Improving HIV Prevention Among Heterosexual Men Seeking STI Services in Malawi: Examining the Benefits, Acceptability, and Associated Costs of a Systems-navigator-delivered Integrated Prevention Package
Phase: NA
Conditions: HIV Infection, Sexually Transmitted Infections, Pre-exposure Prophylaxis, Systems Navigation
Sponsor: HIV Prevention Trials Network

 
HPTN 112 
Improving HIV prevention among heterosexual cisgender men seeking STI 
services in Malawi: examining the benefits, acceptability, and associated costs 
of a systems-navigator-delivered integrated prevention package 
 
DAIDS Document ID: 39057 
 
A Study by the HIV Prevention Trials Network (HPTN)  
 
 
Sponsored by:  
Division of AIDS (DAIDS), United States (US) National Institute  
of Allergy and Infectious Diseases (NIAID), US National Institutes of Health (NIH)  
 
 
 
 
 
 
 
Non-IND Study  
 
Protocol Chair: 
Sarah E. Rutstein, MD, PhD 
 
Protocol Co-Chair: 
Mitch Matoga, MBBS 
 
 
 
Version 2.0 
19 December 2023 
 
 
 
 
 
 
 
 

 
 
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HPTN 112 
Improving HIV prevention among heterosexual cisgender men seeking STI services in 
Malawi: examining the benefits, acceptability, and associated costs of a systems-navigator-
delivered integrated prevention package 
 
TABLE OF CONTENTS 
 
HPTN 112 ................................................................................................................................... 1 
TABLE OF CONTENTS............................................................................................................. 2 
PROTOCOL SIGNATURE PAGE .............................................................................................. 6 
LIST OF ABBREVIATIONS AND ACRONYMS ...................................................................... 7 
PROTOCOL TEAM ROSTER .................................................................................................... 9 
SCHEMA ................................................................................................................................. 12 
OVERVIEW OF STUDY DESIGN ........................................................................................... 14 
1.0 
INTRODUCTION ................................................................................................................. 15 
1.1 
Background and Rationale ...................................................................................... 15 
1.2 
Rationale for Study Design ..................................................................................... 17 
2.0 
STUDY OBJECTIVES .......................................................................................................... 18 
2.1 
Primary Objective(s) ............................................................................................... 18 
2.1.1 
Effect of a Systems-Navigator .................................................................... 18 
2.1.2 
Acceptability and barriers. .......................................................................... 18 
2.2 
Secondary Objectives ............................................................................................. 18 
2.2.1 
Feasibility of a future randomized controlled trial. ...................................... 19 
2.3 
Exploratory Objectives ........................................................................................... 19 
2.3.1 
Prevention-effective PrEP use. ................................................................... 19 
2.3.2 
PrEP modality preferences ......................................................................... 19 
2.3.3 
Effect of a Systems-Navigator .................................................................... 19 
2.3.4 
Quantify costs and resources ...................................................................... 19 
2.3.5 
Laboratory assessments. .............................................................................. 19 
2.3.6 
Event-driven PrEP ...................................................................................... 19 
2.3.7 
PrEP related stigma .................................................................................... 19 
3.0 
STUDY DESIGN ................................................................................................................. 19 
3.1 
Participating Site .................................................................................................... 20 
3.2 
Study Duration ....................................................................................................... 21 
4.0 
STUDY POPULATION ......................................................................................................... 21 
4.1 
Inclusion Criteria .................................................................................................... 22 
4.2 
Exclusion Criteria ................................................................................................... 23 

 
 
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4.3 
Recruitment Process ............................................................................................... 24 
4.4 
Co-Enrollment Guidelines ...................................................................................... 25 
4.5 
Participant Retention .............................................................................................. 25 
4.5.1 
Retention in PrEP care................................................................................ 25 
4.5.2 
Retention in study ...................................................................................... 26 
4.6 
Participant Withdrawal ........................................................................................... 27 
5.0 
STUDY INTERVENTION PACKAGE ....................................................................................... 27 
5.1 
Systems navigators: selection and training .............................................................. 28 
5.2 
Systems navigators: counseling and tracing ............................................................ 28 
5.3 
Risk assessment and POC STI testing ..................................................................... 29 
5.4 
PrEP re-engagement and “re-start”.......................................................................... 30 
6.0 
STUDY PROCEDURES ......................................................................................................... 30 
6.1 
Determination of Eligibility .................................................................................... 30 
6.2 
Enrollment Visit ..................................................................................................... 31 
6.2.1 
Enrollment for participants initiating PrEP ................................................. 31 
6.3 
Follow-Up Visits .................................................................................................... 32 
6.3.1 
Quarterly visits ........................................................................................... 32 
6.4 
Procedures for Participants with Suspected or Confirmed HIV Infection................. 33 
6.4.1 
Enrollment ................................................................................................. 33 
6.4.2 
After study enrollment ................................................................................ 34 
6.5 
Other Study Procedures .......................................................................................... 34 
6.5.1 
Sexually transmitted infections ................................................................... 34 
6.5.2 
HIV and risk reduction counseling.............................................................. 34 
6.6 
Qualitative data collection ...................................................................................... 34 
6.7 
Cost and resource data collection ............................................................................ 35 
6.8 
Visit Windows ........................................................................................................ 35 
6.9 
Interim Contacts and Visits ..................................................................................... 36 
7.0 
MONITORING AND ADVERSE EVENT REPORTING................................................................ 36 
7.1 
Adverse Event Reporting ........................................................................................ 36 
7.2 
Monitoring and Clinical Data Review ..................................................................... 37 
7.3 
Social Impact Reporting ......................................................................................... 37 
8.0 
STATISTICAL CONSIDERATIONS ......................................................................................... 38 
8.1 
Review of study design ........................................................................................... 38 
8.2 
Objectives and Endpoints ....................................................................................... 38 
8.2.1 
Primary Objective(s) and Endpoints ........................................................... 38 
8.2.2 
Secondary Objective(s) and Endpoints ....................................................... 39 

 
 
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8.2.3 
Exploratory Objectives and Endpoints ........................................................ 40 
8.3 
Sample Size ............................................................................................................ 41 
8.4 
Accrual and Retention ............................................................................................ 42 
8.5 
Statistical Analysis ................................................................................................. 42 
8.5.1 
Primary Analyses ....................................................................................... 42 
8.5.2 
Secondary Analyses ................................................................................... 43 
8.6 
Qualitative Analyses ............................................................................................... 43 
9.0 
LABORATORY SPECIMENS AND BIOHAZARD CONTAINMENT ............................................... 44 
9.1 
Local Laboratory Specimens ................................................................................... 44 
9.1.1 
Specimen Storage at Study Site .................................................................. 45 
9.1.2 
Virology ..................................................................................................... 46 
9.1.3 
Pharmacology ............................................................................................ 46 
9.1.4 
Other HPTN LC testing .............................................................................. 46 
9.2 
Quality Control and Quality Assurance Procedures ................................................. 46 
9.3 
HIV Diagnostic Testing .......................................................................................... 47 
9.4 
HIV RNA Testing ................................................................................................... 47 
9.5 
Biohazard Containment .......................................................................................... 47 
10.0 HUMAN SUBJECTS CONSIDERATIONS ................................................................................. 47 
10.1 Ethical Review ....................................................................................................... 47 
10.2 Informed Consent ................................................................................................... 48 
10.3 Risks ...................................................................................................................... 49 
10.4 Benefits .................................................................................................................. 49 
10.5 Incentives ............................................................................................................... 50 
10.6 Confidentiality ........................................................................................................ 50 
10.6.1 
Certificate of Confidentiality ...................................................................... 50 
10.7 Communicable Disease Reporting Requirements .................................................... 50 
10.8 Study Discontinuation ............................................................................................ 50 
11.0 ADMINISTRATIVE PROCEDURES ......................................................................................... 50 
11.1 Protocol Registration .............................................................................................. 51 
11.2 Study Activation ..................................................................................................... 51 
11.3 Study Coordination ................................................................................................. 51 
11.4 Study Monitoring.................................................................................................... 52 
11.5 Protocol Compliance .............................................................................................. 53 
11.6 Investigator’s Records ............................................................................................ 53 
11.7 Use of Information and Publications ....................................................................... 53 
11.8 ClinicalTrials.gov ................................................................................................... 53 

 
 
