Enhancing Recruitment, Linkage to Care and Treatment for HIV-Infected Men Who Have Sex With Men (MSM) in the United States
Phase: NA
Conditions: HIV
Sponsor: HIV Prevention Trials Network

HPTN 078 
Enhancing Recruitment, Linkage to Care and Treatment for HIV-Infected Men Who Have 
Sex with Men (MSM) in the United States 
 
 
 
A Study of the HIV Prevention Trials Network (HPTN) 
 
 
 
Sponsored by: 
Division of AIDS (DAIDS) 
United States (US) National Institute of Allergy and Infectious Diseases (NIAID) 
US National Institute of Mental Health (NIMH) 
US National Institute on Drug Abuse (NIDA) 
US National Institutes of Health (NIH) 
 
 
 
Protocol Chair: 
Chris Beyrer, MD, MPH 
Johns Hopkins University 
Baltimore, MD, USA 
 
Protocol Co-Chair 
Robert H. Remien, PhD 
Columbia University 
New York, NY, USA 
 
DAIDS Document ID: 11995 
 
 
Final Version 2.0 
July 3, 2017 
 

 
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Enhancing Recruitment, Linkage to Care and Treatment for HIV-Infected Men Who Have Sex 
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TABLE OF CONTENTS 
 
TABLE OF CONTENTS .............................................................................................................. ii 
LIST OF ABBREVIATIONS AND ACRONYMS .................................................................... iv 
PROTOCOL TEAM ROSTER ................................................................................................... vi 
INVESTIGATOR SIGNATURE PAGE ..................................................................................... ix 
SCHEMA ........................................................................................................................................ x 
OVERVIEW OF STUDY DESIGN........................................................................................... xiii 
1.0 
INTRODUCTION ............................................................................................................ 1 
1.1 
Background and Prior Research ............................................................................ 1 
1.2 
Rationale ................................................................................................................ 3 
2.0 
STUDY OBJECTIVES AND DESIGN ........................................................................... 5 
2.1 
Primary Objectives ................................................................................................ 5 
2.2 
Secondary Objectives ............................................................................................ 5 
2.3 
Exploratory Objectives .......................................................................................... 5 
2.4 
Modeling Objective ............................................................................................... 6 
2.5 
Study Design .......................................................................................................... 6 
3.0 
STUDY POPULATION ................................................................................................... 7 
3.1 
Inclusion Criteria ................................................................................................... 7 
3.2 
Exclusion Criteria .................................................................................................. 7 
3.3 
Recruitment Process .............................................................................................. 8 
3.4 
Co-Enrollment Guidelines ..................................................................................... 8 
3.5 
Participant Retention .............................................................................................. 8 
3.6 
Participant Withdrawal and Early Termination ..................................................... 8 
3.7 
Study Sites ............................................................................................................. 9 
4.0 
STUDY INTERVENTION ............................................................................................. 10 
4.1 
Linkage to Care and ART Initiation (MyLife, MyChoices, MyCare (Step 1)) ... 13 
4.2 
Adherence Counseling (MyCare (Step 2)) .......................................................... 14 
4.3 
Communication, Retention and Follow-up (MyHealth) ...................................... 14 
5.0 
STUDY PROCEDURES ................................................................................................ 15 
5.1 
Screening Visits ................................................................................................... 15 
5.2 
Enrollment Visit (M0) ......................................................................................... 16 
5.3 
Tailored Communication ..................................................................................... 16 
5.4 
Monthly Contact .................................................................................................. 16 
5.5 
Follow-up Visits (M3, M6, M9, M12, M18) ....................................................... 16 
5.6 
Final Visit (M24) ................................................................................................. 17 
5.7 
Data Collection on ART Initiation and Visit Attendance .................................... 17 
5.8 
Questionnaires ..................................................................................................... 17 
6.0 
SAFETY MONITORING AND ADVERSE EVENT REPORTING ......................... 19 
6.1 
Safety Monitoring ................................................................................................ 19 
6.2 
Social Impact Reporting ...................................................................................... 19 

 
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7.0 
STATISTICAL CONSIDERATIONS .......................................................................... 20 
7.1 
Review of Study Design ...................................................................................... 20 
7.2 
Endpoints ............................................................................................................. 20 
7.3 
Accrual, Follow-up and Sample Size................................................................... 22 
7.4 
Random Assignment ............................................................................................ 23 
7.5 
Blinding ............................................................................................................... 23 
7.6 
Data Analysis ....................................................................................................... 23 
8.0 
HUMAN SUBJECTS CONSIDERATIONS ................................................................ 26 
8.1 
Ethical Review ..................................................................................................... 26 
8.2 
Informed Consent ................................................................................................ 26 
8.3 
Incentives ............................................................................................................. 26 
8.4 
Confidentiality ..................................................................................................... 26 
8.5 
Communicable Disease Reporting Requirements ............................................... 27 
8.6 
Study Discontinuation.......................................................................................... 27 
9.0 
LABORATORY SPECIMENS AND BIOHARDS CONTAINMENT ...................... 28 
9.1 
Local Laboratory Specimens ............................................................................... 28 
9.2 
LC Specimens ...................................................................................................... 28 
9.3 
Quality Control and Quality Assurance Procedures ............................................ 29 
9.4 
QC for HIV Diagnostic Testing ........................................................................... 29 
9.5 
Phylogenetic Analysis .......................................................................................... 29 
9.6 
Specimen Storage and Possible Future Research Testing ................................... 29 
9.7 
Biohazard Containment ....................................................................................... 29 
9.8 
Resistance Testing at Local Laboratories. ........................................................... 29 
10.0 
MODELING COMPONENT ........................................................................................ 30 
10.1 
Background and Prior Research .......................................................................... 30 
10.2 
Rationale .............................................................................................................. 30 
10.3 
Model Population and Setting .............................................................................. 31 
10.4 
Main Model Outcomes ........................................................................................ 31 
10.5 
Modeling Stages .................................................................................................. 31 
11.0 
ADMINISTRATIVE PROCEDURES .......................................................................... 40 
11.1 
Protocol Registration ........................................................................................... 40 
11.2 
Study Activation .................................................................................................. 40 
11.3 
Study Coordination .............................................................................................. 40 
11.4 
Study Monitoring ................................................................................................. 41 
11.5 
Protocol Compliance............................................................................................ 41 
11.6 
Investigator’s Records ......................................................................................... 41 
11.7 
Use of Information and Publications ................................................................... 42 
12.0 
REFERENCES ................................................................................................................ 43 
Appendix I: Schedule of Study Visits, Evaluations and Procedures ....................................... 52 
Appendix II: Schedule of Questionnaire Domain Administration .......................................... 53 
Appendix III: Informed Consent Templates ............................................................................. 54 
Appendix IV: Tailored Case Management Intervention Components ................................... 79 
 
 
 

 
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LIST OF ABBREVIATIONS AND ACRONYMS 
ACA 
 
Affordable Care Act 
AIDS  
Acquired Immunodeficiency Syndrome 
ART 
 
antiretroviral therapy 
ARV 
 
antiretroviral drug 
CAB 
 
Community Advisory Board 
CCM  
Chronic Care Model 
CD4 
Cluster of Differentiation 4 (a glycoprotein found on the surface of T-helper cells that 
serves as a receptor), in the context of this protocol, CD4+ refers to cells with this 
glycoprotein) 
CDC 
 
Centers for Disease Control and Prevention 
CFR 
 
Code of Federal Regulations 
CI 
 
confidence interval 
CLIA  
Continuous Laboratory Improvement Act 
CM 
 
Case Manager 
CRF 
 
case report form 
DAIDS  
Division of AIDS 
DC-RDS 
deep-chain respondent driven sampling 
DR 
 
direct recruitment 
EC 
 
Ethics Committee 
FDA 
 
(United States) Food and Drug Administration 
HCV 
 
Hepatitis C virus 
HHS 
 
(United States Department of) Health and Human Services 
HIV 
 
Human Immunodeficiency Virus 
HPTN  
HIV Prevention Trials Network 
ID 
 
identification 
ICF 
 
informed consent forms 
ICH 
 
International Council for Harmonisation 
IoR 
 
Investigator of Record 
IRB 
 
Institutional Review Board 
LC 
 
(HPTN) Laboratory Center 
LDMS  
Laboratory Data Management System 
LGBT  
Lesbian, gay, bisexual, and transgender 
LOC 
 
(HPTN) Leadership and Operations Center 
MMWR 
Morbidity and Mortality Weekly Report 
MRC  
(HPTN) Manuscript Review Committee 
MSM  
Men Who Have Sex with Men  
NHBS  
National HIV Behavioral Surveillance 
NIAID  
(United States) National Institute of Allergy and Infectious Diseases 
NIDA  
(United States) National Institute on Drug Addiction 
NIH 
 
(United States) National Institutes of Health 
NSFG  
National Survey of Family Growth 
NIMH  
(United States) National Institute of Mental Health 
OHRP  
Office for Human Research Protections 
PAF 
 
population attributable fraction 
PEP 
 
post-exposure prophylaxis 

 
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LIST OF ABBREVIATIONS AND ACRONYMS (continued) 
PF 
 
preventable fraction 
PrEP 
 
pre-exposure prophylaxis 
PRO 
 
(DAIDS) Protocol Registration Office 
PSRC  
(DAIDS) Prevention Science Review Committee 
PUMA  
Prevention Umbrella for MSM in the Americas 
QA 
 
quality assurance 
QC 
 
quality control 
RDS 
 
respondent driven sampling 
RSC 
 
Regulatory Support Center 
SAMISS 
Substance Abuse/Mental Illness Symptoms Screener 
SDMC  
(HPTN) Statistical and Data Management Center 
SES 
 
socio-economic status 
SMC 
 
(HPTN) Study Monitoring Committee 
SOC 
 
standard of care 
SRC 
 
(HPTN) Scientific Review Committee 
SSP 
 
Study Specific Procedures 
STI 
 
Sexually Transmitted Infection 
TasP 
 
Treatment as Prevention 
UAI 
 
unprotected anal intercourse 
US 
 
United States 
VL 
 
viral load 
 

 
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PROTOCOL TEAM ROSTER 
Adeola Adeyeye, MD, MPA 
Medical Officer  
Prevention Science Program, DAIDS, NIAID, 
NIH 
Room 8B36 MSC 9832, 5601 Fishers Lane 
Rockville, MD 20852 
Phone: 240-669-5005 
Email: adeyeyeao@niaid.nih.gov 
 
Stefan Baral, MD, MPH, FRCPC 
Associate Professor 
Department of Epidemiology 
Director, Key Populations Program 
Center for Public Health and Human Rights 
John Hopkins School of Public Health 
615 N. Wolfe Street, Room E7146 
Baltimore, MD  21205  
Phone: 410-502-8975 
Email: sbaral@jhsph.edu 
 
Chris Beyrer, MD, MPH 
Professor of Epidemiology, International Health, 
and Health, Behavior and Society 
Director, Center for Public Health and Human 
Rights 
Associate Director, Johns Hopkins Center for 
AIDS Research  
Johns Hopkins University 
615 N. Wolfe St, E 7152 
Baltimore, MD, 21205 
Phone: 410 614 5247 
Email: cbeyrer@jhu.edu 
 
Marie-Claude Boily, PhD  
Professor of Mathematical Epidemiology 
Department of Infectious Diseases 
Epidemiology 
School of Public Health 
Imperial College London 
Norfolk Place, St-Mary’s Campus 
London, UK W2 1PG 
Phone: 44-0-207-594-3263 
Email: mc.boily@ic.ac.uk 
 
Marcus D. Bolton, MEd 
Sr. Community Programs Manager  
HPTN LOC, FHI 360 
359 Blackwell St., Durham, NC 27701 
Phone: 919-544-7040, Ex. 11678 
Email: mbolton@fhi360.org 
 
Vanessa Cummings, B.S, MT (ASCP) 
HPTN Laboratory Center QA/QC 
Representative 
Johns Hopkins Univ. School of Medicine 
Pathology Building, Room 311 
600 North Wolfe Street 
Baltimore, MD 21287 
Phone: 410-614-0479 
Email: vcummin1@jhmi.edu 
 
Carlos Del Rio, MD 
Emory Center for AIDS Research 
Ponce de Leon Center 
341 Ponce de Leon Avenue, Northeast 
Atlanta, GA 30308 
Phone: 404-727-1557 
Email: cdelrio@emory.edu 
 
Dobromir Dimitrov, PhD 
Senior Staff Scientist 
SCHARP-FHCRC 
1100 Fairview Ave. N, M2-C200 
PO Box 19024 
Seattle, WA 98109 
Phone: 206-667-1933 
Email: dobromir@scharp.org 
 
Lynda Emel, PhD 
Associate Director HPTN SDMC 
SCHARP-FHCRC 
1100 Fairview Ave. N, E3-129 
PO Box 19024 
Seattle, WA 98109 
Phone: 206-667-5803  
Email: lemel@scharp.org 

 
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PROTOCOL TEAM ROSTER (Continued) 
Susan Eshleman, MD, PhD 
HPTN Laboratory Center Virologist 
Johns Hopkins Univ. School of Medicine 
720 Rutland Ave. 
Ross Building, Room 646 
Baltimore, MD, 21205 
Phone: 410-614-4734 
Email: seshlem@jhmi.edu 
 
Jason Farley, PhD, MPH, ANP-BC, FAAN, 
AACRN 
Associate Professor 
Co-Director, Johns Hopkins Center for AIDS 
Research 
Department of Community-Public Health 
Johns Hopkins University School of Nursing 
525 N. Wolfe Street 
Baltimore, MD 21205 
Phone: 410-502-7563 
Email: jfarley1@jhu.edu 
 
Theresa Gamble, PhD 
Scientist II 
HPTN LOC, FHI 360 
359 Blackwell St. Durham, NC 27701 
Phone: 919-544-7040, Ex. 11350 
Email: tgamble@fhi360.org 
 
James Hughes, PhD 
Professor of Biostatistics 
University of Washington 
Mailstop 357232 
Seattle, WA 98195  
Phone: 206-616-2721 
Email: jphughes@u.washington.edu 
 
Risha Irvin, MD, MPH 
Assistant Professor 
Division of Infectious Diseases 
Johns Hopkins University  
Fisher Center for Environmental Infectious 
Diseases 
725 N Wolfe Street, Room 218A 
Baltimore, MD 21205 
Phone: 443-287-4843 
Email: rirvin1@jhmi.edu 
 
Anna LeViere, MPH 
Clinical Research Manager 
HPTN LOC, FHI 360 
359 Blackwell St. Durham, NC 27701 
Phone: 919-544-7040, Ex. 11585 
Email: aleviere@fhi360.org 
 
Kenneth Mayer, MD 
Infectious Disease Attending and Director of HIV 
Prevention Research 
Beth Israel Deaconess Medical Center 
Professor of Medicine 
Harvard Medical School 
Medical Research Director 
The Fenway Institute, Fenway Health 
Boston, MA 02215 
Phone: 617-927-6087 
Email: Khmayer@gmail.com 
 
Laura A. McKinstry, MPH 
Clinical Data Manager 
Statistical Center for HIV/AIDS Research and 
Prevention (SCHARP) 
Vaccine and Infectious Disease Division (VIDD) 
1100 Fairview Avenue North E3-129 
PO Box 19024 
Seattle, WA 98109 
Phone: 206.667.7322 
Email: lamckins@scharp.org 
 
 
 
 

 
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PROTOCOL TEAM ROSTER (Continued) 
Greg Millett, MPH 
Vice President and Director, Public Policy 
amfAR 
1150 17th Street, NW 
Suite 406 
Washington, DC 20036 
Phone: 202-331-8600 
Email: Greg.Millett@amfar.org 
 
Kate Mitchell, PhD 
Research Fellow 
Imperial College London 
Department of Infectious Diseases 
Epidemiology 
School of Public Health 
Imperial College London 
Norfolk Place, St-Mary’s Campus 
London, UK W2 1PG 
Email: kate.mitchell@imperial.ac.uk 
 
E. Turner Overton, MD 
University of Alabama at Birmingham  
1530 3rd Ave S 
CCB Rm 330A 
Birmingham, AL 35294 
Phone: 205-966-2373 
Email: toverton@uab.edu 
 
Robert H. Remien, PhD 
Professor of Clinical Psychology (in Psychiatry) 
Director, HIV Center for Clinical and 
Behavioral Studies 
Associate Director, Division of Gender, 
Sexuality and Health, NY State Psychiatric 
Institute and Columbia University 
722 West 168th Street, Floor R3, Room 308 
New York, NY 10032 
Phone: 646-774-6933 
Email: rhr1@cumc.columbia.edu 
 
 Paul Richardson, MSc 
Senior QA/QC Coordinator HPTN LC 
Johns Hopkins Univ. Dept. of Pathology 
Pathology Building, Room 306 
600 North Wolfe Street 
Baltimore, MD 21287 
Phone: 410-502-0435 
Email: pricha18@jhmi.edu 
 
Ethan Wilson 
Statistical Research Associate 
Statistical Center for HIV/AIDS Research and 
Prevention (SCHARP) 
Fred Hutchinson Cancer Research Center 
1100 Fairview Ave. N., Mail Stop M2-C200 
Seattle, WA 98109  
Phone: 206.667.7207 
Email: eawilson@fredhutch.org 
 
Patrick Wilson, PhD 
Associate Professor of Sociomedical Sciences 
Columbia University 
Mailman School of Public Health 
722 W. 168th Street, 5th Floor 
New York, NY 10032 
Phone: 212-305-1852 
Email: pw2219@columbia.edu 
 
 
 
 

 
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Version 2.0 / July 3, 2017 
INVESTIGATOR SIGNATURE PAGE 
 
A Study of the HIV Prevention Trials Network (HPTN) 
 
 
Sponsored by: 
Division of AIDS (DAIDS) 
United States (US) National Institute of Allergy and Infectious Diseases (NIAID) 
US National Institute of Mental Health (NIMH) 
US National Institute on Drug Abuse (NIDA) 
US National Institutes of Health (NIH) 
 
I, the Investigator of Record (IoR), agree to conduct this study in full accordance with the provisions of 
this protocol, including all appendices, as well as in compliance with United States (US) Health and 
Human Service regulations (45 Code of Federal Regulations [CFR] 46); applicable US Food and Drug 
Administration (FDA) regulations; standards of the International Conference on Harmonisation (ICH) 
Good Clinical Practices (E6); Institutional Review Board (IRB)/Ethics Committee (EC) 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 agree to maintain all study 
documentation for a minimum of three years after submission of the site’s final Financial Status Report to 
the Division of AIDS (DAIDS), unless otherwise specified by DAIDS or the HIV Prevention Trials 
Network (HPTN) Leadership and Operations Center (LOC). Publication of the results of this study will 
be governed by HPTN policies. Any presentation, abstract, or manuscript will be submitted to the HPTN 
Manuscript Review Committee (MRC) and the Division of AIDS (DAIDS) for review prior to 
submission. 
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  
 
 

 
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SCHEMA 
Purpose: 
The purpose of this study is to develop and assess the efficacy of an integrated strategy 
that includes feasible and scalable interventions to identify, recruit, link to care, retain 
in care, attain, and maintain viral suppression among HIV-infected men who have sex 
with men (MSM) in the United States (US). 
Design: 
This study will use deep-chain respondent driven sampling (DC-RDS) and direct 
recruitment (DR) to identify and recruit HIV-infected MSM who are not virally 
suppressed. A subset of these men will be enrolled into one of two study arms. The 
intervention arm will provide a Case Manager (CM) intervention package designed to 
enhance linkage to care, antiretroviral treatment (ART) initiation, treatment adherence 
and retention in care. The control arm will provide the standard of care (SOC) for 
linkage to care, initiation of ART, treatment adherence and retention in care. The 
primary outcome of the study is viral suppression, 24 months after enrollment. 
Phylogenetic methods will be used to evaluate the relationship between viruses in study 
participants. Mathematical modeling will be performed using demographic, behavioral, 
and clinical data generated from this study and other sources to estimate the 
population-level impact of the CM intervention on HIV incidence and to estimate the 
level of identification, linkage, ART coverage and viral suppression that would be 
required to achieve a substantial reduction in HIV incidence among MSM in the US 
settings where the study is conducted. 
Intervention: 
The study intervention [MyLife, MyChoices, MyCare (Step 1), MyCare (Step 2), and 
MyHealth] is a program designed to enhance linkage, ART initiation, adherence and 
retention in care for MSM diagnosed with HIV. It will be administered by a trained CM 
and will include health care and supportive services navigation, adherence counseling, 
and tailored support for care engagement and treatment adherence. 
Population: 
HIV-infected and HIV-uninfected adolescent (> 16 years old) and adult MSM, 
including transgender women, in selected US cities will be screened for this study. 
Enrollment will be limited to HIV-infected men who are not virally suppressed.  
Study Size: 
Approximately 2700 MSM will be identified and recruited using a DC-RDS and DR 
strategies in four cities; 356 HIV-infected MSM who are not virally suppressed will be 
randomized (1:1) to the CM intervention and SOC control study arms of the study.   
Study Regimen: There are no specific drug regimens under investigation in this study. 
Study Duration: The overall study duration is 60 months: 24 months for DC-RDS recruitment and 
enrollment; 24 months of follow-up for participants who are randomized into the CM 
intervention and SOC control study arms; and approximately 12 months after the 
completion of participant study visits for data analyses, phylogenetic assessments and 
modeling. 
Study Sites: 
Alabama Vaccine Research Center (Birmingham, AL); Fenway Health (Boston, MA); 
Johns Hopkins Adult AIDS (Baltimore, MD); and the Ponce de Leon Ctr (Atlanta, GA) 

 
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SCHEMA (Continued) 
Primary Objectives: 
• 
Assess the ability of DC-RDS to identify and recruit HIV-infected MSM in the US who are 
not virally suppressed. 
• 
Compare the efficacy of the two study arms (CM intervention vs. SOC control) in achieving 
durable viral suppression (defined as HIV VL < 200 copies/ml) 24 months after enrollment. 
Secondary Objectives:  
• 
Assess HIV prevalence and the proportion of HIV-infected men who are virally suppressed 
by comparing early wave (approximately 1-6) vs. later (deep) wave (approximately 7-12) 
DC-RDS participants. 
• 
Compare the proportion of men in the two study arms who are virally suppressed at 3, 6, 9, 
12 and 18 months after enrollment.  
• 
Assess linkage to care and retention in care in the two study arms by comparing the 
1) proportion of men with at least one care visit within 30 days of enrollment, 2) time to the 
first care visit, and 3) proportion of men with at least four care visits (one in each six-month 
interval, with at least 60 days between these visits) over the 24 months after enrollment. 
• 
Compare the proportion of men with HIV-hepatitis C virus (HCV) co-infection in the two 
study arms who are linked to care (defined as one care visit within 30 days of enrollment) and 
who achieve (HIV) viral suppression 24 months after enrollment. 
• 
Examine the association between baseline behavioral, socio-demographic, and clinical 
characteristics (including syphilis) of HIV-infected men and viral suppression status for all 
men screened via DC-RDS and for the men in the two study arms 24 months after enrollment. 
• 
Compare the two study arms with respect to ART adherence at 24 months after enrollment 
and changes in sexual risk behavior, health care utilization, stigma, substance use and mental 
health from baseline to 24 months after enrollment. 
• 
Evaluate the feasibility and scalability of the CM intervention by measuring the number of 
intervention contacts (e.g., text message, email, phone, in person) per participant over 24 
months. 
• 
Compare the experience of linkage to and ongoing HIV care among participants in the two 
study arms by conducting and analyzing exit interviews with participants and CMs.  
 
