMC. Data will be transferred to the HPTN SDMC, processed, and cleaned. 
Quality Control reports and data queries will be generated on a routine basis and 
distributed to the study sites for verification and resolution. 
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, retention, and EAE incidence will be monitored 
HPTN 074, Final Version 2.0 
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closely by the team as well as the HPTN SMC. The Protocol Chair, DAIDS Medical 
Officer, Protocol Biostatistician, and LOC Protocol Specialist will address issues related 
to study eligibility and EAE management and reporting as needed to assure consistent 
case management, documentation, and information-sharing across sites. 
10.4 Study Monitoring 
On-site study 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 
• 
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., informed consent forms, clinic and laboratory records, other source documents, 
case report forms), 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, SDMC, LC, NIAID, NIDA, and US and in-country 
government and regulatory authorities. A site visit log will be maintained at the study 
site to document all visits. 
10.5 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 NIAID Medical 
Officer. All protocol amendments must be submitted to and approved by the relevant 
IRB(s)/EC(s) and the DAIDS RSC prior to implementing the amendment. 
10.6 Investigator's Records 
The study site investigator will maintain, and store in a secure manner, complete, 
accurate, and current study records throughout the study. The investigator will retain all 
study records for at least three years after submission of the CTU' s final Financial Status 
Report to DAIDS, which is due within 90 days after the end of the CTU's cooperative 
agreement with DAIDS, unless otherwise specified by DAIDS or the HPTN LOC. 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 for and/or enrolled in the study -
including informed consent forms, locator forms, case report forms, notations of all 
contacts with the participant, and all other source documents. 
HPTN 074, Final Version 2.0 
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10.7 Use of Information and Publications 
Publication of the results of this study will be governed by the HPTN Manual of 
Operations and policies. Any presentation, abstract, or manuscript will be submitted by 
the Investigator to the HPTN Manuscript Review Committee, and DAIDS for review 
prior to submission. 
HPTN 074, Final Version 2.0 
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Appendix I. Schedule of Procedures and Evaluations - Index 
.... 
t)I) 
= 
= 
., 
""' 
·= 
.5 
.::a:: 
., 
0 
., 
., 
., 
,_ 
,_ 
~ 
., 
= 
00 
~ 
Administrative, Behavioral and Regulatory Procedures 
Informed consent 
X 
X 
Demographic information 
X 
Locator information 
X 
X 
X 
Randomization 
X 
HIV pre-test, risk reduction, and post-test counseling 
X 
X 
Referral for AR T2 
X 
X 
Brief assessment of injection risk behavior, substance use, substance use treatment, and ART use for eligibility 
X 
Baseline/Exit assessment sexual behavior, substance use, substance use treatment and ART experience interviews 
X 
Follow up sexual behavior, substance use, substance use treatment and ART experience interviews 
X 
Assessment of barriers and facilitators to HIV care and substance use treatment, mediators and moderators of key outcomes. 
X 
X 
Social network interview 
X 
X 
Social impact assessment 
X 
X 
Referral to needle and syringe exchange programs (iflegal and available) 
X 
Referral to substance use treatment 
X 
Brief, standardized injection and sexual transmission risk reduction counseling 
X 
X 
X 
Referral for diagnosis and treatment ofSTis, HBV, HCV and TB (as appropriate) 
X 
X 
X 
Clinical Procedures 
Blood collection 
X 
X 
X 
Urine collection 
X 
X 
AE Assessment 
X 
Laboratory Procedures 
HIV testing (see SSP Manual) 
X 
X 
CD4 cell count3 
x3 
HIV viral load4 
X4 
Urine testing for substances of abuse5 
X 
X 
Plasma storage6 
X 
X 
X 
Urine storage6 
X 
X 
Dried urine storage6,7 
X 
1 Weeks 52, 65, 78, 91 or 104 may be an Exit visit for participants. Follow-up is for 52-104 weeks. Follow alternative procedures as indicated ifit is an Exit visit. 
2 If clinically indicated ( according to national guidelines) and/or participant is randomized to the intervention group. 
..... 
;: .... 
-
., "' 
;t:: 
t:~ 
~ 
~--
~ 
=> 
O' 
X 
X 
X 
x. 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
x3 
x3 
X 
X 
X 
X 
X 
X 
x1 
x1 
3 CD4 cell count testing will be performed at Screening if any HIV test is reactive or positive; after Enrollment, CD4 cell count will only be performed at Weeks 26, 52, 78, and 104. 
4 Viral load testing will be performed in real-time at study sites at Screening if any HIV test is reactive or positive. 
5 Urine testing for substances of abuse will be ih real-time study sites using locally-available methods; this testing can be performed in the clinic or laboratory. 
6 Plasma, urine, and dried urine samples will be stored for Quality Assurance testing and other assessments at the HPTN LC (see Section 9.2). 
7 Dried urine will be stored at Enrollment and as supplies permit at Weeks 26 and 52/ Exit. 
HPTN 074, Final Version 2.0 
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Appendix II. Schedule of Procedures and Evaluations - Network injection partners 
.... 
l:)l) 
.Q 
= 
= 
.. 
.., 
,__ 
-
·= 
.5 
.:.: 
.B~ 
;<,:: 
.. 
0 
.. 
... "' 
~ 
.. 
.. 
c,s·-
... 
... 
~ 
=> 
~ 
... 
= 
OI 
00 
~ 
Administrative, Behavioral and Regulatory Procedures 
Informed consent 
X 
X 
Demographic information 
X 
Locator information 
X 
X 
X 
X 
X 
HIV pre-test, risk reduction, and post-test counseling2 
X 
X 
X 
X 
X 
Brief assessment of injection risk behavior, substance use, and substance use treatment for eligibility 
X 
Baseline/Exit sexual behavior, substance use, and substance use treatment interviews 
X 
X 
Follow up sexual behavior, substance use, and substance use treatment interviews 
X 
X 
Assessment of barriers and facilitators to substance use treatment, mediators and moderators of key outcomes 
X 
X 
X 
X 
Social network interview 
X 
X 
X 
X 
Social impact assessment 
X 
X 
X 
X 
Confirmation via local procedures ofrelationship to index participant (network association) 
X 
Referral to needle and syringe exchange programs (if legal and available) 
X 
Referral to substance use treatment 
X 
Brief, standardized injection and sexual transmission risk reduction counseling 
X 
X 
X 
X 
X 
Referral for diagnosis and treatment of STis, HBV, HCV and TB (as appropriate) 
X 
X 
X 
X 
X 
Clinical Procedures 
Blood collection 
X 
X 
X 
X 
X 
Urine collection 
X 
X 
X 
X 
AE Assessment 
X 
X 
X 
Laboratory Procedures 
HIV testing (see SSP manual)2 
X 
X 
X 
X 
X 
Urine testing for substances of abuse3 
X 
X 
X 
X 
Plasma storage4 
X 
X 
X 
X 
X 
Urine storage4 
X 
X 
X 
X 
Dried urine storage4,5 
X 
xs 
xs 
Note: Network injection partners (including replacement partners) will be followed until the index participant's Exit visit. Network injection partners who are replaced will continue to be followed and will have all follow-up 
assessments performed. 
1 Weeks 52, 65, 78, 91 or, 104 may be an Exit visit for participants. Follow-up is for 52-104 weeks. Follow alternative procedures as indicated ifit is an Exit visit. 
2 HIV testing (and associated counseling) is not required if HIV infection was confirmed at a previous visit. Additional testing is required at a subsequent visit (HIV confirmatory visit) if a participant has a positive 
or reactive HIV test result after Enrollment. See Appendix III. 
3 Urine testing for substances of abuse will be performed in real-time at study sites using locally-available methods. 
4 Plasma, urine, and dried urine will be stored for Quality Assurance testing and other assessments at the HPTN LC (see Section 9.2). 
5 Dried urine will be stored at Enrollment and as supplies permit at Weeks 26 and 52/ Exit. 
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Appendix III. Additional procedures for network injection partners who have a reactive or positive HIV test result at any visit after 
Enrollment* 
*Network injection partners will continue to be followed in the study after confirmation of HIV infection; all other assessments for network injection 
partners will be conducted during subsequent follow-up visits, with the exception of HIV counseling and testing. 
This additional HIV confirmation visit should occur within 14 days of the first reactive/positive HIV test result and must occur on a different date 
than the date at which the first reactive/positive HIV test result was obtained. 
HIV confirmation visit 
Weeks 26, 52, 78 and 104 
following a reactive or 
(if HIV infection has been 
positive HIV result 
confirmed) 
Clinical Procedures 
Blood collection 
X 
Laboratory Evaluations 
HIV testing (see SSP Manual) 
X 
CD4 count 
X 
X 
Sample Storage 
Additional plasma storage 1 
X 
1 Plasma will be stored for Quality Assurance testing and other assessments at the HPTN LC (see Section 9.2). 
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Appendix IV- Schedule of Procedures and Evaluations - Index participants during the 12 month extension period beyond original Exit 
t.o 
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-
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.t: 
i::z::~ ;.:a 
~ 
.. =;;.. 
raal 
~O' 
~dministrative, Behavioral and Regulatory Procedures 
Informed consent 
xi 
Demographic information 
Locator information 
X 
X 
Referral for AR T2 
X 
Baseline/Exit assessment sexual behavior, substance use, substance use treatment and ART experience interviews 
X 
Follow up sexual behavior, substance use, substance use treatment and ART experience interviews 
X 
Assessment of barriers and facilitators to HIV care and substance use treatment, mediators and moderators of key outcomes 
X 
X 
Social network interview 
X 
X 
Social impact assessment 
X 
X 
Referral to needle and syringe exchange programs (iflegal and available) 
X 
X 
Referral to substance use treatment 
X 
X 
Brief, standardized injection and sexual transmission risk reduction counseling 
X 
X 
Referral for diagnosis and treatment ofSTis, HBV, HCV and TB (as appropriate) 
X 
X 
Clinical Procedures 
Blood collection (20ml whole blood for 10 ml plasma) 
X 
X 
Urine collection 
X 
X 
AE Assessment 
X 
X 
Laboratory Procedures 
HIV testing (see SSP Manual) 
xi 
CD4 cell count3 
x3 
x3 
HIV viral load4 
Urine testing for substances of abuse5 
X 
X 
Plasma storage6 
X 
X 
Urine storage6 
X 
X 
1 The first Quarterly visit after the Index participants' initial Exit visit will be a Re-Enrollment/Quarterly visit (up to 4 additional visits per participant). HIV testing per the site's normal algorithm 
must be performed to ensure that the correct participant is re-enrolled. Any Quarterly visit may be an Exit visit for participants. Follow-up is for up to 52 additional weeks. Follow alternative 
procedures as indicated if it is an Exit visit. Participants will have a re-enrollment visit, two quarterly visits and one exit visit (up to 4 visits total in the extension- Extension re-enrollment, Month 
3, Month 6 and Exit after the Extension). 
2 If clinically indicated ( according to national guidelines) and/or participant is randomized to the intervention group. 
3 CD4 cell count testing will be performed 6 months and 12 months (Exit) after re-Enrollment. 
4 Viral load testing will be performed at the HPTN LC. 
5 Urine testing for substances of abuse will be in real-time study sites using locally-available methods; this testing can be performed in the clinic or laboratory. 
6 Plasma and urine samples will be stored for Quality Assurance testing and other assessments at the HPTN LC (see Section 9.2). 