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12.0 REFERENCES ................................................................. ERROR! BOOKMARK NOT DEFINED. 
13.0 APPENDICES I-IV.......................................................................................................... 56 
13.1 APPENDIX I: Clinic Flow ..................................................................................... 57 
13.2 APPENDIX II: Schedule of Evaluations for HIV-Uninfected Participants .............. 58 
13.3 APPENDIX III: Schedule of Evaluations for Participants who Seroconvert ............ 59 
13.4 APPENDIX IV: Sample Enrollment Informed Consent .......................................... 60 
13.5 APPENDIX V: Sample Key Stakeholder Informed Consent ................................... 69 
13.6 APPENDIX VI: Sample Adolescent (age 15-17) Assent Form ................................ 74 
13.7 APPENDIX VII: Sample Parental Consent for Participants Age 15-17 ................... 83 
 
 
 
 

 
 
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HPTN 112 
Improving HIV prevention among heterosexual cisgender men seeking STI 
services in Malawi: examining the benefits, acceptability, and associated costs 
of a systems-navigator-delivered integrated prevention package 
 
  
PROTOCOL SIGNATURE PAGE 
 
DAIDS Document ID # 39057 
 
Version 2.0 
 19 December 2023 
 
 
I will conduct the study in accordance with the provisions of this protocol and all applicable 
protocol-related documents. I agree to conduct this study in compliance with United States (US) 
Health and Human Service regulations (45 CFR 46); applicable US Food and Drug 
Administration regulations; standards of the International Conference on Harmonization 
Guideline for Good Clinical Practice (E6); Institutional Review Board/Ethics Committee 
determinations; all applicable in-country, state, and local laws and regulations; and other 
applicable requirements (e.g., US National Institutes of Health, Division of AIDS) and 
institutional policies. 
 
I have read and understand the information in this protocol and will ensure that all associates, 
colleagues, and employees assisting in the conduct of the study are informed about the 
obligations incurred by their contribution to the study.  
 
 
 
 
 
____________________________________ 
Name of Investigator of Record (print name) 
 
 
 
 
____________________________________ 
_______________________ 
Signature of Investigator of Record 
Date (DD/MONTH/YYYY) 
 
 

 
 
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HPTN 112 
Improving HIV prevention among heterosexual cisgender men seeking STI services in 
Malawi: examining the benefits, acceptability, and associated costs of a systems-navigator-
delivered integrated prevention package 
 
LIST OF ABBREVIATIONS AND ACRONYMS 
 
AE 
Adverse Event  
AIDS 
Acquired immunodeficiency syndrome  
ARV 
ART 
Antiretroviral  
Antiretroviral Therapy 
CAB 
Community Advisory Board 
CAB-LA 
Long-acting injectable formulation of cabotegravir 
CBC 
Complete blood count 
CFR 
Code of Federal Regulations 
CLIA 
Clinical Laboratory Improvement Amendments of 1988 
CPQA 
Clinical Pharmacology Quality Assurance 
CRF 
CRM 
CRMS   
CRS 
Case Report Form 
(LOC) Clinical Research Manager 
(DAIDS) Clinical Research Management System 
Clinical Research Site 
CTA 
CT/NG 
Clinical Trials Agreement 
Chlamydia trachomatis/Neisseria gonorrhoeae 
DAERS 
DAIDS Adverse Experience Reporting System  
DAIDS 
DBS 
Division of AIDS 
Dried Blood Spot 
DHHS 
US Department of Health and Human Services 
DSMB 
Data and Safety Monitoring Board 
EQA 
External Quality Assurance 
EWG 
(HPTN) Ethics Working Group 
GCLP 
Good Clinical Laboratory Practices 
HIV 
Human Immunodeficiency Virus 
HPTN 
HIV Prevention Trials Network 
ICF 
IDI 
Informed Consent Form 
In-depth Interview 
IoR 
Investigator of Record 
IQA 
(DAIDS) Immunology Quality Assurance 
IRB 
Institutional Review Board 
LAI  
LC 
Long-acting Injectable  
(HPTN) Laboratory Center 

 
 
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LDMS 
Laboratory Data Management System 
LL 
Local laboratory 
LOC 
LTF 
MO 
MoH 
Leadership and Operations Center 
Loss to Follow-Up 
Medical Officer 
(Malawi) Ministry of Health 
MOP 
(HPTN) Manual of Operations 
NIAID 
(United States) National Institute of Allergy and Infectious Diseases 
NIH 
(United States) National Institutes of Health 
PRO 
POC 
Protocol Registration Office 
Point of Care  
RSC 
Regulatory Support Center 
SDMC 
SSA 
SSP 
(HPTN) Statistical and Data Management Center 
Sub-Saharan Africa 
Study Specific Procedures (Manual) 
SMC 
Study Monitoring Committee 
STI 
Sexually Transmitted Infection 
SOE 
Schedule of Events 
SOC 
SOP 
Standard of Care 
Standard Operating Procedures 
TLFB 
QA 
Timeline Follow-back 
Quality Assurance 
QC 
Quality Control 
US 
WHO 
United States 
World Health Organization 
  
 
 

 
 
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HPTN 112 
Improving HIV prevention among heterosexual cisgender men seeking STI services 
in Malawi: examining the benefits, acceptability, and associated costs of a systems-
navigator-delivered integrated prevention package 
 
PROTOCOL TEAM ROSTER 
 
PROTOCOL CHAIR  
Sarah E. Rutstein, MD, PhD 
University of North Carolina at Chapel Hill   
Department of Medicine 
130 Mason Farm Road 
Chapel Hill, NC, 27519, USA 
Phone: 919-843-5859 
Email: sarah_rutstein@med.unc.edu 
 
 
PROTOCOL CO-CHAIR 
Mitch Matoga, MBBS, MSc 
UNC Project Malawi 
Tidziwe Center Annex 
100 Mzimba road, Kamuzu Central Hospital 
Campus 
Lilongwe, Malawi, Room 312 
Phone: +265999511726 
Email: mmatoga@unclilongwe.org 
 
Hans M.L. Spiegel, MD, PhD, DTMH, 
FAAP 
Medical Officer, PMPRB/Prevention Sciences 
Program, 
Pediatric Infectious Diseases, Contractor, 
Kelly Government Solutions 
NIH/NIAID/DAIDS  
5601 Fishers Lane  
Room 9B40A 
Rockville, MD 20852 
Tel:  240-292-4633 
Email: hans.spiegel@nih.gov 
 
erica hamilton, MPH 
Clinical Research Manager  
FHI 360  
359 Blackwell Street, Suite 200 
Durham, NC 27701, USA 
Phone: 919-321-3493  
Email: ehamilton@fhi360.org 
 
 
 
 
Maxine Awekey, MPH 
Clinical Trials Assistant 
FHI 360 
1221 22nd St L St. NW 
Washington, DC 20037 
Phone: 202-884-8072 
Email: mawekey@fhi360.org 
 
CaTiffaney Griswould, MPH, CCRC 
Senior Community Program Manager 
FHI 360 
359 Blackwell Street, Suite 200 
Durham, NC 27701, USA 
Phone: 202-884-8909 
Email: cgriswould@fhi360.org 
 
Eric Miller, B.S.  
Senior Communications Officer 
FHI 360 
359 Blackwell Street, Suite 200 
Durham, NC 27701, USA 
Phone: 919-321-3511 
Rikki Oneil, B.S.  
Budget Analyst 
FHI 360 
359 Blackwell Street, Suite 200 
Durham, NC 27701, USA 
Phone: 919-321-3591 

 
 
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Email: emiller@fhi360.org 
 
 
Email: roneil@fhi360.org 
 
Gabriela Salinas-Jimenez 
Administrative Associate III  
FHI 360 
359 Blackwell Street, Suite 200 
Durham, NC 27701, USA 
Phone: 919-544-7040 
Email: gsalinas-jimenez@fhi360.org 
 
 
 
 
Ting Ye, PhD 
Study Statistician 
Department of Biostatistics 
University of Washington  
Office #357 
Hans Rosling Center for Population Health 
Box 351617 
Seattle, WA 98195 
Phone: 206-543-1044 
Email: tingye1@uw.edu 
Mark Marzinke, PhD, DABCC 
Analytical Pharmacologist 
HPTN Laboratory Center 
Johns Hopkins University School of Medicine 
1800 Orleans Street 
Sheikh Zayed Tower Room B1-1020F 
Baltimore, MD 21287 
Phone: 443-287-7516 
Email: mmarzin1@jhmi.edu 
 