 

 
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SCHEMA (Continued) 
Exploratory Objectives: 
• 
Use phylogenetic methods to evaluate the relationship between HIV strains in study 
participants. Men who were likely to have been recently infected at enrollment will be 
identified using a multi-assay algorithm. Evaluate the relationship of behavioral, socio-
demographic, and clinical characteristics to viral networks (e.g., clusters, linked infections). 
• 
Use laboratory assessments to characterize the study cohort and to evaluate the impacts of 
study interventions. These assessments may include analysis of HIV drug resistance and 
antiretroviral (ARV) drug use. Additional analyses may be conducted to analyze HCV 
strains, including phylogenetic analysis of HCV. Samples from this study may also be used to 
evaluate the performance of assays related to HIV and HCV infection.   
Modeling Objective: 
• 
Develop, calibrate, and use a mathematical model of HIV transmission among MSM in the 
US to assess the short and long-term population-level impact of the study strategy, and its 
independent CM intervention components (e.g., HIV testing, ART uptake, retention in care 
and viral suppression), on HIV incidence and to estimate the level of viral suppression 
required to reduce HIV incidence in the MSM community by 10%, 20%, 30%, and 50% over 
2, 5 and 10 years, and the likelihood of and time to elimination. 
 

 
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1.0 
INTRODUCTION 
1.1 
Background and Prior Research 
The United States (US) is currently undergoing a widespread and severe HIV epidemic among 
gay, bisexual, and other men who have sex with men (MSM), which has been underway since at 
least 2003.1 In their most recent report, the US Centers for Disease Control and Prevention (CDC) 
reported that 62% of all new infections in the US were among MSM, a group who represent at 
most 2-4% of US adult men, and 1-2% of all adults.2 The US epidemic is strikingly concentrated 
in MSM populations—the only group among whom HIV infections burdens were rising in 2011. 
This epidemic is characterized by marked racial and ethnic disparities, with the highest HIV 
burdens among Black MSM, followed by Latino MSM.3 The US MSM epidemic is marked by 
much higher incidence densities among the youngest MSM, those aged 13-24.4 HPTN 061, an 
incidence study in Black MSM, found a 3% incidence rate overall in this population, with a 5.9% 
incidence rate in those 18 to 29 years old.5 There is also a marked geographic component to the 
US epidemic among MSM, with the highest rates of incident HIV infection in Black, Latino, and 
White MSM found in the South. These health disparities are not limited to HIV prevalence and 
incidence burdens, but rather are also seen in lower rates of regular HIV testing, in lack of 
awareness of HIV status, in late presentation for HIV care, in poor adherence to antiretroviral 
therapy (ART), and in the failure to achieve viral suppression.3 
The continuum of care, or cascade of care, has been useful to help characterize HIV burdens and 
understand gaps in HIV responses. The CDC estimate for the US population as a whole is that of 
the 1.2 million estimated persons living with HIV infection, 1 in 7 do not know they are living 
with HIV, only 4 in 10 are in care, and only 3 in 10 have sustained viral suppression.6 African 
American MSM do less well across each step of this continuum, with an overall outcome of being 
half as likely to be fully virally suppressed if living with HIV infection compared to men of all 
other racial/ethnic categories.3 To address these health disparities, and to improve responses for 
gay and other MSM it is critical to reach higher proportions of HIV-infected MSM who are not 
virally suppressed, enhance their linkage to care, and increase the proportion of these men who 
can achieve, and maintain, HIV suppression. Intervention strategies and packages that can 
achieve these goals must be acceptable, feasible and scalable. This study will attempt to address 
two critical steps in the continuum of care for MSM in the US: enhanced outreach and 
recruitment of MSM living with HIV infection but not virally suppressed through deep-chain 
respondent driven sampling (DC-RDS); and enhanced treatment and care to increase the 
proportion of MSM who achieve sustained viral suppression through a case management (CM) 
intervention. 
1.1.1 
The Need to Enhance Recruitment  
The US CDC estimates that 14% of Americans living with HIV infection remain undiagnosed 
and unaware of their HIV infection status.6 An additional 60% of those living with HIV are not 
currently in HIV care6—meaning that almost 70% of persons in the US with HIV infection are 
not currently on treatment or virally suppressed. This is a challenge for the health of these 
individuals, but also represents a pool of untreated HIV infections that drive ongoing 
transmission. Despite active testing and outreach campaigns in many jurisdictions, uptake of HIV 
testing remains too low in many communities, including among MSM, and is particularly 
challenging in minority communities and among younger age groups of MSM. Black MSM are 
nearly 5 fold less likely to have had a recent HIV test compared to White MSM in the US.3 
Active recruitment, and the use of innovative techniques for recruitment, is an urgent HIV 
research priority for controlling HIV infection among MSM. 

 
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Respondent driven sampling (RDS) has demonstrated effectiveness in reaching hard to sample 
populations, including among minority and low socio-economic status (SES) MSM in the US. 
Long Chain RDS, where referral chains are maintained over long waves of recruitment, is an 
innovative approach that has the potential to reach more hidden, marginalized and HIV-untested, 
unlinked, and not virally suppressed MSM living with HIV infection.   
1.1.2 
Deep-Chain Respondent Driven Sampling (DC-RDS) 
RDS relies on the identification and enumeration of a discrete number of “seeds” who are 
incentivized to refer members of their social or sexual networks, who then repeat the process, 
generating successive waves of recruitment. RDS has been used successfully in the US and 
abroad to recruit marginalized MSM. RDS studies have reported success in recruiting MSM who 
have very low incomes, are homeless, men engaged in sex work, non-gay-identified and/or 
bisexually active men.7, 8 Moreover, studies that have used RDS to recruit black MSM in the US 
consistently find substantial proportions of HIV infected but untreated MSM in each respective 
study.8-10 These studies obtained fairly similar samples despite varying demographics and risk 
profiles among initial seeds across the studies. This suggests that RDS can be a useful recruitment 
tool for research on marginalized populations and a method that has demonstrated considerable 
success in doing so in the US context, which is the focus of the proposed HPTN 078 study. 
DC-RDS, also referred to as long chain RDS, where recruitment chains continue to propagate 
beyond the standard sixth wave of recruitment, has shown the potential to reach the most 
marginalized subsets of study participants, hence our interest in using this approach as a 
recruitment tool.11, 12 A novel secondary aim of the study will be to compare early (approximately 
wave 1-6) versus later (approximately wave 7-12) recruitment waves to assess the ability of 
DC-RDS to identify HIV-infected MSM who are not virally suppressed in the selected cities. 
1.1.3 
Evidence for Effectiveness of Early ART 
There is strong biological plausibility that effective early ART can reduce sexual transmission of 
HIV between MSM by decreasing HIV viral load and, hence, infectiousness. Ecological evidence 
from San Francisco suggests that early ART initiation and high levels of treatment coverage may 
be associated with decreases in new HIV infections among MSM at population levels.13 However, 
the ecological and other epidemiologic data are mixed, and recent reports from the United 
Kingdom and from France suggest rising rates of HIV infection in MSM despite high ART 
coverage of HIV-infected men in care.14, 15 
In HPTN 05216, early ART initiation was confirmed to have high efficacy in preventing 
transmission among HIV serodiscordant couples. However, only 37 male-male discordant 
couples were recruited into HPTN 052 – with only one male-male couple in the US. Furthermore, 
recent epidemiologic and modeling data suggest that, in many populations of MSM, primary 
partnerships account for only a minority (30-35% in the PUMA [Prevention Umbrella for MSM 
in the Americas] modeling estimates) of HIV transmissions, with the majority occurring between 
non-primary sexual partners.17 Thus, the population-level effectiveness of ART as HIV 
prevention among MSM is unknown and may not be measured most effectively through 
approaches based on discordant couples. Enhanced treatment of HIV-infected men within 
networks and at community levels may be important in reducing the spread of the epidemic 
among MSM. 

 
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1.1.4 
Engagement in Care among MSM in the US 
As there is a dearth of research on engagement-in-care strategies specific to the MSM population, 
challenges remain particularly prevalent among minority MSM in the US. Health care system 
navigation may offer a promising engagement-in-care strategy for MSM.18 Among young MSM 
of color there is a particular need for strengthened and tailored strategies for retention in care with 
links to social supportive services due to the multiple challenges in this group (e.g., access to 
health care, poverty, unemployment, stigma).19-21 
1.1.5 
Interventions to Optimize Retention and Adherence  
It is established that a combination of components and strategies best addresses challenges to HIV 
treatment and care; thus, the intervention package for linkage, retention and treatment adherence, 
with case management at its core, will draw from several evidence-based interventions.22-25 The 
Care Coordination Model as outlined by Craig et al in 201126 has been shown to optimize linkage 
to and retention in care.27-29 With the advent of the Affordable Care Act (ACA), and the 
uncertainty about the continuation of the ACA in some states, care coordination must include 
negotiating affordable care options available to study participants.  
Behavioral interventions with the strongest beneficial impact on treatment adherence are 
cognitive-behavioral counseling interventions with a primary focus on treatment adherence.30-32 
In these sessions, patients are provided with tailored counseling to focus on problem solving and 
communication to address risk reduction, HIV disclosure, social support for adherence, and 
barriers to ART adherence.32-34  
Use of mobile technology to provide supportive reminders for medication adherence has also 
been shown to be effective in enhancing retention and adherence.35-37 Specifically, a tailored text-
messaging strategy has recently shown promise with MSM.38 
1.2 
Rationale 
The purpose of this study is to develop and assess the efficacy of an integrated strategy that 
includes feasible and scalable interventions to identify, recruit, link to care, retain in care, and 
attain viral suppression among HIV-infected MSM in the US. This research is important since 
MSM are the most disproportionately affected population for HIV in the US, and there is an 
urgent need to develop innovative strategies to address this health disparity across the continuum 
of care. Sex between men accounted for an estimated 62% of newly identified HIV infections in 
the US in 2012, according to the US CDC, making enhancement of the effectiveness of 
engagement in care and treatment for MSM of primary importance for controlling the US 
domestic HIV epidemic. This study is focused on US urban MSM living with HIV infection who 
are not successfully virally suppressed. All MSM identified as HIV-infected and not virally 
suppressed will be offered linkage to care and immediate ART—an option not available in many 
other settings with severe epidemics among MSM. Since current HPTN sites, and concentrations 
of MSM in the US are primarily urban, this study will focus on urban MSM populations but may 
yield insights of relevance to improving outcomes for sub-urban and rural MSM in the US. 
The recruitment component of this study will help refine the designs of future research and 
program efforts to enhance outreach, increase testing uptake and increase linkage for 
HIV-infected MSM who are not virally suppressed. This population includes all MSM with 
non-suppressed HIV viral loads, including men who are HIV-infected and not previously 
diagnosed, men who are aware of their HIV infection but not currently linked to care, and men 

 
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who may have been in care, or are currently in care, but are not successfully virally suppressed. 
Men in all of these groups who meet enrollment criteria will be offered enrollment in the 
enhanced case management intervention for linkage, retention, treatment initiation and 
medication adherence. DC-RDS will be assessed for its efficacy in reaching more hidden, 
marginalized, previously undiagnosed, and HIV-infected and not virally suppressed MSM. Future 
trials of enhanced treatment interventions, and of Treatment as Prevention (TasP) at community 
levels among MSM, will depend on the ability to reach these challenging subsets of MSM and to 
link them to care and treatment. 
Despite clear evidence of treatment as prevention and the impact of ART on the quality and 
quantity of life, current data on success across the HIV treatment cascade demonstrates a need to 
improve both access to care and treatment adherence. Interventions to ensure MSM living with 
HIV and not virally suppressed are linked to and remain in care to achieve virologic control are 
limited and have had mixed results.39, 40 Case management models, in which skilled providers 
facilitate HIV treatment plans to ensure appropriate and timely care are given, have been shown 
to be safe and improve treatment outcomes.41-43 Presently, these interventions are limited to key 
affected populations and there is little evidence to describe the specific aspects of a case 
management model for linkage to care. Many studies utilizing case management models have 
demonstrated substantial improvements in disease outcomes, including HIV. 
The Chronic Care Model (CCM) identifies essential elements of a health care system that 
encourage high-quality chronic disease care in a bundled approach.41, 44-46 These elements provide 
the conceptual framework for the CM intervention, which is an approach to improve linkage, 
retention and controlled viremia in HIV-infected MSM. Tailoring of a culturally-sound case 
management model for MSM living with HIV and not virally suppressed may improve linkage, 
access, and retention in care and ultimately result in better sustained virologic control. 
The use of modeling is critical to assess the potential impact of increases in the proportion of 
HIV-infected MSM who are successfully virally suppressed on HIV incidence in MSM networks 
and communities. Since this study will have an endpoint of viral suppression among HIV-infected 
MSM, modeling will be used to estimate the potential impact of the proposed CM intervention 
strategy, should it be successful, on ongoing sexual HIV transmission in selected urban US MSM 
networks. This ongoing MSM transmission, despite current efforts across the US, remains the 
largest component of incident HIV infections in the country. 
Phylogenetic analysis of HIV infections among MSM could add important insights to the 
outreach and recruitment aims of this study. Since DC-RDS is a chain referral approach that is 
dependent on social and sexual networks, and participants recruit their network members for 
iterative recruitment waves, DC-RDS allows for the construction of network chains of referral 
and relatedness. As recruitment waves propagate beyond initial seeds, recruitment goes further 
into populations, eventually reaching significant proportions of populations with shared 
characteristics and who are connected through social networks. The ability to assess linkages at 
viral levels within these networks may provide critical insights into HIV transmission dynamics 
in urban MSM communities. 
 
 

 
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2.0 
STUDY OBJECTIVES AND DESIGN 
2.1 
Primary Objectives 
The primary objectives of the study are to: 
• 
Assess the ability of DC-RDS to identify and recruit HIV-infected MSM in the US who are 
not virally suppressed. 
• 
Compare the efficacy of the two study arms (CM intervention vs. SOC control) in achieving 
durable viral suppression (defined as HIV VL < 200 copies/ml) 24 months after enrollment. 
2.2 
Secondary Objectives 
The secondary objectives of the study are to: 
• 
Assess HIV prevalence and the proportion of HIV-infected men who are virally suppressed 
by comparing early wave (approximately 1-6) vs. later (deep) wave (approximately 7-12) 
DC-RDS participants. 
• 
Compare the proportion of men in the two study arms who are virally suppressed at 3, 6 and 
9, 12 and 18 months after enrollment.  
• 
Assess linkage to care and retention in care in the two study arms by comparing the 
1) proportion of men with at least one care visit within 30 days of enrollment, 2) time to the 
first care visit, and 3) proportion of men with at least four care visits (one in each six month 
interval, with at least 60 days between these visits) over the 24 months after enrollment. 
• 
Compare the proportion of men with HIV-hepatitis C virus (HCV) co-infection in the two 
study arms who are linked to care (defined as one care visit within 30 days of enrollment) and 
who achieve (HIV) viral suppression 24 months after enrollment. 
• 
Examine the association between baseline behavioral, socio-demographic, and clinical 
characteristics (including syphilis) of HIV-infected men and viral suppression status for all 
men screened via DC-RDS and for the men in the two study arms 24 months after enrollment. 
• 
Compare the two study arms with respect to ART adherence at 24 months after enrollment 
and changes in sexual risk behavior, health care utilization, stigma, substance use and mental 
health from baseline to 24 months after enrollment. 
• 
Evaluate the feasibility and scalability of the CM intervention by measuring the number of 
intervention contacts (e.g., text message, email, phone, in person) per participant over 24 
months. 
• 
Compare the experience of linkage to and ongoing HIV care among participants in the two 
study arms by conducting and analyzing exit interviews with participants and CMs.  
2.3 
Exploratory Objectives 
The exploratory objectives of the study are to: 
• 
Use phylogenetic methods to evaluate the relationship between HIV strains in study 
participants. Men who were likely to have been recently infected at enrollment will be 
identified using a multi-assay algorithm. Evaluate the relationship of behavioral, socio-
demographic, and clinical characteristics to viral networks (e.g., clusters, linked infections).   

 
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• 
Use laboratory assessments to characterize the study cohort and to evaluate the impacts of 
study interventions. These assessments may include analysis of HIV drug resistance and 
antiretroviral (ARV) drug use. Additional analyses may be conducted to analyze HCV 
strains, including phylogenetic analysis of HCV. Samples from this study may also be used to 
evaluate the performance of assays related to HIV and HCV infection.   
2.4 
Modeling Objective 
The modeling objective of the study is to: 
• 
Develop, calibrate, and use a mathematical model of HIV transmission among MSM in the 
US to assess the short and long-term population-level impact of the study strategy, and its 
independent CM intervention components (e.g., HIV testing, ART uptake, retention in care 
and viral suppression), on HIV incidence and to estimate the level of viral suppression 
required to reduce HIV incidence in the MSM community by 10%, 20%, 30%, and 50% over 
2, 5 and 10 years, and the likelihood of and time to elimination. 
2.5 
Study Design 
The overall design of this study reflects the primary goal, which is to develop and assess an 
integrated scalable strategy to identify, recruit, link to care, retain in care, and achieve HIV viral 
suppression among urban US MSM who are HIV-infected and not successfully virally 
suppressed. To outreach, identify and recruit HIV-infected MSM who are not virally suppressed, 
DC-RDS and DR will be implemented in four US cities (Atlanta, GA; Baltimore, MD; 
Birmingham, AL; and Boston, MA). Participating cities will have HPTN sites with evidence of 
high HIV burdens among MSM and interest in participating in the study. DC-RDS has been 
shown to be effective in reaching and identifying hard to reach subsets of MSM, including low 
SES, non-gay identified, and ethnic and racial minority MSM who are less likely be in HIV care 
and to be virally suppressed. The primary outcome of the recruitment component of the study is 
to assess the ability of DC-RDS to identify and recruit HIV-infected MSM in the US who are not 
virally suppressed. 
MSM recruited through DC-RDS who meet enrollment criteria will be randomized (1:1) to one of 
two study arms. The intervention arm will provide a Case Manager (CM) intervention package 
designed to enhance linkage to care, antiretroviral treatment (ART) initiation, treatment 
adherence and retention in care using a case management-based intervention. The SOC control 
arm will provide the standard of care (SOC) for linkage to care, initiation of ART, treatment 
adherence and retention in care. The primary outcome of the CM intervention phase is viral 
suppression 24 months after enrollment.  
Phylogenetic methods will be used to evaluate the relationship between viral strains in study 
participants and the relationship of viral networks (e.g., clusters, linked infections) to behavioral, 
socio-demographic, and clinical characteristics. Mathematical modeling will be performed using 
demographic, behavioral, and clinical data generated from this study and other sources to 
estimate the population-level impact of the CM intervention on HIV incidence and to estimate the 
level of identification, linkage, ART coverage and viral suppression that would be required to 
achieve a substantial reduction in HIV incidence among MSM in the US settings where the study 
is conducted.  
 

 
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3.0 
STUDY POPULATION 
Approximately 2700 sexually active MSM (~675 in each participating city) will be recruited for 
HIV testing via DC-RDS and direct recruitment (DR). The study’s focus is on cisgender MSM; 
however, transgender women who meet eligibility criteria will be included. Out of this cohort, 
356 HIV-infected MSM who are not virally suppressed and meet the inclusion and exclusion 
criteria described below will be enrolled into the CM intervention and SOC control study arms. 
3.1 
Inclusion Criteria 
Individuals who meet all of the following criteria are eligible for study screening: 
• 
Biological male (at birth) 
• 
Self-report of history of anal intercourse with another man   
• 
16 years or older  
Individuals who are eligible for screening and who meet all of the following criteria are eligible 
for enrollment into the CM intervention and SOC control arms:  
• 
HIV-infected, as defined in the HPTN 078 Study-Specific Procedures (SSP) Manual 
• 
Not virally suppressed (defined as HIV VL > 1000 copies/ml) 
• 
Can receive HIV care at one of the participating clinics (as chosen by each site) 
• 
No current plan to relocate in the 24 months following enrollment 
3.2 
Exclusion Criteria 
Individuals who meet any of the following criteria will be excluded from study screening: 
• 
Unable or unwilling to provide consent/assent for study participation 
• 
Active or previous participation in an HIV vaccine trial 
• 
Any condition that, in the opinion of the Investigator of Record (IoR), would make 
participation in the study unsafe, complicate interpretation of study outcome data, or 
otherwise interfere with achieving the study objectives. 
Individuals who are eligible for screening, but who meet the following criteria are excluded from 
enrollment into the CM intervention and SOC control arms: 
• 
Current participation in a linkage or ART adherence study 

 
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3.3 
Recruitment Process 
DC-RDS will be used to recruit MSM into this study, to the extent possible. In this method, seeds 
will be identified by each site. Seeds will be the individuals who begin the recruitment chains; 
they will be selected to represent a range of characteristics (including ethnic and racial minority 
status) and because they are well-networked within the population. These seeds will undergo 
training to become a recruiter. They will then be given coupons with which to recruit others to the 
study. Seeds must meet the screening inclusion/exclusion criteria of the study and are considered 
study participants.  
As this protocol is testing the ability of DC-RDS methodology to find HIV-positive, MSM who 
are not virally suppressed, DC-RDS recruitment will continue throughout the duration of the 
screening and enrollment period. However, DR will be used in addition to DC-RDS to fully 
enroll the CM intervention investigation. These new participants may be treated as seeds, if a site 
still needs to initiate additional recruitment chains. There will be no difference in study 
procedures for participants recruited via DC-RDS or DR, except that those identified via DR may 
or may not be treated as seeds, and thus, may or may not distribute coupons to others.  
All seeds, and subsequent participant/recruiters, must not recruit anyone other than peers they 
know personally who are MSM. These recruits will come to the site and, if they are eligible and 
agree to participate, will undergo the study’s screening procedures before becoming recruiters 
themselves. Participants will return to the clinic to be reimbursed for the coupons that were 
brought back to the clinic by other MSM. In addition, a post-recruitment questionnaire will be 
administered to characterize how many people in total were approached in the distribution of the 
coupons and the characteristics (e.g., age, race) of those who did and did not accept a coupon. 
If necessary, more than 2700 MSM will be recruited via DC-RDS and DR to achieve the required 
sample size for enrollment.   
3.4 
Co-Enrollment Guidelines 
Participants will not be eligible for study participation (screening or enrollment) if they are 
actively or have ever been enrolled in an HIV vaccine trial, since this may affect the anti-HIV 
antibody profile, complicating HIV diagnosis, and use of cross-sectional methods to identify men 
who may have been recently infected at the time of enrollment. Participants will not be eligible 
for enrollment into the CM intervention and SOC control arms if they are currently participating 
in a linkage or ART adherence study. Once randomized, participants cannot be co-enrolled into 
other linkage or ART adherence studies. 
3.5 
Participant Retention 
Locator information will be collected from each participant, so that they can be found if their 
phone number or address changes. Each site will be asked to create a retention plan to maximize 
the level of participation in study-required visits (follow-up visits and the final visit); however, 
sites will use their standard-of-care for retaining participants in clinical care throughout the study. 
The HPTN 078 SSP Manual will outline procedures for participants who wish to change clinics. 
3.6 
Participant Withdrawal and Early Termination 
Participants may voluntarily withdraw from the study for any reason at any time. Site IoRs may, 
with the approval of the Protocol Chair and the Protocol statistician, withdraw participants before 

 
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their scheduled termination visit to protect their safety, and/or if participants are unable or 
unwilling to comply with study procedures. Participants also may be withdrawn if the study 
sponsors, government or regulatory authorities or site Institutional Review Boards (IRBs) 
terminate the study prior to its planned end date. Every reasonable effort will be made to 
complete a final evaluation (M24 visit procedures) of participants who terminate from the study 
prior to Month 24, and study staff will record the reason(s) for all withdrawals in participant 
study records. 
3.7 
Study Sites 
Participants may be followed at participating HIV clinics in each of the four cities. All 
participating clinics must be able to provide the current SOC for HIV-infected MSM and be 
willing to provide participant information to the study team for analysis.  In addition, a survey 
documenting standard-of-care practices will be completed for each clinic that cares for 
HIV-infected MSM enrolled in the study. 
 