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SAMPLE INFORMED CONSENTS 
Appendix IV A. Sample Screening Consent 
HPTN 074: Integrated treatment and prevention for people who inject drugs: A vanguard 
study for a network-based randomized HIV prevention trial comparing an integrated 
intervention including supported antiretroviral therapy to the standard of care 
Final Version 2.0, 26 July 2017 
DAIDS Document ID: 11917 
Study Implementers: HIV Prevention Trials Network (HPTN) and the U.S. National Institutes 
of Health (NIH), Bethesda, MD, USA. 
Study Sponsors: NIH, Division of AIDS (DAIDS), US National Institute of Allergy and 
Infectious Diseases (NIAID) and US National Institute on Drug Abuse (NIDA), Bethesda, MD, 
USA. 
PRINCIPAL INVESTIGATOR: [Insert Name] 
PHONE: [Insert Number] 
INTRODUCTION 
You are being asked to take part in a research study that will help us design a new and better way 
to prevent the spread of HIV (human immunodeficiency virus, the virus that causes AIDS) among 
people who inject drugs. This study is sponsored by the United States National Institutes of 
Health. The person in charge of the study at this site is [insert name of principal investigator]. 
Before you decide whether or not to take part in the screening tests for this research study, you 
need to know the purpose of the screening tests, the possible risks and benefits of being screened, 
and what will be expected of you during the tests. This consent form provides that information. 
The study staff will discuss the information with you. They will answer any questions you may 
have. After the screening tests have been fully explained to you, you can decide whether or not 
you want to participate. If you understand the tests and agree to participate, you will be asked to 
sign this consent form or make your mark in front of someone. You will be offered a copy of 
this form to keep. 
Please note that: 
• 
Your participation in the screening tests is entirely voluntary. 
• 
You may decide not to take part or to withdraw from the screening tests at any time without 
losing the benefits of your standard health care. 
• 
You are only being asked to take part in the screening tests at this time. Even if you agree to 
have the screening tests, you do not have to join or may notbe eligible to join the research 
study. 
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Study Purpose 
We are doing this study to help us develop a new and better way to prevent the spread of HIV 
from HIV-infected people who inject drugs to HIV uninfected people with whom they share 
needles/syringes or drug solutions. 
• 
First, this study will help estimate the number of people who inject drugs who get new 
HIV infections in the countries where the sites are located. 
• 
Second, this study will help researchers learn more about who, among HIV infected / 
HIV uninfected people who inject drugs, would be willing to take part in future studies 
related to HIV prevention. Researchers will also learn about whether or not taking part in 
this trial helps participants in their everyday lives. 
• 
Third, in the intervention arm, the team will be comparing certain special support 
services with services which are usually available in your area and how these special 
support services might help people who inject drugs continue to take their HIV and/or 
substance use treatment. 
• 
Fourth, we will be looking at the group of people who inject drugs with HIV infected 
drug users to see how big this group is and how often people join or leave the group. 
All of these things will help us design a future study that will determine whether treating HIV-
infected injection drug users with anti-HIV drugs and providing other support services including 
treatment for substance use where available will prevent them from passing the HIV virus to their 
injection drug partners. During the study, everyone with HIV will be referred for health care, 
which may include medications to treat HIV infection, substance use, or other conditions. 
(Insert language as applicable) We will not provide treatment for HIV infection or substance use 
treatment or any medications at [INSERT NAME OF CLINIC/SITE]; instead we will send you to· 
[REFERRAL LOCATION] ifwe recommend that you begin treatment. 
Purpose of the screening tests: 
• 
The purpo_se of the screening tests is to find out if you are eligible for the research study 
described above. Some people may not be asked to join the research study because of 
information found during the screening tests. 
• 
The screening tests for the study include interview questions and at least one blood test 
for HIV. 
• 
You may also have another blood test during these visits. If you agree to be screened for 
the study you may have up to two visits over the course of several weeks, and each visit 
will last about [ one to two hours]. 
• 
You will be told the results of all of your screening tests as soon as they are available. 
• 
After the screening tests, you will find out whether you are eligible for the research study. 
If you are eligible, the study staff will fully explain the research study to you and answer 
any questions you have. After the research study has been fully explained to you and if 
you decide to participate, you will be asked to sign another consent form. 
Screening Visit 
The first study visit is called the screening visit where we will test your blood for HIV. The 
screening visit will take about one to two hours. During this visit we will: 
• 
Ask you questions about your age and other personal information to see if you are 
eligible to participate. 
HPTN 074, Final Version 2.0 
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• 
Ask your name and contact information so that we can keep in touch with you during the 
study. 
• 
We will draw [XX] mL of blood (about [XX] amount). This blood will be tested for 
HIV. We will talk to you about things you do which might put you at risk for HIV and 
talk to you about the results of this test. Some of the blood will be stored to check that 
test results from the study are correct and to perform other tests related to HIV 
prevention. 
• 
We will refer you to a place where you can talk to someone about your substance use and 
how to reduce your risk of getting HIV or giving HIV to someone else if you are infected. 
[SITE TO ADJUST: You can also exchange your used needles for clean ones.] 
• 
We will tell you the results of any tests we do at the study site during the study and refer 
you to [XX] clinic for treatment. If you have any concerns about any other infections 
(including tuberculosis, hepatitis, etc.) we will refer you to the appropriate place, which 
will examine you to see if you have any other infections and will offer you treatment. 
As stated above, this is a study of HIV-infected people who inject drugs and HIV-uninfected 
people with whom they share needles/syringes or drug solutions. The results of your HIV tests 
will help us figure out if you can be in this study. 
If you have HIV: 
If your blood test shows that you do have HIV, we will continue with the following activities: 
• 
We will draw additional blood (no more than XX mL, which is about XX teaspoons 
[ change to local equivalent, if appropriate]). This blood will be tested to see what affect 
HIV has had on your body's ability to fight off infections and how much virus is in your 
blood. We will also study the virus to understand more about HIV transmission. 
• 
In order to participate in the study, we will ask you to identify at least one person with 
whom you regularly share needles/syringes or drug solutions who you believe does not 
have HIV and who is willing and eligible to participate. 
• 
We will also give you referral cards and ask you to give these to people with whom you 
have used drugs in the past month. We will screen these people and see if they are also 
able and willing to enroll in this study. We recommend that you tell them that you are 
HIV positive so that they can protect their own health. We can work with you to tell your 
injection partner about your HIV infection if you would like our help. Even if you are 
not eligible for this study, we may want to use your store blood and urine for future 
testing related to HIV infection and how HIV spreads in the community. If you agree to 
this use of your samples, we will ask you to initial the end of this form. 
If you do not have HIV: 
• If your blood test shows that you do not have HIV, you might still be eligible to 
participate in the study. 
• 
We may ask you other questions related to your injection drug use, and whether or not 
you are willing to talk to people who you may share drugs with and ask them to come to 
this clinic to be tested for HIV. In order for you to be eligible, you must also have 
someone who you regularly share needles/syringes or drug solutions, who enrolls in our 
study. 
• If we find that you are eligible, we may need to test you again to see that you still do not 
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have HIV. 
RISKS and/or DISCOMFORTS: 
If you participate in this screening, there are a few risks or discomforts you should know about. 
• 
You may feel discomfort, dizzy, or even faint when your blood is drawn. Redness, pain, 
swelling, bruising, or an infection may occur where the needle goes into your arm. 
• 
You may become embarrassed, worried, or anxious when discussing your sexual or drug 
use practices, talking about HIV, or discussing or waiting for your test results. Learning 
that you have HIV may make you worried or anxious. It is also possible that 
participation in this screening process may cause disagreements between you and the 
people you share drugs with if you tell them that you are HIV positive and ask them if 
they want to be part of this study. A trained counselor will help you deal with any 
feelings or questions you may have. 
• 
We will make every effort to protect your privacy and confidentiality. Your visits here 
will take place in private. People may think that you are infected with HIV or at risk of 
HIV because of sexual behavior or drug use. Because of this, others may treat you 
unfairly or discriminate against you. For example, you could have problems getting or 
keeping a job. You could also have problems being accepted by your family or 
community. (Sites to insert local registration requirements for antiretrovirals and 
substance use and the inherent risks) 
POTENTIAL BENEFITS: 
• 
You may get no direct benefit from the screening tests. However, you will receive 
counseling about HIV and information on your HIV status. 
• 
You and your partner will receive information about how to prevent the spread of HIV 
and you will get free condoms. [ SITE TO ADJUST: We will also refer you to a place 
where you can exchange dirty syringes for clean ones.] 
• If you have HIV, but not eligible for the study, you will be told where you can receive 
health care, counseling, substance use treatment and other services, as well as 
information about other research studies. 
REASONS WHY YOU MAY BE WITHDRAWN FROM THE SCREENING TESTS 
WITHOUT YOUR CONSENT: 
You may be removed from the screening process without your consent for the following reasons: 
• 
The study is stopped or cancelled. 
• 
Undergoing the screening tests would be harmful to you. 
• 
You are not able to attend the screening visits or complete the screening tests. 
• 
You are not willing to refer at least one person you share drugs with for study screening. 
• 
At least one person who you share drugs with is not willing or able to attend screening 
visits or complete the screening tests. 
• 
You are not willing to find out your HIV test result. 
COSTS AND COMPENSATION: 
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There is no cost to you for the screening tests. At the end of each visit, you will be given [insert 
amount of money or incentive package to compensate participant for food, travel expenses, lost 
work time, successful enrollment of network partners, etc.] 
CONTACT INFORMATION 
You will be asked to provide your address and phone number(s). The staff will ask you for 
names of people who will always know how to find you and places where you can be found. It 
is possible that the staff may visit you at your house or contact one of the people on your contact 
list if you are not able to attend your visits or if the staff have important information for you. If 
we talk to people on this list, we will not tell them why we are trying to reach you. If you are not 
willing to give us this information, you should not agree to be in this study. 
CONFIDENTIALITY: 
The study team will try to protect the privacy of your study records and test results, to the extent 
permitted by law, but cannot guarantee that your study records and test results will never be 
released to others. As part of the study team's efforts to protect your study records from 
disclosure, you will be identified in the study records by a code, and the study team leadership 
will keep the link between the code and your identity separate from your study 
records. Unless required by law or unless you give your written permission, study records 
that identify you will not be released to other parties or entities. However, your study records 
may be reviewed by various government agencies that have a legal right to do so, such as the 
sponsor of the study (US National Institutes of Health [NIH]), the [insert name of site] 
Institutional Review Board (IRB), study staff, study monitors, and (insert applicable local 
authorities]. (If applicable: It is also possible that a court or other government agency could 
order that study records identifying you be released to others.) Any publication or 
presentation of the results of findings of this study will not use your name and will not 
include any information that will identify you. 
A description ofthis study will be available on www.ClinicalTrials.gov. This web site will not 
include information that can identify you. At most the web site will include a summary of the 
results. You can search this web site at any time. 
YOUR SAMPLES: 
As part of screening for this study we will collect samples of your blood. There may be some 
leftover blood samples after all of the study-related testing has been completed. We would like 
to use these samples for future research related to HIV infection to develop new HIV tests, HIV 
vaccines and treatments and to learn more about HIV transmission and HIV prevention. If you 
agree to this use of your samples, we will ask you to initial the end of this form. 
If you do not agree to have your leftover samples stored you can still be in this study. If you 
agree to store your samples but change your mind later, you can contact study staff. We will 
then destroy your leftover samples. If you agree, your leftover samples will be stored 
indefinitely [insert local guidelines]. Any future use of your samples that is not described here 
needs to be reviewed and approved by the NIH and local authorities. If these studies involve 
laboratories other than the study site laboratories and the HPTN Laboratory Center, we will need 
HPTN 074, Final Version 2.0 
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26 July 2017 

approval from your local authorities to store or transfer them elsewhere. Your leftover samples 
will not be sold or used for commercial reasons. 