Yaw O. Agyei, MPH 
HPTN LC International QA/QC Coordinator 
Johns Hopkins University School of Medicine 
600 North Wolfe Street 
Pathology Building Room 306 
Baltimore MD 21287 
Phone: (+1) 240-515-6055 
Email: yagyei1@jhmi.edu 
 
Shahnaz Ahmed, BS 
HPTN LC Coordinator/Protocol Specialist 
HPTN Laboratory Center  
Johns Hopkins University School of Medicine  
600 North Wolfe Street  
Pathology Building Room 311 
Baltimore, MD 21287 
Phone: 972-522-8557 
Email: sahmed60@jhmi.edu 
 
Jessica M. Fogel, PhD 
HPTN LC Protocol Virologist 
HPTN Laboratory Center 
Johns Hopkins University School of Medicine 
720 Rutland Avenue 
Ross Bldg., Room 646 
Baltimore, MD 21205 
Phone: 410-614-6498 
Email: jfogel@jhmi.edu 
 
Irving F. Hoffman, PA, MPH 
Associate Professor 
Director of International Operations 
University of North Carolina at Chapel Hill 
School of Medicine, Department of Medicine 
Division of Infectious Diseases 
2151 Bioinformatics 
Campus Box 7030 
Chapel Hill, NC 27599 USA 
Phone: 919-966-6324 
Vivian Go, PhD 
Professor of Health Behavior 
University of North Carolina Chapel Hill 
Gillings School of Global Public Health 
Department of Health Behavior 
361 Rosenau Hall 
Campus Box 7440 
Chapel Hill, NC 27599-7440 USA 
Phone: 919-966-3908 
Email: vgo@email.unc.edu 

 
 
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Email: irving_hoffman@med.unc.edu 
 
 
 
Mina Hosseinipour, MD, MPH 
Scientific Director at UNC Project-Malawi 
UNC Project, Tidziwe Centre 
Private Baf A-104 
Lilongwe, Malawi 
Phone: 265-175-5056 
Email: mina_hosseinipour@med.unc.edu 
 
William C. Miller, MD, PhD, MPH 
Research Professor 
Department of Epidemiology 
CB#7435 
Gillings School of Global Public Health 
UNC-Chapel Hill 
Chapel Hill, NC 27599-7435 
919-966-7430  
Julie Pulerwitz, ScM, ScD 
Senior Advisor, Socio-behavioral Science 
Research, Population Council 
Professorial Lecturer, Prevention and 
Community Health Dept., Milken Institute 
School of Public Health, George Washington 
University 
Population Council 
4301 Connecticut Avenue, NW #280 
Washington, DC 20008 
Phone: 202-237-9400 
Email: jpulerwitz@popcouncil.org 
 
Jane Chen, PhD 
Researcher 
University of North Carolina Chapel Hill 
Gillings School of Global Public Health 
Department of Health Behavior 
361 Rosenau Hall 
Campus Box 7440 
Chapel Hill, NC 27599-7440 USA 
Phone: 919-966-2537 
Email: janechen@live.unc.edu 
 
Myron Cohen, MD 
HPTN Principal Investigator 
Global Health Director, 
Institute for Global Health and Infectious 
Diseases 
University of North Carolina  
130 Mason Farm Road 
Chapel Hill, NC, 27517 
Phone: 910-302-8343 
Email: mscohen@med.unc.edu 
Brandon Brown, MPH, PhD 
Professor of Medicine 
Department of Social Medicine, Population and 
Public Health  
University of California Riverside School of 
Medicine 
900 University Ave, Riverside, CA 92521 
Phone: 951-827-3953Email: 
brandon.brown@medsch.ucr.edu 
 

 
 
 
  
HPTN 112 
Improving HIV prevention among heterosexual cisgender men seeking STI services in 
Malawi: examining the benefits, acceptability, and associated costs of a systems-navigator-
delivered integrated prevention package 
 
SCHEMA 
 
Purpose: 
To evaluate the potential benefit(s), acceptability, and associated costs 
of a systems navigator-delivered HIV prevention intervention in 
promoting and supporting persistent use of evidence-based HIV pre-
exposure prophylaxis (PrEP) among heterosexual cisgender men 
receiving care for sexually transmitted infections (STIs) in Lilongwe, 
Malawi. 
Design: Single site pilot effectiveness-implementation hybrid type 1 trial   
Population: 
The study population will consist of the following participant types:  
1. HIV seronegative heterosexual cisgender males seeking STI 
services who have accepted PrEP services 
2. Other key stakeholders relevant to systems navigation program 
implementation   
Study Size: 
Approximately 200 heterosexual cisgender males, presenting as HIV-
seronegative and initiating PrEP (followed prospectively) and 
approximately 15 other key stakeholders. 
Study Duration: 
The proposed study duration is 15 months (65 weeks), including up to 
39 weeks for participant recruitment. Seronegative participants will be 
on study for at least 26 weeks, and up to 52 weeks. 
Study Location: Bwaila STI clinic, Lilongwe, Malawi 
Study Regimen: 
Systems navigation integrated into PrEP services delivered at an STI 
clinic in promotion of persistent effective PrEP use - either daily oral, 
2-1-1 event driven, or injectable.  
Navigators will: 
• conduct brief counseling (and risk-focused) sessions, 
• POC STI testing, 
• assess barriers of PrEP use, and contact persons who default 
from PrEP care to facilitate PrEP re-engagement, offering 
PrEP “restart” kits as appropriate. 
Primary Objective(s): 
• To assess the effect of a systems-navigator facilitated HIV 
prevention package on PrEP persistence among heterosexual 
cisgender men seeking STI clinical services in Lilongwe, 
Malawi at 26 weeks.  
• To assess acceptability and barriers of implementing a 
systems-navigator delivered HIV prevention package among 
key stakeholders in the clinic and heterosexual cisgender men 
initiating PrEP at STI clinics.  
Secondary Objectives: 
• To assess feasibility of a future randomized controlled trial.  

 
 
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Exploratory 
Objectives: 
• To assess prevention-effective PrEP use among heterosexual 
cisgender men initiating PrEP at STI clinics. 
• To assess PrEP modality preferences among heterosexual 
cisgender men initiating PrEP at STI clinics. 
• To assess the effect of a systems-navigator facilitated HIV 
prevention package on PrEP persistence among heterosexual 
cisgender men seeking STI clinical services in Lilongwe, 
Malawi, at 39 and 52 weeks.  
• To quantify costs and resources necessary to develop and 
integrate a systems-navigator delivered HIV prevention 
package into an urban STI clinic, informing future cost-
effectiveness model development. 
• To perform laboratory assessments that may include evaluation 
of factors related to HIV infection or other STIs; 
characterization of HIV in participants who acquire HIV; 
characterization of the host response to antiretroviral drugs; 
and evaluation of virologic, pharmacologic, or STI-based 
laboratory assays. 
• To evaluate event-driven PrEP drug concentrations within the 
context of TLFB reported PrEP use and sex acts. 
• To explore the perceived and experienced PrEP related stigma 
and potential influence of perceived gender norms on PrEP 
persistence among heterosexual cisgender men initiating PrEP 
at the STI clinic. 
 
 
 

 
 
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HPTN 112 
Improving HIV prevention among heterosexual cisgender men seeking STI services in 
Malawi: examining the benefits, acceptability, and associated costs of a systems-navigator-
delivered integrated prevention package 
 
OVERVIEW OF STUDY DESIGN 
 
 

 
 
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1.0 
INTRODUCTION 
 
Cisgender men who present to a sexually transmitted infection (STI) clinic in Malawi 
demonstrate risk for transmission and acquisition of HIV infection. Recent evidence 
suggests a small number of cisgender men will present with new onset or recognized 
diagnosis of HIV. The majority of cisgender men will not be living with HIV, but still at 
risk for HIV infection. This protocol is a pilot effectiveness-implementation hybrid-1 
study. It describes research to assess the benefits, acceptability, and feasibility of a future 
larger trial of a systems navigation-delivered intervention, integrated into routine STI 
care as a strategy to engage heterosexual cisgender men in evidence-based HIV 
prevention activities, specifically biomedical pre-exposure prophylaxis (PrEP). The 
overall goal of this pilot study is to inform a future broader implementation science trial, 
engaging cisgender men from STI clinics to improve uptake and persistent use of PrEP, 
reducing incident infections among HIV-uninfected heterosexual cisgender men and their 
cisgender female sexual partners.  
 