 

 
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4.0 
STUDY INTERVENTION 
The study CM intervention [MyLife, MyChoices, MyCare (Step 1), MyCare (Step 2), and 
MyHealth] is a program designed to enhance linkage, ART initiation, adherence and retention in 
care for MSM diagnosed with HIV. It will be administered by a trained CM and will include 
health care and supportive services navigation, adherence counseling, and tailored support for 
care engagement and treatment adherence. Table 1 and Figure 1 summarize each component, the 
element of the HIV care cascade it addresses and the evidence behind the CM intervention; a 
more complete table is included in Appendix IV. 
Table 1: Tailored Case Management Intervention Components in At Risk US Populations 
(2005 – 2015)  
HPTN 078 Intervention 
Component 
Cascade Component 
Citations 
MyLife 
- 
Linkage to care 
- 
Engagement in care  
- 
Retention in care 
- 
Self-management 
- 
Viral suppression 
- 
Inter-personal relationship building 
- 
Durability 
Hightow; 201148 
Quinlivan; 201349 
Rajabiun; 200750 
Yehia; 201551 
MyChoices 
- 
Linkage to care 
- 
Engagement in care 
- 
Retention in care 
Christopoulos; 201352 
Craw; 201053 
MyCare 
(Step 1) 
- 
Linkage to care 
- 
Engagement in care 
- 
Retention in care 
- 
Viral suppression 
- 
Durability 
Bradford; 200727 
Willis; 201347 
MyCare 
(Step 2) 
- 
Engagement in care 
- 
Retention in care 
- 
Adherence  
- 
Viral suppression 
- 
Inter-personal relationship building  
- 
Durability 
Hayley; 201458 
Holtzman; 201559 
Naar-King; 200960  
Nelsen; 201361 
Remien; 200562  
Simoni; 200632  
MyHealth 
- 
Linkage to care 
- 
Engagement in care 
- 
Retention in care 
- 
Adherence  
- 
Self-management  
- 
Inter-personal relationship building  
- 
Viral suppression 
- 
Durability  
Gilman; 201254 
Hightow; 201155 
Lewis; 201338 
Maulsby; 201556  
Schnall; 201557 
 
 

 
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Figure 1: Relationship between the HIV Care Cascade and the CM Intervention 
 
The CM will help each participant enrolled into the CM intervention arm to link to HIV care, 
initiate ART, remain adherent to medication and keeping clinical appointments. Each CM will 
have prior case management experience and will be trained to carry out the specified intervention 
aimed at improving disease management and reducing HIV viral load for patients with HIV. The 
CM-to-participant ratio will be approximately 1:42 over the 24-month period. As shown in Figure 
2, the frequency, content and type (in person, email, phone, text message) of interactions will be 
driven by each patient’s desire and need for support, but will minimally follow the schedule of 
events (see Appendix I). All CM-participant interactions will be documented (frequency and 
duration) to assess the feasibility and scalability of the CM intervention. To ensure uniformity 
and fidelity of the intervention across sites, each CM will undergo a standardized, comprehensive 
training program, and each mandatory session (at required study visits) will be audio recorded 
and a small percentage will be assessed against a standard counselling index, as described in the 
HPTN 078 SSP Manual.  

 
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Figure 2: Overview of CM-Administered Study Intervention 
 
Note: Some participants may choose to meet in person with the CM on a very frequent basis (e.g. 
weekly); these visits will be documented, however, such visits are not mandatory and there are no 
required study procedures during them.   
 
This CM-led model builds upon the existing CDC-endorsed Comprehensive Risk Counseling and 
Services for Persons with HIV63, which focuses on the prevention of HIV transmission. The 
model combines aspect of clinical care coordination to include; a) recruitment and engagement 
(MyLife); b) inventory of available resources (MyChoices); c) patient navigation to clinical care 
(MyCare (Step 1)); d) adherence counseling (MyCare (Step 2); e) retention and follow-up 
(MyHealth). 
The approach of the CM follows an approach similar to HPTN 073 in the use of a 
self-determination theoretical approach, which hypothesizes that reestablishing autonomy is a key 
element for long-term engagement in care for some patients.49 Additionally, the 
Gelberg-Andersen Behavioral Model for vulnerable populations64 will be used to identify 
enabling, predisposing and need variables that impact adherence and retention in care, which has 
been effectively demonstrated in women living with HIV, but not in an MSM group.65 The role of 
the CM within each of the five components is described below.  
Participants enrolled into the SOC control arm will be provided with the existing programs for 
referral to HIV treatment and support services without additional CM coordination. 

 
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4.1 
Linkage to Care and ART Initiation (MyLife, MyChoices, MyCare (Step 1)) 
4.1.1 
Engagement (MyLife) 
The MyLife component is the first step of the CM intervention as developing a therapeutic or 
interpersonal relationship with the participant is the paramount first step. Engaging with the 
participant is an effective strategy that has been shown to improve retention.58 Part of this 
engagement process is to attempt to understand the participant’s state of mind after the HIV 
diagnosis and address any HIV-related questions they may have. It may become necessary to end 
the first session here depending on the individuals needs related to their diagnosis. This session 
will include an HIV counseling intervention about the new diagnosis and an overview of the case 
management model in support of the patient. The CM will be taught motivational interviewing 
skills to facilitate participant engagement into clinical practice. 
After the initial question-answer period, the CM will seek to understand the predisposing, 
enabling and health needs of the participant.64 A standardized instrument will be utilized to elicit 
this information from the patient. Once these data are available, the CM will discuss and assist the 
participant to develop an individually-tailored plan that is designed utilizing self-determination 
theory. Self-determination theory is anchored by three core components: (1) autonomy 
support-provision of evidence-based health guidance and supporting the participant-endorsement 
of the plan they believe best meets their needs and fits within their life circumstance; (2) 
competence support-expression of belief in the participants’ ability to implement their self-
endorsed plan and provision of guidance for acquiring the necessary skills and resources for 
successful implementation; and (3) relational support-expression/demonstration of genuine care 
and concern for the participant’s successful implementation of the plan (e.g., follow-up 
phone/text check-ins). These three components are theorized to facilitate the adoption and 
maintenance of health behaviors. A comprehensive training program on the use of this model will 
be provided to all CMs. 
4.1.2 
Inventory of Available Resources (MyChoices) 
MyChoices will involve a discussion of resources available to meet the participants stated 
healthcare needs. The CM will have a comprehensive listing of available HIV, substance abuse, 
mental health, and other available resources to discuss with the participant. The CM will provide 
guidance on options that work within the delineated plan and make modifications based on the 
participant’s needs and review of the available resources. 
4.1.3 
Patient Navigation to Clinical Care (MyCare (Step 1)) 
MyCare (Step 1) supports the decision to initiate HIV care and will include motivational 
interviewing activities to coach the client toward seeking and initiating care. Once care decisions 
have been made by the participant, the CM will offer to facilitate entry into the care facility 
selected by the patient. This will include the establishment of necessary appointments, facilitation 
of paperwork and registration materials, pre-clinical laboratory evaluations, evaluation of 
provider options within the clinical site as well as introductions of the clinical team through either 
website review, phone calls, or a clinic visit with onsite team prior to the first visit. All 
participants will be encouraged to initiate (or re-initiate) ART in consultation with their 
healthcare provider. 

 
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4.2 
Adherence Counseling (MyCare (Step 2)) 
In conjunction with ART initiation, the CM will deliver evidence-based adherence counseling, 
which will be modeled after Life Steps31, a single-session intervention that is grounded in 
cognitive-behavioral principles that are at the core of several successful ART adherence 
interventions.25, 32, 62, 66 The adherence counseling will address basic education about HIV and 
ART, planning and problem-solving for accessing and maintaining a steady supply of medication, 
formulation of a daily medication schedule, cues for pill-taking, coping with side effects and/or 
other patient concerns, developing a plan to mitigate side effects, and responses to slips in 
adherence. This counseling will be provided face-to-face prior to, at the time of, or in the very 
early stage of ART initiation. Participants will be encouraged to bring a support partner to the 
adherence counseling sessions, if they so desire, which has been shown to be effective for long-
term medication adherence.62, 66, 67 The counseling intervention allows for tailoring to the 
participants specific needs, as well as additional counseling sessions, if needed. MyCare (Step 2) 
adds to this evidence-based approach by recognizing that adherence to treatment is a personal 
choice that is grounded in a variety of behavioral and psychosocial domains. Intention to adhere 
to treatment will be added as part of the MyCare (Step 2) component.61 
4.3 
Communication, Retention and Follow-up (MyHealth) 
MyHealth is based on the premise that all patients engaged in self-management and supportive 
strategies will feel more empowered to take ownership of their own healthcare needs. In addition, 
there is accumulated evidence for the acceptability and preference for two-way text messaging for 
adherence support among diverse populations, including MSM.35-38  As such, tailored 
communication support will be offered to facilitate ongoing adherence. The CM will work with 
each participant to determine their desire for supportive adherence reminders, their preferred 
method of communication (text message, email or phone call), and the frequency and schedule 
for these messages. In this way, the participant is being empowered to take the lead with 
recommendations and guidance from the CM. This type of messaging is interactive in that it 
allows for a response from participants, in case a participant needs additional information or 
assistance. The frequency and content of these communications may change over the course of 
the intervention, depending on the needs of the participant. 
 

 
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5.0 
STUDY PROCEDURES 
An overview of the study visits and procedures is presented in Appendix I. Additional 
information is provided below on visit-specific study procedures. Detailed instructions to guide 
and standardize all study procedures across sites will be provided in the SSP Manual. 
5.1 
Screening Visits 
There are several algorithms for screening visits (see HPTN 078 SSP Manual). The timing of 
screening activities will vary between algorithms, but all screening activities described below will 
be completed for each algorithm. Additionally, re-screening for eligibility is allowed under 
certain circumstances (see HPTN 078 SSP Manual). 
All individuals will be consented for screening procedures, which include the provision of contact 
information, completion of several questionnaires (see Appendix II) and samples collected for 
laboratory assessments. All participants will undergo HIV screening (via one Food and Drug 
Administration (FDA)-approved HIV rapid test [either oral fluid or finger stick or whole blood], 
self-report, or clinic record) and have blood drawn for HCV and syphilis testing. For those who 
report being previously diagnosed with HIV infection, have HIV infection documented in a clinic 
record, or have a reactive rapid HIV test, additional blood will be collected for HIV confirmatory 
testing (see HPTN 078 SSP Manual), HIV viral load and CD4+ cell count. In addition, pre- and 
post-test HIV counseling and HIV/sexually transmitted infection (STI) risk reduction counseling 
will be provided to all participants, as appropriate. Participants will also be assessed for social 
impacts that may have occurred during the recruitment process.  
Participants who participate in DC-RDS will also be given instructions about the recruitment 
process and coupons for distribution. Additionally, if applicable at later visits, a post-recruitment 
questionnaire will be administered to DC-RDS participants who have distributed their coupons.  
All participants, regardless of eligibility, may be provided with their test results by phone or 
in-person, per site standards. If the HCV and/or syphilis test are positive, participants will be 
referred for care via site standards. Participants who are eligible and willing to enroll may be 
provided with their test results in-person on the day of their enrollment visit.  
5.1.1 
Procedures for Participants Who are Determined to be HIV-Uninfected 
Participants who are determined to be HIV-uninfected (see HPTN 078 SSP Manual) will be given 
information on HIV prevention, including current information about pre-exposure prophylaxis 
(PrEP) and post-exposure prophylaxis (PEP). These participants are not eligible for enrollment 
into the CM intervention or SOC control arms.  
5.1.2 
Procedures for Participants Who are Confirmed to be HIV-Infected 
Participants who are confirmed to be HIV-infected (see HPTN 078 SSP Manual) will be screened 
for participation in the intervention, and, if eligible, will be invited to be enrolled into the CM 
intervention or SOC control arms. If an individual is eligible for randomization, but chooses not 
to participate further in the study, they will be referred to local HIV care facilities. 

 
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5.1.3 
Procedures for Participants Whose HIV Status is Inconclusive 
Participants whose HIV status is not clear after their last screening visit will be referred to a local 
care provider for further evaluation and follow-up.  If such a participant is later confirmed to be 
HIV-infected, they may be re-assessed for eligibility (see HPTN 078 SSP Manual). 
5.2 
Enrollment Visit (M0) 
The Enrollment Visit will take place as soon as participants are determined to be eligible. During 
this visit, participants will be consented for enrollment and randomized to either the CM 
intervention or SOC control arm. Participants will be asked to sign a release of medical 
information, their locator information will be confirmed, they will be asked to complete a 
questionnaire (see Appendix II), and they will have blood drawn for plasma storage. All 
participants will be offered HIV testing for their partners. Depending on the results of the 
partners’ HIV test results, partners will be referred to appropriate HIV care services or other HIV-
related studies. [Note: partner testing will be done outside of the study and results will not be 
recorded.] In addition, the intervention will begin at this visit for those randomized to the CM 
intervention arm, and, if appropriate, ART may be initiated at this visit. (Note that ART is not 
provided by the study, nor prescribed by the CM.)  
5.3 
Tailored Communication 
Once an individual is enrolled into the CM intervention arm, they will decide how much, if any, 
text message, email or phone reminders they would like to receive to support ART adherence. 
These reminders will be tailored to the needs of the participant so that they are effective, while 
maintaining privacy. The CM will facilitate the distribution of these messages and respond to 
requests for assistance via these two-way modes of communication. This tailored communication 
to support ART adherence will not be offered to participants in the SOC control arm. 
5.4 
Monthly Contact 
The CM will contact each participant randomized to the CM intervention arm on a monthly basis 
to confirm their locator information, to check-in with the participant regarding HIV and ART 
management, and to collect any social impacts due to study participation. Participants may 
choose this contact to be in person or by text message, email or phone call. No monthly contact 
will be made with participants in the SOC control arm. 
5.5 
Follow-up Visits (M3, M6, M9, M12, M18) 
Follow-up Visits will take place at Months 3, 6, 9, 12 and 18 for all participants (CM intervention 
and SOC control arms). During these face-to-face visits, locator information will be confirmed, 
social impacts will be collected, partner HIV testing will be offered, HIV viral load and CD4 cell 
count testing will be conducted, and plasma will be stored. For those randomized to the CM 
intervention arm, the intervention will be implemented by the CM. 

 
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5.6 
Final Visit (M24) 
The Final Visit will take place at Month 24. This visit will be identical to a Follow-up Visit, 
except that blood will be collected for syphilis testing and questionnaires will be administered 
(see Appendix II). An exit interview will also be conducted or scheduled with all participants. If 
the syphilis test is positive, participants will be given their test results and referred for care via 
site standards. An exit interview will be conducted with each CM after they complete the final 
visit for their last participant.  
5.7 
Data Collection on ART Initiation and Visit Attendance 
Information about ART initiation, if it takes place during study follow-up, and overall visit 
attendance will be collected from all participants’ medical records. 
5.8 
Questionnaires 
5.8.1 
Participant Questionnaires 
Questionnaires in the following domains will be administered over the course of the study: 
demographic; PrEP/PEP/ART use history; HIV testing history; sexual matrix module/sexual risk 
behavior; health care utilization; engagement in the lesbian, gay, bisexual and transgender 
(LGBT) community; post recruitment questions; medication adherence; stigma; substance abuse; 
and mental health. The schedule for these questionnaires is provided in Appendix II. When 
possible, the domain questionnaires will be adapted from recent MSM-focused HPTN studies 
such as HPTN 061 and 073 to allow cross comparison. Additionally, validated questions/scales 
from the literature will be used to gain information in domains that are vital to understanding the 
impact of the study design and intervention. Information on the focus of each domain is provided 
below: 
• 
Demographic: Data collected in this domain will include information such as age, gender, 
marital status, education, annual income, race/ethnicity and health insurance status. 
• 
PEP/PrEP/ART: Information collected in this domain will focus on actual behaviors and use 
of PEP/PrEP/ART in the last 12 months. Daily and intermittent use of PrEP in the community 
will also be evaluated. 
• 
HIV testing history: The HIV testing history domain will document how many times the 
participant has been tested for HIV in the past year and the month and year of the most recent 
HIV test. In addition, this domain will document whether the participant received the results 
and if so, the result of the test.  
• 
Sexual matrix module/Sexual risk behavior: Information collected within these domains 
will include information on number of partners, frequency and types of sexual acts, and 
geography of the sexual experiences. This information will help identify sexual exposures 
inside and outside the defined community. The questions in this domain will be adapted from 
both HPTN 061 and HPTN 073 as well as the Berry sexual activity matrix.68, 69 
• 
Health care utilization: Information collected in this domain will include information on 
health care utilization and services and assess engagement at baseline. Trust between the 
clinician and patient will also be evaluated. Information in this domain will also be collected 

 
HPTN 078, Final Version 2.0 
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at the final visit to assess any supplemental services that have been accessed outside the 
study.   
• 
Engagement in the LGBT community: Information collected in this domain will include 
information on how well people are engaged and connected in the LGBT community. This 
domain will supplement the post recruitment questions and allow the team to evaluate the 
effectiveness of DC-RDS in finding those connected and individuals that are hidden in the 
community. This may reveal any association with the likelihood of being undiagnosed. 
• 
Post recruitment questions: Information collected in this domain will focus on evaluating 
the effectiveness of DC-RDS and recruitment strategies by participants.70, 71 
• 
Stigma: Information collected in this domain will be very focused on self-stigma 
(internalized homo-negativity) and HIV stigma (with consideration of impact on HIV testing 
and adherence). This questionnaire domain is being adapted from Herek et al 1997.72 
• 
Substance abuse and mental health: Information collected in this section will focus on 
depression, post-traumatic stress disorder, anxiety and substance abuse.  These assessments 
will be brief screeners that the case manager can use to intervene or provide referrals. The 
Substance Abuse/Mental Illness Symptoms Screener (SAMISS)73, 74 will be the primary 
source for this domain. 
• 
Medication adherence: This domain will be self-reported medication adherence. A three-
item scale developed by Wilson et al,75 which has recently been shown to be correlated with 
HIV viral load outcomes across different populations, will be used. 
• 
Exit Interview: A questionnaire and a semi-structured qualitative interview will be 
administered to participants asking them to describe their experiences with linkage-to-care, 
adherence and the CM intervention; information will be collected from both arms about 
outside interventions/care.  Such exit interviews will also be conducted with the CMs, with 
the questions tailored for their role in the study.  
5.8.2 
Site Questionnaires 
Site questionnaires will be administered to each site providing care to HPTN 078 enrolled 
participants to document their standard of care. These surveys will be administered annually to 
capture sites’ normal procedures throughout the duration of the study.  
 
 

 
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6.0 
SAFETY MONITORING AND ADVERSE EVENT REPORTING 
6.1 
Safety Monitoring 
As this study only involves low-risk activities (recruitment activities; testing for HIV, HCV, and 
syphilis; questionnaires; support for linkage-to-care, care engagement and ART adherence) and 
contains no biomedical intervention or clinical care (ART prescription or other medical 
treatment), standard adverse event reporting will not be undertaken. The study team will collect 
and report all social impacts that are brought to the attention of study staff members. Research staff 
will be trained to recognize and report social impacts as well as provided with referrals for 
counseling and social service support, if necessary. Reports of social impacts will be reviewed 
quarterly or more often, if indicated, and reported to the DAIDS Medical Officer together with 
any actions that are taken. Social impacts will be summarized and reported to appropriate 
Institutional Review Boards (IRB)(s) on an annual basis. 
Confidential HIV and STI surveillance reporting will be done according to local regulations. 
Participants will be reminded of these requirements via the Informed Consent Form.   
6.2 
Social Impact Reporting 
It is possible that participants' involvement in the study could become known to others, and that a 
social impact may result (i.e., because participants could be perceived as being HIV-infected or at 
"high risk" for HIV infection). For example, participants could be treated unfairly, or could have 
problems being accepted by their families and/or communities. A social impact that is reported by 
the participant and judged by the Investigator of Record (IoR) or designee to be serious or 
unexpected will be reported to the responsible site’s IRBs at least annually, or according to their 
individual requirements. Social impacts will be collected and reported on case report forms 
(CRFs) during regular visits. In the event that a participant reports a social impact, every effort 
will be made by study staff to provide appropriate care and counseling to the participant as 
necessary, and/or referral to appropriate resources for the safety of the participant. While 
maintaining participant confidentiality, study sites may engage their Community Advisory Board 
(CAB) in exploring the social context surrounding instances of social impacts, to minimize the 
potential occurrence of such a harm. 
 