RESEARCH-RELATED INJURY: 
[Site-specific: insert institutional policy] It is unlikely that you will be injured as a result of 
having the screening tests. 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 for monetary 
compensation or other forms of compensation for such injuries either through this institution or 
the NIH. You do not give up any legal rights by signing this consent form. 
PROBLEMS or QUESTIONS: 
For questions about this study or a research-related injury, contact: 
[insert name of the investigator or other study staff! 
[insert telephone number and physical address of above] 
For questions about your rights as a research subject, contact: 
[insert name or title of person on the Institutional Review Board (IRB) or other 
organization appropriate for the site] 
[insert telephone number and physical address of above] 
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SIGNATURE PAGE: SAMPLE SCREENING CONSENT 
HPTN 074: Integrated treatment and prevention for people who inject drugs: A vanguard 
study for a network-based randomized HIV prevention trial comparing an integrated 
intervention including supported antiretroviral therapy to the standard of care 
Final Version 2.0, 26 July 2017 
If you have read this informed consent, or have had it read and explained to you, and understand 
the information, and you voluntarily agree to enroll in this study, please sign your name or make 
your mark below. 
Participant's Name (print) 
Participant's Signature or Thumbprint and Date 
For staff: I have explained the purpose of the screening to the volunteer and have answered all 
of his/her questions. To the best of my knowledge, he/she understands the purpose, procedures, 
risks and benefits of this study. 
Study Staff Conducting 
Consent Discussion (print) 
Study Staff Signature and Date 
Please carefully read the statements below (or have them read to you) and think about your choice. 
No matter what you decide it will not affect whether you can be in the research study, or your 
routine health care. 
____ I agree to have samples of my blood used for future testing related to HIV infection and 
how HIV spreads in the community. 
____ I do not agree to have samples of my blood stored and used for future testing related to 
HIV infection and how HIV spreads in the community. 
For witnesses for illiterate volunteers: I attest that the information contained in this written 
consent form has been read and explained to the participant. He/she appears to understand the 
purpose, procedures, risks and benefits of the screening tests and has voluntarily accepted to 
participate in this study. 
For those placing thumbprint only: I attest that the participant who states that his/her name is 
___________ has placed his/her thumbprint on this consent form of his/her 
own free will on this day _______ _ 
HPTN 074, Final Version 2.0 
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Witness' Name (print) 
Witness's Signature and Date 
HPTN 074, Final Version 2.0 
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Appendix IV-B. Sample Enrollment Consent for Index 
HPTN 074: Integrated treatment and prevention for people who inject drugs: A vanguard 
study for a network-based randomized HIV prevention trial comparing an integrated 
intervention including supported antiretroviral therapy to the standard of care 
Final Version 2.0, 26 July 2017 
DAIDS Document ID: 11917 
Study Implementers: HIV Prevention Trials Network (HPTN) and the U.S. National Institutes 
of Health (NIH), Bethesda, MD, USA. 
Study Sponsors: NIH, Division of AIDS (DAIDS), US National Institute of Allergy and 
Infectious Diseases (NIAID) and US National Institute on Drug Abuse (NIDA), Bethesda, MD, 
USA. 
PRINCIPAL INVESTIGATOR: [Insert Name] 
PHONE: [Insert Number] 
INTRODUCTION 
You are being asked to take part in a research study that will help us design a new and better way 
to prevent the spread of HIV (human immunodeficiency virus, the virus that causes AIDS) among 
people who inject drugs by referring people who inject drugs for substance use treatment where 
available and referring HIV-infected drug users for treatment with anti-HIV drugs. This study is 
sponsored by the United States National Institutes of Health. The person in charge of the study 
at this site is [insert name of principal investigator]. 
This study includes groups of people who inject drugs in which one person is infected with HIV 
and the other people are not. The person who is infected with HIV will tell the clinic about 
people with whom they share drugs who are not infected with HIV. About 500 people who are 
HIV infected will take part in this study including 167 at this site. About 750 people who are not 
HIV infected but share drugs with someone who is HIV infected will also take part in the study 
including about 250 at this site. The people in this study will come from sites in Asia and 
Eastern Europe. Each person will be in this study for two years at the most. You will asked to 
be in the study for [SITE TO ADJUST FOR EARLY ENROLLEES]. 
Before you decide whether to take part in this research study, you need to know the purpose, the 
possible risks and benefits to you, and what will be expected of you during the study. This 
consent form provides that information. The study staff will discuss the information with you 
and they will answer any questions you may have. After the study has been fully explained to 
you, you can decide whether or not you want to participate. Once you understand this study, and 
if you agree to take part, you will be asked to sign this consent form or make your mark in front 
of someone. You will be offered a copy of this form to keep. 
HPTN 074, Final Version 2.0 
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Please note that: 
• 
Your participation in this study is entirely voluntary. 
• 
You may decide not to take part or to withdraw from this study at any time without 
losing the benefits of your standard health care. 
PURPOSE OF THE STUDY: 
We are doing this study to help us develop a new and better way to prevent the spread of HIV 
from HIV infected people who inject drugs to HIV uninfected people with whom they share 
needles/syringes or drug solutions. What we learn will help us design a future study that will 
determine whether treating HIV infected injection drug users with anti-HIV drugs and providing 
other support services including treatment for substance use where available will prevent them 
from passing the HIV virus to their injection drug partners. During the study, everyone with 
HIV will be referred for health care, which may include medications to treat HIV infection, 
substance use, or other conditions. We will not provide treatment for HIV infection or substance 
use or any medications at [INSERT NAME OF CLINIC/SITE]; instead we will send you to 
[REFERRAL LOCATION] ifwe recommend that you begin treatment. [SITE TO ADJUST] 
You may also be offered medication that will help you stop using drugs. You do not need to accept 
this treatment in order to be part of this study. 
At [REFERRAL LOCATION], some people will also be referred for anti-HIV drugs to treat 
their HIV infection, and will be asked to start taking these drugs as soon as they join the study. 
Others may start to take the anti-HIV drugs later in the study, after their T-cell count [ or 
whatever term is commonly used locally] is lower or if they become sick. The T-cell count is a 
blood test that we use to measure the amount of damage that HIV has done to your body. 
Regardless of which group you are in, if you have HIV we will recommend that you start anti-
HIV drugs before your T-cell count gets so low that would make you very sick. If you decide to 
take part in the study, you and the people you use drugs with who emoll in this study will be 
placed in 1 of 2 groups ( called the "Intervention" and "Control" groups). Both groups are very 
important to this study, and, and you cannot choose which group you are in. Your group will be 
chosen "by lot" (like drawing straws or flipping a coin) [ or other equivalent local term J. Your 
injection partners who you encourage to emoll in this study will be in the same group as you. 
You have a greater chance of being placed in the "Control" group, meaning that you will receive 
the usual clinical and counseling services available and will start taking anti-HIV drugs later in 
the study after your T-cell count is lower or you become sick, but you cannot choose your group. 
The "Intervention" group will receive more intensive services such as meeting with someone 
who you can talk to about your drug use and how to access drug and HIV treatment here at the 
clinic. Participants in the intervention group will also be referred to start taking anti-HIV drugs 
as soon as they join the study. People in both groups will have generally the same study visits, 
but people in the intervention group will have more visits, some of a different kind, than the 
other group. 
PROCEDURES: 
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If you agree to join this study, you will be asked to come back to the site on a regular basis. We 
will tell you the results of any tests we do during the study at the study site which may impact 
your health. A few of your samples will be sent out of the country for testing because it is not 
possible to do these tests at our site. [Sites should modify as needed} 
Enrollment visit 
During your first study visit, the study will be explained to you. You will have time to ask 
questions and discuss any concerns you may have with the study staff. This visit may last up to 
[XX] hours. This visit may be broken up into two visits. During this visit, we will also: 
• 
Ask you to update the contact information you gave at screening. 
• 
Ask you questions about your use of anti-HIV drugs, substance use, access to health care, 
sexual practices, people with whom you share drugs or related equipment, and other 
things about your personal life. 
• 
We will ask you for the names of the people with which you regularly share 
needles/syringes or drug solutions. 
• 
We will assign you to a study group. Your group will be determined "by lot", as we said 
above. 
• 
We will draw [XX] mL of blood (about [XX] amount). This blood will be tested for 
HIV. We will talk to you about ways to reduce the chances that you may pass HIV on to 
the people with whom you have sex or share drugs. 
• 
We will also ask you for a urine sample for drug testing. 
• 
We will store blood and urine samples for other testing related to this study. This may 
include tests for drugs, medications used to treat HIV infection and substance use, and 
other HIV-related tests. The stored blood samples may also be used to learn more about 
how HIV is spread throughout the community. 
• 
We will ask you if you have had any good or bad things happen to you because you are 
taking part in this study. 
• 
We will tell you the results of any tests we do during the study at the study site and will 
refer you to [XXX] clinic for treatment for anything we may find if needed. 
• If you are assigned to the study group which starts taking anti-HIV drugs early or if the 
virus has started making you sick, we will refer you to [XXX] to begin receiving anti-
HIV drugs. You will have the opportunity to meet with a counselor to talk about 
problems you may have getting drug and HIV treatments and work with you to overcome 
these problems. They may also help you with ways to be sure that you take your HIV 
medications. For a couple of sessions you can also bring in a family member or friend so 
that they can assist you with your HIV health care. 
• 
We will refer you to a place where you can talk to someone about your substance use and 
how to reduce the chances that you may pass HIV on to the people with whom you have 
sex or share drugs. [SITE TO ADJUST: You can also exchange your used needles for 
clean ones.] 
One month visit 
One month after the enrollment visit, we will ask you to come in for a visit which will last about 
XX hours. During this visit we will: 
• 
Ask you to confirm or update your contact information. 
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• 
We will talk to you about ways to reduce the chances that you may pass HIV on to the 
people with whom you have sex or share drugs. 
• 
We will ask you for the names of the people with which you regularly share 
needles/syringes or drug solutions. 
• 
We will ask you questions about your use of anti-HIV drugs, substance use, sexual 
partners, people with whom you share drugs and other things about your personal life. 
• 
We will ask you if you have had any good or bad things happen to you because you are 
taking part in this study. 
• 
We will ask you whether there have been any changes to your health since your last visit. 
• 
Ask you if you have had any problems accessing health care like treatment for your HIV 
or substance use. 
• 
We will draw [XX] mL of blood (about [XX] amount). 
• 
We will also ask you for a urine sample for drug testing. 
• 
We will store blood and urine samples for other testing related to this study. This may 
include tests for drugs, medications used to treat HIV infection and substance use, and 
other HIV-related tests. The stored blood samples may also be used to learn more about 
how HIV is spread throughout the community. 
• 
We will tell you the results of any tests we do during the study at the study site and will 
refer you to [XXX] clinic for treatment if needed. 
• 
We will store blood and urine samples for other future research, if you allow us to do so. 
• 
We will refer you to a place where you can talk to someone about your substance use and 
how to reduce the chances that you may pass HIV on to the people with whom you have 
sex or share drugs. [SITE TO ADJUST: You can also exchange your used needles for 
clean ones.] 
Every 3 months and your last visit 
After your enrollment visit, we will ask you to come back for a visit one month later and then 
every 3 months for [SITE TO ADJUST ACCORDING TO ENROLLMENT DATE:XX] for 
another visit. Each of these visits will last about XX hours. During these visits we will: 
• 
Ask you to confirm or update your contact information again. 