1.1 
BACKGROUND AND RATIONALE  
 
Despite dramatic reductions in HIV incidence globally, progress towards ending the 
epidemic have stalled. A vaccine has not yet been generated; evidence-based strategies 
include integrated biomedical and behavioral strategies. HIV status neutral interventions 
include effective treatment of HIV infection and provision of PrEP to people who are at 
high risk of acquiring HIV. The rollout of PrEP has been hampered by inconsistent 
referral, inadequate uptake, and poor persistence despite ongoing HIV risk.1-6 It is 
necessary to identify patients at high risk of acquiring HIV, efficiently link them to 
appropriate prevention services, while maintaining access to those services throughout 
the period of HIV risk.  
 
PrEP services were rolled out in 2020 in Malawi. The PrEP services target populations at 
high risk of HIV acquisition, which include individuals who buy or sell sex, key 
populations, sero-different couples, cisgender adolescent girls and young women, and 
STI patients. 
 
Persons seeking STI services are a compelling population on which to focus HIV 
prevention resources; an incident STI is an objective indicator of unprotected sex and, in 
high HIV incidence settings, a reasonable proxy for HIV risk. In Malawi, persons with 
STIs are prioritized for HIV prevention, including PrEP, and PrEP was integrated into a 
Lilongwe-based STI clinic in November 2021.7 STIs are managed using a syndromic 
approach hence STI diagnostic testing is not part of standard of care. Most patients 
(>80%) present with discharge or genital ulcer syndromes. HIV prevalence among STI 
patients is around 5-10% and our past research in this clinic demonstrates that about 0.5% 
of HIV seronegative patients have acute HIV infection, highlighting the importance of 
engaging this population in effective HIV prevention interventions.8-10 
 

 
 
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Our preliminary work integrating oral PrEP into a Malawi STI clinic suggests 
acceptability of PrEP provision alongside STI services among heterosexual cisgender 
men, and enthusiasm for highly effective,11,12 and now approved for use long-acting 
injectable (LAI) PrEP. Likewise, published literature encourages an increase in integrated 
services to reduce the incidence of both HIV and STIs.13 Although the World Health 
Organization includes persons with STIs as a priority PrEP population,7 our ongoing 
study is one of the first to incorporate PrEP with STI clinics in sub-Saharan Africa 
(SSA).14 Reflecting the demographics of persons seeking testing, >60% of the 150 
enrolled PrEP users in our cohort are heterosexual cisgender males (unpublished). 
Through this work, we have identified important gaps in PrEP service delivery including 
drop-off of referral from clinic staff (only 20% of all PrEP-eligible persons receiving STI 
services were offered PrEP) and poor PrEP persistence.  
 
Besides demonstrating persistent HIV risk within this population, with nearly one-quarter 
of cisgender male participants having an incident gonorrhea or chlamydia infection 
during the 6 months of follow-up, this work has also started to identify important barriers 
to persistent PrEP use among heterosexual cisgender males who initiate PrEP. 
Preliminary review of persistence data from an ongoing pilot study of PrEP in Malawi 
(unpublished) suggests that although 41/115 (35%) of cisgender men remained persistent 
on PrEP for 6 months after enrollment (adequate doses based on pill count and on-time 
follow-up consistent with adherence to daily oral PrEP), 17% were lost-to-follow-up 
immediately after initiating PrEP, and another 11% were lost-to-follow-up following 
their first (1-month) PrEP follow-up visit. Ongoing analysis of qualitative data from this 
same cohort suggests challenges with taking a pill every day, barriers in disclosing to 
friends and family, and changes in relationship status that influence perceived risk.  
 
Fluctuations in HIV risk and perceived HIV risk influence both the initiation of and 
consistent effective use of PrEP. Historically, these dynamics have been evaluated only in 
sero-different couples or among heterosexual cisgender women. Tailored counseling may 
facilitate improved PrEP uptake and use, and even brief risk-reduction counseling 
sessions may be effective, particularly when delivered in so-called “teachable moments”, 
which may include the presentation with an STI.   
 
Efficiently and effectively addressing barriers to uptake of PrEP and persistent use of 
PrEP is critical to improve HIV prevention outcomes, especially among historically 
understudied heterosexual cisgender men in SSA, including in Malawi, for whom 
healthcare engagement is sporadic. Our single-site pilot study is responsive to the HIV 
Prevention Trials Network (HPTN) call for concepts (fall 2022), which requested small 
pilot studies that focused on understanding the prevention opportunity for heterosexual 
cisgender men living in SSA – a population identified as an existing and important gap 
within network research in this region. We have further focused the population to 
cisgender men who are at increased risk of acquiring HIV, namely, cisgender men who 
are presenting to an STI clinic with symptoms consistent with an STI or a recent 
exposure to a person with an STI.  
 

 
 
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Our study addresses crucial network priority areas, specifically evaluating integrated 
strategies that improve sexual health outcomes related to HIV and non-HIV STIs.  
 
1.2 
RATIONALE FOR STUDY DESIGN  
 
HPTN 112 is a pilot effectiveness-implementation hybrid type 1 trial designed to assess 
the feasibility and acceptability of a novel STI-clinic based intervention to facilitate rapid 
and continued engagement in effective HIV prevention services (PrEP), among 
heterosexual cisgender men. Although cisgender women in Malawi account for the 
majority of incident HIV, largely due to effective antenatal HIV screening, cisgender men 
make up a growing proportion of new infections. Failure to prevent infections among 
cisgender men, or rapidly diagnose and link cisgender men with prevalent infection to 
antiretroviral therapy (ART), fuels incident infections among cisgender women and 
contributes to the stagnating HIV incidence in Malawi. The STI clinic represents a unique 
clinical setting in which cisgender men with documented HIV risk are rarely directly 
engaged in effective prevention tools. Given the limited sample size, short recruitment 
period, and heterogeneity of determinants of persistent PrEP use across different 
populations, transgender persons and cisgender women are not included in this initial 
pilot.  
 
Systems navigation and counseling is a theory-derived evidence-based intervention that 
could improve referral to, uptake of, and persistence of effective HIV prevention 
interventions including PrEP. Systems navigation includes identifying persons most 
likely to benefit from HIV prevention tools and helping them navigate complex, dynamic 
obstacles to uptake and retention. This intervention draws from a combination of social 
cognitive theory15 and social identity theory,16 using counseling and engagement to 
develop a person’s capacity and confidence to remain engaged in PrEP care.  
 
PrEP efficacy is associated with having adequate (effective or target) drug concentrations 
during periods of potential HIV exposure. Inadequate adherence to daily oral PrEP can 
lead to lower drug concentrations at anatomic sites of viral exposure, thus compromising 
PrEP effectiveness; the challenges associated with oral PrEP adherence may be mitigated 
by longer-acting agents, including LAI PrEP. Although LAI PrEP removes the need for 
daily dosing, timely injections are necessary to achieve and maintain target drug 
concentrations. Alternatively, so-called “on-demand” or “event-driven” PrEP, in which 
PrEP users take pills only around the time they have sex, may be protective against HIV 
acquisition and, depending on frequency of sex acts, could increase the interval between 
dosing compared to daily oral PrEP. However, data for use of this strategy has been 
mixed, and little is known about acceptability and effective use among heterosexual 
cisgender men. By triangulating timing of self-reported sex acts, self-reported event-
driven PrEP use, and PrEP drugs levels collected at quarterly intervals, this study will be 
able to explore how these measures can be combined to better evaluate prevention-
effective event-driven PrEP use among men.  
 

 
 
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Importantly, although a registered product approved for use in Malawi, and eventually 
expected to be available to cisgender men, LAI PrEP is not currently available at the time 
of this writing. It is expected to become an option for cisgender men during the proposed 
enrollment period. All three types of PrEP available (or to be available) to participants in 
this study (daily oral, “event-driven”, and LAI) are approved for use in Malawi.  
However, there are no prior studies documenting preference for, uptake of, or adherence 
to LAI PrEP (compared to daily oral or “event-driven”) among heterosexual cisgender 
men. Our preliminary work in this clinic suggests that between 50-60% of cisgender men 
may prefer injectable PrEP over pills, but this has only been examined in a hypothetical 
scenario to-date. This study will provide crucial information regarding preferences for 
PrEP modalities in this understudied population.  
 