 

 
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7.0 
STATISTICAL CONSIDERATIONS 
7.1 
Review of Study Design 
This study is designed to i) evaluate the utility of DC-RDS for finding HIV-infected MSM who 
are not virally suppressed, and ii) assess the efficacy of an CM intervention package for linking 
HIV-infected MSM to care and, ultimately, achieving viral suppression. Approximately 2700 
MSM will be identified and recruited (see Sections 7.2.1 and 7.6.1 for definition of recruitment) 
using DC-RDS and DR strategies in four cities (~675 per city). We expect that approximately 378 
of these will be HIV-infected MSM who are not virally suppressed and that 356 of these will be 
willing to participate. These 356 individuals will be randomized to the CM intervention and SOC 
control study arms of the study. The CM intervention arm will provide a package designed to 
enhance linkage to care, ART initiation, treatment adherence, and retention in care. The 
intervention will be delivered by a trained CM. The SOC control arm will provide the SOC for 
linkage to care, initiation of ART, and treatment. The primary outcome of the study is viral 
suppression 24 months after enrollment. 
7.2 
Endpoints 
7.2.1 
Primary Endpoints 
Consistent with the primary study objective to assess the ability of DC-RDS to identify and 
recruit HIV-infected MSM in the US who are not virally suppressed, the following endpoints will 
be assessed: 
• 
HIV status at screening for each MSM recruited by DC-RDS  
• 
HIV viral load at screening for each HIV-infected MSM recruited by DC-RDS 
Consistent with the primary study objective to compare the efficacy of the two study arms (CM 
intervention vs. SOC) in achieving viral suppression (defined as HIV VL <200 copies/ml) 24 
months after enrollment, the following endpoint will be assessed:  
• 
HIV viral load at 24 months after enrollment 
7.2.2 
Secondary Endpoints 
Consistent with the secondary study objective to assess HIV prevalence and the proportion of 
men who are virally suppressed by comparing early wave (approximately 1-6) vs. later (deep) 
wave (approximately 7-12) DC-RDS participants, the following endpoint will be assessed: 
• 
Date and wave of recruitment for each man recruited by DC-RDS  
Consistent with the secondary study objective to compare the proportion of men in the two study 
arms who are virally suppressed (defined as HIV VL <200 copies/ml) at 3, 6, 9, 12 and 18 
months after randomization the following endpoints will be assessed: 
• 
HIV viral load at 3, 6, 9, 12 and 18 months after enrollment 
Consistent with the secondary study objective to compare the proportion of men in the two study 
arms who are linked to care and retained in care the following endpoints will be assessed: 

 
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• 
Number and time of all care visits from randomization through the end of 24 month 
follow-up 
Consistent with the secondary study objective to compare the proportion of men with HIV-HCV 
co-infection who are linked to care and who achieve HIV viral suppression 24 months after 
enrollment between the two study arms the following endpoint will be assessed: 
• 
HCV status at baseline 
• 
HIV viral load at 24 months after enrollment 
Consistent with the secondary study objective to examine the association between baseline 
behavioral, socio-demographic, and clinical characteristics of HIV-infected men and viral 
suppression status for all men screened via DC-RDS and for the men in the two study arms 24 
months after enrollment the following endpoints will be assessed: 
• 
Self-reported sexual risk behavior (number of male sexual partners, episodes of 
unprotected anal intercourse [UAI], characteristics of 3 most recent partners) at baseline 
using a standardized assessment tool  
• 
Age, education, and other socio-demographic measures at baseline 
• 
CD4, HIV viral load and syphilis status at baseline 
Consistent with the secondary study objective to compare ART adherence at 24 months and 
changes in sexual risk behavior, health care utilization, stigma, substance use and mental health 
between the two study arms over 24 months, the following endpoint(s) will be assessed:  
• 
Self-reported sexual risk behavior (number of male sexual partners, episodes of UAI, 
characteristics of 3 most recent partners) at baseline and 24 months using a standardized 
assessment tool  
• 
ART adherence at 24 months 
• 
Health care utilization at baseline and 24 months using a standardized assessment tool 
• 
Stigma at baseline and 24 months using a standardized assessment tool 
• 
Substance use at baseline and 24 months using a standardized assessment tool 
• 
Mental health at baseline and 24 months using a standardized assessment tool 
Consistent with the secondary study objective to evaluate the feasibility and scalability of the CM 
intervention package, the following endpoint(s) will be assessed: 
• 
Number of contacts (text message, email, phone, in person) for each participant 
randomized to the CM intervention arm over follow-up 
Consistent with the secondary study objective to compare the experience of linkage to and 
ongoing HIV care among participants in the two study arms, the following endpoint(s) will be 
assessed: 

 
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• 
Satisfaction with the CM intervention components, as measured on a Likert scale during 
a standardized exit interview 
• 
Usefulness of the CM intervention components, as measured on a Likert scale during a 
standardized exit interview 
• 
Open-ended questions for process evaluation  
7.2.3 
Exploratory Endpoints 
• 
Consistent with the exploratory study objective to use phylogenetic methods to evaluate the 
relationship between behavioral, socio-demographic, and clinical characteristics and viral 
networks (e.g., clusters, linked infections).   
• 
The phylogenetic relationship between HIV sequences 
Consistent with the exploratory study objective to use laboratory assessments to characterize the 
study cohort and to evaluate the impacts of study interventions, the following endpoint(s) may be 
assessed: 
• 
Laboratory measures that may include HIV drug resistance, detection of ARV drugs and 
other assessments 
7.3 
Accrual, Follow-up and Sample Size 
We will recruit approximately 2700 men via DC-RDS and DR. We expect that 20% (540) will be 
HIV-infected MSM and that 70% of those (378) will not be suppressed. These 378 individuals 
form the pool of individuals eligible for enrollment and randomization. If necessary, more than 
2700 MSM will be recruited via both methods to achieve the required sample size for enrollment. 
We expect that 40% of the MSM randomized to the SOC control arm will be linked to care and 
70% of those linked to care will be suppressed by 24 months following enrollment.6 We expect 
that almost none of those not linked to care will be suppressed. Thus, overall, we expect about 
28% of the MSM in the SOC control condition will be suppressed at 24 months. In the CM 
intervention arm we expect to raise the linkage rate to at least 55% and the suppression rate, 
among those linked, to 85%. Thus, we expect that at least 46% of the MSM in the CM 
intervention arm will be suppressed at 24 months. Table 2 shows the required sample size for an 
individually randomized trial with 90% power, assuming 10% lost-to-follow-up per year, for 
various effect sizes. For our target effect size of risk difference of 18% points, we require 356 
MSM. 
Table 2. 
Number needed to be randomized to the CM intervention or SOC control to 
have 90% power to detect the indicated difference in proportion of those virally 
suppressed at 24 months, assuming α = 0.05 (two-tailed), power = 90%, loss to 
follow-up = 10%/year (overall retention of 80% at the end of 2 years).  
Difference in proportion suppressed at 24 
months between arms1 
0.12 
0.18 
0.24 
Number randomized 
780 
356 
190 
1Valid for SOC control group viral suppression rates between ~30 – 50%. 

 
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Table 3 shows the precision of estimates of i) awareness of HIV-infected status and ii) viral 
suppression among those who are HIV-infected, based on the DC-RDS sample. 
Table 3. 
Precision for estimating the indicated proportions, assuming 20% of DC-RDS 
recruits are HIV-infected 
Number recruited 
via DC-RDS 
Expected number 
HIV-infected 
Awareness of 
HIV-infected status 
(expected proportion = 
0.20) 
Virally suppressed at 
enrollment among 
HIV-infected (expected = 
0.25) 
2000 
400 
+/-0.039 
+/-0.042 
1500 
300 
+/-0.045 
+/-0.049 
1000 
200 
+/-0.055 
+/-0.060 
 
7.4 
Random Assignment 
HIV-infected MSM who are recruited by the DC-RDS or DR, are eligible and agree to participate 
in the study will be randomized in a 1:1 ratio to the CM intervention and SOC control arms using 
randomly-permuted blocks, stratified by site. 
The randomization scheme will be generated and maintained by the HPTN SDMC. Additional 
details regarding the process of randomization will be included in the SSP Manual. 
7.5 
Blinding 
Participants and study investigators will not be blinded to the randomization assignments. 
7.6 
Data Analysis 
7.6.1 
Primary Analysis 
To assess the ability of DC-RDS to recruit HIV-infected MSM who are not virally suppressed we 
will measure the proportion of the men that are recruited by DC-RDS (where recruitment is 
defined as providing a blood draw for HIV and HIV viral load testing) who are HIV-infected and 
not virally suppressed. An estimate and a 95% confidence interval (CI) based on RDS methods76 
will be reported. MSM recruited via other methods will not be included in this analysis. 
Among the HIV-infected MSM who are enrolled and randomized we will compare the rates of 
viral suppression (defined as HIV VL <200 copies/ml) at 24 months after enrollment. The 
absolute difference in the probability of viral suppression between the CM intervention and SOC 
control arms and a 95% CI will be reported. A chi-squared test with a two-sided alpha level of 
0.05 will be used for testing the hypothesis: 
Ho: No difference in suppression between arms 
Ha: Difference in suppression between arms 
The analysis will follow the intent to treat principle. If a participant drops out prior to 24 months, 
their viral suppression status at last study assessment will be used in the analysis. A sensitivity 
analysis will be conducted to evaluate the effect of different assumptions about the viral 
suppression status of those who drop out. 

 
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As a secondary analysis, we will repeat the above for the subgroup of randomized participants 
who are HCV seropositive at baseline. 
7.6.2 
Secondary Analysis 
We will divide the MSM who are recruited into early and later waves of DC-RDS (the definition 
of “early” and “late” will be included in the statistical analysis plan). We will use a two sample 
test of proportions (with standard errors adjusted for RDS sampling;76) to compare i) the 
proportion HIV-infected and ii) the proportion HIV-infected and not suppressed, between the 
early and later recruits. MSM recruited via other methods will not be included in this analysis. A 
two-sided alpha level of 0.05 will be used for hypothesis testing. 
We will also repeat the analysis of HIV viral suppression (described in Section 7.6.1) at 3, 6, 9, 
12 and 18 months of follow-up. As in the primary analysis, viral suppression status at last study 
assessment will be used for participants who drop out prior to a time point. Chi-squared tests with 
a two-sided alpha level of 0.05 will be used at each time point. 
Among the HIV-infected MSM who are enrolled and randomized, we will compare the rates of 
linkage to care (defined as at least one care visit within 30 days of enrollment) between the CM 
intervention and SOC control arm. Any randomized participant who drops out of the study prior 
to 30 days will be counted as “not linked” for the purpose of this analysis. The absolute difference 
in the probability of linkage between the CM intervention and SOC control arms and a 95% CI 
will be reported. A chi-squared test with a two-sided alpha level of 0.05 will be used for 
hypothesis testing. Similarly, we will use a Cox regression model to compare time to first linkage 
visit between the two study arms. A hazard ratio and 95% CI will be reported. Both analyses will 
follow the intent to treat principle. 
We will also compare the proportion of MSM who are retained in care (defined as at least four 
care visits [one in each six-month interval, with at least 60 days between these visits] over the 24 
months after enrollment) between the CM intervention and SOC control arm. Any randomized 
participant who drops out of the study without at least two care visits as defined above will be 
counted as “not retained” for the purpose of this analysis. The absolute difference in the 
probability of retention between the CM intervention and SOC control arms and a 95% CI will be 
reported. A chi-squared test with a two-sided alpha level of 0.05 will be used for hypothesis 
testing. The analysis will follow the intent to treat principle. 
We will build a multiple logistic regression model to examine the associations between viral 
suppression at 24 months (outcome) and various demographic characteristics, sexual risk 
behaviors and clinical characteristics. Further details will be provided in a separate Statistical 
Analysis Plan. 
Additional analyses will examine the effect of the CM intervention on various sexual risk 
behavior, ART adherence, stigma, health care use, substance use and mental health measures over 
the 24 month follow-up. The general approach to these analyses will be to build a regression 
model (linear, log, or logistic, whichever is appropriate for the scale of the measure) that uses the 
24 month value of the measure as the outcome (or most recent assessment for participants that 
drop out prior to 24 months) and includes the baseline value of the measure (except for ART 
adherence, where no baseline value is available) and CM intervention arm as covariates. The 
coefficient of the CM intervention arm covariate will be used to quantify the CM intervention 
effect. An estimate of the CM intervention effect and a 95% CI will be provided for each 
outcome. Further details will be provided in a separate Statistical Analysis Plan. 

 
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Among those randomized to the CM intervention arm we will measure the number of contacts 
(text message, email, phone, in person) per participant over follow-up. Summary statistics (mean, 
median, interquartile range, etc.), standardized by the number of months in follow-up, will be 
provided. 
We will summarize the distribution of responses on satisfaction with and usefulness of the CM 
intervention components from the exit interviews using means, medians and interquartile ranges. 
7.6.3 
Qualitative Analysis 
We will conduct qualitative analysis of all open-ended process evaluation data by coding and 
analyzing the qualitative data utilizing a qualitative software package for systematic data 
management (e.g., NVivo) to evaluate participants' and CMs’ reactions, preferences and 
recommendations for treatment interventions. 
7.6.4 
Exploratory Analysis 
Phylogenetic trees will be built using HIV sequences from study participants and other relevant 
sequences (e.g., controls). If viral networks are identified (e.g., clusters, linked infections), we 
will evaluate the relationship of behavioral, socio-demographic, and clinical characteristics to 
viral networks.  
If other exploratory laboratory assessments are performed (e.g., drug resistance, ARV drug use, 
HCV phylogenetics), the HPTN Laboratory Center (LC) will identify specific endpoints for 
analysis. 
 
 

 
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8.0 
HUMAN SUBJECTS CONSIDERATIONS 
8.1 
Ethical Review 
This protocol and the template informed consent form(s) contained in Appendix III will be 
reviewed and approved by the HPTN Scientific Review Committee (SRC) and NIAID 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 —will also be 
reviewed and approved by the ethical review bodies responsible for oversight of research 
conducted at each study site.  
Subsequent to initial review and approval, the responsible IRBs will review the protocol at least 
annually. The Investigators of Record will make safety and progress reports to the IRBs 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 are responsible for the submission of continuing review 
documentation to the DAIDS Protocol Registration Office, in accordance with the current DAIDS 
Protocol Registration Policy and Procedure Manual. 
8.2 
Informed Consent 
Written informed consent will be obtained from each study participant prior to conducting 
study-related procedures. Each study site is responsible for developing a study informed consent 
form for local use, based on the templates in Appendix III, which describe the purpose of the 
study, the procedures to be followed, and the risks and benefits of participation, in accordance 
with all applicable regulations. Based on local IRB approval and state law, sites may seek a 
waiver of parental consent for either the DC-RDS activities alone or both the DC-RDS and CM 
activities. However, only sites that are granted a waiver of parental consent for the DC-RDS 
activities will be allowed to screen minors (16 and 17 year olds).   
Participants will document their provision of informed consent by signing the informed consent 
forms. (Further details regarding DAIDS requirements for documenting the informed consent 
process are provided in the DAIDS Standard Operating Procedure for Source Documentation.)  
All participants will be offered a copy of their informed consent forms. 
8.3 
Incentives 
Pending IRB approval, participants may be compensated for their time and effort for 
study-required activities, or reimbursed for travel to study-required visits or time away from work 
for study-required activities. Site-specific reimbursement amounts will be specified in the study 
informed consent forms. 
8.4 
Confidentiality 
All study-related information will be stored securely at each study site. All participant 
information will be stored in locked file cabinets in areas with access limited to study staff. All 

 
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laboratory specimens, reports, study data collection, process, and administrative forms will be 
identified by a coded number only to maintain participant confidentiality. All records that contain 
names or other personal identifiers, such as locator forms and informed consent forms, will be 
stored separately from study records identified by code number. All local databases will be 
secured with password-protected access systems. Forms, lists, logbooks, appointment books, and 
any other listings that link participant identification (ID) numbers to other identifying information 
will be stored in a separate, locked file in an area with limited access. 
Participant’s study information will not be released without the written permission of the 
participant, except as necessary for monitoring by NIAID and its contractors; representatives of 
the HPTN Leadership and Operations Center (LOC), SDMC, or HPTN LC; Office for Human 
Research Protections (OHRP) or other government and regulatory authorities; or site IRBs. 
The HPTN will obtain a Certificate of Confidentiality from the U.S. Department of Health and 
Human Services that will be applicable for this study. Sites may register under the Certificate 
through the HPTN LOC once they have obtained local IRB approval for the study. This 
Certificate protects study staff from being compelled to disclose study-related information by any 
Federal, State or local civil, criminal, administrative, legislative, or other body. 
8.5 
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. 
8.6 
Study Discontinuation 
The study also may be discontinued at any time by NIAID, the HPTN, OHRP or other 
government or regulatory authorities, or site IRBs. 
 
 

 
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9.0 
LABORATORY SPECIMENS AND BIOHARDS CONTAINMENT 
Laboratory procedures are described below and in Appendix I. 
9.1 
Local Laboratory Specimens 
Specimens will be collected for testing at the local laboratory. Laboratory evaluations/procedures 
will include:  
• 
HIV testing (see SSP Manual) 
• 
Syphilis testing 
• 
HCV testing (see SSP Manual) 
• 
CD4 cell count testing  
• 
HIV viral load testing 
• 
Plasma storage 
Local laboratories and clinics where testing is performed must be certified under the Continuous 
Laboratory Improvement Amendment (CLIA-certified) or must be in possession of a CLIA 
Waiver. Additional local and State guidelines must also be followed. 
Each study site will adhere to standards of good clinical laboratory practice, and local standard 
operating procedures for specimen management including proper collection, processing, labeling, 
transport, and storage of specimens to the local laboratories. Specimen storage at the local 
laboratory will be documented using the HPTN Laboratory Data Management System (LDMS) as 
described in the SSP Manual. 
9.2 
LC Specimens  
Specimens will be collected for testing at the HPTN LC. Laboratory evaluations and procedures 
will include: 
• 
HIV quality assurance (QA) testing 
• 
Other testing* 
*Stored plasma will be used for QA testing and other assessments at the HPTN LC. This may 
include cross-sectional incidence testing (to identify participants who are recently infected at 
Enrollment). Stored samples will also be used for phylogenetic analysis. Other assessments that 
may be performed include ARV drug testing; HIV resistance testing; characterization of HIV and 
HCV and the host response to viral infection. Samples collected in the study may also be used to 
evaluate assays related to HIV and HCV infection. In some cases, testing will be performed at a 
commercial laboratory or another laboratory designated by the HPTN LC. These assessments will 
be performed retrospectively; results will not be returned to study sites or participants (with the 
possible exception of HIV diagnostic testing, if results obtained at the HPTN LC differ from site 
results). 

 
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9.3 
Quality Control and Quality Assurance Procedures 
HPTN LC staff will conduct periodic visits to each site to assess the implementation of on-site 
laboratory quality control (QC) procedures, including proper maintenance of laboratory testing 
equipment and use of appropriate reagents. HPTN LC staff will follow up directly with site staff 
to resolve any QC or QA problems identified through proficiency testing and/or on-site 
assessments.    
9.4 
QC for HIV Diagnostic Testing 
The HPTN LC will perform HIV diagnostic testing for QC. Algorithms for HIV diagnostic 
testing are provided in the SSP Manual. 
9.5 
Phylogenetic Analysis 
Phylogenetic methods will be used to explore the relationship between viruses from study 
participants. HIV sequencing will be performed at the HPTN LC or another laboratory designated 
by the HPTN LC. HIV sequencing will be performed by bulk (population) sequencing; next 
generation/deep sequencing may also be performed. The HPTN LC will determine the methods 
used for phylogenetic analysis (e.g., the HIV genomic regions analyzed, use of local and other 
control sequences, methodology used for data analysis).  
9.6 
Specimen Storage and Possible Future Research Testing 
Study site staff will store all plasma specimens collected in this study at for at least three years 
after the end of the study (completion of the last study visit). In addition, study participants will 
be asked to provide written informed consent for their plasma specimens to be stored after the end 
of the study for possible future testing related to HIV and HCV infection, evaluation of laboratory 
assays relevant to the study objectives, and other assessments. The specimens of participants who 
do not consent to long-term storage and additional testing will be destroyed after all protocol-
related testing has been completed; sample destruction must be coordinated with the HPTN LC 
and HPTN SDMC. 
9.7 
Biohazard Containment 
As the transmission of HIV and other blood-borne pathogens can occur through contact with 
contaminated needles, blood, and blood products, appropriate blood and secretion precautions 
will be employed by all personnel in the drawing of blood and shipping and handling of all 
specimens for this study, as currently recommended by the US CDC. All infectious specimens 
will be transported in accordance with US regulations (42 Code of Federal Regulations [CFR] 
72). 
9.8 
Resistance Testing at Local Laboratories. 
HIV resistance testing may be performed at local laboratories for clinical management using 
locally-available resistance test methods. Study specimens may not be used for this testing; 
additional specimens must be collected for this testing. Resistance testing may also be performed 
at the HPTN LC or a laboratory designated by the HPTN LC using stored specimens; results of 
this testing will not be returned to study sites or study participants. 