• 
We will talk to you about ways to reduce the chances that you may pass HIV on to the 
people with whom you have sex or share drugs. 
• 
We will ask you if you have had any good or bad things happen to you because you are 
taking part in this study. 
• 
We will ask you whether there have been any changes to your health since your last visit. 
• 
Ask you if you have had any problems accessing health care like treatment for your HIV 
or substance use. 
• 
We will ask you questions about your use of anti-HIV drugs, substance use, sexual 
partners, people with whom you share drugs and other things about your personal life. 
• 
We will draw [XX] mL of blood (about [XX] amount). At Weeks 26, 52, 78 and 104 
(depending on how long you are in the study) we will test your T-cell count and amount 
of virus in your to measure the amount of damage that HIV has done to your body. 
• 
We will also ask you for a urine sample for drug testing. 
• 
We will store blood and urine samples for other testing related to this study. This may 
include tests for drugs, medications used to treat HIV infection and substance use, and 
HPTN 074, Final Version 2.0 
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other HIV -related tests. The stored blood samples may also be used to learn more about 
how HIV is spread throughout the community. 
• 
We will tell you the results of any tests we do during the study at the study site and will 
refer you to [XXX] clinic for treatment if needed. 
• 
We will store some blood and urine samples for other future research, if you allow us to 
do so. 
• 
We will refer you to a place where you can talk to someone about your substance use and 
how to reduce the chances that you may pass HIV on to the people with whom you have 
sex or share drugs. [SITE TO ADJUST: You can also exchange your used needles for 
clean ones.] 
Risks Associated with Early versus Delayed Treatment with Anti-HIV Drugs: 
During this study, you may receive anti-HIV drugs as soon as you start the study, or later, if your 
body weakens or you become sick. There are risks associated with both ways the anti-HIV drugs 
are given in the study. Your doctor at [ site to complete] will talk to you about the risks of any 
anti-HIV medications that you are given. 
If you get the drugs immediately, when you are feeling healthy, the drugs may make you feel 
sick. By taking the drugs right away and staying on them, you may experience side effects that 
last a long time. These side effects can be very serious. Also, when you take anti-HIV drugs 
there is a risk that the drugs will stop working to fight the virus. The longer you take the 
drugs, the greater the chance is that the drugs may stop working. If this happens, your HIV 
infection may develop into AIDS. 
In some studies, people have found that taking anti-HIV drugs sooner may help your body stay 
strong. If you receive the drugs only when you become sick, you may be too sick for the drugs 
to help your body in fighting the infection. The damage done to your immune system by the 
virus may be permanent, even when you are treated with the anti-HIV drugs. By waiting to take 
the anti-HIV drugs, you may be more likely to spread HIV to anyone you have sex with. 
Pregnancy and Breastfeeding: 
If you are a woman and you become pregnant, you should tell your doctor right away. You are 
welcome to continue study participation if you become pregnant. If you are not already in care 
for your HIV infection, we will help you find a place where you can be treated while you are 
pregnant. Taking anti-HIV medications while you are pregnant may help you protect your baby 
from becoming infected with HIV. 
Other Risks: 
• 
You may feel discomfort, dizzy, or even faint when your blood is drawn. Redness, pain, 
swelling, bruising, or an infection may occur where the needle goes into your arm. 
• 
You may become embarrassed, worried, or anxious when discussing your sexual 
practices, ways to protect your partner against HIV, or discussing or waiting for your test 
results during the study. 
• 
Knowing that you have HIV or other infections passed through sex may make 
you worried or anxious. A trained counselor will help you deal with any feeling 
or questions you have. 
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We will make every effort to protect your privacy and confidentiality while you are in this study. 
However, it is possible that you could have problems if people learn that you are here for this 
study. People may think that you are infected with HIV or at risk of HIV because of sexual 
behavior or drug use. It is also possible that others may find out that you have been screened for 
this study and assume that you are a person who injects drugs. If people think you are infected 
with HIV or a person who injects drugs, this could cause you problems finding or keeping a job. 
Others may treat you unfairly, including your family and community. (Sites to insert local 
registration requirements for antiretrovirals and substance use and the inherent risks.) 
Telling other people you are HIV-positive can pose risks to you including violence. In addition, 
this information may change the relationships you have with other people, which may be 
difficult for you in how you feel and when you're with other people. Further, it is possible that 
those you tell, will tell others that you are HIV-positive. 
POTENTIAL BENEFITS: 
There may be no direct benefit to you from this study. However, you will be sent to [XX] to 
receive the anti-HIV drugs either at the beginning of the study, or when your T-cell count has 
fallen or you become very sick. Although we will not provide the anti-HIV drugs here, we will 
work to make sure that you can receive them at [XXX.] The anti-HIV drugs are not a cure for HIV 
infection or AIDS, but we know that they can make people infected with HIV feel better, not get as 
sick, and live longer. We will tell you the results of any tests done at the study site during the 
study or other information related to your health that is obtained during the study at the study 
site. You will be able to talk to counselors about your health and feelings. We will refer 
you to [XXX] where someone will talk to you about ways to reduce your drug use and slow the 
spread of HIV. You will also receive free condoms throughout the entire course of the 
study. In addition, knowledge gained from this study may help others infected with HIV in 
the future. Although participation in this study may also prevent you from spreading the HIV 
virus to others, no guarantee can be made, you should not share drugs, needles or works with 
anyone. 
ACCESS TO CARE AFTER THE STUDY ENDS: 
After this study ends, you will have on-going access to care for substance use and treat your HIV 
infection. 
NEW FINDINGS: 
You will be told of any new information learned during the course of the study that might cause 
you to change your mind about staying in the study. At the end of the study, you will 
be told when study results may be available and how to learn about them. 
REASONS WHY YOU MAY BE WITHDRAWN FROM THE STUDY WITHOUT YOUR 
CONSENT: 
You may be removed from the study without your consent for the following reasons: 
• 
The study is stopped or cancelled. 
• 
Staying in the study would be harmful to you. 
• 
You are not able to attend study visits or complete the study procedures. 
HPTN 074, Final Version 2.0 
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• 
We are not able to enroll at least one HIV negative person with whom you regularly share 
needles/syringes or drug solutions. 
ALTERNATIVES TO PARTICIPATION: 
If you choose not to take part in this study, it will have no effect on your access to regular services 
at this site. There may be other studies at this site in which you may be eligible to 
participate. Even if you choose to participate in this study, it is not known whether taking 
anti-HIV drugs can prevent you from giving HIV to others. 
COSTS AND COMPENSATION: 
There will be no cost to you for study-related visits or other procedures. There will (or will not: 
Sites to insert appropriate cost language) be a cost to you at XX or XX for which you may be 
sent for anti-HIV drugs or treatment for your substance use. At the end of each visit to this site, 
you will be given [insert amount of money or incentive package to compensate participant for 
food, travel expenses, lost work time, etc.] 
CONTACT INFORMATION 
You will be asked to provide your address and phone number( s ). The staff will ask you for 
names of people who will always know how to find you and places where you can be found. It 
is possible that the staff may visit you at your house or contact one of the people on your contact 
list if you are not able to attend your visits or if the staff have important information for you. If 
we talk to people on this list, we will not tell them why we are trying to reach you. If you are not 
willing to give us this information, you should not agree to be in this study. We will also ask you 
to give us contact information at the last study visit so we can contact you and share with you the 
results of this study. 
CONFIDENTIALITY: 
The study team will try to protect the privacy of your study records and test results, to the extent 
permitted by law, but cannot guarantee that your study records and test results will never be 
released to others. As part of the study team's efforts to protect your study records from 
disclosure, you will be identified in the study records by a code, and the study team leadership 
will keep the link between the code and your identity separate from your study 
records. Unless required by law or unless you give your written permission, study records 
that identify you will not be released to other parties or entities. However, your study records 
may be reviewed by various government agencies that have a legal right to do so, such as the 
sponsor of the study (US National Institutes of Health [NIH]), the [insert name of site] 
Institutional Review Board (IRB), study staff, study monitors, and (insert applicable local 
authorities]. (If applicable: It is also possible that a court or other government agency could 
order that study records identifying you be released to others.) Any publication or 
presentation of the results of findings of this study will not use your name and will not 
include any information that will identify you. 
A description of this study will be available on www.ClinicalTrials.gov. This web site will not 
include information that can identify you. At most the web site will include a summary of the 
results. You can search this web site at any time. 
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During the study, some of your samples (blood and urine) may be stored for tests done later. 
These samples will be stored in containers that do not have your name on them but rather a code 
to protect your privacy. 
YOUR SAMPLES: 
We will store blood and urine samples for testing related to this study. These samples will be used 
for study-related testing. This may include tests for drugs, medications used to treat HIV infection 
and substance use, tests of how HIV spreads in the community, and other tests related to the HIV 
virus and your body's response to HIV infection. There may be some left over samples of blood 
and urine samples after all of the study-related testing has been completed. We would like to use 
these samples for future research studies. If you agree to this use of your samples, we will ask 
you to initial the end of this form. 
If you do not agree to have your left over samples stored you can still be in this study. If you 
agree to store your samples but change your mind later, you can contact the study staff listed on 
this form. We will then destroy your samples. If you agree, your left over samples will be stored 
indefinitely [insert local guidelines]. Any future use or the ability to store your samples longer 
needs to be reviewed and approved by the NIH and local authorities. If these studies involve 
other laboratories, we will need approval from your local authorities to store or transfer them 
elsewhere. Your left over samples will not be sold or used for commercial reasons. 
RESEARCH-RELATED INJURY: 
The study staff will ask you questions about your health at every study visit. If you have any 
health problems between visits, please contact the study staff. If you have a medical emergency 
that requires immediate care, [insert site-specific instructions]. [ Sites to specify institutional 
policy:] If you are injured as a result of being in this study, 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 for monetary compensation or other forms of compensation for such injuries either 
through this institution or the NIH. You do not give up any legal rights by signing this consent 
form. 
PROBLEMS or QUESTIONS: 
For questions about this study or a research-related injury, contact: 
• 
[site insert name of the investigator or other study staff] 
• 
[site insert telephone number and physical address of above J 
For questions about your rights as a research subject, contact: 
• 
[site insert name or title of person on the Institutional Review Board (!RB) or other 
organization appropriate for the site J 
• 
[site insert telephone number and physical address of above J 
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SIGNATURE PAGE: SAMPLE ENROLLMENT CONSENT FOR INDEX 
HPTN 074: Integrated treatment and prevention for people who inject drugs: A vanguard 
study for a network-based randomized HIV prevention trial comparing an integrated 
intervention including supported antiretroviral therapy to the standard of care 
Final Version 2.0, 26 July 2017 
If you have read this informed consent, or have had it read and explained to you, and understand 
the information, and you voluntarily agree to enroll into this study, please sign your name or 
make your mark below. 
Please carefully read the statements below ( or have them read to you) and think about your choice. 
No matter what you decide it will not affect whether you can be in the research study, or your 
routine health care. 
---- I agree to have samples of my blood used for future testing related to HIV infection. 
---- I agree to have samples of my urine used for future testing related to HIV infection. 
---- I do not agree to have samples of my blood stored and used for future testing related to 
HIV infection. 
____ I do not agree to have samples of my urine stored and used for future testing related to 
HIV infection. 
If you have read this informed consent, or have had it read and explained to you, and understand 
the information, and you voluntarily agree to enroll into this study, please sign your name or 
make your mark below. 