Fluctuations in oral PrEP also expose patients to HIV risk.17 As such, our study design 
integrates a “return-to-PrEP” kit, including a 14-day supply of oral PrEP and a home HIV 
test kit for participants who, after counseling sessions, decline interest in additional PrEP. 
Participants who no longer feel they need PrEP are encouraged to return to the PrEP 
clinic and are offered this “re-start” kit alongside instructions for self-testing and use of 
the pill pack to facilitate immediate protection if they are not able to plan far enough to 
restart PrEP in a timely manner. This “re-start” kit will be provided by systems 
navigators (see Section 5.4). 
 
Our STI-clinic based recruitment approach capitalizes on the synergistic co-STI/HIV 
epidemics globally and in the region and population of interest. Findings could inform a 
multi-site/multi-country implementation science study in which systems navigation is 
integrated into STI clinics as a strategy to recruit and retain high-risk heterosexual 
cisgender men in effective HIV prevention tools, including PrEP. 
 
2.0 
STUDY OBJECTIVES  
 
The overall goal of this study is to evaluate the benefit(s), acceptability, and associated 
costs of integrating systems navigation and brief counseling into STI clinic based PrEP 
provision. The primary, secondary, and exploratory objectives of the study are listed 
below. Endpoints related to each objective are described in Section 8.2. 
 
2.1 
PRIMARY OBJECTIVE(S)  
 
2.1.1 To assess the effect of a systems-navigator facilitated HIV prevention package 
on PrEP persistence among cisgender heterosexual men seeking STI clinical 
services in Lilongwe, Malawi at 26 weeks.  
 
2.1.2 To assess acceptability and barriers of implementing a systems-navigator 
delivered HIV prevention package among key stakeholders in the clinic and 
heterosexual cisgender men initiating PrEP at STI clinics. 
 
2.2 
SECONDARY OBJECTIVES  

 
 
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2.2.1 To assess feasibility of a future randomized controlled trial.  
 
 
2.3 
EXPLORATORY OBJECTIVES 
 
2.3.1 To assess prevention-effective PrEP use among heterosexual cisgender men 
initiating PrEP at STI clinics. 
 
2.3.2 To assess PrEP modality preferences among heterosexual cisgender men 
initiating PrEP at STI clinics. 
 
2.3.3 To assess the effect of a systems-navigator facilitated HIV prevention package 
on PrEP persistence among heterosexual cisgender men seeking STI clinical 
services in Lilongwe, Malawi at 39 and 52 weeks.  
 
2.3.4 To quantify costs and resources necessary to develop and integrate a systems-
navigator delivered HIV prevention package into an urban STI clinic, 
informing future cost-effectiveness model development. 
 
 
2.3.5 To perform laboratory assessments that may include evaluation of factors 
related to HIV infection or other STIs, characterization of HIV in participants 
who acquire HIV, characterization of the host response to antiretroviral drugs, 
and evaluation of virologic, pharmacologic, or STI-based laboratory assays. 
 
2.3.6 To evaluate event-driven PrEP drug concentrations within the context of 
TLFB reported PrEP use and sex acts. 
 
2.3.7 To explore the perceived and experienced PrEP related stigma and potential 
influence of perceived gender norms on PrEP persistence among heterosexual 
cisgender men initiating PrEP at the STI clinic. 
 
3.0 
STUDY DESIGN  
 
HPTN 112 is a single site pilot effectiveness-implementation hybrid type 1 trial enrolling 
heterosexual cisgender men presenting for STI care in Lilongwe, Malawi. HIV 
seronegative participants will be randomized (1:2) to standard of care PrEP services 
(SOC) or systems navigator-assisted PrEP care (intervention) as described briefly below.  
 
Standard of care PrEP services include PrEP eligibility assessment, rapid HIV antibody 
testing prior to provision and/or refill of PrEP, and PrEP follow-up with a PrEP nurse in 
accordance with contemporary PrEP guidelines. Specifically, SOC services do not 
generally include POC STI testing (with the exception of rapid syphilis and Hepatitis B 
antigen testing, if kits are available, at PrEP initiation) nor tracing for missed PrEP visits. 

 
 
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Participants randomized to the SOC condition will receive these standard PrEP services 
as provided by the Malawi MoH.  
 
The intervention package (intervention arm only) is integrated into PrEP visits and 
includes evaluation of barriers and facilitators to ongoing PrEP use, POC STI testing to 
inform counseling regarding ongoing PrEP care engagement, tracing for any missed PrEP 
visits, and offering a PrEP “restart” kit for cisgender men who choose to discontinue 
PrEP during the follow-up period. Recognizing increasingly cyclical PrEP use patterns, 
navigators serve as a direct entry point to retain or re-engage participants in HIV 
prevention care. Additional details regarding selection of systems navigators and 
specifics regarding the intervention package are described in Section 5.0. 
 
All PrEP services, including determining PrEP eligibility and monitoring of PrEP use and 
safety, will be conducted by the Malawi Ministry of Health, per their PrEP management 
guidelines. No additional safety monitoring will be conducted to inform participant care 
or safety specific to PrEP through this study. All three types of PrEP available (or to be 
available) to participants in this study (daily oral, “event-driven”, and LAI) are approved 
for use in Malawi.   
 
Throughout the study design, we distinguish between PrEP visits and study visits. PrEP 
visits are conducted on a timeline determined by the MoH and should align with the 
modality of PrEP that a participant has selected. During a PrEP visit, the navigator will 
meet with the participant, discuss risk and PrEP use, and offer POC STI testing to inform 
the risk discussion. Navigators will conduct tracing activities for any missed PrEP visit, 
in accordance to PrEP-user stated preferences for tracing (see Section 5.0). Study visits, 
on the other hand, occur every 13 weeks regardless of PrEP modality, and are completed 
by study nurses. These visits include in-depth behavioral surveys and specimen 
collection. Participants receive a financial incentive to attend and complete the study 
visits, and these visits continue regardless of a participant’s decision to continue or 
discontinue PrEP use. Tracing for missed study visits will utilize study staff – these staff 
members are distinct from Systems Navigators, who only trace for missed PrEP visits in 
the intervention arm. This distinction and separation is crucial to inform our primary 
outcomes (effect of navigation on PrEP persistence) and avoid contamination of 
interpreting the PrEP use outcomes in the context of financial incentives that are external 
to the study intervention.  
 
In-depth qualitative interviews will be conducted with a subset of cisgender men who 
initiate PrEP (approximately 20 at last study visit) and with other key stakeholders 
(approximately 15) including persons involved in provision of navigation, STI or HIV 
care or prevention (including clinic management or oversight), or development of HIV 
prevention policy or programming at local or national level. The purpose of these 
interviews is to explore facilitators and barriers to acceptability of the intervention 
components.  
 
3.1 
PARTICIPATING SITE  

 
 
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Bwaila Sexually Transmitted Infection (STI) Clinic is located in Lilongwe, Malawi. 
Bwaila STI Clinic is an affiliate of UNC Project Malawi. UNC Project Malawi is the 
official CRS for this study and will be registered to the protocol and responsible for data 
management and LDMS. 
 
The Bwaila STI clinic is located within the Bwaila Hospital, a free secondary level public 
facility. The Bwaila hospital is in a busy town area in the center of the Lilongwe city, the 
capital city of Malawi. It has a catchment population of about 130,000 people. At the 
Bwaila STI clinic, PrEP services are co-located within the STI clinic, an integrated 
program launched in November 2021. HIV testing is standard of care and is offered as a 
routine opt-out service. HIV status ascertainment is around 98%. All STI patients who 
test HIV negative may be offered PrEP. On average, the STI clinic sees about 50 HIV 
seronegative patients per day of whom about 45% are cisgender male. Among the 
seronegative patients, about 5-10% accept to start PrEP daily. Hepatitis B testing before 
PrEP initiation is standard of care however, clients can start PrEP and be tested later if 
testing is unavailable at initiation. 
 
The UNC Project Malawi works in collaboration with a Community Advisory Board 
(CAB). The CAB consists of diverse members that span across all demographics 
including adolescents and backgrounds. The CAB meets routinely every quarter and 
when a need arises. Aside from the general CAB, the UNC Project Malawi CAB has an 
adolescent arm called the Adolescent CAB, which provides guidance on studies that 
involve adolescents. The protocol team held a consultative meeting with the UNC Project 
Malawi CAB where the members were briefed about the HPTN 112 protocol. CAB 
members provided feedback on the general approach of the study and guidance on how to 
select appropriate system navigators. In addition, the members provided guidance on the 
best ways for the system navigators to approach participants in their communities. In 
addition, the Malawi MoH Department of HIV, Viral Hepatitis and STIs provided their 
support for the study. Finally, the protocol team will brief the Lilongwe District Health 
Office Research Committee on the HPTN 112 protocol and obtain a letter of support on 
the same. 
 