 
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10.0 
MODELING COMPONENT 
10.1 
Background and Prior Research 
Mathematical models of HIV transmission are widely used to understand the dynamics of HIV 
transmission, to assess the population-level impact of HIV prevention and treatment interventions 
and to inform policy decisions.77 They are also increasingly and innovatively being used at 
different stages of the clinical trial process: to inform product development, to inform the design 
of optimal combination prevention, to inform the design and conduct of large community-based 
clinical trials, and to interpret and help generalize results to the wider population.78 Models of 
HIV transmission amongst MSM have been used to estimate the impact of role segregation 
(taking only the insertive or receptive role in anal intercourse),79-81 and serosorting (having anal 
sex only with MSM of the same HIV status),82, 83 which both lead to lower overall HIV 
prevalence. Models have also been used to understand the racial disparities in HIV prevalence 
seen amongst MSM in the US,84 which are related to preferential mixing by race, and differences 
in access to care and treatment. Models have been used to estimate the impact of pre-exposure 
prophylaxis for MSM in the US85 and Peru,86 informed by effectiveness estimates from the iPrEx 
trial of PrEP for MSM. Modelling has also been used to estimate the likely impact of increasing 
HIV testing and treatment amongst MSM. For example, modeling has been used to predict a 
moderate impact of increased testing frequency alone for MSM,15, 87 to estimate the impact of 
behavior change following HIV testing88 and to predict a more substantial impact from increased 
testing coupled with immediate ART treatment for MSM.15, 89, 90  
In the current study, models will be used to estimate the likely population level impact on HIV 
transmission of the increased rates of identification of HIV-infected non-virally suppressed MSM 
and the increased level of viral suppression achieved in the trial, and to estimate the effect of the 
different trial components, which aim to increase the identification of unsuppressed HIV-infected 
MSM and increase linkage to care, ART initiation and retention in care.  
10.2 
Rationale 
Mathematical modelling will be used to translate the results of the study and estimate the 
potential population-level impact of the tested CM intervention on HIV, since the trial does not 
include HIV incidence as an endpoint and will measure the impact of the CM intervention at an 
individual rather than a community level. Rather than measuring the impact of the CM 
intervention upon HIV incidence, the first main objective of the study is to measure the success of 
the DC-RDS strategy in finding MSM who are not virally suppressed (primary objective), while 
also capturing useful information about the risk profile (behavioral, socio-demographic and 
clinical) of the population reached and retained at different stages of the treatment cascade 
(secondary objective). The second primary objective of the study is to measure the impact of the 
CM intervention upon the proportion of MSM achieving viral suppression after 24 months 
(primary objective), and the time to viral suppression (secondary objective), as well as collecting 
data on intermediate steps including the proportion linked to care and remaining engaged in care 
(secondary objective). 
Given the focus on treatment outcomes and the endpoint of viral suppression, and the fact that the 
CM intervention can influence multiple outcomes on the causal HIV prevention pathway among 
HIV-infected MSM (e.g. increased initiation and retention in treatment, changes in sexual 
behavior), it is difficult to understand the prevention potential of the individual-level CM 
intervention on population-level HIV incidence based on the trial results alone. Mathematical 
models are needed to translate the results of the CM intervention components implemented in this 

 
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study into estimates of the potential population-level impact of the combined CM intervention 
package on future HIV acquisition and transmission, taking into account the specific risk profile 
of those adopting the CM intervention and the existing epidemiological and prevention contexts 
where the interventions are taking place. 
Models can also be used to estimate the level of treatment-as-prevention efforts required to 
reduce HIV incidence at the population level by a substantial amount as rapidly as possible, and 
to assess whether the results of this trial in terms of CM intervention uptake, retention, adherence, 
and the risk profile of the population reached and responding favorably to the CM intervention 
warrant roll-out of the CM intervention to the wider MSM population. 
10.3 
Model Population and Setting 
The modelled population will be all sexually active MSM (both HIV-infected and 
HIV-uninfected) in each of the four different sites included in the trial. 
10.4 
Main Model Outcomes 
The main model outcomes include the following:  
• 
Predicted population-level reduction in incidence and prevalence achieved by the CM 
intervention, and by individual components of the CM intervention (HIV testing, ART 
uptake, retention in care and viral suppression) over 2, 5 and 10 years at each site. 
• 
Predicted preventable fraction (PF): The fraction of new HIV infections averted by a given 
CM intervention package, or its independent components, over a fixed time period 
• 
Estimated level of viral suppression required to reduce HIV incidence at each site by 10%, 
20%, 30%, and 50% over 2, 5 and 10 years. 
• 
Estimates of whether or not the CM intervention would be likely to result in HIV elimination 
(HIV incidence less than one new HIV infection per 1000 people per year91) at each site, and 
the time taken to reach this elimination threshold, both with achieved levels of viral 
suppression, and for the different levels of viral suppression required to meet incidence 
reduction targets.  
• 
Population attributable fraction (PAF): The contribution of different risk groups or risk 
factors to HIV transmission over different time periods. 
10.5 
Modeling Stages 
We will develop and analyze a dynamical, deterministic compartmental model of sexual HIV 
transmission and HIV prevention among MSM in different US settings, and use it to estimate the 
impact of the CM intervention at the population level.  
 
 

 
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For each setting, the modeling study will include a number of stages:  
• 
Model development and coding 
• 
Model parameterization  
• 
Model calibration and fitting to HIV prevalence and incidence data from various site specific 
sources 
• 
Model analysis: estimation of CM intervention impact, including uncertainty and sensitivity 
analysis 
More details about the different stages are given in the following sections. 
10.5.1 Model Development and Coding 
The proposed model is a dynamic, deterministic compartmental model which describes HIV 
transmission via anal sex between and among different risk groups of MSM, as well as rates of 
HIV progression and levels of testing and treatment over time. Within the model, the MSM 
population will be divided into different categories stratified by age, race, sexual risk activity (e.g. 
rate of partner acquisition, frequency of sex acts)92, 93  and sexual role behavior (exclusively 
insertive, exclusively receptive, or versatile in anal sex) (Figure 3).80, 94  
Figure 3: Behavioral Groups and Sexual Mixing in the Model. 
 

 
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MSM are divided into different groups relating to sexual role behavior (exclusively insertive, 
exclusively receptive, or versatile in anal sex), age, race and sexual risk activity.  MSM in each of 
these groups may be uninfected with HIV (gray), infected and not virally suppressed (red; highly 
infectious), or infected, treated and virally suppressed (green; reduced infectiousness). Sexual 
mixing between these groups will be informed by data on mixing patterns by age, race, sexual 
risk and sexual role. As ART coverage increases (i.e. the proportion of sexual partners on ART 
increases), HIV viral load will decrease (viral suppression increases) and so HIV incidence will 
decrease. 
In the model, HIV infection and progression will be modelled as a number of discrete stages 
through which MSM move – susceptible (uninfected), acute HIV infection (stage 1), chronic HIV 
infection, divided into three stages (stages 2-4), and AIDS (stage 5; Figure 4).95 This staging 
allows the model to reflect changes in infectivity, CD4 levels and symptoms which occur as a 
function of time since infection, and to capture historical changes in the timing of treatment 
initiation. HIV-infected MSM with acute infection or AIDS will have increased infectivity, and 
those on ART and virally suppressed will have reduced infectivity (Figures 3 and 4). HIV-
infected MSM may move between different categories reflecting their testing and treatment 
status, including those unaware of their HIV positive status, those tested, linked into pre-ART 
care, those on ART and partially or fully virally suppressed and those who are lost to follow-up, 
have discontinued ART and those living with HIV who have never been tested. This last category 
contains individuals who may also initiate ART when they present with symptoms (Figure 4).  
Figure 4: Infection and Treatment States. 
 
 

 
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MSM in the model are divided into separate categories by infection and treatment status. Infected 
MSM are divided by infection stage, with the chronic phase subdivided into several stages 
(reflecting CD4 levels when untreated) to allow more accurate timing of AIDS, appearance of 
symptoms and ART initiation and modelling historical increases in treatment which was based on 
CD4 levels. MSM on ART have greatly reduced infectivity when they are virally suppressed. The 
level of infectiousness is indicated in pink/red/green. MSM start ART either due to presenting 
symptoms or following testing. 
The force of HIV infection (or per capita HIV incidence rate) for susceptible MSM will be 
estimated (following calibration, details below) based upon the frequency and type of sex acts 
(insertive/receptive) they have, as well as condom use with different types of partner (main, 
casual and commercial), their circumcision status, PrEP and PEP use, who their sexual partners 
are likely to be (based upon mixing preferences related to age, race, sexual risk activity and 
serostatus and data on the proportion of sexual partners resident inside and outside of the study 
community), and levels of HIV prevalence and ART use among those partners (Figure 5). To 
capture the impact of other STIs upon HIV transmission risk, syphilis prevalence measured at 
baseline will be used together with published estimates of the increased risk of HIV transmission 
in the presence of syphilis to estimate associated increases in HIV transmission in each setting, 
assuming stable syphilis prevalence. The final model structure will depend upon the site-specific 
data available (from the trial and other complementary sources) to determine parameters and also 
upon important identified sources of heterogeneity.  
Figure 5: Force of Infection. 
 

 
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This figure summarizes the different factors which contribute to the force of infection (per capita 
incidence rate), including characteristics of the susceptible MSM and of their sexual partners. 
The model will incorporate the effects over time of past and existing interventions (e.g., increases 
in condom and ART use), and future interventions (the CM intervention and standard of care, 
including associated levels of linkage to care, ART initiation and adherence and retention in 
care), upon HIV susceptibility, transmissibility and rate of disease progression. Changes in levels 
of HIV testing will also be represented, as will documented changes in sexual behavior (including 
number and type of partners and sexual mixing patterns). 
The model will consist of coupled nonlinear ordinary differential equations and will be coded 
with a flexible programming language (e.g. C++). 
10.5.2 Model Parameterization 
The data required to inform model parameters and calibrate the model cover five main domains: 
demography, sexual behavior, natural history of HIV, intervention, and epidemiological HIV 
data. This information should ideally be obtained from representative samples of the population. 
We will use data from the trial (which may need to be standardized to reflect the wider MSM 
population, and to account for the recruitment process), and we will also comprehensively review 
and make use of other relevant sources of data such as HIV surveillance data, the published 
literature, systematic reviews and official reports. The trial will provide data to inform the 
modelling of future interventions, including data on the demography, sexual behavior, prior HIV 
testing, HIV prevalence, viral status, and ART use of those recruited through DC-RDS. The trial 
will also provide estimates of the proportion of people linking to and retained in care, initiating 
ART and achieving viral suppression, with and without the CM intervention package. In addition, 
the trial will provide data on the demographic and risk profiles of those retained at each stage of 
the HIV care cascade. Complementary data from other sources will be needed to inform 
modelling of past behavior and interventions and to characterize the wider MSM population at 
each site (including demographic, sexual behavior and HIV testing data). Other data will also be 
required to model the progression of HIV and effectiveness of different interventions, and to 
capture historical changes in behavior and ART coverage. Likely sources of data to inform the 
CM intervention and standard of care scenarios are summarized in Table 4; the final data sources 
used may vary depending upon the exact sites used for the trial. 
 
 

 
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Table 4. Model parameters and likely data sources 
Data 
Domain 
Parameters 
Trial Data Used 
Other Data Used 
Demography 
Age composition, natural 
death rates, MSM 
population size, migration 
RDS-derived estimates of 
population size, age, 
mobility data, data on 
whether sex partners are 
resident inside/outside the 
community 
Age composition: overall 
for national sample 
(NHBS); Natural death 
rates: National Vital 
Statistics reports; total 
population size: US Census 
data; Proportion of people 
reporting same-sex sexual 
activity: National Survey 
of Family Growth (NSFG) 
 
Sexual 
Behavior 
Number and type of male 
anal sex partners (per unit 
time), frequency of 
insertive and receptive anal 
sex with different partners, 
preference for partners by 
age, race, HIV status and 
sexual activity, role 
behavior, condom use with 
different partners. Changes 
in these behaviors over 
time 
Number of partners and 
sex acts, role behavior, 
condom use at baseline 
(RDS + CM intervention 
cohort) and after 24 
months (CM intervention 
cohort only), partner 
characteristics at baseline 
(RDS + CM intervention 
cohort) 
Number of main and casual 
partners last year: Overall 
estimate from CDC NHBS 
surveys for MSM 2005, 
2008, 2011, 2014; overall 
number of male partners 
last year: NSFG, national 
estimate; condom use at 
last sex act: overall 
estimate from NHBS 
surveys 2005, 2008, 2011, 
2014; levels of consistent 
condom use: NHBS 
individual sites 2005, 
2008, 2011, 2014; role 
behavior92 
Natural 
History of 
HIV 
Duration, probability of 
infection per sex act (by 
role), infectivity by HIV 
viral load 
(no trial data will be used) 
Duration of different 
stages of infection: 
European cohort studies96 
Relative infectiousness of 
different stages of 
infection: published 
analyses 97 
Probability of infection per 
anal sex act: published 
literature and existing 
systematic reviews97-99 
Infectivity by HIV viral 
load:15, 100-102 
 

 
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Data 
Domain 
Parameters 
Trial Data Used 
Other Data Used 
CM 
intervention 
and SOC 
Rates of HIV testing, 
linkage to care, ART 
initiation, viral 
suppression; PrEP and PEP 
use; changes in these over 
time and differences 
between study arms. 
Retention in care and ART 
adherence. Loss to follow-
up. 
Effectiveness of male 
circumcision, condoms, 
ART, PrEP in reducing 
infectiousness 
Current levels PrEP and 
PEP use, HIV testing, ART 
coverage in RDS sample; 
levels of HIV testing post-
recruitment among RDS 
sample; linkage to care, 
ART initiation, adherence, 
retention in care, viral 
suppression for each arm 
of the trial, by risk group, 
and loss to follow-up. 
Testing: CDC NHBS 
surveys for MSM (for 
NHBS sites) 
Linkage to care, ART 
initiation, viral 
suppression: CDC MMWR 
reports 
Published literature and 
systematic reviews on 
effectiveness of male 
circumcision,103 
condoms,104, 105 ART, PrEP 
HIV 
Epidemiology 
HIV prevalence and 
incidence, changes over 
time, distribution of 
transmission by sources of 
infection; distribution 
among treated and 
untreated 
HIV prevalence in RDS 
population 
HIV incidence estimates 
using laboratory assays (if 
conducted) 
Phylogenetic analysis 
Baseline distribution of 
treated and untreated 
HIV-infected; both 
suppressed and 
unsurpassed 
Prevalence: CDC NHBS 
surveys for MSM 2005, 
2008, 2011, 2014 (for 
NHBS sites) 
Incidence: CDC estimates 
for MSM 2005 (selected 
NHBS sites), cohort data 
where available 
MMWR, Morbidity and Mortality Weekly Report; NHBS, National HIV Behavioral Surveillance; NSFG, National 
Survey of Family Growth.  
For each model parameter, a most likely value and a range of plausible values (a priori range) 
will be obtained. 

 
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10.5.3 Model Calibration and Fitting 
The model, including past and current levels of interventions, will be calibrated to available HIV 
prevalence and incidence data over time (which is representative of the sites modelled) within a 
Bayesian framework where a priori information on the key parameters from available data 
sources is updated through a comparison of the model simulations and epidemiological HIV 
data.106 The parameter ranges constructed in the model parameterization stage will be 
exhaustively sampled and explored at the calibration stage, using state of the art fitting methods 
previously used107-109 in order to identify multiple parameter sets that agree with the 
epidemiological HIV data (HIV prevalence and incidence), producing a set of model predictions 
which reflect HIV patterns by risk group in the target population while taking into account 
uncertainty in parameter assumptions. This set of simulations will form our baseline scenario and 
baseline parameter sets. As per standard procedure in modelling studies ,94, 95, 107, 108, 110 this 
calibrated set of simulations will also produce the necessary baseline estimates of population 
level HIV incidence required to subsequently be able to assess the impact of scaling up future 
interventions. 
10.5.4 Model Analysis 
The calibrated model for each site will be used to conduct the following analyses: (1) assess the 
population level impact of the overall study strategy on HIV incidence and prevalence, and the 
preventable fraction of HIV infections averted; (2) assess the population level impact of the 
individual components of the CM intervention (including HIV testing, ART uptake, retention in 
care, viral suppression)  on HIV incidence and prevalence and the preventable fraction of HIV 
infections averted by these individual components; (3) estimate the level of viral suppression 
required to reduce HIV incidence at each site by 10%, 20%, 30%, and 50% over 2, 5 and 10 
years; (4) estimate the likelihood of and time taken to reach HIV elimination; (5) estimate the 
PAF for different risk groups, the stage in the cascade of care and the risk factors over different 
time periods; (6) uncertainty and sensitivity analyses. 
10.5.4.1 Overall CM Intervention Impact 
The model will be run for each site under two alternative scenarios, standard of care (baseline) 
and CM intervention, with levels of testing, linkage, ART initiation and retention, and viral 
suppression going into the future informed by the levels measured in each arm of the trial (table 
1). Predicted overall CM intervention impact will be determined by comparing the predicted 
cumulative HIV incidence, HIV incidence rate and HIV prevalence in the CM intervention and 
baseline scenarios over 2, 5 and 10 years, with all trial components included in the intervention 
arm. This will yield estimates of the impact of the total CM intervention package on population-
level HIV incidence and prevalence, and the preventable fraction PF(dt) of HIV infections. In 
these analyses we will take into account differences in CM intervention coverage and uptake by 
risk group. Each modelling outcome will be presented as the mean, median and uncertainty range 
(95% percentiles of the model predictions based on the multiple posterior parameter sets). 
 
 

 
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10.5.4.2 Impact of Individual CM Intervention Components 
We will then use the models to estimate the impact of the observed independent CM intervention 
components, by running additional model scenarios in which only some of the CM intervention 
components (increased rates of HIV testing, increased linkage, ART uptake, retention in 
treatment and viral suppression) are included, and comparing these with the baseline model in the 
same way as for the full CM intervention model, above, to estimate the reduction in incidence and 
prevalence and the PF associated with each CM intervention component and combination of 
components. Each modelling outcome will be presented as the mean, median and uncertainty 
range (95% percentiles of the model predictions based on the multiple posterior parameter sets). 
10.5.4.3 Required Viral Suppression to Achieve Incidence Reduction Targets 
We will also use the models to estimate the level of viral suppression and associated CM 
intervention efforts that need to be achieved in order to reduce HIV incidence in the MSM 
community by 10%, 20%, 30%, and 50% over 2, 5 and 10 years.  
10.5.4.4 HIV Elimination 
We will estimate whether HIV is predicted to be eliminated if the CM intervention were carried 
on into the future for each site, both with achieved levels of viral suppression, and for the 
different levels of viral suppression required to meet the incidence reduction targets (10%, 20%, 
30%, and 50% reduction over 2, 5 and 10 years). Elimination is defined as HIV incidence going 
below one new HIV infection per 1000 people per year.91 Where elimination is predicted, we will 
estimate the predicted time taken to reach the elimination threshold.   
Each study outcome will be presented as the mean, median and uncertainty range (95% 
percentiles of the model predictions based on the multiple posterior parameter sets). 
10.5.4.5 Population Attributable Fraction (PAF) 
We will determine the main drivers of HIV acquisition and transmission in the MSM populations 
studied by calculating the short and long term transmission PAF.111, 112 The PAF(dt) will be 
derived by comparing the number of new infections using two defined risk parameters: 1) 
assuming that the given risk factor increases risk of HIV acquisition or transmission or the 
relevant risk behavior; 2) assuming no increase in risk associated with the factor under study. The 
key risk groups for whom we will calculate PAFs will be: sexual role groups (insertive or 
receptive, versatile), untested MSM, and HIV-infected MSM who not virally suppressed.  
10.5.4.6 Uncertainty and Sensitivity Analyses 
We will conduct an uncertainty analysis using the multiple calibrated simulations to assess the 
influence of key epidemiological and intervention factors/parameters (in CM intervention and 
SOC control arms) on impact predictions (using a technique such as partial rank correlation), and 
determine under which conditions a CM intervention will have the largest impact (using 
techniques such as regression trees analysis).   
We will conduct a sensitivity analysis to determine the influence on the impact estimates 
(incidence and prevalence reduction and PF) of key parameters such as the evolution of the SOC 
over time, and determine a threshold of high sensitivity where impact is considerably reduced. 

 
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11.0 
ADMINISTRATIVE PROCEDURES 
11.1 
Protocol Registration  
Initial Registration of the protocol by the DAIDS Protocol Registration Office (PRO) is required 
prior to implementation of this protocol. As part of this process, each site must have the protocol 
and protocol informed consent form(s) approved, as appropriate, by their local IRB/ethics 
committee (EC) and any other applicable regulatory entity. Upon receiving final approval, sites 
will submit all required protocol registration documents to the 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. In the case of Initial Registration, 
site-specific informed consent forms (ICFs) will be reviewed and approved by the DAIDS PRO. 
Sites will receive an Initial Registration Notification from the DAIDS PRO that indicates 
successful completion of the protocol registration process. A copy of the Initial Registration 
Notification should be retained in the site's regulatory files. 
Following Initial Registration, any full protocol amendments require submission of a protocol 
registration packet to the DAIDS PRO as described above; however, the DAIDS PRO will not 
review and approve site-specific ICFs. Sites will receive a Registration Notification when the 
DAIDS PRO receives a complete registration packet.  
For additional information on the protocol registration process and specific documents required 
for initial and amendment registrations, refer to the current version of the DAIDS Protocol 
Registration Manual, which can be found at http://rsc.tech-res.com/protocolregistration/. 
11.2 
Study Activation 
Pending successful protocol registration and submission of all required documents, the HPTN 
LOC staff will “activate” a site. Study implementation may not be initiated until a study 
activation notice is provided to the site by the HPTN LOC. In addition, if study “activation” is 
determined to be necessary for any subsequent amendments, study implementation may not be 
initiated until a study activation notice is provided to the site by the HPTN LOC. 
11.3 
Study Coordination 
Study implementation will be directed by this protocol as well as the SSP Manual. The SSP 
Manual will outline procedures for conducting study visits; data and forms processing; social 
harm assessment, management and reporting; and other study operations. 
Study CRFs and other study instruments will be developed by the protocol team and HPTN 
SDMC. Data will be transferred to the HPTN SDMC for data entry, cleaning, reporting and 
analysis. Quality control reports and queries will be generated and distributed to the study sites on 
a routine schedule 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, adherence, follow-up, and social harm incidence will be monitored 
closely by the team as well as the HPTN Study Monitoring Committee (SMC). The Protocol 
Chair, DAIDS Medical Officer, Protocol Biostatistician, SDMC Project Manager, and HPTN 
LOC representatives will address issues related to study eligibility and social harm management 

 
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and reporting as needed to assure consistent case management, documentation, and information-
sharing across sites. 
11.4 
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, CRFs), as well as 
observe the performance of study procedures. Investigators also will allow inspection of all study-
related documentation by authorized representatives of the HPTN LOC, HPTN SDMC, HPTN 
LC, NIAID, site IRBs/ECs, and US regulatory authorities (OHRP). A site visit log will be 
maintained at each study site to document all visits. 
11.5 
Protocol Compliance 
The study will be conducted in full compliance with the protocol. The protocol will not be 
amended without prior written approval by the Protocol Chair and DAIDS Medical Officer. All 
protocol amendments must be submitted to and approved by the relevant IRB(s) and the DAIDS 
RSC prior to implementing the amendment. 
11.6 
Investigator’s Records 
All site Investigators of Record (IoR) will be responsible for maintaining, and storing in a secure 
manner, complete, accurate, and current study records throughout the study. Under the US 
Department of Health and Human Services (HHS) regulations, the IoR is required to retain all 
study records relating to research for at least three [3] years after completion of the research, or 
longer if needed to comply with local regulations.  Completion of a clinical research study occurs 
when the following activities have been completed: 
• 
All research-related interventions or interactions with human subjects;  
• 
All protocol-required data collection of identifiable private information described in the 
IRB/EC-approved research plan;  
• 
All analysis of identifiable private information described in the IRB/EC-approved research 
plan;  
• 
Primary analysis of either identifiable private or de-identified information.  
Study records include administrative documentation — including protocol registration documents 
and all reports and correspondence relating to the study — as well as documentation related to 

 
HPTN 078, Final Version 2.0 
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Page 42 of 88 
each participant screened and/or enrolled in the study — including informed consent forms, 
locator forms, CRFs, notations of all contacts with the participant, and all other source 
documents. 
11.7 
Use of Information and Publications 
Publication of the results of this study will be governed by the HPTN Manual of Operations. Any 
presentation, abstract, or manuscript will be submitted to the HPTN Manuscript Review 
Committee and DAIDS for review prior to submission. 
 