Participant's Name (print) 
Participant's Signature or Thumbprint and Date 
For staff: I have explained the purpose of the screening to the volunteer and have answered all 
of his/her questions. To the best of my knowledge, he/she understands the purpose, procedures, 
risks and benefits of this study. 
Study Staff Conducting 
Consent Discussion (print) 
Study Staff Signature and Date 
For witnesses for illiterate volunteers: I attest that the information contained in this written 
consent form has been read and explained to the participant. He/she appears to understand the 
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26 July 2017 

purpose, procedures, risks and benefits of the study and has voluntarily accepted to participate in 
this study. 
For those placing thumbprint only: I attest that the participant who states that his/her name is 
____________ has placed his/her thumbprint on this consent form of his/her 
own free will on this day _______ _ 
Witness' Name (print) 
Witness's Signature and Date 
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Appendix IV-C. Sample Enrollment Consent for Network Injection Partners 
HPTN 074: Integrated treatment and prevention for people who inject drugs: A vanguard 
study for a network-based randomized HIV prevention trial comparing an integrated 
intervention including supported antiretroviral therapy to the standard of care 
Final Version 2.0, 26 July 2017 
DAIDS Document ID: 11917 
Study Implementers: HIV Prevention Trials Network (HPTN) and the U.S. National Institutes 
of Health (NIH), Bethesda, MD, USA. 
Study Sponsors: NIH, Division of AIDS (DAIDS), US National Institute of Allergy and 
Infectious Diseases (NIAID) and US National Institute on Drug Abuse (NIDA), Bethesda, MD, 
USA. 
PRINCIPAL INVESTIGATOR: [Insert Name] 
PHONE: [Insert Number] 
INTRODUCTION 
You are being asked to take part in a research study that will help us design a new and better way 
to prevent the spread of HIV (human immunodeficiency virus, the virus that causes AIDS) 
among people who inject drugs by referring people who inject drugs for substance use treatment 
where available and referring HIV-infected drug users for treatment with anti-HIV drugs. The 
person in charge of the study at this site is [insert name of principal investigator]. 
This study includes groups of people who inject drugs in which one person is infected with HIV 
and the other people are not. You are being asked to be in this study because someone who you 
inject drugs with has HIV and told you about the study. About 500 people who are HIV infected 
will take part in this study including 167 at this site. About 750 people who are not HIV infected 
but share drugs with someone who are HIV infected will also take part in the study including 
about 250 at this site. The people in this study will come from Asia and Eastern Europe. Each 
person will be in this study for two years at the most. You will asked to be in the study for 
[SITE TO ADJUST FOR EARLY ENROLLEES]. 
Before you decide whether to take part in this research study, you need to know the purpose, the 
possible risks and benefits to you, and what will be expected of you during the study. This 
consent form provides that information. The study staff will discuss the information with you 
and they will answer any questions you may have. After the study has been fully explained to 
you, you can decide whether or not you want to participate. Once you understand this study, and 
if you agree to take part, you will be asked to sign this consent form or make your mark in front 
of someone. You will be offered a copy of this form to keep. 
Please note that: 
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• 
Your participation in this study is entirely voluntary. 
• 
You may decide not to take part or to withdraw from this study at any time without 
losing the benefits of your standard health care. 
PURPOSE OF THE STUDY: 
We are doing this study to help us develop a new and better way to prevent the spread of HIV 
from HIV infected people who inject drugs to HIV uninfected people with whom they share 
needles/syringes or drug solutions. What we learn will help us design a future study that will 
determine whether treating HIV infected injection drug users with anti-HIV drugs and providing 
other support services including treatment for substance use where available will prevent them 
from passing the HIV virus to their injection drug partners. During the study, everyone with 
HIV will be referred for health care, which may include medications to treat HIV infection, 
substance use, or other conditions. We will not provide treatment for HIV infection or substance 
use or any medications at [INSERT NAME OF CLINIC/SITE]; instead we will send you to 
[REFERRAL LOCATION] if we recommend that someone begins treatment. [SITE TO 
ADJUST] You may also be offered medication that will help you stop using drugs. You do not 
need to accept this treatment in order to be part of this study. 
If you decide to take part in the study, your injection partner, who encouraged you to enroll in 
this study by giving you the referral card, will be placed in 1 of 2 groups ( called the 
"Intervention" and "Control" groups). This group will be chosen "by lot" (like drawing straws 
or flipping a coin) [or other equivalent local term]. 
You have a greater chance of being placed in the "Control" group, meaning that you will receive 
the usual clinical and counseling services available and your injection partner will start taking 
anti-HIV drugs later in the study. The "Intervention" group will receive more intensive services 
and your injection partner will be referred to start taking drugs as soon as they join the study. 
Both groups are very important to this study. You cannot choose which group you are in. You 
have a greater chance of being placed in the "Control" group, meaning that you will receive the 
usual clinical and counseling services available, but you cannot choose your group. You will be 
in the same group as your injection partner (the one who encouraged you to enroll in this study 
by giving you the referral card). Both groups are very important to this study. People in both 
groups will have generally the same study visits, but people in the intervention group will have 
more visits, some of a different kind, than the other group. 
PROCEDURES: 
If you agree to join this study, you will be asked to come back to the site on a regular basis. We 
will tell you the results of any tests we do during the study at the study site which may impact 
your health. A few of your samples will be sent out of the country for testing because it is not 
possible to do tests are our site. [Sites should modify as needed] 
Enrollment visit 
During your first study visit, the study will be explained to you. You will have time to ask 
questions and discuss any concerns you may have with the study staff. This visit may last up to 
XX hours. This visit may be broken up into two visits. During this visit, we will also: 
HPTN 074, Final Version 2.0 
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• 
Ask you to update the contact information you gave at screening. 
• 
Ask you questions about your substance use, access to health care, sexual practices, 
people with whom you share drugs or related equipment, and other things about your 
personal life. 
• 
We will ask you for the names of the people with which you regularly share 
needles/syringes or drug solutions. 
• 
We will draw [XX] mL of blood (about [XX] amount). We will talk to you about things 
you do which might put you at risk for HIV, test this blood for HIV and talk to you about 
the results of this test. 
• 
We will talk to you about ways to reduce the chances that you may become infected with 
HIV. 
• 
We will ask you if you have had any good or bad things happen to you because you are 
taking part in this study. 
• 
We will ask you if you have had any problems accessing health care like treatment for 
your substance use. 
• 
We will also ask you for a urine sample for drug testing. 
• 
We will store blood and urine samples for other testing related to this study. This may 
include tests for substances of abuse and medications used to treat substance use. 
• 
We will tell you the results of any tests we do at the study site and will refer you to 
[XXX] clinic for treatment if needed. 
• 
We will take samples of blood and urine that we will store for other future research, if 
you allow us to do so. 
• 
We will assign you to a study group. Your group will be determined "by lot", as we said 
above. 
One month visit 
One month after the enrollment visit, we will ask you to come in for a visit which will last about 
XX hours. During this visit we will: 
• 
Ask you to confirm or update your contact information. 
• 
We will talk to you about ways to reduce the chances that you may become infected with 
HIV. 
• 
Ask you questions about your substance use, access to health care, sexual practices, 
people with whom you share drugs or related equipment, and other things about your 
personal life. 
• 
We will ask you for the names of the people with which you regularly share 
needles/syringes or drug solutions. 
• 
We will ask you if you have had any good or bad things happen to you because you are 
taking part in this study. 
• 
We will ask you whether there have been any changes to your health since your last visit. 
• 
We will ask you if you have had any problems accessing health care like treatment for 
your substance use. 
• 
We will draw [XX] mL of blood (about [XX] amount). We will talk to you about things 
you do which might put you at risk for HIV, test this blood for HIV and talk to you about 
the results of this test. 
• 
We will also ask you for a urine sample for drug testing. 
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• 
We will store blood and urine samples for other testing related to this study. This may 
include tests for substance of abuse and medications used to treat substance use. If you 
become infected during the study, these samples may also be used to test for medications 
used to treat HIV infection and for other HIV-related testing. 
• 
We will also store blood and urine samples for other future research, if you allow us to do 
so. 
• 
We will tell you the results of any tests we do at the site during the study and refer you to 
[XX] clinic for treatment if needed. 
Every 3 months and your last visit 
After your enrollment visit, we will ask you to come back for a visit one month later and then 
every 3 months for one year (SITE TO ADJUST FOR EARLY ENROLLEES) for another visit. 
Depending on when you join the study, some participants may be asked to come for one year and 
others will be asked to come for up to two years. Each of these visits will last about XX hours. 
During these visits we will: 
• 
Ask you to confirm or update your contact information again. 
• 
We will draw [XX] mL of blood (about [XX] amount). We will talk to you about things 
you do which might put you at risk for HIV, test this blood for HIV and talk to you about 
the results of this test. 
• 
We will ask you if you have had any good or bad things happen to you because you are 
taking part in this study. 
• 
We will ask you whether there have been any changes to your health since your last visit. 
• 
We will ask you if you have had any problems accessing health care like treatment for 
your substance use. 
• 
Ask you questions about your substance use, access to health care, sexual practices, 
people with whom you share drugs or related equipment, and other things about your 
personal life. 
• 
We will ask you for the names of the people with which you regularly share 
needles/syringes or drug solutions. 
• 
This blood will be tested for HIV. 
• 
We will also ask you for a urine sample for drug testing. 
• 
We will store blood and urine samples for other testing related to this study. This may 
include tests for substance of abuse and medications used to treat substance use. If you 
become infected during the study, these samples may also be used to test for medications 
used to treat HIV infection and other HIV -related tests. 
• 
We will also store blood and urine samples for other future research, if you allow us to do 
so. 
• 
We will tell you the results of any tests we do at the site during the study and refer you to 
[XXX] clinic for treatment if needed. 
If you test positive for HIV 
If you have a test result at any study visit that indicates you may have been infected with HIV, 
we will arrange to confirm the test result. If the confirmatory tests show that you do have HIV 
infection, we will perform tests to see how well your body can fight off infections and measure 
the amount of virus in your blood. If we confirm that you are infected with HIV later in the 
study we will ask you to continue to come to the study clinic as scheduled. [Insert any 
HPTN 074, Final Version 2.0 
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additional local testing that may be performed]. [Insert any local reporting requirements.] We 
will also refer you for HIV treatment and care. If you become infected during the study, stored 
blood and urine samples may also be used to test for medications used to treat HIV infection and 
other HIV -related tests as noted above. The stored blood samples may also be used to learn 
more about how HIV is spread throughout the community. 
Risks: 
• 
You may feel discomfort, dizzy, or even faint when your blood is drawn. Redness, pain, 
swelling, bruising, or an infection may occur where the needle goes into your arm. 
• 
You may become embarrassed, worried, or anxious when discussing your sexual 
practices, ways to protect yourself against HIV, or discussing or waiting for your test 
results during the study. 
We will make every effort to protect your privacy and confidentiality while you are in this study. 
However, it is possible that you could have problems if people learn that you are here for this 
study. People may think that you are infected with HIV or at risk of HIV because of sexual 
behavior or drug use. It is also possible that others may find out that you have been screened for 
this study and assume that you are a person who injects drugs. If people think you are infected 
with HIV or a person who injects drugs, this could cause you problems finding or keeping a job. 
Others may treat you unfairly, including your family and community. (Sites to insert local 
registration requirements for antiretrovirals and substance use and the inherent risks) 
Even if the person you share drugs with is getting treatment for their HIV, you should not share 
drugs, needles or works with your partner or anyone else in order to protect yourself from getting 
HIV. If your partner is just starting treatment or does not take it when they are supposed to, they 
may have a high level of HIV in their body ( called "viral load") which will make it easier to pass 
HIV to you. Also, we do not know for sure at this time if being treated for HIV will make it less 
likely that they will pass the virus to you if you are sharing drugs, needles or works. 