3.2 
STUDY DURATION  
 
The proposed study duration is approximately 15 months (65 weeks) total, with 
individual participants being followed on study for at least 26 weeks and up to 52 weeks. 
We expect accrual to require up to 39 weeks.  
 
4.0 
STUDY POPULATION  
 
Cisgender men account for approximately half of all persons seeking STI services at 
Bwaila STI clinic (approximately 15,000 annual visits) and nearly all identify as only 
having sex with cisgender women. Given the limited sample size, short recruitment 
period, and heterogeneity of determinants of persistent PrEP use across different 

 
 
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populations, transgender persons and cisgender women are not included in this initial 
pilot. Furthermore, our past work in this space suggests that individuals who identify as 
gender non-binary typically seek sexual health services at other area drop-in centers, 
rather than the STI clinic where this study will be conducted. 
 
Approximately 200 HIV seronegative cisgender individuals assigned male at birth (here 
and throughout referred to as cisgender men) who have presented to care for STI 
management will be included in this study. Participants will be selected for the study 
according to the criteria in Section 4.1 and 4.2 and the co-enrollment guidelines in 
Section 4.4. Participants will be recruited, eligibility will be determined, and then 
enrolled as described in Section 4.3.  
 
Requirements related to participant retention and withdrawal from the study are described 
in Sections 4.5 and 4.6, respectively. All participants will be recruited from the Bwaila 
STI clinic (Section 3.1). A subset of HIV seronegative participants will also be 
interviewed (approximately 20) during study participation.  
 
We will also interview key stakeholders relevant to the adoption and implementation of 
systems navigation as a strategy to improve HIV prevention integration in the STI clinic.  
 
4.1 
INCLUSION CRITERIA  
 
In HPTN 112, there are two populations eligible to participate in the study, 1. Persons 
initiating PrEP (n=200, 20 of whom will also participate in stakeholder interviews), and 
2. Other key stakeholders (approximately 15). 
 
1. Cisgender adult and adolescent cisgender men who meet all of the following criteria 
are eligible for inclusion in this study as a participant initiating PrEP: 
 
1. Age ≥18 years or age 15-17 (with assent and parent/guardian consent) 
2. Able to provide informed consent 
3. No plans to move outside study area for at least 26 weeks after study enrollment 
4. Willing to provide contact/locator information, including phone number, to 
facilitate tracing 
5. Willing to participate in study activities, including specimen collection  
6. Willing to participate in study activities, including systems navigation, 
counseling, and POC STI testing 
7. Sought STI clinic services within 7 days of enrollment 
8. Initiated on PrEP at STI clinic within 7 days of enrollment* 
9. Reports at least one cisgender female sex partner in the 6 months prior to 
enrollment 
10. Self-identifies as heterosexual 
 
* Newly initiating PrEP or re-initiating PrEP after at least 13 weeks from last PrEP use 
or injection. 

 
 
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All participants will have been prescribed PrEP prior to enrollment. As such, they will 
have been deemed PrEP eligible according to contemporary Malawi PrEP guidelines. At 
time of writing, eligibility for oral PrEP includes:  
 
1. HIV seronegative  
2. At substantial risk for HIV, with prioritization of persons who: 
o Buy or sell sex 
o STI clients 
o Sero-different couples including HIV-negative people for whom 
their partner living with HIV is: not on ART, on ART <6 months, 
has high viral load, or is non-adherent to ART. 
3. No concern for acute HIV infection based on provider screening for signs 
or symptoms consistent with acute HIV.  
4. Willingness to attend scheduled PrEP visits  
5. No contraindication to use of TDF and 3TC 
6. Bodyweight ≥30kg (66lbs.) 
7. No known renal diseases 
8. No diabetes mellitus 
2. Individuals who meet all of the following criteria are eligible for inclusion in this study 
as other key stakeholders: 
 
1. Age ≥18 years at the enrollment visit 
2. Able to provide informed consent 
3. Involved in provision of clinical service navigation, systems navigation, 
STI or HIV care or prevention (including clinic management or oversight), 
or development of HIV prevention policy or programs at local or national 
level 
4.2 
EXCLUSION CRITERIA  
 
Exclusion for the two participant groups is as follows: 
 
1. Cisgender adult and adolescent men who meet any of the following criteria are 
ineligible for inclusion in this study as a participant initiating PrEP: 
1. Appearance of psychological disturbance or cognitive impairment that 
would limit the ability to understand study procedures, as determined by 
the investigators   
2. Any other condition that, in the opinion of the investigators, would make 
participation in the study unsafe, or otherwise interfere with the conduct of 
the study  

 
 
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3. Current participation in any HIV prevention study or other study 
considered to interfere the interpretation of study outcomes (see Section 
4.4). 
 
2. Individuals who meet any of the following criteria are ineligible for inclusion in this 
study as other key stakeholder: 
1. Appearance of psychological disturbance or cognitive impairment that 
would limit the ability to understand study procedures, as determined by 
the investigators   
2. Any other condition that, in the opinion of the investigators, would make 
participation in the study unsafe, or otherwise interfere with the study 
activities   
 
4.3 
RECRUITMENT PROCESS  
 
Details of study recruitment flow are specified in Appendix I.  
 
This study includes two types of participants: 
1. Approximately 200 HIV seronegative cisgender male PrEP eligible participants will 
be recruited. This will include heterosexual cisgender men who report to the STI 
clinic seeking services and are PrEP eligible according to Malawi HIV testing 
algorithms. PrEP eligible participants enrolling in this study should be initiating 
PrEP.  
2. Approximately 15 other key stakeholders will be recruited using purposive sampling 
to engage stakeholders with diverse roles, responsibilities, and exposure/experience 
with the intervention. 
 
We anticipate that recruitment of participants will take place for up to 39 weeks. All 
participants will be enrolled from the Bwaila STI clinic. The site will use its previously 
established systems for recruiting participants. As part of the routine system, individuals 
with a suspected STI are referred to the STI clinic from the outpatient department. Upon 
arrival at the STI clinic, the patients are registered into the STI clinic electronic medical 
registration (EMR) system and escorted to the waiting area. At the waiting area, patients 
receive group health education. During the group health education, clinic staff will 
introduce the HPTN 112 study in brief through oral and written (study flyer) description 
to prospective participants and will encourage cisgender men to participate in eligibility 
determination activities at the study site. Staff will inform cisgender men that those who 
are interested in the study will receive more information about the study through a one-
on-one discussion.  
  
After group health education, which includes introduction to any enrolling study at the 
clinic, as part of local standard of care, the patients undergo HIV testing using the 
Malawi HIV Testing and Counselling guidelines, including risk reduction counselling as 
part of routine services. All HIV seronegative patients are offered a brief discussion of 

 
 
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PrEP services and HIV risk, based on self-reported risk behaviors and assessed for PrEP 
eligibility as standard of care. Those who are interested are referred to the PrEP nurse for 
discussion and initiation. After being started on PrEP by the nurse, potential participants 
will be approached by study staff and receive information regarding the study and 
undergo eligibility assessment. This form will include all data relevant for determining 
eligibility; no identifying information will be included on this form. If eligible and 
interested in participation, potential participants will undergo study consent, enrollment, 
and randomization procedures (see Section 6.1). Systems navigators will engage 
cisgender men randomized to the intervention arm at this point. 
  
A sample of the assent and consent forms can be found in Appendices V and VI. If 
during the eligibility assessment, they are found to be ineligible, recruitment will be 
discontinued, and participants will be dismissed.  
 
Throughout enrollment procedures, study staff will emphasize that enrollment in the trial 
does not require a commitment to use of PrEP throughout the follow-up period. 
Participants will also be reminded that study remuneration is being provided at the 
designated quarterly study visits, not as part of their scheduled PrEP care. 
 
4.4 
CO-ENROLLMENT GUIDELINES  
 
HIV seronegative participants should not be currently participating in any HIV 
prevention study and may not enroll in any HIV prevention trial during this study; these 
guidelines are needed to facilitate high levels of retention, and to avoid confounding in 
the interpretation of the primary and secondary endpoint data. Limitations are made 
explicit in the informed consent forms. 
  