 

 
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based modelling analysis. The Lancet Global health 2013; 1(5): e289-99. 
109. Vickerman P, Platt L, Hawkes S. Modelling the transmission of HIV and HCV among 
injecting drug users in Rawalpindi, a low HCV prevalence setting in Pakistan. Sexually 
transmitted infections 2009; 85 Suppl 2: ii23-30. 
110. Boily MC, Lowndes CM, Vickerman P, et al. Evaluating large-scale HIV prevention 
interventions: study design for an integrated mathematical modelling approach. Sexually 
transmitted infections 2007; 83(7): 582-9. 
111. Mishra S, Pickles M, Blanchard JF, Moses S, Boily MC. Distinguishing sources of HIV 
transmission from the distribution of newly acquired HIV infections: why is it important for 
HIV prevention planning? Sexually transmitted infections 2014; 90(1): 19-25. 
112. Mishra S, Pickles M, Blanchard JF, Moses S, Shubber Z, Boily MC. Validation of the 
modes of transmission model as a tool to prioritize HIV prevention targets: a comparative 
modelling analysis. PloS one 2014; 9(7): e101690. 

 
HPTN 078, Final Version 2.0 
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Page 51 of 88 
APPENDICES 
 

 
HPTN 078, Final Version 2.0 
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APPENDIX I: SCHEDULE OF STUDY VISITS, EVALUATIONS AND PROCEDURES 
Note: Monthly visits will be defined as a predetermined number of weeks, as described in the SSP. In addition, in special cases, 
the screening and enrollment visits may take place on the same day (see SSP).  
X, all participants; I, CM intervention arm only. 
1Monthly contact is only provided to participants in the CM intervention arm; these interactions may be conducted in person or 
by phone, text message or email. 
2Social impact assessments will not be collected until after first study encounter. 
3Test results may be given at the enrollment visit, including post-testing counseling 
4In special cases, participants may receive additional coupons after screening. See SSP for detailed instructions. 
5Treatment or referral for HCV and/or Syphilis treatment may be given at the enrollment visit.  
6If the syphilis test is positive, participants will be given their test results and referred for care via site standards.  
7Procedures for HIV and HCV testing are described in the SSP Manual. 
8Syphilis testing will be performed using blood specimens according to local standards.  
9If HIV positive by self-report, clinic record or by having a reactive HIV rapid test at screening, blood will be collected for HIV 
confirmatory testing, HIV viral load and CD4+ cell count. 
10Stored plasma will be used for Quality Assurance testing and other assessments at the HPTN LC (see Section 9.2). These 
assessments will be performed retrospectively; results will not be returned to study sites or participants except as noted in 
Section 9.2.  
Note: At the start of the study, plasma was stored at screening (not at enrollment). If plasma is not available from enrollment, 
plasma from screening may be used for HPTN LC testing 
 
 
 
 
 
Screening 
Enrollment 
(M0) 
Monthly 
Contact1 
Follow-up 
(M3, M6, M9, 
M12, M18) 
Final (M24) 
Administrative and Behavioral Evaluations/Procedures 
Informed consent 
X 
X 
 
 
 
Release of medical information 
 
X 
 
 
 
Contact/locator information 
X 
X 
I 
X 
X 
Questionnaire administration (see Appendix II) 
X 
X 
 
 
X 
Recruiter training 
X 
 
 
 
 
Coupon reimbursement 
X 
 
 
 
 
Social impact assessment 
X2 
 
I 
X 
X 
Pre- and post-test HIV counseling, including 
HIV/STI risk reduction counseling 
X 
X3 
 
 
 
Offer of partner HIV counseling and testing 
 
X 
 
X 
X 
Coupon disbursement 
X4 
 
 
 
 
Case manager (CM) intervention 
 
I 
I 
I 
I 
Exit interview 
 
 
 
 
X 
Clinical Evaluations/Procedures 
Blood collection 
X 
X 
 
X 
X 
Syphilis treatment or referral, if indicated 
X 
X5 
 
 
X6 
HCV treatment or referral, if indicated 
X 
X5 
 
 
 
Laboratory Evaluations/Procedures 
HIV testing 
X7,9 
 
 
 
 
Hepatitis C virus testing 
X7 
 
 
 
 
Syphilis testing 
X8 
 
 
 
X 
CD4 cell count testing 
X9 
 
 
X 
X 
HIV viral load testing 
X9 
 
 
X 
X 
Plasma storage10 
 
X 
 
X 
X 

 
HPTN 078, Final Version 2.0 
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APPENDIX II: SCHEDULE OF QUESTIONNAIRE DOMAIN ADMINISTRATION 
Questionnaire Domain 
Screening  
 
Enrollment 
(M0) 
(Intervention 
participants 
[CM 
Intervention and 
SOC control 
arms]) 
Final (M24) 
(Intervention 
participants 
[CM 
Intervention and 
SOC control 
arms]) 
Demographics 
X 
 
 
PrEP/PEP/ART use 
X 
 
 
HIV testing history 
X 
 
 
Engagement in LGBT 
community 
X 
 
 
Post-recruitment 
questions* 
X 
 
 
Health care utilization 
X 
 
X 
Sexual matrix module / 
sexual risk behavior 
X 
 
X 
Stigma 
X 
 
X 
Substance use and 
mental health 
 
X 
X 
Medication adherence 
 
 
X 
Exit Interview 
Questionnaire 
 
 
X** 
*These questions will only be asked of those who were given coupons to distribute and who 
distributed, or attempted to distribute, them. For those enrolled, this questionnaire may be 
administered at or after enrollment, as applicable. 
**The exit interview will be conducted with both participants and CMs. 
\ 
 

 
HPTN 078, Final Version 2.0 
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APPENDIX III: INFORMED CONSENT TEMPLATES 
 

 
HPTN 078, Final Version 2.0 
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Enhancing Recruitment, Linkage to Care and Treatment for HIV-Infected Men Who Have 
Sex with Men (MSM) in the United States 
HPTN 078 
Version 2.0 
July 3, 2017 
DAIDS Document ID: 11995 
 
HIV SCREENING INFORMED CONSENT FORM 
 
Sponsored by: Division of AIDS (DAIDS), United States (US) National Institute of Allergy and 
Infectious Diseases (NIAID), US National Institute of Mental Health (NIMH), US National 
Institute on Drug Abuse (NIDA) and US National Institutes of Health (NIH). 
PRINCIPAL INVESTIGATOR: [Insert Name] 
PHONE: [Insert Number] 
INTRODUCTION: You are being asked to take part in a research study. This study is looking at 
the best way to find men who have sex with men (MSM) and transgender women, who may be at 
risk for getting HIV (Human Immunodeficiency Virus). To find out if you are eligible for this 
study, a rapid HIV test will be done to test for HIV. [Sites may add reference to the inclusion of 
transgender women to the extent that they want, may change third person pronouns (eg., he to 
they) as they see fit for their site or may choose to have a separate consent for transgender 
women.] 
If your rapid test is positive for HIV, repeat testing is needed to confirm (prove) this result. If 
your second sample is proved to be positive for HIV, it means that you have HIV. This means 
that you can pass the virus to others by sexual contact, by sharing needles, and by donating blood 
and organs. A negative rapid test means that you do not have HIV but should be tested again if 
you have been exposed within the last 3-6 months. 
YOUR PARTICIPATION IS VOLUNTARY: You may refuse to be screened. You may also 
refuse the HIV test or to give your contact information. You may withdraw your consent for 
screening at any time. 
SCREENING PROCESS: You will receive a rapid HIV test. The rapid test will use a drop of 
blood from your finger or a swab from the inside of your mouth. You will be provided pre- and 
post-test counseling [sites to revise per their requirements]. We will also ask for your contact 
information so that we can reach you when your test results are complete. [Sites to add expected 
duration]. When your results are ready, you will be scheduled for an appointment. This 
appointment will be to discuss your results and receive further testing, if you choose. 
If you already know that you are HIV positive, you don’t need to take a rapid HIV test. If you 
would like, you may still give your contact information to be scheduled for an appointment. This 
appointment will do further screening to see if you are eligible for this study.   
RISKS AND/OR DISCOMFORTS: You may be nervous while you are waiting for your HIV 
test result. If the test shows that you have HIV, you may worry about your health and future. You 
will receive counseling before and after the test to help address your concerns [sites to revise per 
their requirements].  

 
HPTN 078, Final Version 2.0 
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We will make every effort to protect the privacy of your HIV test results. However, it is possible 
that others may learn that you are part of this screening. They may think that you are infected 
with HIV. Because of this you could have trouble finding or keeping a job. You could also have 
problems with your family, friends and community.  
There is also a small risk of infection if you have the finger stick for blood draw.  
BENEFITS: The benefits of being screened for HIV include knowing your HIV status. Finding 
HIV infection early can also be important for your treatment.  
ALTERNATIVES TO PARTICIPATION: [Sites to include/alter the following if applicable: If 
you would like, we will tell you how to get HIV testing anonymously at other places.] 
REIMBURSEMENT: You will receive [site to add amount] for your time to be tested for HIV 
today. [Sites to insert information about local reimbursement for the study.]   
CONFIDENTIALITY: All of your contact information will be kept private. Your test results 
will also be kept private.  This information will not be shared with others.  All records will be 
stored in locked files at the study clinic.  
[Sites to include/amend the following if applicable:] [Local/state/national] regulations require 
study staff to report the names of people who test positive for HIV to the [local health authority]. 
Outreach workers from the [health authority] may then contact you about telling your partners, 
since they also should be tested. If you do not want to tell your partners yourself, the outreach 
workers will contact them, according to the privacy guidelines of the [health authority]. 
PROBLEMS OR QUESTIONS: If you ever have any questions about the screening procedures, 
or if you have a research-related injury, you should contact [insert name of the investigator or 
other study staff] at [insert telephone number and/or physical address]. 
If you have questions about your rights as a research participant, you should contact [insert name 
or title of person on the IRB or other organization appropriate for the site] at [insert physical 
address and telephone number]. 
If you have read this consent form, or had it read and explained to you, and you understand the 
information, and you voluntarily agree to test for HIV and give your contact information, please 
sign your name or make your mark below.  
 
_________________________________ 
________________________________ 
Participant Name (print) 
 
 
Participant Signature and Date 
 
 
 
 
 
 
[sites to include if applicable] consent or assent 
_________________________________ 
________________________________ 
Study Staff Conducting  
 
 
Study Staff Signature and Date 
Consent Discussion (print) 
 
_________________________________ 
_________________________________ 
Witness Name (print) 
 
 
 
Witness Signature and Date 
(As appropriate) 
 

 
HPTN 078, Final Version 2.0 
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Enhancing Recruitment, Linkage to Care and Treatment for HIV-Infected Men Who Have 
Sex with Men (MSM) in the United States 
HPTN 078 
Version 2.0 
July 3, 2017 
DAIDS Document ID: 11995 
 
SCREENING INFORMED CONSENT FORM 
 
Sponsored by: Division of AIDS (DAIDS), United States (US) National Institute of Allergy and 
Infectious Diseases (NIAID), US National Institute of Mental Health (NIMH), US National 
Institute on Drug Abuse (NIDA) and US National Institutes of Health (NIH). 
PRINCIPAL INVESTIGATOR: [Insert Name] 
PHONE: [Insert Number] 
INTRODUCTION 
You are being asked to take part in a research study. This study is designed to find the best way to 
find men who have sex with men (MSM) and offer them HIV testing. Joining this study is 
voluntary. You may refuse to join, or you may withdraw your consent to be in the study, for any 
reason. This study is for MSM and transgender women, who may be at risk for getting Human 
Immunodeficiency Virus, or HIV. HIV is the virus that causes Acquired Immunodeficiency 
Syndrome, or AIDS. [Sites may add reference to the inclusion of transgender women to the extent 
that they want, may change third person pronouns (eg., he to they) as they see fit for their site or 
may choose to have a separate consent for transgender women.] 
Before you decide whether to join the study, we would like to explain the purpose of the 
screening, the risks and benefits, and what is expected of you.  
YOUR PARTICIPATION IS VOLUNTARY 
This consent form gives information about the screening. Once you understand the screening, and 
if you agree to take part, you will be asked to sign your name or make your mark on this form. 
You will be offered a copy of this form to keep.  
Before you learn about screening, it is important that you know the following: 
• 
Your participation is voluntary. You do not have to take part in any of the screening tests, 
questionnaires or procedures. 
• 
You may decide not to take part in screening, or you may decide to leave the screening at any 
time. 
• 
If you decide not to take part in the screening, you can still join another study at a later time if 
there is one available and you qualify. 
• 
If you decide not to take part in the screening, or decide to stop participating at any time, 
there will be no penalty or loss of the normal benefits provided to you at our clinic. 

 
HPTN 078, Final Version 2.0 
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PURPOSE OF THE SCREENING  
The purpose of the screening is to find MSM using a method called “respondent driven sampling” 
or “RDS.” In RDS, we ask MSM to invite other MSM they know to come to our clinic for 
screening. We will also invite MSM to take part in this study that we find in other ways.  
We plan to screen about 2700 people from four US cities (about 675 in each participating city) in 
two years. During screening, we will test MSM for HIV, hepatitis C virus and syphilis. We will 
also ask each MSM to complete a questionnaire. If we find MSM who are HIV-infected, we may 
invite them to take part in another study. This other study is testing whether case manager support 
can help MSM receive regular HIV care and regularly take their HIV medication.  
Information from the screening procedures will be used to prevent the spread of HIV in the MSM 
community.   
SCREENING PROCEDURES 
If you agree to participate, you will be asked to take part in up to three screening visits.   
Screening will happen after you read, discuss, understand, and sign this form. We will help you 
understand the form and answer your questions before you sign this form. The procedures done 
during Screening will take about [sites to fill in the amount of time] hours each time.  
During screening: 
• 
We will confirm where you live and how to contact you. 
• 
We will ask you to answer a questionnaire.  This questionnaire will ask you about yourself 
(like your age and race) and your sexual behavior and partners. It will also ask you about 
your use of HIV drugs, HIV testing history and health care use. Finally, it will ask you about 
your involvement in the lesbian, gay, bisexual and transgender (LGBT) community and 
stigma you may have faced because you are an MSM. 
• 
We will ask you if you have had any problems because you are a part of this screening. 
• 
We will talk to you about HIV and other infections that can be spread sexually. We will give 
you information to help you protect yourself from getting them or passing them on to others. 
• 
We may give you a rapid HIV test. The rapid test will use a drop of blood from your finger or 
arm or a swab from the inside of your mouth. If your rapid test is positive for HIV, repeat 
testing is needed to confirm (prove) this result. If your second sample is proved to be positive 
for HIV, it means that you have HIV. A negative rapid test means that you do not have HIV 
but should be tested again if you have been exposed within the last 3-6 months. 
• 
We will collect a small amount of blood about 33 mL = about 6 teaspoons) to test for 
hepatitis C virus (HCV) and syphilis.  
• 
If you are HIV-infected, a small amount of blood (about 14 mL = about 3 teaspoons) will be 
collected to make sure you have HIV. This blood will also be used to measure your CD4 cell 
count and viral load. These tests tell us how much HIV is in your blood (viral load) and how 
much the virus has affected your ability to fight the virus (CD4).  
• 
We may give you coupons and ask you to invite MSM you know to come to the clinic for 
screening.  

 
HPTN 078, Final Version 2.0 
July 3, 2017 
Page 59 of 88 
• 
We will give you the results of your HIV, hepatitis C virus and syphilis tests.  If you have any 
of these infections, you will be referred for treatment [sites to add specifics about how this 
will take place at their site]. 
• 
If we can’t tell if you are infected or not after your HIV tests, you will be referred for further 
testing and care.  
• 
If you were asked to invite people you know to come for HIV testing, we will ask you 
questions about who you invited. 
If you are HIV-uninfected: If your HIV test results show that you aren’t infected, we will 
give you information about how to prevent getting HIV. 
If you are HIV-infected: If your HIV test results show that you are infected, we will check 
your viral load test to see if you are eligible for another study. If so, we may ask you if you 
are interested in being in the study. The study is testing if case manager support can help 
those who are HIV-infected. If you do not want to take part in this study, we will tell you 
where you can go to receive HIV care.  
RISKS AND/OR DISCOMFORTS 
Blood Draws 
Taking blood samples may cause some pain, bruise your arm, or make you feel lightheaded.  In 
rare cases, you may faint. There is also a small chance of infection when blood is drawn.  
HIV Testing and Potential Social Harm 
You may be nervous while you are waiting for your HIV test result. If the tests show that you 
have HIV, you may worry about your health and future. You will receive counseling before and 
after the test to help address your concerns. We will make every effort to protect your 
confidentiality during the study. However, it is possible that others may learn that you are part of 
this screening. They may think that you are infected with HIV or are at high risk for infection 
with HIV. Because of this you could have trouble finding or keeping a job. You could also have 
problems with your family, friends and community.   
Sensitive Questions 
The questions we will ask you about your sexual behavior and partners or about stigma you may 
have faced may make you feel uneasy. However, you do not have to answer any question that you 
do not want to. You can also stop answering the questions at any time.  
BENEFITS 
We will test you for HIV, hepatitis C virus and syphilis. If you have any of these infections, we 
will help you receive care and treatment. We will also tell you how to avoid passing them on to 
your sexual partners. The counseling you get during this study may help you avoid HIV and other 
infections that can be spread sexually. 
You may not receive any other direct benefit from being in this study. You or others in your 
community may benefit from these screening activities in the future. The information found 
during screening may help prevent HIV and other infections in the MSM community.   

 
HPTN 078, Final Version 2.0 
July 3, 2017 
Page 60 of 88 
NEW INFORMATION 
You will be told about any new information that might affect your willingness to take part in 
screening. You will also be told when the results of the study may be ready, and how to learn 
about them.   
WHY YOU MAY BE WITHDRAWN FROM SCREENING WITHOUT YOUR CONSENT 
You may be withdrawn from screening without your consent if any of the following occur:  
• 
You are unable or unwilling to follow all of the screening procedures or instructions.   
• 
Screening is stopped or canceled. 
• 
The study staff feels that taking part in the screening activities would be harmful to you. 
• 
You are not able to attend the screening visits or complete all of the screening procedures. 
• 
Other reasons, as decided by the study staff.  
ALTERNATIVES TO PARTICIPATION 
You may choose not to participate in the study. [Sites to include/amend the following if 
applicable: You do not need to participate in the screening activities to be tested for HIV at our 
site. If you wish, we will tell you how to get HIV counseling and testing at other places.] 
COSTS TO YOU 
There will be no cost to you for any screening visits, laboratory tests or other procedures. 
REIMBURSEMENT 
You will receive [site to add amount] for your time, effort, and travel to and from the clinic for 
each scheduled screening visit. [Sites to insert information about local reimbursement for the 
study.]   
CONFIDENTIALITY 
All the information you give us as part of this study will be kept private.  All your laboratory test 
results will also be kept private.  You will get a unique study identification number that will be 
used instead of your name on your documents.  However, at every screening visit we will ask you 
to identify yourself.  This is to make sure that it is you who provides samples and information to 
us.  Also, we want to make sure that no other person than you can get your confidential laboratory 
test results.  Only the study staff will be able to see records that identify you by name.  This 
information will not be shared with others.  All records will be stored in locked files at the study 
clinic.  Results of your laboratory tests will be made available only to you when you visit the 
clinic.  Your name will never be used in any publication or presentation about these screening 
activities. 
[Sites to modify this suggested language as appropriate:] If you are under 18 years old, we 
[must/do not need to] inform your parents or guardian about the results of your HIV and syphilis 
tests, unless you would like us to tell them.  If you are under 18 years old, we [must/do not need 
to] inform your parents or guardian about the results of your hepatitis C (HCV) test, unless you 
would like us to tell them.  If [we must / you choose to have us] inform them of these test results, 
we will talk to you about the best way to inform them before we do so. 

 
HPTN 078, Final Version 2.0 
July 3, 2017 
Page 61 of 88 
Your records may be looked at by the sponsor of the study, the US National Institutes of Health 
(NIH). They may also be looked at by NIH representatives, other government and regulatory 
authorities, [insert name of site] IRB/EC, study staff, study monitors and [insert applicable local 
regulatory authorities].   
In addition to the efforts made by the study staff to help keep your personal information 
confidential, we have obtained a Certificate of Confidentiality from the U.S. Federal Government.  
This Certificate protects researchers from being forced to tell people who are not connected with 
this study, such as the court system, about your participation.  The Certificate of Confidentiality 
does not prevent you from releasing information about yourself and your participation in the 
study.  The Certificate cannot be used to resist a demand for information from personnel of the 
US Government that is used for auditing or evaluation of federally funded projects or for 
information that must be disclosed in order to meet the requirements of the US FDA.  Even with 
the Certificate of Confidentiality, if the study staff learns of possible child abuse and/or neglect or 
a risk of harm to you or others, we will tell the proper authorities. 
A description of this study will be 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. 
[Sites to include/amend the following if applicable:] In this study, you will be tested for HIV, 
hepatitis C virus and syphilis. [Local/state/national] regulations require study staff to report the 
names of people who test positive for [HIV and other infections [sites should add that HCV and 
syphilis are reportable diseases if this is true for their location]] to the [local health authority]. 
Outreach workers from the [health authority] may then contact you about telling your partners, 
since they also should be tested. If you do not want to tell your partners yourself, the outreach 
workers will contact them, according to the privacy guidelines of the [health authority]. 
RESEARCH-RELATED INJURY 
[Sites to specify institutional policy:] It is unlikely that you will be injured because of your study 
participation. If you are injured, the [institution] will give you immediate necessary treatment for 
your injuries. You [will/will not] have to pay for this treatment. You will be told where you can 
get further treatment for your injuries. There is no program to pay money or give other forms of 
payment for such injuries either through this institution or the US NIH. You do not give up any 
legal rights by signing this consent form. 
PROBLEMS OR QUESTIONS 
If you ever have any questions about the screening activities, or if you have a research-related 
injury, you should contact [insert name of the investigator or other study staff] at [insert 
telephone number and/or physical address]. 
If you have questions about your rights as a research participant, you should contact [insert name 
or title of person on the IRB or other organization appropriate for the site] at [insert physical 
address and telephone number]. 

 
HPTN 078, Final Version 2.0 
July 3, 2017 
Page 62 of 88 
SIGNATURE PAGE 
Enhancing Recruitment, Linkage to Care and Treatment for HIV-Infected Men Who Have 
Sex with Men (MSM) in the United States 
HPTN 078 
Version 2.0 
July 3, 2017 
DAIDS Document ID: 11995 
 
SCREENING INFORMED CONSENT FORM 
 
If you have read this consent form, or had it read and explained to you, and you understand the 
information, and you voluntarily agree to complete the screening activities, please sign your name 
or make your mark below.  
 