POTENTIAL BENEFITS: 
We will tell you the results of any tests or other information related to your health during the 
study at the study site. You will be able to talk to counselors about your health and 
feelings. We will refer you to [XXX] where someone will talk to you about ways to reduce your 
drug use and slow the spread of HIV. You will also receive free condoms throughout the 
entire course of the study. In addition, knowledge gained from this study may help others 
infected with or at risk of infection with HIV in the future. 
NEW FINDINGS: 
You will be told of any new information learned during the course of the study that might cause 
you to change your mind about staying in the study. At the end of the study, you will 
be told when study results may be available and how to learn about them. 
REASONS WHY YOU MAY BE WITHDRAWN FROM THE STUDY WITHOUT YOUR 
CONSENT: 
You may be removed from the study without your consent for the following reasons: 
• 
The study is stopped or cancelled. 
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• 
Staying in the study would be harmful to you. 
• 
You are not able to attend study visits or complete the study procedures. 
• 
The person who referred you to this study, who you regularly share needles/syringes or 
drug solutions leaves the study. 
ALTERNATIVES TO PARTICIPATION: 
If you choose not to take part in this study, it will have no effect on your access to regular services 
at this site. There may be other studies at this site in which you may be eligible to 
participate. 
COSTS AND COMPENSATION: 
There will be no cost to you for study-related visits or other procedures. There will (or will not: 
Sites to insert appropriate cost language) be a cost to you at [XX] or [XX] for which you may be 
sent for treatment for your substance use. At the end of each visit to this site, you will be given 
[insert amount of money or incentive package to compensate participant for food, travel expenses, 
lost work time, etc.] 
CONTACT INFORMATION 
You will be asked to provide your address and phone number(s). The staff will ask you for 
names of people who will always know how to find you and places where you can be found. It 
is possible that the staff may visit you at your house or contact one of the people on your contact 
list if you are not able to attend your visits or if the staff have important information for you. If 
we talk to people on this list, we will not tell them why we are trying to reach you. If you are not 
willing to give us this information, you should not agree to be in this study. 
CONFIDENTIALITY: 
The study team will try to protect the privacy of your study records and test results, to the extent 
permitted by law, but cannot guarantee that your study records and test results will never be 
released to others. As part of the study team's efforts to protect your study records from 
disclosure, you will be identified in the study records by a code, and the study team leadership 
will keep the link between the code and your identity separate from your study 
records. Unless required by law or unless you give your written permission, study records 
that identify you will not be released to other parties or entities. However, your study records 
may be reviewed by various government agencies that have a legal right to do so, such as the 
sponsor of the study (US National Institutes of Health [NIH]), the [insert name of site] 
Institutional Review Board (IRB), study staff, study monitors, and (insert applicable local 
authorities]. (If applicable: It is also possible that a court or other government agency could 
order that study records identifying you be released to others.) Any publication or 
presentation of the results of findings of this study will not use your name and will not 
include any information that will identify you. 
A description of this study will be available on www.ClinicalTrials.gov. This web site will not 
include information that can identify you. At most the web site will include a summary of the 
results. You can search this web site at any time. 
During the study, some of your samples (blood and urine) may be stored for tests done later. These 
samples will be stored in containers that do not have your name on them but rather a code to 
protect your privacy. 
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YOUR SAMPLES: 
We will store blood and urine samples for testing related to this study. These samples will be 
used for study-related testing. This may include tests for drugs, medications used to treat HIV 
infection and substance use, and if you become infected with HIV, other tests related to the HIV 
virus and your body's response to HIV infection. There may be some left over samples of blood 
and urine samples after all of the study-related testing has been completed. We would like to use 
these samples for future research studies. If you agree to this use of your samples, we will ask 
you to initial the end of this form. The stored blood samples will also be used to learn more 
about how HIV is spread throughout the community. 
If you do not agree to have your left over samples stored you can still be in this study. If you 
agree to store your samples but change your mind later, you can contact study staff. We will 
then destroy your samples. If you agree, your left over samples will be stored indefinitely [insert 
local guidelines]. Any future use or the ability to store your samples longer needs to be reviewed 
and approved by the NIH and local authorities. If these studies involve other laboratories, we 
will need approval from your local authorities to store or transfer them elsewhere. Your left over 
samples will not be sold or used for commercial reasons. 
RESEARCH-RELATED INJURY: 
The study staff will ask you questions about your health at every study visits. If you have any 
health problems between visits, please contact the study staff. If you have a medical emergency 
that requires immediate care, [insert site-specific instructions].[Sites to specify institutional 
policy:] If you are injured as a result of being in this study, 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 for monetary compensation or other forms of compensation for such injuries either 
through this institution or the NIH. You do not give up any legal rights by signing this consent 
form. 
PROBLEMS or QUESTIONS: 
For questions about this study or a research-related injury, contact: 
• 
[site insert name of the investigator or other study staff] 
• 
[site insert telephone number and physical address of above] 
For questions about your rights as a research subject, contact: 
• 
[site insert name or title of person on the Institutional Review Board (!RB) or other 
organization appropriate for the site J 
• 
[site insert telephone number and physical address of above J 
HPTN 074, Final Version 2.0 
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SIGNATURE PAGE: SAMPLE ENROLLMENT CONSENT FOR NETWORK 
INJECTION PARTNERS 
HPTN 074: Integrated treatment and prevention for people who inject drugs: A vanguard 
study for a network-based randomized HIV prevention trial comparing an integrated 
intervention including supported antiretroviral therapy to the standard of care 
Final Version 2.0, 26 July 2017 
Please carefully read the statements below ( or have them read to you) and think about your choice. No 
matter what you decide it will not affect whether you can be in the research study, or your routine health 
care. 
I agree to have samples of my blood used for future testing related to HIV infection. 
I agree to have samples of my urine used for future testing related to HIV infection. 
I do not agree to have samples ofmy blood stored and used for future testing related to HIV 
infection. 
I do not agree to have samples of my urine stored and used for future testing related to HIV 
infection. 
If you have read this informed consent, or have had it read and explained to you, and understand the 
information, and you voluntarily agree to enroll into this study, please sign your name or make your mark 
below. 
Participant's Name (print) 
Participant's Signature or Thumbprint and Date 
For staff: I have explained the purpose of the screening to the volunteer and have answered all of his/her 
questions. To the best of my knowledge, he/she understands the purpose, procedures, risks and benefits of 
this study. 
Study Staff Conducting 
Consent Discussion (print) 
Study Staff Signature and Date 
For witnesses for illiterate volunteers: I attest that the information contained in this written consent form 
has been read and explained to the participant. He/she appears to understand the purpose, procedures, 
risks and benefits of the study and has voluntarily accepted to participate in this study. 
For those placing thumbprint only: I attest that the participant who states that his/her name is 
----------- has placed his/her thumbprint on this consent form of his/her own free 
will on this day --------
Witness' Name (print) 
Witness's Signature and Date 
HPTN 074, Final Version 2.0 
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26 July 2017 

Appendix IV-D. Sample Key Informant Interview Informed Consent for Selected Study 
Index Participants, Navigators, Counselors or Key Clinic Personnel at the HIV Care and 
Substance Use Treatment Sites 
HPTN 074: Integrated treatment and prevention for people who inject drugs: A vanguard 
study for a network-based randomized HIV prevention trial comparing an integrated 
intervention including supported antiretroviral therapy to the standard of care 
Final Version 2.0, 26 July 2017 
DAIDS Document ID: 11917 
Study Implementers: HIV Prevention Trials Network (HPTN) and the U.S. National Institutes 
of Health (NIH), Bethesda, MD, USA. 
Study Sponsors: NIH, Division of AIDS (DAIDS), US National Institute of Allergy and 
Infectious Diseases (NIAID) and US National Institute on Drug Abuse (NIDA), Bethesda, MD, 
USA. 
PRINCIPAL INVESTIGATOR: [Insert Name] 
PHONE: [Insert Number] 
Introduction 
You have been invited to participate in a research study which includes an interview to discuss 
your role as either: 1) provider or supervisor of providers to participants for antiretrovirals or 
substance use therapy, 2) as a navigator or counselor for participants, or 3) an Index participant 
assigned to the intervention arm in HPTN 074: Integrated treatment and prevention for people 
who inject drugs: A vanguard study for a network-based randomized HIV prevention trial 
comparing an integrated intervention including supported antiretroviral therapy to the standard of 
care. This "Key Informant Interview" is an individual discussion about a specific set of topics. 
The purpose of this interview is to help us learn more about: 
Common barriers and facilitators for providers and for clinic participants for feasibility and 
barriers to the intervention provided during this study. This includes those services participants 
were referred for outside of this clinic including: 
o Uptake of HIV testing 
o Initiation of HIV care 
o Initiation of substance use treatment 
o Medication adherence 
Approximately 4-10 navigators and counselors at the [insert name J clinic as well as persons 
directly involved in antiretroviral or substance use dispensation during HPTN 074 and up to 15 
HIV positive study participants randomized to the intervention arm at each of the three study 
centers and referral locations will participate in individual Key Informant Interviews near the 
time when all participants at each of the sites are just beginning the study and up to 20 HIV 
HPTN 074, Final Version 2.0 
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26 July 2017 

positive study participants randomized to the intervention arm at each of the three study centers 
when they have completed all visits. This means a total of about 12-30 navigators, counselors, 
and persons directly involved with antiretroviral or substance use dispensation and up to 60 HIV 
positive study participants randomized to the intervention arm from all three study centers 
combined. The information from these interviews will help us better understand what we learn 
from the rest of the study. We hope the information we learn will help us reduce the number of 
people who inject drugs who become infected with HIV in the future, as well as how best to 
support HIV-infected people who inject drugs seeking treatment for HIV and substance use. The 
information gathered from these interviews will be combined with the rest of the information that 
is collected during this research study. 
Procedures 
{Sites to adjust as needed] The interview will be led by an individual that is not directly a 
member of our research team here at [insert clinic] but is affiliated with our overall research 
organization. The individual will not be someone who has a supervisory role for your position. 
As stated previously, you will be asked to identify common barriers and facilitators for 
participants to: 
• 
Uptake of HIV testing 
• 
Initiation of HIV care 
• 
Initiation of substance use treatment 
• 
Medication adherence 
Your participation in this interview is voluntary. You are not required to participate in this 
interview in order to remain employed at [insert site]. Although we hope that you will be 
comfortable answering all of the questions openly and honestly, please keep in mind that you 
may refuse to answer any of the questions, or stop your participation completely, at any time. 
Your decision about whether or not to participate in this study is confidential and we will not tell 
other people whether or not you participated. 
{To be modified to reflect site practices]: The interview will take place in a location that the 
study team has determined will provide you with privacy and confidentiality. The study team 
will talk with you about this so you know where to go for the interview. 
Each interview should take about one hour. There will be no cost to you for participation. You 
will receive [insert local amount] for your time and effort. 
What Are the Potential Benefits? 
You may not receive any other direct benefit from being in this study; however, the information 
gathered during this study may help to provide better access to antiretrovirals and substance use 
therapies for people who inject drugs. 
What Are the Possible Risks or Discomforts? 
As noted, to minimize discomfort and to protect your privacy, the interview will be conducted in 
a private area that will allow you to speak comfortably without being overheard. The greatest 
HPTN 074, Final Version 2.0 
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26 July 2017 

risk may involve your privacy and confidentiality. The steps that the study team has taken to 
protect your privacy are described below. 