Participants can participate in this study if they are enrolled in other studies not offering 
HIV prevention, such as observational studies. Examples of excluded studies including 
any phase 1 HIV vaccine study, any assessment of novel biological products, and studies 
with multiple visits, the engagement in which could influence interpretation of HPTN 
112 study outcomes. All co-enrollments should be discussed and approved by the 
principal investigator in coordination with select members of the protocol team. Studies 
that include any intervention, including behavioral interventions that may influence HIV 
or STI prevention outcomes, can be assessed on a case-by-case basis.  
 
4.5 
PARTICIPANT RETENTION  
 
4.5.1 Retention in PrEP care 
As part of the proposed intervention, systems navigators will be tasked with 
tracing for missed PrEP visits, as described below (section 5.2). Tracing activities 
are conducted in accordance to the stated preference of the participant, and can 
include phone and in-person tracing. Notably, these PrEP tracing tasks are distinct 
from study follow-up visits, which will occur separately from PrEP visits. The 
separation (see Section 3.0) is designed to avoid conflating PrEP persistence 

 
 
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outcomes with study activities, the latter of which have remuneration provided. 
PrEP visit reminders (and tracing) will coincide with the PrEP follow-up schedule 
as dictated by the Malawi Ministry of Health.  
 
4.5.2 Retention in study 
Participants do not need to continue PrEP to remain in the study. Once a 
participant enrolls in this study, the study site will make every effort to retain him 
for at least 26 weeks of study follow-up to minimize possible bias associated with 
loss-to-follow-up.   
 
Study staff will remind participants of upcoming visits using phone calls and will 
trace (phone) participants who miss a visit within 7 days post scheduled visit date. 
Participants who do not report to the study site within 14 days of a scheduled visit 
will be traced physically by study staff. All tracing is conducted with attention to 
confidentiality, through which neither the identity of the participant nor the nature 
of the study, would be disclosed to any person without the explicit guidance from 
the participant (or their guardian). All participants provide preferred locator 
information (including mode of tracing, location at which one could be traced, 
names or contact information of persons who can be contacted in the event 
participant is not located) and tracing attempts follow these preferences. Locator 
information and preferences are updated at each study visit. Specifically, study 
staff discuss how they should identify themselves when texting, calling, or 
visiting a participant and staff confirm with the participant whether limited 
messages can be left with specific contacts. If the participant is aged 15-17, the 
guardian’s preferences for tracing will be recorded and updated at each contact as 
needed. A basic philosophy of the retention strategy is that follow-up begins at 
recruitment and is a priority at every visit. Components of such procedures 
include: 
  
• Thorough explanation of the study visits schedule and procedural requirements 
during the informed consent process, with re-emphasis at each study visit. 
  
• Collection of detailed locator information at the enrollment visit, with active 
review and updating of this information at each subsequent visit. 
  
• Use of mapping techniques to establish the location of participant residences 
and other venues that participants frequent.  
 
• Use of appropriate and timely visit reminder mechanisms. 
  
• Visit calendars and flyers or other handouts will be offered at enrollment to 
assist with retention. 
  

 
 
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• Immediate and multifaceted follow-up on missed visits, including 
outreach/locator efforts such as phone calls, text messages, or home contacts, 
consistent with stated participant (or guardian) preference.  
• Mobilization of trained outreach workers or “tracers” to complete in-person 
contact with participants at their homes and/or other community locations. 
  
• Regular review of follow-up procedures and current status by site leadership 
and staff. 
  
• Regular communication with the study community at large to build trust and 
increase awareness about the study and prevention of HIV. Specifically, 
briefing of CAB, relevant stakeholders working withing catchment from which 
potential participants may arise, and local Chiefs and other influential gate 
keepers.  
 
4.6 
PARTICIPANT WITHDRAWAL  
Regardless of the participant retention methods described above, participants may 
voluntarily withdraw from the study for any reason at any time. The investigators also 
may withdraw participants from the study in order to protect their safety and/or if they 
are unwilling or unable to comply with required study procedures after consultation with 
the Protocol Chair, DAIDS Medical Officer, Statistical and Data Management Center 
(SDMC) Protocol Statistician, and LOC Clinical Research Manager (CRM). Participant 
non-adherence to the intervention is not a reason for participant withdrawal from the 
study. Additionally, seronegative participants must agree to initiate PrEP to enroll in the 
study, but they do not have to continue to take PrEP to remain on study. 
 
Participants also may be withdrawn if the study sponsor, government or regulatory 
authorities, or site institutional review boards (IRBs) or ethics committees (ECs) 
terminate the study prior to its planned end date. 
  
Participants will not be considered withdrawn unless the participant actively withdraws 
or dies, or the investigators withdraw the participant for the reasons given above.  
Every reasonable effort will be made to complete a final evaluation of participants who 
terminate from the study early, and study staff will record the reason(s) for all 
withdrawals from the study in participants’ study records. 
 
5.0 
STUDY INTERVENTION PACKAGE 
The study intervention components, as described below, are integrated into the PrEP visit 
for participants randomized to the intervention arm. Timing for PrEP visits will be 
determined by the MoH PrEP nurse, aligning with contemporary recommendations for 
PrEP follow-up. According to the Malawi Ministry of Health PrEP program, persons who 
initiate oral PrEP are scheduled for PrEP follow-up visits at months 1, 3 and every 3 
months thereafter. Injectable PrEP guidelines are not yet available but are expected to 
include a visit at 1-month and then every two months thereafter, aligning with scheduled 

 
 
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injections. The study intervention will not interfere with regular PrEP care – PrEP nurses 
will still proceed with any PrEP adherence counseling as well as any HIV risk reduction 
counseling consistent with Malawi PrEP guidelines at each PrEP visit. 
 
The study intervention package includes: 1. Access to a systems navigator, intended to 
engage with participants at each PrEP visit and who can trace participants who do not 
attend a scheduled PrEP visit; 2. POC STI testing; and 3. A PrEP re-engagement or “re-
start” kit offered to participants who choose to stop PrEP.  
 
Study intervention activities occur primarily at the Bwaila STI clinic, with the notable 
exception of tracing for missed visits, which fundamentally will occur in the field. PrEP 
visits, and any associated meetings with systems navigators, will occur at the Bwaila STI 
clinic, whereas HPTN 112 study visits (conducted by non-navigator study staff), will 
occur in a separate building. The schedule and content of study visits is further specified 
in Section 6.3, and occur quarterly regardless of a participants’ ongoing PrEP use or PrEP 
schedule. 
 
5.1 
SYSTEMS NAVIGATORS: SELECTION AND TRAINING 
Navigators will be cisgender male and will be selected from the community with 
guidance from the Community Advisory Board (CAB). Navigators must be 
knowledgeable about the community’s dynamics and reflect the demographics of 
the target population. They will undergo extensive training including but not 
limited to: basic knowledge of STIs, HIV, and PrEP; PrEP modalities, including 
potential benefits and expected challenges; motivational interviewing; 
psychosocial counselling; techniques for active listening and rapport building; and 
HPTN 112 procedures. Although not required, navigators may themselves have 
been previously or currently prescribed PrEP. The navigators will also be trained 
regarding personal safety, discrete tactics for follow-up tracing, and 
confidentiality. These components and attributes have been developed in 
coordination with local CAB members. All training materials will be developed in 
advance of study implementation with a separate Systems Navigation Manual, the 
content of which will include a series of didactics as well as role playing and 
direct observation. Navigators will receive periodic refresher training and regular 
evaluations. 
 
Navigators engage with participants during PrEP visits (and in the field for tracing 
related to a missed PrEP visit) – although these are activities intentionally 
distinguished from study visits (see Appendix I). Because this protocol is still 
considered research, all navigators will receive training related to ethical conduct 
of clinical research.  
 
5.2 
SYSTEMS NAVIGATORS: COUNSELING AND TRACING 
Participants meet with a systems navigator after enrollment into the study (and 
randomization to intervention arm). Navigators help identify motivators for PrEP 
use and potential barriers to continued consistent use. During meetings with 

 
 
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participants, the navigator will use a standardized list to evaluate progress or 
barriers to PrEP and persistent effective PrEP use, formulating plans to overcome 
any identified barriers (i.e., offering reminders for appointments, assistance 
identifying champions to help support and encourage PrEP use, or adherence 
strategies to improve use of PrEP as prescribed).  
 