 
 
 
 
____________________________________ 
Participant Name (print) 
 
Participant Signature and Date 
 
 
 
 
 
[sites to include if applicable] consent or assent 
 
 
 
 
____________________________________ 
Study Staff Conducting  
 
Study Staff Signature and Date 
Consent Discussion (print) 
 
 
 
 
 
____________________________________ 
Witness Name (print) 
 
 
Witness Signature and Date 
(As appropriate) 
 
 

 
HPTN 078, Final Version 2.0 
July 3, 2017 
Page 63 of 88 
Enhancing Recruitment, Linkage to Care and Treatment for HIV-Infected Men Who Have 
Sex with Men (MSM) in the United States 
HPTN 078 
Version 2.0 
July 3, 2017 
DAIDS Document ID: 11995 
 
ENROLLMENT INFORMED CONSENT FORM 
 
Sponsored by: Division of AIDS (DAIDS), United States (US) National Institute of Allergy and 
Infectious Diseases (NIAID), US National Institute of Mental Health (NIMH), US National 
Institute on Drug Abuse (NIDA) and US National Institutes of Health (NIH). 
PRINCIPAL INVESTIGATOR: [Insert Name] 
PHONE: [Insert Number] 
INTRODUCTION 
You are being asked to take part in a research study. This study is testing if support from a case 
manager can help HIV-infected people receive regular HIV care and regularly take their HIV 
medication. Joining this study is voluntary. You may refuse to join, or you may withdraw your 
consent to be in the study, for any reason.  This research study is for men who have sex with men 
(MSM) and transgender women, who have Human Immunodeficiency Virus, or HIV. HIV is the 
virus that causes Acquired Immunodeficiency Syndrome, or AIDS. [Sites may add reference to 
the inclusion of transgender women to the extent that they want, may change third person 
pronouns (eg., he to they) as they see fit for their site or may choose to have a separate consent 
for transgender women.] 
Before you decide whether to join the study, we would like to explain the purpose of the study, 
the risks and benefits, and what is expected of you.  
YOUR PARTICIPATION IS VOLUNTARY 
This consent form gives information about the study you are being invited to join. Once you 
understand the study, and if you agree to take part, you will be asked to sign your name or make 
your mark on this form. You will be offered a copy of this form to keep.  
Before you learn about the study, it is important that you know the following: 
• 
Your participation is voluntary.  You do not have to take part in any of the tests, 
questionnaires or procedures in the study. 
• 
You may decide not to take part in the study, or you may decide to leave the study at any 
time. 
• 
If you decide not to take part in the study, you can still join another study at a later time if 
there is one available and you qualify. 
• 
If you decide not to take part in the study, or decide to stop participating at any time, there 
will be no penalty or loss of the normal benefits provided to you at our clinic. 

 
HPTN 078, Final Version 2.0 
July 3, 2017 
Page 64 of 88 
PURPOSE OF THE STUDY 
The purpose of this study is to find out if support from a case manager can help HIV-infected 
people receive regular HIV care and regularly take their HIV medication. 
The purpose of this study is also to help researchers understand how HIV spreads in the 
community. We will look at the different types of virus found in the blood samples of different 
people in the community who are living with HIV. In science, we call this phylogenetics.  
STUDY GROUPS 
We plan to enroll 356 HIV-infected men and follow them for two years. Half of the participants 
will receive the intervention (support from a case manager [CM]) and the other half will not. At 
the end of the study, the two groups will be compared to see if the CM support helped 
participants stay in HIV care and take their HIV drugs regularly.  
You will be “randomized” to either the group who will get case manager support or the group 
who will get the same care that patients normally get to stay in HIV care and take their HIV drugs 
regularly.  “Randomization” means that you are put into a group by chance. It is like flipping a 
coin. You have will an equal chance of being in either group. Both groups are important to the 
study. 
CM Intervention Group 
If you are in the CM intervention group, you will receive support from a case manager who will 
help you link to and stay in HIV care. When you are ready, the case manager will also help you 
start HIV medication and take it properly. The help from the case manager will be specific to 
your needs.  
Standard-of-Care (SOC) Control Group 
If you are in the SOC control group, you will get the same care that patients normally get to stay 
in HIV care and take their HIV drugs properly.   
Co-Enrollment in Other Studies 
While you are in this study, you may not take part in other studies that help you link to HIV care 
or take your HIV medication properly.   
STUDY PROCEDURES 
If you join the study, you will be asked to take part in 7 study visits over two years. If you are in 
the case manager group, you will also be contacted about the study monthly.  
Enrollment Visit 
Your enrollment visit will happen after you read, understand, and sign this form. We will help 
you understand the form and answer your questions before you sign this form. The procedures 
done at the Enrollment Visit will take about [sites to fill in the amount of time] hours. 
During this visit: 
• 
We will confirm where you live and how to contact you. 

 
HPTN 078, Final Version 2.0 
July 3, 2017 
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• 
We will give you the results of your HIV, hepatitis C virus and syphilis tests if you did not 
receive them at screening. If you have any of these infections, you will be referred for 
treatment [sites to add specifics about how this will take place at their site]. 
• 
We will ask you to give us permission to review your medical records.  
• 
We will ask you to answer a questionnaire.  This questionnaire will ask you about your use of 
recreational drugs and alcohol. It will also ask about your mental health. 
• 
We will invite you to bring your sexual partner(s) for HIV testing. [Note: Partner testing is 
conducted outside of the study and results are not recorded.] 
• 
If you are in the case manager group, the study case manager (CM) will talk to you about 
HIV. They will give you information to help you decide where you would like to go for HIV 
care and when to start HIV drugs. You will choose how much support you need from the case 
manager. You can talk with the case-manager by text, email, phone, or in-person. The session 
with the case manager will be audio-recorded. 
• 
We will collect a small amount of blood (about 34 mL = about 7 teaspoons) which will be 
stored. This blood will be used to check the results of tests performed at the study site and 
other study testing. This testing will give us information about the HIV virus and how the 
virus spreads in the community. The blood may also be used to test for the presence of HIV 
drugs and to learn more about how the body responds to HIV infection. If you have hepatitis 
C, the blood may also be used for testing to learn more about the hepatitis C virus and how it 
spreads in the community. Results from testing using stored samples will not be returned to 
you or the study site. 
Monthly Contact 
If you are in the case manager group, you will be contacted every month to confirm where you 
live and how to find you. We will ask if you are having any problems with your health or your 
HIV medication. We will ask you if you have had any problems because you are a part of this 
study. You may choose to have us call, email or text you every month. You can also ask to meet 
with the case manager monthly, or more often, if you want more support.   
Follow-up Visits  
You will be asked to return to the clinic for a total of 5 Follow-up Visits. The procedures done at 
the Follow-up Visits will take about [sites to fill in the amount of time] hours. 
During this visit: 
• 
We will confirm where you live and how to contact you. 
• 
We will ask you if you have had any problems because you are a part of this study. 
• 
We will invite you to bring your sexual partner(s) for HIV testing. 
• 
We will collect a small amount of blood (about 34 mL = about 7 teaspoons) to do CD4 cell 
count and viral load testing. Some of the blood will be stored for additional testing. These 
tests will give us information about the HIV virus and how the virus spreads in the 
community. The blood may also be used to test for the presence of HIV drugs and to learn 
more about how the body responds to HIV infection. If you have hepatitis C, the blood may 
also be used for testing to learn more about the hepatitis C virus and how it spreads in the 

 
HPTN 078, Final Version 2.0 
July 3, 2017 
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community. Results from testing using stored samples will not be returned to you or the study 
site. 
• 
If you are in the case-manager group, you will meet with the case manager to talk about your 
HIV care. You will also talk about your HIV medication if you have started taking it.  The 
case manager will help you with any problems you are having. The session with the case 
manager will be audio-recorded. 
Final Visit 
At the end of two years, you will be asked to return to the clinic for a Final Visit. The procedures 
done at the Final Visit will take about [sites to fill in the amount of time] hours. 
During this visit: 
• 
We will confirm where you live and how to contact you. 
• 
We will ask you to answer a questionnaire.  This questionnaire will ask you about your sexual 
behavior and partners, medication adherence, health care use. It will also ask you about your 
use of recreational drugs and alcohol, your mental health and stigma you may have faced 
because you are an MSM. 
• 
We will ask you if you have had any problems because you are a part of this study. 
• 
We will invite you to bring your sexual partner(s) for HIV testing. 
• 
We will ask you to take part in an exit interview. This interview may also include a 
questionnaire. Both the questionnaire and the interview will ask you about how you felt about 
being in the study.  
• 
We will collect a small amount of blood (about 40 mL = about 8 teaspoons) to do CD4 cell 
count, HIV viral load and syphilis testing. Some of this blood will be stored for additional 
testing. These tests will give us information about the HIV virus and how the virus spreads in 
the community. The blood may also be used to test for the presence of HIV drugs and to learn 
more about how the body responds to HIV infection. If you have hepatitis C, the blood may 
also be used for testing to learn more about the hepatitis C virus and how it spreads in the 
community. Results from testing using stored samples will not be returned to you or the study 
site. 
• 
We will contact you when the results of your syphilis test are available.  You will be given 
your results [sites to input information according to site standards]. If your test is positive, 
you will be referred for care and treatment [sites to input information on site standards]. 
• 
If you are in the case-manager group, you will meet with the case manager to talk about your 
HIV care. You will also talk about your HIV medication if you have started taking it.  The 
case manager will help you with any problems you are having. The session with the case 
manager will be audio-recorded. 
If You Decide to Leave the Study Early 
If you decide to leave the study early (before completing the final study visit), you will be asked 
to complete a final evaluation. This will include all of the procedures listed for the final visit.  
When You Decide to Start HIV Drugs 

 
HPTN 078, Final Version 2.0 
July 3, 2017 
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If you decide to start taking HIV medication, we will ask your doctors for information about 
when you started these drugs. We will also ask what your CD4 cell count and HIV viral load test 
results were at that time.  
HIV Test Results for Your Sexual Partner 
If your sexual partner is HIV-uninfected:  If your sexual partner is found to be HIV negative at 
any study visit, we will give both of you information about how to prevent the spread of HIV.  
If your sexual partner is HIV-infected:  If your sexual partner is found to be HIV positive at 
any study visit, we will talk to him about what this test result means and where they can receive 
HIV care.  
RISKS AND/OR DISCOMFORTS 
Blood Draws 
Taking blood samples may cause some pain, bruise your arm, or make you feel lightheaded.  In 
rare cases you may faint. There is also a small chance of infection when blood is drawn.  
Sensitive Questions 
The questions we will ask you about your sexual behavior and partners, recreational drug and 
alcohol use, your mental health or about stigma you may have faced may make you feel uneasy. 
However, you do not have to answer any question that you do not want to. You can also stop 
answering the questions at any time.  
Potential Social Harm 
We will make every effort to protect your privacy during the study. However, it is possible that 
others may learn that you are part of the study. They may think that you are infected with HIV. 
Because of this you could have trouble finding or keeping a job. You could also have problems 
with your family, friends and community.   
BENEFITS 
The counseling you get during this study may help you avoid spreading HIV to anyone else. We 
will offer to test your sexual partner for HIV. We will test you for syphilis. If you have syphilis, 
we will refer you for care and treatment. 
If you are in the CM intervention group, you will receive help from a case manager to stay in HIV 
care and take your HIV drugs properly.  
You may not receive any other direct benefit from being in this study. You or others in your 
community may benefit from this study in the future.  The information found during this study 
may help prevent HIV and other infections in the MSM community. 
NEW INFORMATION 
You will be told about any new information learned during this study that might affect your 
willingness to take part in the study. You will also be told when the results of the study may be 
ready, and how to learn about them.   

 
HPTN 078, Final Version 2.0 
July 3, 2017 
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WHY YOU MAY BE WITHDRAWN FROM THE STUDY WITHOUT YOUR CONSENT 
You may be withdrawn from the study without your consent if any of the following occur:  
• 
You are unable or unwilling to follow all of the study procedures or instructions.   
• 
The study is stopped or canceled. 
• 
The study staff feels that staying in the study would be harmful to you. 
• 
You are not able to attend clinic visits or complete all of the study procedures. 
• 
Other reasons, as decided by the study staff.  
ALTERNATIVES TO PARTICIPATION 
You may choose not to take part in the study. [Sites to include/amend the following if applicable: 
There may be other studies going on here or in the community that you may be eligible for. Some 
of these studies may be able to help you stay in HIV care or take your HIV medication.  If you 
wish, we will tell you about other studies that we know about.]   
COSTS TO YOU 
There will be no cost to you for any study-related visits, laboratory tests or other procedures. 
REIMBURSEMENT 
You will receive [site to add amount] for your time, effort, and travel to and from the clinic for 
each scheduled visit. [Sites to insert information about local reimbursement for the study.]   
CONFIDENTIALITY 
All the information you give us as part of this study will be kept private.  All your laboratory test 
results will also be kept private.  You will get a unique study identification number that will be 
used instead of your name on your documents.  However, at every study visit we will ask you to 
identify yourself.  This is to make sure that it is you who provides samples and information to us.  
Also we want to make sure that no other person than you can get your confidential laboratory test 
results.  Only the study staff will be able to see records that identify you by name.  This 
information will not be shared with others.  All records will be stored in locked files at the study 
clinic.  Results of your laboratory tests will be made available only to you when you visit the 
clinic.  Your name will never be used in any publication or presentation about the study. 
[Sites to modify this suggested language as appropriate:] If you are under 18 years old, we 
[must/do not need to] inform your parents or guardian about the results of your HIV and syphilis 
test, unless you would like us to tell them.  If you are under 18 years old, we [must/do not need 
to] inform your parents or guardian about the results of your hepatitis C (HCV) test, unless you 
would like us to tell them.  If [we must / you choose to have us] inform them of these test results, 
we will talk to you about the best way to inform them before we do so. 
Your records may be reviewed by the sponsor of the study, the US National Institutes of Health 
(NIH). They may also be looked at by NIH representatives, other government and regulatory 
authorities, [insert name of site] IRB/EC, study staff, study monitors and [insert applicable local 
regulatory authorities].   
In addition to the efforts made by the study staff to help keep your personal information 
confidential, we have obtained a Certificate of Confidentiality from the U.S. Federal Government.  

 
HPTN 078, Final Version 2.0 
July 3, 2017 
Page 69 of 88 
This Certificate protects researchers from being forced to tell people who are not connected with 
this study, such as the court system, about your participation.  The Certificate of Confidentiality 
does not prevent you from releasing information about yourself and your participation in the 
study.  The Certificate cannot be used to resist a demand for information from personnel of the 
US Government that is used for auditing or evaluation of federally funded projects or for 
information that must be disclosed in order to meet the requirements of the US FDA.  Even with 
the Certificate of Confidentiality, if the study staff learns of possible child abuse and/or neglect or 
a risk of harm to you or others, we will tell the proper authorities. 
A description of this study will be  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. 
[Sites to include/amend the following if applicable:] In this study, you will be tested for syphilis 
and your sexual partner may be tested for HIV. [Local/state/national] regulations require study 
staff to report the names of people who test positive for [HIV and other infections] to the [local 
health authority]. Outreach workers from the [health authority] may then contact you about 
telling your partners, since they also should be tested. If you do not want to tell your partners 
yourself, the outreach workers will contact them, according to the privacy guidelines of the 
[health authority]. 
RESEARCH-RELATED INJURY 
[Sites to specify institutional policy:] It is unlikely that you will be injured because of your study 
participation. If you are injured, the [institution] will give you immediate necessary treatment for 
your injuries. You [will/will not] have to pay for this treatment. You will be told where you can 
get further treatment for your injuries. There is no program to pay money or give other forms of 
compensation for such injuries either through this institution or the US NIH. You do not give up 
any legal rights by signing this consent form. 
PROBLEMS OR QUESTIONS 
If you ever have any questions about the study, or if you have a research-related injury, you 
should contact [insert name of the investigator or other study staff] at [insert telephone number 
and/or physical address]. 
If you have questions about your rights as a research participant, you should contact [insert name 
or title of person on the IRB or other organization appropriate for the site] at [insert physical 
address and telephone number]. 
 

 
HPTN 078, Final Version 2.0 
July 3, 2017 
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SIGNATURE PAGE 
Enhancing Recruitment, Linkage to Care and Treatment for HIV-Infected Men Who Have 
Sex with Men (MSM) in the United States 
 
HPTN 078 
Version 2.0 
July 3, 2017 
DAIDS Document ID: 11995 
 
ENROLLMENT INFORMED CONSENT FORM 
 
If you have read this consent form, or had it read and explained to you, and you understand the 
information, and you voluntarily agree to join the study, please sign your name or make your 
mark below.  
 
 
 
 
 
____________________________________ 
Participant Name (print) 
 
Participant Signature and Date 
 
 
 
 
 
____________________________________ 
Study Staff Conducting  
 
Study Staff Signature and Date 
Consent Discussion (print) 
 
 
 
 
 
____________________________________ 
Witness Name (print) 
 
 
Witness Signature and Date 
(As appropriate) 
 
 

 
HPTN 078, Final Version 2.0 
July 3, 2017 
Page 71 of 88 
SIGNATURE PAGE FOR PARTICIPANTS BELOW THE LEGAL AGE TO PROVIDE 
INDEPENDENT INFORMED CONSENT 
Enhancing Recruitment, Linkage to Care and Treatment for HIV-Infected Men Who Have 
Sex with Men (MSM) in the United States 
HPTN 078 
Version 2.0 
July 3, 2017 
DAIDS Document ID: 11995 
 
ENROLLMENT INFORMED CONSENT FORM 
 
Participant Assent 
If you have read this consent form, or had it read and explained to you, and you understand the 
information, and you voluntarily agree to join the study, please sign your name or make your 
mark below.  
 
 
 
 
 
____________________________________ 
Participant Name (print) 
 
Participant Signature and Date 
 
Parent/Legal Guardian Consent 
If you have read this consent form, or had it read and explained to you, and you understand the 
information, and you voluntarily agree for your child to join the study, please sign your name or 
make your mark below.  
 
 
 
 
 
____________________________________ 
Parent/Guardian Name (print) 
 
Parent/Guardian Signature and Date 
 
 
 
 
____________________________________ 
Study Staff Conducting  
 
Study Staff Signature and Date 
Consent Discussion (print) 
 
 
 
 
 
____________________________________ 
Witness Name (print) 
 
 
Witness Signature and Date 
(As appropriate) 
 
 

 
HPTN 078, Final Version 2.0 
July 3, 2017 
Page 72 of 88 
Enhancing Recruitment, Linkage to Care and Treatment for HIV-Infected Men Who Have 
Sex with Men (MSM) in the United States 
HPTN 078 
Version 2.0 
July 3, 2017 
DAIDS Document ID: 11995 
 
SAMPLE STORAGE AND FUTURE USE CONSENT FORM 
 
Sponsored by: Division of AIDS (DAIDS), United States (US) National Institute of Allergy and 
Infectious Diseases (NIAID), US National Institute of Mental Health (NIMH), US National 
Institute on Drug Abuse (NIDA) and US National Institutes of Health (NIH). 
PRINCIPAL INVESTIGATOR: [Insert Name] 
PHONE: [Insert Number] 
POSSIBLE FUTURE TESTS 
If you give permission, some of the plasma (a part of the blood) collected from you will be kept 
after the study ends for possible testing related to HIV and hepatitis C virus and to better 
understand laboratory tests related to this study. If you do not agree to have your left over plasma 
stored you can still be in this study.  If you agree to store your plasma but change your mind later, 
you can contact study staff.  We will then destroy your samples.  If you agree, your left over 
plasma will be stored for at least three years after the study ends. Any future use, not related to 
HIV or hepatitis C virus, needs to be reviewed and approved by the NIH and local authorities.  
Your left over samples will not be sold or used for commercial reasons. 
 
 

 
HPTN 078, Final Version 2.0 
July 3, 2017 
Page 73 of 88 
SIGNATURE PAGE 
Enhancing Recruitment, Linkage to Care and Treatment for HIV-Infected Men Who Have 
Sex with Men (MSM) in the United States 
HPTN 078 
Version 2.0 
July 3, 2017 
DAIDS Document ID: 11995 
 
SAMPLE STORAGE AND FUTURE USE CONSENT FORM 
 
If you have read this consent form, or had it read and explained to you, and you understand the 
information, and you voluntarily agreed to join the study, please sign your name or make your 
mark below.  
 
_____  My initials indicate that some of the plasma collected from me may be stored for future 
testing after study-related testing has been completed. 
_____  I do not agree to allow left over plasma samples to be saved for long-term storage or 
future testing after study-related testing has been completed. 
 
____________________ 
________________________ 
______________ 
Participant Name (print) 
Participant Signature 
 
Date 
 
____________________ 
________________________ 
______________ 
Study Staff Conducting   
Study Staff Signature 
 
Date 
Consent Discussion (print) 
 
 
 
 

 
HPTN 078, Final Version 2.0 
July 3, 2017 
Page 74 of 88 
SIGNATURE PAGE FOR PARTICIPANTS BELOW THE LEGAL AGE TO PROVIDE 
INDEPENDENT INFORMED CONSENT 
Enhancing Recruitment, Linkage to Care and Treatment for HIV-Infected Men Who Have 
Sex with Men (MSM) in the United States 
HPTN 078 
Version 2.0 
July 3, 2017 
DAIDS Document ID: 11995 
 
SAMPLE STORAGE AND FUTURE USE CONSENT FORM 
 
Participant Assent 
If you have read this consent form, or had it read and explained to you, and you understand the 
information, and you voluntarily agreed to join the study, please sign your name or make your 
mark below.  
_____  My initials indicate that some of the plasma collected from me may be stored for future 
testing after study-related testing has been completed. 
_____  I do not agree to allow left over plasma samples to be saved for long-term storage or 
future testing after study-related testing has been completed. 
 
 
 
 
____________________________________ 
Participant Name (print) 
 
Participant Signature and Date 
 
Parent/Legal Guardian Consent 
If you have read this consent form, or had it read and explained to you, and you understand the 
information, and you voluntarily agreed for your child to join the study, please sign your name or 
make your mark below.  
 