What are the alternatives to participating in this study? 
[Sites to amend as applicable] If you choose not to take part in this study, it will have no effect 
on your current employment. We will not tell your employer about whether or not you decide to 
participate in the interview. 
How Will Your Privacy Be Protected? 
The study team will try to protect the privacy of your study records and test results, to the extent 
permitted by law, but cannot guarantee that your study records and test results will never be 
released to others. As part of the study team's efforts to protect your study records from 
disclosure, you will be identified in the study records by a code, and the study team leadership 
will keep the link between the code and your identity separate from your study 
records. Unless required by law or unless you give your written permission, study records 
that identify you will not be released to other parties or entities. However, your study records 
may be reviewed by various government agencies that have a legal right to do so, such as the 
sponsor of the study (US National Institutes of Health [NIH]), the [insert name of site] 
Institutional Review Board (IRB), study staff, study monitors, and (insert applicable local 
authorities]. (If applicable: It is also possible that a court or other government agency could 
order that study records identifying you be released to others.) Any publication or 
presentation of the results of findings of this study will not use your name and will not 
include any information that will identify you. 
A description of this study will be available on www.ClinicalTrials.gov. This web site will not 
include information that can identify you. At most the web site will include a summary of the 
results. You can search this web site at any time. 
PROBLEMS or QUESTIONS: 
For questions about this study or a research-related injury, contact: 
• 
[site insert name of the investigator or other study staff] 
• 
[site insert telephone number and physical address of above} 
For questions about your rights as a research subject, contact: 
• 
[site insert name or title of person on the Institutional Review Board (!RB) or other 
organization appropriate for the site] 
• 
[site insert telephone number and physical address of above] 
HPTN 074, Final Version 2.0 
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SIGNATURE PAGE: Sample Key Informant Interview Informed Consent for Selected 
Study Participants, Navigators, Counselors or Key Clinic Personnel at the HIV Care and 
Substance Use Treatment Sites 
HPTN 074: Integrated treatment and prevention for people who inject drugs: A vanguard 
study for a network-based randomized HIV prevention trial comparing an integrated 
intervention including supported antiretroviral therapy to the standard of care 
Final Version 2.0, 26 July 2017 
If you have read this informed consent, or have had it read and explained to you, and understand 
the information, and you voluntarily agree to enroll into this study, please sign your name or 
make your mark below. 
Please carefully read the statements below (or have them read to you) and think about your choice. 
No matter what you decide it will not affect whether you can be in the research study, or your 
routine health care. If you have read this informed consent, or have had it read and explained to 
you, and understand the information, and you voluntarily agree to enroll into this study, please 
sign your name or make your mark below. 
Participant's Name (print) 
Participant's Signature or Thumbprint and Date 
For staff: I have explained the purpose of the screening to the volunteer and have answered all 
of his/her questions. To the best of my knowledge, he/she understands the purpose, procedures, 
risks and benefits of this study. 
Study Staff Conducting 
Consent Discussion (print) 
Study Staff Signature and Date 
For witnesses for illiterate volunteers: I attest that the information contained in this written 
consent form has been read and explained to the participant. He/she appears to understand the 
purpose, procedures, risks and benefits of the study and has voluntarily accepted to participate in 
this study. 
For those placing thumbprint only: I attest that the participant who states that his/her name is 
___________ has placed his/her thumbprint on this consent form of his/her 
own free will on this day _______ _ 
Witness' Name (print) 
Witness's Signature and Date 
HPTN 074, Final Version 2.0 
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26 July 2017 

Appendix IV-E. Sample Re-Enrollment Consent for Index Extension (up to 12 additional 
months) 
HPTN 074: Integrated treatment and prevention for people who inject drugs: A vanguard 
study for a network-based randomized HIV prevention trial comparing an integrated 
intervention including supported antiretroviral therapy to the standard of care 
Final Version 2.0, 26 July 2017 
DAIDS Document ID: 11917 
Study Implementers: HIV Prevention Trials Network (HPTN) and the U.S. National Institutes 
of Health (NIH), Bethesda, MD, USA. 
Study Sponsors: NIH, Division of AIDS (DAIDS), US National Institute of Allergy and 
Infectious Diseases (NIAID) and US National Institute on Drug Abuse (NIDA), Bethesda, MD, 
USA. 
PRINCIPAL INVESTIGATOR: [Insert Naine] 
PHONE: [Insert Number] 
INTRODUCTION 
You are being asked to take part in a research study that will help us design a new and better way 
to prevent the spread of HIV (human immunodeficiency virus, the virus that causes AIDS) ainong 
people who inject drugs by referring people who inject drugs for substance use treatment where 
available and referring HIV-infected drug users for treatment with anti-HIV drugs. This study is 
sponsored by the United States National Institutes of Health. The person in charge of the study 
at this site is [insert naine of principal investigator]. 
The main study included groups of people who inject drugs in which one person is infected with 
HIV and the other people are not. As you are aware, you recently completed participation in that 
main study which is referred to as HPTN 074. We are asking that you participant in an extension 
to that study, adding up to 12 additional months of follow-up. Up to 500 people who are HIV 
infected will take part in this extension including about 200 at this site. The people in this study 
will come from sites in Asia and Eastern Europe. Each person will be in this study for up to 12 
months at the most. 
Before you decide whether to take part in the 12 month extension to this research study, you 
need to know the purpose, the possible risks and benefits to you, and what will be expected of 
you during the study. This consent form provides that information. The study staff will discuss 
the information with you and they will answer any questions you may have. After the study has 
been fully explained to you, you can decide whether or not you want to continue to participate in 
this 12 month extension to HPTN 074. Once you understand this study, and if you agree to take 
HPTN 074, Final Version 2.0 
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26July2017 

part, you will be asked to sign this consent form or make your mark in front of someone. You 
will be offered a copy of this form to keep. 
Please note that: 
• 
Your participation in this study is entirely voluntary. 
• 
You may decide not to take part or to withdraw from this study at any time without 
losing the benefits of your standard health care. 
• 
You will be in the same "arm" of the study that you were previously in. In other 
words, if you were in the intervention arm, you will remain in that arm. If you were 
in the standard of care arm, you will remain in that arm. Should you have any 
questions, please feel free to ask the study staff for clarification. 
PURPOSE OF THE STUDY: 
We are doing this study to help us develop a new and better way to prevent the spread of HIV 
from HIV infected people who inject drugs to HIV uninfected people with whom they share 
needles/syringes or drug solutions and to look at the pattern of how people will continue to take 
ART and compare that to their HIV viral suppression over a longer period of time in order to see 
if the study intervention can be successful in helping people over a longer period of time. What 
we learn will help us design a future study that will determine whether treating HIV infected 
injection drug users with anti-HIV drugs and providing other support services including 
treatment for substance use where available and during the original portion of the study 
prevented them from passing the HIV virus to their injection drug partners. During the study, 
everyone with HIV will be referred for health care, which may include medications to treat HIV 
infection, substance use, or other conditions. We will not provide treatment for HIV infection or 
substance use or any medications at [INSERT NAME OF CLINIC/SITE]; instead we will send 
you to [REFERRAL LOCATION] ifwe recommend that you begin treatment. [SITE TO 
ADJUST] You may also be offered medication that will help you stop using drugs. You do not 
need to accept this treatment in order to be part of this study. 
At [REFERRAL LOCATION], some people will also be referred for anti-HIV drugs to treat 
their HIV infection, and will be asked to start taking these drugs as soon as they join the study. 
You will continue with the same treatment arm you were assigned during the main study. Others 
may start to take the anti-HIV drugs later in the study, after their T-cell count [or whatever term 
is commonly used locally J is lower or if they become sick. The T-cell count is a blood test that 
we use to measure the amount of damage that HIV has done to your body. Regardless of which 
group you are in, if you have HIV we will recommend that you start anti-HIV drugs before your 
T-cell count gets so low that would make you very sick. If you decide to continue in the study, 
you and the people you use drugs with who enroll in this study will continue in the same group 
that you were in for the main HPTN 074 study (called the "Intervention" and "Control" groups). 
Both groups are very important to this study, and you cannot choose which group you are in. 
Your group will be chosen "by lot" (like drawing straws or flipping a coin) [or other equivalent 
HPTN 074, Final Version 2.0 
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26 July 2017 

local term]. If you have any questions about what group you are in, please ask the research staff 
at this site. 
PROCEDURES: 
If you agree to join this study, you will be asked to come back to the site on a regular basis. We 
will tell you the results of any tests we do during the study at the study site which may impact 
your health. A few of your samples will be sent out of the country for testing because it is not 
possible to do these tests at our site. [Sites should modify as needed] 
Re-Enrollment visit 
During your first study visit for this extension, the study will be explained to you. You will have 
time to ask questions and discuss any concerns you may have with the study staff. This visit 
may last up to [XX] hours. This visit may be broken up into two visits. During this visit, we 
will also: 
• 
Ask you questions about your use of anti-HIV drugs, substance use, access to health care, 
sexual practices, people with whom you share drugs or related equipment, and other 
things about your personal life. 
• 
We will draw [20] mL of blood (about [4 teaspoons] amount). This blood will be tested 
for HIV. We will talk to you about ways to reduce the chances that you may pass HIV on 
to the people with whom you have sex or share drugs. 
• 
We will also ask you for a urine sample for drug testing. 
• 
We will store blood and urine samples for other testing related to this study. This may 
include tests for drugs, medications used to treat HIV infection and substance use, and 
other HIV -related tests. The stored blood samples may also be used to learn more about 
how HIV is spread throughout the community. 
• 
We will ask you if you have had any good or bad things happen to you because you are 
taking part in this study. 
• 
We will tell you the results of any tests we do during the study at the study site and will 
refer you to [XXX] clinic for treatment for anything we may find if needed. 
• 
We will refer you to [XXX] to begin receiving anti-HIV drugs. If you are in the 
"Intervention" group, you will have the opportunity to meet with a counselor to talk 
about problems you may have getting drug and HIV treatments and work with you to 
overcome these problems. They may also help you with ways to be sure that you take 
your HIV medications. For a couple of sessions you can also bring in a family member· 
or friend so that they can assist you with your HIV health care. 
• 
We will refer you to a place where you can talk to someone about your substance use and 
how to reduce the chances that you may pass HIV on to the people with whom you have 
sex or share drugs. [SITE TO ADJUST: You can also exchange your used needles for 
clean ones.] 
Every 3 months and your last visit (4 visits total including this re-Enrollment visit) 
After your re-enrollment visit, we will ask you to come back for a visit every 3 months for 
another visit. Each of these visits will last about XX hours. During these visits we will: 
HPTN 074, Final Version 2.0 
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26 July 2017 

• 
Ask you to confirm or update your contact information again. 
• 
We will talk to you about ways to reduce the chances that you may pass HIV on to the 
people with whom you have sex or share drugs. 
• 
We will ask you if you have had any good or bad things happen to you because you are 
taking part in this study. 
• 
We will ask you whether there have been any changes to your health since your last visit. 
• 
Ask you if you have had any problems accessing health care like treatment for your HIV 
or substance use. 
• 
We will ask you questions about your use of anti-HIV drugs, substance use, sexual 
partners, people with whom you share drugs and other things about your personal life. 
• 
We will draw [20] mL of blood (about [4 teaspoons] amount). 
• 
We will also ask you for a urine sample for drug testing. 
• 
We will store blood and urine samples for other testing related to this study. This may 
include tests for drugs, medications used to treat HIV infection and substance use, and 
other HIV-related tests. The stored blood samples may also be used to learn more about 
how HIV is spread throughout the community. 
• 
We will tell you the results of any tests we do during the study at the study site and will 
refer you to [XXX] clinic for treatment if needed. 
• 
We will store some blood and urine samples for other future research, if you allow us to 
do so. 
• 
We will refer you to a place where you can talk to someone about your substance use and 
how to reduce the chances that you may pass HIV on to the people with whom you have 
sex or share drugs. [SITE TO ADJUST: You can also exchange your used needles for 
clean ones.] 
Risks Associated with Early versus Delayed Treatment with Anti-HIV Drugs: 
During this study, you may receive anti-HIV drugs as soon as you start the study, already be on 
anti-HIV drugs, or receive anti-HIV drugs later, if your body weakens or you become sick. There 
are risks associated with all ways the anti-HIV drugs are given in the study. Your doctor at [ site to 
complete] will talk to you about the risks of any anti-HIV medications that you are given. 
If you get the drugs immediately, when you are feeling healthy, the drugs may make you feel 
sick. By taking the drugs right away and staying on them, you may experience side effects that 
last a long time. These side effects can be very serious. Also, when you take anti-HIV drugs 
there is a risk that the drugs will stop working to fight the virus. The longer you take the 
drugs, the greater the chance is that the drugs may stop working. If this happens, your HIV 
infection may develop into AIDS. 
In some studies, people have found that taking anti-HIV drugs sooner may help your body stay 
strong. If you receive the drugs only when you become sick, you may be too sick for the drugs 
to help your body in fighting the infection. The damage done to your immune system by the 
virus may be permanent, even when you are treated with the anti-HIV drugs. By waiting to take 
the anti-HIV drugs, you may be more likely to spread HIV to anyone you have sex with. 
Pregnancy and Breastfeeding: 
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If you are a woman and you become pregnant, you should tell your doctor right away. You are 
welcome to continue study participation if you become pregnant. If you are not already in care 
for your HIV infection, we will help you find a place where you can be treated while you are 
pregnant. Taking anti-HIV medications while you are pregnant may help you protect your baby 
from becoming infected with HIV. 
Other Risks: 
• 
You may feel discomfort, dizzy, or even faint when your blood is drawn. Redness, pain, 
swelling, bruising, or an infection may occur where the needle goes into your arm. 
• 
You may become embarrassed, worried, or anxious when discussing your sexual 
practices, ways to protect your partner against HIV, or discussing or waiting for your test 
results during the study. 
• 
Knowing that you have HIV or other infections passed through sex may make 
you worried or anxious. A trained counselor will help you deal with any feeling 
or questions you have. 
We will make every effort to protect your privacy and confidentiality while you are in this study. 
However, it is possible that you could have problems if people learn that you are here for this 
study. People may think that you are infected with HIV or at risk of HIV because of sexual 
behavior or drug use. It is also possible that others may find out that you have been screened for 
this study and assume that you are a person who injects drugs. If people think you are infected 
with HIV or a person who injects drugs, this could cause you problems finding or keeping a job. 
Others may treat you unfairly, including your family and community. (Sites to insert local 
registration requirements for antiretrovirals and substance use and the inherent risks.) 
POTENTIAL BENEFITS: 
There may be no direct benefit to you from this study. However, you will be referred to receive 
anti-HIV drugs. Although we will not provide the anti-HIV drugs here, we will work to make sure 
that you can receive them at [XXX.] The anti-HIV drugs are not a cure for HIV infection or AIDS, 
but we know that they can make people infected with HIV feel better, not get as sick, and live 
longer. We will tell you the results of any tests done at the study site during the study or other 
information related to your health that is obtained during the study at the study site. You will 
be able to talk to counselors about your health and feelings. We will refer you to [XXX] 
where someone will talk to you about ways to reduce your drug use and slow the spread of HIV. 
You will also receive free condoms throughout the entire course of the study. In 
addition, knowledge gained from this study may help others infected with HIV in the future. 
Although participation in this study may also prevent you from spreading the HIV virus to 
others, no guarantee can be made, you should not share drugs, needles or works with anyone. 
ACCESS TO CARE AFTER THE STUDY ENDS: 
After this study ends, you will have on-going access to care for substance use and treat your HIV 
infection. 
NEW FINDINGS: 
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You will be told of any new information learned during the course of the study that might cause 
you to change your mind about staying in the study. At the end of the study, you will 
be told when study results may be available and how to learn about them. 
If the researchers find that the Intervention arm is beneficial to helping people get into HIV care, 
and helps lower their HIV virus, those in the standard of care arm will be offered the opportunity for 
all services provided in the intervention arm, including help from a "systems navigator" in order to 
assist with getting drugs to treat HIV infection and decrease substance use. The study researchers 
estimate that this information may be available as early as the first part of 2018. Please refer to the 
research staff should you have any questions. 
REASONS WHY YOU MAY BE WITHDRAWN FROM THE STUDY WITHOUT YOUR 
CONSENT: 
You may be removed from the study without your consent for the following reasons: 
• 
The study is stopped or cancelled. 
• 
Staying in the study would be harmful to you. 
• 
You are not able to attend study visits or complete the study procedures. 
• 
We are not able to enroll at least one HIV negative person with whom you regularly share 
needles/syringes or drug solutions. 
ALTERNATIVES TO PARTICIPATION: 
If you choose not to take part in this study, it will have no effect on your access to regular services 
at this site. There may be other studies at this site in which you may be eligible to 
participate. Even if you choose to participate in this study, it is not known whether taking 
anti-HIV drugs can prevent you from giving HIV to others. 
COSTS AND COMPENSATION: 
There will be no cost to you for study-related visits or other procedures. There will (or will not: 
Sites to insert appropriate cost language) be a cost to you at XX or XX for which you may be 
sent for anti-HIV drugs or treatment for your substance use. At the end of each visit to this site, 
you will be given [insert amount of money or incentive package to compensate participant for 
food, travel expenses, lost work time, etc.] 
CONTACT INFORMATION 
You will be asked to provide your address and phone number(s). The staff will ask you for 
names of people who will always know how to find you and places where you can be found. It 
is possible that the staff may visit you at your house or contact one of the people on your contact 
list if you are not able to attend your visits or if the staff have important information for you. If 
we talk to people on this list, we will not tell them why we are trying to reach you. If you are not 
willing to give us this information, you should not agree to be in this study. We will also ask you 
to give us contact information at the last study visit so we can contact you and share with you the 
results of this study. 
CONFIDENTIALITY: 
The study team will try to protect the privacy of your study records and test results to the extent 
permitted by law, but in some cases, local law can require this information to be released. As 
part of the study team's efforts to protect your study records from disclosure, you will be 
HPTN 074, Final Version 2.0 
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26 July 2017 

identified in the study records by a code, and the study team leadership will keep the link 
between the code and your identity separate from your study records. Unless required by law 
or unless you give your written permission, study records that identify you will not be 
released to other parties or entities. However, your study records may be reviewed by various 
government agencies that have a legal right to do so, such as the sponsor of the study (US 
National Institutes of Health [NIH]), the [insert name of site] Institutional Review Board (IRB)/ 
Ethics Committee (EC), study staff, study monitors, and (insert applicable local authorities]. (If 
applicable: It is also possible that a court or other government agency could order that study 
records identifying you be released to others.) Any publication or presentation of the 
results of findings of this study will not use your name and will not include any 
information that will identify you. 
A description ofthis study will be available on www.ClinicalTrials.gov. This web site will not 
include information that can identify you. At most the web site will include a summary of the 
results. You can search this web site at any time. 
During the study, some of your samples (blood and urine) may be stored for tests done later. 
These samples will be stored in containers that do not have your name on them but rather a code 
to pro{ect your privacy. 
YOUR SAMPLES: 
We will store blood and urine samples for testing related to this study. These samples will be used 
for study-related testing. This may include tests for drugs, medications used to treat HIV infection 
and substance use, tests of how HIV spreads in the community, and other tests related to the HIV 
virus and your body's response to HIV infection. There may be some left over samples of blood 
and urine samples after all of the study-related testing has been completed. We would like to use 
these samples for future research studies. If you agree to this use of your samples, we will ask 
you to initial the end of this form. 
If you do not agree to have your left over samples stored you can still be in this study. If you 
agree to store your samples but change your mind later, you can contact the study staff listed on 
this form. We will then destroy your samples. If you agree, your left over samples will be stored 
indefinitely [insert local guidelines]. Any future use or the ability to store your samples longer 
needs to be reviewed and approved by the NIH and local authorities. If these studies involve 
other laboratories, we will need approval from your local authorities to store or transfer them 
elsewhere. Your left over samples will not be sold or used for commercial reasons. 
RESEARCH-RELATED INJURY: 
The study staff will ask you questions about your health at every study visit. If you have any 
health problems between visits, please contact the study staff. If you have a medical emergency 
that requires immediate care, [insert site-specific instructions]. [Sites to specify institutional 
policy:] If you are injured as a result of being in this study, 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 for monetary compensation or other forms of compensation for such injuries either 
through this institution or the NIH. You do not give up any legal rights by signing this consent 
form. 
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26 July 2017 

PROBLEMS or QUESTIONS: 
For questions about this study or a research-related injury, contact: 
• 
[site insert name of the investigator or other study staff} 
• 
[site insert telephone number and physical address of above J 
For questions about your rights as a research subject, contact: 
• 
[site insert name or title of person on the Institutional Review Board (!RB) or other 
organization appropriate for the site J 
• 
[site insert telephone number and physical address of above] 
HPTN 074, Final Version 2.0 
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SIGNATURE PAGE: SAMPLE RE-ENROLLMENT CONSENT FOR INDEX 
HPTN 074: Integrated treatment and prevention for people who inject drugs: A vanguard 
study for a network-based randomized HIV prevention trial comparing an integrated 
intervention including supported antiretroviral therapy to the standard of care 
Final Version 2.0, 26 July 2017 
If you have read this informed consent, or have had it read and explained to you, and understand 
the information, and you voluntarily agree to emoll into this study, please sign your name or 
make your mark below. 
Please carefully read the statements below (or have them read to you) and think about your choice. 
No matter what you decide it will not affect whether you can be in the research study, or your 
routine health care. 
____ I agree to have samples of my blood used for future testing related to HIV infection. 
____ I agree to have samples of my urine used for future testing related to HIV infection. 
____ I do not agree to have samples of my blood stored and used for future testing related to 
HIV infection. 
____ I do not agree to have samples of my urine stored and used for future testing related to 
HIV infection. 
If you have read this informed consent, or have had it read and explained to you, and understand 
the information, and you voluntarily agree to emoll into this study, please sign your name or 
make your mark below. 
Participant's Name (print) 
Participant's Signature or Thumbprint and Date 
For staff: I have explained the purpose of the screening to the volunteer and have answered all 
of his/her questions. To the best of my knowledge, he/she understands the purpose, procedures, 
risks and benefits of this study. 
Study Staff Conducting 
Consent Discussion (print) 
Study Staff Signature and Date 
For witnesses for illiterate volunteers: I attest that the information contained in this written 
consent form has been read and explained to the participant. He/she appears to understand the 
HPTN 074, Final Version 2.0 
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26 July 2017 

purpose, procedures, risks and benefits of the study and has voluntarily accepted to participate in 
this study. 
For those placing thumbprint only: I attest that the participant who states that his/her name is 
___________ has placed his/her thumbprint on this consent form of his/her 
own free will on this day --------
Witness' Name (print) 
Witness's Signature and Date 
HPTN 074, Final Version 2.0 
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26 July 2017