 
 
 
____________________________________ 
Parent/Guardian Name (print) 
 
Parent/Guardian Signature and Date 
 
 
 
 
____________________________________ 
Study Staff Conducting  
 
Study Staff Signature and Date 
Consent Discussion (print) 
 
 
 
 
____________________________________ 
Witness Name (print) 
 
 
Witness Signature and Date 
(As appropriate)  
 

 
HPTN 078, Final Version 2.0 
July 3, 2017 
Page 75 of 88 
Enhancing Recruitment, Linkage to Care and Treatment for HIV-Infected Men Who Have 
Sex with Men (MSM) in the United States 
HPTN 078 
Version 2.0 
July 3, 2017 
DAIDS Document ID: 11995 
 
EXIT INTERVIEW FOR CASE MANAGERS CONSENT FORM  
 
Sponsored by: Division of AIDS (DAIDS), United States (US) National Institute of Allergy and 
Infectious Diseases (NIAID), US National Institute of Mental Health (NIMH), US National 
Institute on Drug Abuse (NIDA) and US National Institutes of Health (NIH). 
PRINCIPAL INVESTIGATOR: [Insert Name] 
PHONE: [Insert Number] 
INTRODUCTION 
You are being asked to take part in a research study that is designed to find out if support from a 
case manager can help HIV-infected people receive consistent HIV care and routinely take their 
HIV medication. Joining this study is voluntary. You may refuse to join, or you may withdraw 
your consent to be in the study, for any reason. As part of the study, you are being asked to take 
part in an exit interview.  
Before you decide whether to join the study, we would like to explain the purpose of the study, 
the risks and benefits to you, and what is expected of you.  
YOUR PARTICIPATION IS VOLUNTARY 
This consent form gives information about the study you are being invited to join. Once you 
understand the study, and if you agree to take part, you will be asked to sign your name or make 
your mark on this form. You will be offered a copy of this form to keep.  
Before you learn about the study, it is important that you know the following: 
• 
Your participation is voluntary. You do not have to take part in the exit interview. 
• 
You may decide to leave the exit interview  at any time. 
• 
If you decide not to take part in the exit interview, you can still join another study at a later 
time if there is one available and you qualify. 
• 
If you decide not to take part in the exit interview, or decide to stop participating at any time, 
there will be no penalty or loss of normal benefits provided to you at our clinic. 
PURPOSE OF THE STUDY 
The purpose of this study is to find out if support from a case manager can help HIV-infected 
people receive consistent HIV care and routinely take their HIV medication.  

 
HPTN 078, Final Version 2.0 
July 3, 2017 
Page 76 of 88 
STUDY PROCEDURES 
If you decide to join the study, you will be asked to participate in an exit interview at the end of 
the study.  This interview may include both a questionnaire to complete as well as a semi-
structured interview (by talking to the interviewee).  Both the questionnaire and the interview will 
ask you about your experience and opinions in administering the CM intervention in this study. 
RISKS AND/OR DISCOMFORTS 
Sensitive Questions 
It is possible that the questions about your experience in administering the CM intervention may 
make you feel uneasy. However, you do not have to answer any question that you do not want to 
and you can stop answering the questions at any time.  
BENEFITS 
You may not receive any direct benefit from being in this study. The information gathered during 
this study may help prevent HIV in the MSM community. 
NEW INFORMATION 
You will be told about any new information learned during this study that might affect your 
willingness to take part in the study. You will also be told when the results of the study may be 
available, and how to learn about them.   
WHY YOU MAY BE WITHDRAWN FROM THE STUDY WITHOUT YOUR CONSENT 
You may be withdrawn from the study without your consent if any of the following occur:  
• 
You are unable or unwilling to follow the study procedures or instructions.   
• 
The study is stopped or canceled. 
• 
The study staff feels that staying in the study would be harmful to you. 
• 
Other reasons, as decided by the study staff.  
ALTERNATIVES TO PARTICIPATION 
You may choose not to participate in the study. [Sites to include/amend the following if 
applicable: There may be other studies going on here or in the community that you may be 
eligible for.  If you wish, we will tell you about other studies that we know about.]   
COSTS TO YOU 
There will be no cost to you for this interview. 
REIMBURSEMENT 
You will receive [site to add amount] for your time and effort for this interview. [Sites to insert 
information about local reimbursement for the study.]   

 
HPTN 078, Final Version 2.0 
July 3, 2017 
Page 77 of 88 
CONFIDENTIALITY 
All the information you give us as part of this study will be kept private.  You will get a unique 
study identification number that will be used instead of your name on your documents.  Only the 
study staff will be able to see records that identify you by name.  This information will not be 
shared with others.  All records will be stored in locked files at the study clinic.  Your name will 
never be used in any publication or presentation about the study. 
Your records may be reviewed by the sponsor of the study, the US National Institutes of Health 
(NIH) and their representatives, other government and regulatory authorities, [insert name of site] 
IRB/EC, study staff, study monitors and [insert applicable local regulatory authorities].   
In addition to the efforts made by the study staff to help keep your personal information 
confidential, we have obtained a Certificate of Confidentiality from the U.S. Federal Government.  
This Certificate protects researchers from being forced to tell people who are not connected with 
this study, such as the court system, about your participation.  The Certificate of Confidentiality 
does not prevent you from releasing information about yourself and your participation in the 
study.  The Certificate cannot be used to resist a demand for information from personnel of the 
US Government that is used for auditing or evaluation of federally funded projects or for 
information that must be disclosed in order to meet the requirements of the US FDA.  Even with 
the Certificate of Confidentiality, if the study staff learns of possible child abuse and/or neglect or 
a risk of harm to you or others, we will tell the proper authorities. 
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. 
RESEARCH-RELATED INJURY 
[Sites to specify institutional policy:] It is unlikely that you will be injured as a result of study 
participation. If you are injured, the [institution] will give you immediate necessary treatment for 
your injuries. You [will/will not] have to pay for this treatment. You will be told where you can 
get additional treatment for your injuries. There is no program to pay money or give other forms 
of compensation for such injuries either through this institution or the US NIH. You do not give 
up any legal rights by signing this consent form. 
PROBLEMS OR QUESTIONS 
If you ever have any questions about the study, or if you have a research-related injury, you 
should contact [insert name of the investigator or other study staff] at [insert telephone number 
and/or physical address]. 
If you have questions about your rights as a research participant, you should contact [insert name 
or title of person on the IRB or other organization appropriate for the site] at [insert physical 
address and telephone number]. 
 

 
HPTN 078, Final Version 2.0 
July 3, 2017 
Page 78 of 88 
SIGNATURE PAGE 
Enhancing Recruitment, Linkage to Care and Treatment for HIV-Infected Men Who Have 
Sex with Men (MSM) in the United States 
HPTN 078 
Version 2.0 
July 3, 2017 
DAIDS Document ID: 11995 
 
EXIT INTERVIEW FOR CASE MANAGERS CONSENT FORM 
 
If you have read this consent form, or had it read and explained to you, and you understand the 
information, and you voluntarily agree to participate in the exit interview, please sign your name 
or make your mark below.  
 
 
 
 
 
____________________________________ 
Participant Name (print) 
 
Participant Signature and Date 
 
 
 
 
 
____________________________________ 
Study Staff Conducting  
 
Study Staff Signature and Date 
Consent Discussion (print) 
 
 
 
 
 
____________________________________ 
Witness Name (print) 
 
 
Witness Signature and Date 
(As appropriate) 
 
 

 
HPTN 078, Final Version 2.0 
July 3, 2017 
Page 79 of 88 
APPENDIX IV: TAILORED CASE MANAGEMENT INTERVENTION COMPONENTS 
IN AT RISK US POPULATIONS(2005 – 2015) 
 

 
HPTN 078, Final Version 2.0 
July 3, 2017 
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HPTN 078 
CM 
Intervention 
Component 
First Author; 
Year; 
Location(s) 
Design; 
Sample Size 
Study Focus / 
Intervention 
Component(s) 
Evidence of Effect 
Cascade 
Component 
My Life 
Yehia; 2015; 
Philadelphia, 
PA51 
Cross 
Sectional; 
Descriptive;  
1359 newly 
HIV diagnosed 
adults  
Testing location  
- 
Testing/diagnosis locations without co-
located outpatient care are associated 
with delayed linkage to care 
- 
Counseling and testing centers, 
correctional centers, and inpatient 
settings are found to delay linkage to 
care in comparison to medical clinics 
- 
Medical clinics integrate testing and 
medical services, facilitating linkage to 
care (decreased wait times, increased 
familiarity with facilities, supportive 
ancillary services) 
- 
Linkage to care 
- 
Engagement in 
care  
Quinlivan; 2013;  
Chapel Hill, NC49 
Qualitative; 30 
HIV-positive 
women of 
color 
Self determination 
theory in HIV  
- 
Autonomy is lost at diagnosis due to 
stigma, feelings of helplessness, and 
lack of competency. Autonomy/self-
motivation and competency should be 
regained to facilitate engagement in 
care  
- 
Welcoming environment at initial 
clinical encounter would influence 
support and self-motivation to return 
for following visits 
- 
Increasing health-related knowledge 
and healthcare navigation facilitates 
feelings of competency 
- 
Retention in care is influenced by 
strong relationships between providers 
and patients, but long-term engagement 
is most influenced by developing 
autonomy and self-management 
- 
 
- 
Linkage to care 
- 
Retention in care 
- 
Self-
management 
- 
Durability 

 
HPTN 078, Final Version 2.0 
July 3, 2017 
Page 81 of 88 
HPTN 078 
CM 
Intervention 
Component 
First Author; 
Year; 
Location(s) 
Design; 
Sample Size 
Study Focus / 
Intervention 
Component(s) 
Evidence of Effect 
Cascade 
Component 
My Life 
(cont) 
Hightow; 2011;  
Chapel Hill, NC48 
Pre-post test; 
81 HIV-
positive MSM 
of color 
Linkage to care 
program 
including: 
- 
Social 
marketing 
- 
Intense 
outreach 
- 
Medical/social 
support  
- 
76% viral suppression at 12 months  
- 
Odds of 1 clinic visit in 4 months post-
intervention versus pre-intervention 
group (OR = 2.58; 95% CI 1.34 – 4.98) 
- 
Likelihood of clinic visit attendance 
decreased over time for both pre- and 
post-intervention groups, yet for the 
intervention group retention was 
significantly greater 
- 
Linkage to care  
- 
Retention in care 
- 
Viral 
suppression 
- 
Durability 
Rajabiun; 2007;  
6 cities from 
northwest, 
midwest, 
midatlantic and 
northeast regions 
50 
Qualitative; 
purposive 
sampling; 76 
HIV-positive 
adults;  
26% MSM  
 
Interviews to 
understand 
participants’ 
experiences with 
engagement and 
retention 
- 
Participants cycle in and out of care 
and this process is facilitated or 
obstructed by the relationship of the 
patient with the provider 
- 
Partnership, validation, trust, respect, 
and emotional intelligence were 
notable characteristics of providers 
who influenced patients to engage and 
remain in care 
- 
When patients felt that their provider 
was patronizing or that they 
encountered stigma, they were less 
likely to remain in care 
- 
Engagement depends upon: 
- 
Acceptance level of diagnosis 
- 
Ability to cope with substance abuse, 
mental illness and stigma 
- 
Healthcare provider relationships  
- 
External support systems  
- 
Ability to overcome practice barriers to 
care  
 
 
- 
Linkage to care 
- 
Retention in care 
- 
Engagement in 
care 
- 
Inter-personal 
relationship 
building  

 
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Component 
First Author; 
Year; 
Location(s) 
Design; 
Sample Size 
Study Focus / 
Intervention 
Component(s) 
Evidence of Effect 
Cascade 
Component 
My Choices 
Craw; 2010;  
Anniston, AL 
Atlanta, GA 
Baltimore, MD 
Baton Rouge, LA 
Chicago, IL 
Columbia, SC 
Jacksonville, FL 
Kansas City, MO 
Miami, FL 
Richmond, VA53 
ARTAS II 
demonstration 
project;  
626 HIV-
positive adults 
Strengths-Based 
Linkage Case 
Management; 
Identify barriers 
and solutions to 
overcome 
challenges to 
engagement in 
care 
  
- 
79% (497 of 626) of participants 
visited an HIV clinician at least once 
within the first 6 months 
- 
Number of case management sessions 
(2-5 sessions) was associated with 
greater linkage (OR = 2.95, 95% CI 
1.88 – 4.62)  
- 
Mean time spent per client was 7.2; 
median 5.8 hours  
- 
Biggest barriers to engagement by 
patient self report were 1) feeling well; 
2) lack of transport; 3) not ready to 
start HIV medications; 4) no insurance; 
5) took too long to get an appointment  
- 
Durability of project was limited due to 
lack of funding 
- 
Those sites that continued the linkage 
program after funding ended had long-
standing relationships with local health 
departments and a steady influx of HIV 
patients 
- 
Linkage to care 
- 
Engagement in 
care 
Christopoulos; 
2013;  
San Francisco, 
CA52 
Qualitative; 34 
HIV-positive 
adults;  
55% MSM 
Qualitative 
interviews around 
engagement and 
linkage in newly 
diagnosed  
- 
Linkage to care experience lays 
groundwork for subsequent retention in 
care  
- 
All patients reported have to learn and 
manage the “administrative” aspects of 
care in order to stay engaged in care  
- 
Patient priorities change over time, 
often shifting from medical/physical 
concerns to psychological/social 
concerns – interventions must 
- 
Linkage to care 
- 
Engagement  in 
care 
- 
Retention in care  

 
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Component 
First Author; 
Year; 
Location(s) 
Design; 
Sample Size 
Study Focus / 
Intervention 
Component(s) 
Evidence of Effect 
Cascade 
Component 
accommodate this shift in order to 
continue to engage patients in care 
My Care 
(Step 1) 
Bradford; 2007;  
Portland, OR 
Seattle, WA 
Boston, MA 
Washington DC27 
Prospective 
cohort; 437 
HIV-positive 
adults   
Health system and 
patient navigation 
through a  
“client navigator 
program” 
- 
Relationship building noted in 86% 
- 
Navigation services were used in 74% 
- 
Participants who had improved 
engagement with their provider  had 
“41% greater odds of undetectable viral 
load” and 32% “greater odds of 
reporting the optimal number of HIV 
visits at 12 months” 
- 
Engagement in 
care 
- 
Retention in care 
- 
Viral 
suppression 
- 
Durability 
Willis; 2013;  
Washington DC47 
Descriptive, 
observational;  
5631 HIV-
positive adults  
Medical Case 
Management 
(MCM) 
- 
56.7% received care at MCM-funded 
facilities of which 76.2% (vs. 59.9% in 
non-MCM funded facilities) were 
retained in care, and 70.6% (vs. 75.7%) 
achieved viral suppression.  
- 
Those receiving care in MCM-funded 
facilities more likely to be retained in 
care (aOR 4.13; 95%CI: 1.93-8.85) and 
as likely (aOR 1.06; 95%CI: 0.68-1.62) 
to be virally suppressed. 
- 
Among 789 newly diagnosed persons, 
those diagnosed in MCM-funded 
facilities were not more likely to be 
linked to care within 3 months (aOR 
0.50; 95%CI: 0.21-1.18). 
 
 
 
 
 
 
 
- 
Linkage to care 
- 
Engagement in 
care 
- 
Retention in care  
- 
Viral 
suppression 
- 
 

 
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First Author; 
Year; 
Location(s) 
Design; 
Sample Size 
Study Focus / 
Intervention 
Component(s) 
Evidence of Effect 
Cascade 
Component 
My Care 
(Step 2) 
Naar-King; 2009;  
Detroit, MI60 
Pilot 
randomized 
trial; 87 HIV-
positive youth 
(16 – 29) 
Motivational 
interviewing by 
peer versus 
professional 
- 
Peer and professional interviewers had 
similar motivational interviewing 
scores 
- 
Established initial effect size for peer-
based MI programs  
- 
Both groups improved the regularity of 
primary care HIV appointments  
- 
Peer outreach is a cost-effective and 
durable program 
- 
Retention in care 
- 
Durability 
Hayley; 2014;  
New York City, 
NY 
Newark, NJ 
Washington DC 
Baltimore, MD  
Durham, NC 
Atlanta, GA58 
Prospective, 
observational 
cohort;   
2099 HIV-
negative 
women at risk 
of HIV 
acquisition 
Interpersonal 
relationship 
building; 
community 
engagement; 
reduction of 
external barriers; 
staff capacity 
building 
participant tracing  
- 
Participant visit completion was 93% at 
6 months 
- 
Participant visit completion was 94% at 
12 months  
- 
Housing instability was a significant 
predictor of missed visits 
- 
Engagement in 
care 
- 
Retention in care 
- 
Inter-personal 
relationship 
building  
- 
Durability  
Remien; 2005;  
New York City, 
NY62   
 
Randomized 
controlled 
trial;  
215 sero-
discordant 
couples with 
suboptimal 
adherence  
4 session, couple 
focused adherence 
to medication 
intervention  
- 
Higher medication adherence post-
intervention in proportion of prescribed 
doses taken (76% versus 60%)  
- 
Greater likelihood of high levels of 
adherence compared to controls  
- 
Effects diminish with time 
- 
No significance difference identified 
between increased adherence and viral 
suppression 
- 
Involvement of relationship partner in 
treatment decisions and adherence is 
durable, cost-effective and improves 
adherence and treatment support 
- 
Engagement in 
care 
- 
Adherence  
- 
Retention in care 
- 
Durability 

 
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First Author; 
Year; 
Location(s) 
Design; 
Sample Size 
Study Focus / 
Intervention 
Component(s) 
Evidence of Effect 
Cascade 
Component 
My Care 
(Step 2) 
(cont) 
Simoni; 2006;  
Multisite32  
Meta analysis; 
19 studies; 
1839 HIV-
positive 
participants; 
53% MSM 
(median across 
all studies) 
Randomized 
behavioral 
interventions 
in adults 
 
 
- 
Behavioral interventions (e.g. 
education, cognitive behavioral 
therapy, motivational interviewing, 
group therapy, cue dosing) increased 
95% adherence (OR = 1.50; 95% CI 
1.16 – 1. n = 1633), but did not meet 
statistical significance for undetectable 
viral load (OR = 1.25; 95% CI 0.99 – 
1.59; n = 1247)  
- 
In the sub-analysis that evaluated 
studies with 50% of greater MSM, the 
results for viral load were OR = 1.83; 
95% CI 0.50 – 6.67) 
- 
Adherence (self-
report) 
- 
Viral 
suppression  
Nelsen; 2013;  
Houston, TX61 
Cross-
sectional 
survey; 244 
HIV-positive 
adults  
Patient intention 
to adhere to HIV 
treatment 
- 
Intention to adhere (measured by the 
13-item Intention to Adhere to HIV 
Treatment Scale) was the only “patient-
centered” outcome that predicated 
adherence (OR 2.2; 95% CI 1.1 – 4.3)  
- 
Adherence  
Holtzman; 2015; 
Philadelphia, 
PA59 
Qualitative 
semi-
structured 
interviews; 51 
HIV-positive 
adults 
Andersen’s 
Behavioral Model 
- 
Low retention and adherence was 
predicted by stigma, mental illness, 
substance abuse, low social support, 
poor reminder strategies, housing, 
insurance, symptoms, competing life 
activities, colocation of services, and 
provider factors 
- 
Barriers specific to retention included 
transportation, clinic experiences, and 
appointment scheduling 
- 
Barriers specific to adherence included 
medication characteristics, pharmacy 
services, health literacy, and health 
benefits 
- 
Retention in care 
- 
Adherence 

 
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Component 
First Author; 
Year; 
Location(s) 
Design; 
Sample Size 
Study Focus / 
Intervention 
Component(s) 
Evidence of Effect 
Cascade 
Component 
My Health 
Lewis; 2013;  
Midwest HIV 
Clinic38  
Pre-
experimental 
proof of 
concept study; 
52 HIV-
positive MSM  
Pre-post test 
design;  
Tailored text 
messaging 
intervention 
- 
Positive receptivity to text messages, 
both in content and frequency 
- 
Overall, participants had an 
improvement in viral load control (<75) 
and CD4 count  
- 
Decrease in number of missed 
medication days  
- 
Message fatigue was common but 
could be addressed through 
customizing and varying the messages 
delivered to make the intervention 
more durable 
- 
Adherence  
- 
Self-
management  
- 
Inter-personal 
relationship 
building  
- 
Viral 
suppression 
- 
Durability  
 
Schnall; 2015; 
New York City57 
Focus Groups; 
50 PLWH  
mHealth 
technology 
- 
Participants suggested several tools for 
meeting their healthcare needs, 
including: reminders/alerts, lab results 
tracking, and notes on health status.  
- 
mHealth technology can function as a 
social actor by providing chat 
boxes/forums, testimonials of lived 
experiences, and personal outreach.  
- 
Examples of media that can be used as 
a persuasive technology include 
games/virtual rewards, coding of health 
tasks, and simulations on how to 
interact and connect with others 
 
 
 
 
 
- 
Adherence 
- 
Self 
management  

 
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Component 
First Author; 
Year; 
Location(s) 
Design; 
Sample Size 
Study Focus / 
Intervention 
Component(s) 
Evidence of Effect 
Cascade 
Component 
My Health 
(cont) 
Hightow; 2011;  
Chapel Hill, NC; 
Bronx, NY; 
Chicago, IL; 
Detroit, MI; 
Houston, TX; 
Los Angeles, CA; 
Oakland, CA; 
Rochester, NY55 
334 MSM of 
color 
National 
HIV/AIDS Bureau 
program: 
Outreach, linkage, 
entry, and 
retention analysis 
- 
Earlier linkage to care was significantly 
associated with the person who made 
the diagnosis also making the initial 
referral to care 
- 
Clinic appointment reminders, case 
finding for patients who had missed 
appointments, transportation assistance 
as well as dedicated providers were all 
factors that contributed to the high 
retention rate of 83% of participants at 
one year 
- 
Dedicated providers contributed to the 
sustainability of the program 
- 
Linkage to care 
- 
Retention in care 
- 
Durability 
Gilman; 2012; 
five sites from 
the Northeast, 
Midwest, and the 
South54 
Site visits; 
seven linkage 
programs in 
five sites 
Hospital-based, 
integrated linkage 
to care programs 
- 
Successful linkage programs are low 
cost, intensive, time limited, flexible, 
and unique 
- 
Successful programs directly employed 
linkage workers, actively referred 
newly diagnosed patients to medical 
care, employed person-centered case 
management, and were culturally and 
linguistically in concordance with 
populations served 
- 
Successful implementation of linkage 
programs requires coordination and 
integration of services among testing 
and treatment sites, sustaining funding 
sources, and ensuring commitment 
from program stakeholders and testing 
staff  
- 
Linkage to care 
- 
Durability 

 
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Component 
First Author; 
Year; 
Location(s) 
Design; 
Sample Size 
Study Focus / 
Intervention 
Component(s) 
Evidence of Effect 
Cascade 
Component 
My Health 
(cont) 
Maulsby; 2015; 
Chicago, IL; New 
York City, NY; 
Louisiana56 
Descriptive; 
2,615 HIV 
positive adults 
Positive Charge 
HIV linkage and 
re-engagement in 
care program 
- 
Through methods such as peer health 
navigation, peer-led group-based 
education, case management, and case 
finding 88% of participants were linked 
to care, 69% were retained in care and 
46% were virally suppressed at follow-
up 
- 
90% of MSM in one site were engaged 
in care following enrollment 
- 
Sustainable programs targeting 
underserved populations are achievable  
- 
Linkage to care 
- 
Retention in care 
- 
Engagement in 
care 
- 
Durability