The navigator will meet with the participant only after they are enrolled in the 
study and then at each subsequent PrEP visit (see Appendix I) to formulate plans 
and strategies for ongoing PrEP use. Contact between PrEP visits will be tailored 
to participant needs, with the goal of maintaining regular contact and facilitate 
PrEP engagement, as informed by the elicited barriers to persistent PrEP use.  
 
Intervention arm participants who miss a scheduled PrEP visit, typically 
considered 7-calendar days past a scheduled date, may be traced by navigators. 
Tracing efforts will be conducted in a manner consistent with the participant’s 
stated preferences in terms of mode (phone, text message, in-person), time of day, 
and location if physical tracing is conducted. As described above, navigators 
receive training in confidentiality and discretion in any tracing attempts. All 
tracing is conducted with attention to confidentiality, through which neither the 
identity of the participant nor the nature of the study or reason for outreach, would 
be disclosed to any person without the explicit guidance from the participant (or 
their guardian). Navigators will first attempt phone and text messages, with 
additional in-person tracing attempts if no response or return to care and stated as 
an option when locator information is collected. Locator information and 
preferences are updated at each encounter. Specifically, navigators discuss how 
they should identify themselves when calling or visiting a participant and whether 
limited messages can be left with specific contacts. If the participant is aged 15-
17, the guardian’s preferences for tracing for any missed PrEP visit will be 
recorded and updated at each contact as needed.  
 
Given the potential field-presence of System Navigators, similar procedures as 
those outlined in Section 4.5.2 will be conducted for community sensitization, 
including regular communication with the study community at large, briefing of 
CAB, engaging relevant stakeholders working withing catchment from which 
potential participants may arise, and alerting local Chiefs and other influential 
gate keepers. These procedures help to maintain the safety of field-based 
navigator tasks, further detailed in Section 10.3. 
   
5.3 
RISK ASSESSMENT AND POC STI TESTING 
At each PrEP visit or tracing contact for a missed PrEP visit, participants will 
complete a brief risk assessment, with the assistance of the navigator. This 
assessment will capture and characterize HIV risk of sexual behaviors of the 
participant (i.e., new partners, partners with unknown or known HIV infection, 
condomless sex, sex while intoxicated, etc.), as well as perceived risk of HIV, and 
self-reported PrEP use. POC urine chlamydia and gonorrhea tests will be done in 

 
 
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addition to STI symptom assessment. All HIV testing for PrEP care is conducted 
by Malawi MoH HIV Testing and Counseling – there is not additional HIV testing 
done by navigators as part of PrEP visits. 
 
All STI test results obtained through study visits, including POC STI testing, will 
be returned to HIV seronegative participants. Especially in the event a participant 
does not receive their results at the clinic, systems navigators will ensure their 
delivery and accompanying referral for treatment if indicated. The combination of 
rapid STI test results, self-reported risk, risk perception, and PrEP use will be 
used to guide structured brief counseling sessions regarding ongoing risk, PrEP 
use, and identify strategies or barriers to PrEP engagement (as above).  
 
5.4 
PREP RE-ENGAGEMENT AND “RE-START” 
For participants who choose to discontinue PrEP, navigators serve as a point of 
contact for re-engagement and will encourage participants to re-initiate PrEP if or 
when HIV risk resumes. It is expected that most participants who choose to 
discontinue PrEP will not attend their scheduled PrEP visit, and thus the decision 
to discontinue PrEP will often be identified at the point of navigator-initiated 
tracing (see above). Any participant who discontinues PrEP will be offered a 
PrEP “re-start” kit, which include a supply of oral PrEP, an HIV-self test, and 
brief instructions to facilitate safe immediate restart in the event that risk recurs 
without their first re-engaging in clinic-based PrEP care. Acceptance and use of 
this kit will be explored in subsequent study visits.   
 
6.0 
STUDY PROCEDURES  
 
An overview of the study visits and procedures is presented in Appendix II with expected 
visit flow for HIV seronegative participants described in Appendix I. Presented below is 
additional information on visit-specific study procedures. Visit windows can be found in 
Section 6.8 and visit coding is described in the SSP Manual. 
 
6.1 
DETERMINATION OF ELIGIBILITY  
 
For each participant, independent written informed consent will be obtained before any 
study procedures are initiated. Eligibility determination procedures may occur over one 
or more visits up to and including the day of Enrollment. Enrollment must occur within 7 
days of eligibility determination. For most participants, eligibility determination 
procedures will occur on the same day as study enrollment. 
 
Eligibility determination includes assessing if a STI clinic patient has been offered PrEP 
(and thus deemed eligible for PrEP according to local guidelines, Section 4.1), and 
confirming that additional study eligibility criteria are met. All HIV testing, a necessary 
component of PrEP eligibility determination, will be conducted by Malawi Ministry of 
Health staff as part of standard procedures for all patients presenting to care at the Bwaila 
STI clinic. If any result or interpretation other than negative or non-reactive is obtained 

 
 
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for any HIV test, the person is not eligible for PrEP and thus not eligible for the study. 
Additional testing to confirm suspected HIV infection will be performed in accordance 
with local guidelines. If HIV infection is confirmed, participants will receive counseling 
and be referred for appropriate care, as necessary, through standard referral channels. 
 
Those individuals who meet eligibility will be offered enrollment (see Section 6.2). 
Individuals deemed not eligible will be informed that they do not meet the eligibility 
criteria for the study and will be referred for appropriate medical care, if necessary.  
 
6.2 
ENROLLMENT VISIT  
 
6.2.1 Enrollment for HIV seronegative participants initiating PrEP 
 
Enrollment will occur following determination of study eligibility and after completion of 
full study consent. This visit may occur up to 7 days following eligibility determination. 
A participant will be considered enrolled after completing all informed consent activities, 
including randomization. All enrolled participants initiating PrEP will have undergone 
HIV antibody testing in accordance with local PrEP eligibility determination processes. 
As part of study participation, they will be evaluated for acute HIV infection with HIV 
RNA testing (see Section 9.1). Persons with any detectable HIV RNA from enrollment 
visit will be linked to appropriate HIV care. They will remain in the study for a maximum 
of an additional 26 weeks following seroconversion to facilitate additional testing and 
confirm viral suppression on antiretroviral therapy.   
 
In both control and intervention arms, we will capture in-depth behavioral and health 
assessments, using validated scales where possible to facilitate exploration of predictors 
of PrEP persistence and inform specific objectives and strategies to improve psychosocial 
counseling interventions. To obtain more granular information regarding sexual activity, 
particularly relevant for cisgender men who choose event-driven oral PrEP, we will use a 
timeline follow-back (TLFB) in which self-reported sex acts over the past 30-days are 
captured in a calendar format. 
 
Administrative, Behavioral, and Regulatory Procedures: 
• Informed consent  
• Locator information 
• Behavioral risk, risk perceptions, and 30-day health assessment  
o timeline follow-back (TLFB; sex acts) 
o substance use 
o mental health 
o anticipated and experienced PrEP-related stigma 
o anticipated and experienced HIV-related stigma 
o gender norms 
• PrEP use assessment*  
• HIV risk reduction counseling 

 
 
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*The PrEP use assessment is a basic assessment of if the individual is using PrEP, 
self-reported adherence, and other related factors. 
 
Clinical Procedures: 
• Symptom-driven physical examination 
• Blood collection 
• Urine collection 
 
Laboratory Procedures: 
• HIV rapid antibody testing 
• HIV RNA  
• Chlamydia trachomatis/Neisseria gonorrhoeae (CT/NG) 
• Syphilis testing (RPR & reflex TPPA if appropriate) 
• Plasma storage 
• Urine storage 
• Dried blood spot (DBS) storage 
 
6.3 
FOLLOW-UP VISITS 
 
Study specific assessments will be conducted separately from STI-clinic based PrEP 
visits.  The proposed study duration is approximately 15 months (65 weeks) total, with 
individual participants being followed on study for at least 26 weeks and up to 52 weeks, 
depending on the time at enrollment. Recruitment will be conducted within 
approximately 39 weeks.  
 
Any participant who has had a reactive/positive HIV test during PrEP follow-up will 
have further testing to confirm infection. In all cases, confirmation of infection requires 
testing samples collected on two different dates. 
 
In both control and intervention arms, study specific visits will be conducted as follows: 
 
6.3.1 Quarterly visits (Weeks 13, 26, 39* and 52*) 
 
The following procedures will be conducted at each quarterly visit: 
 
Administrative and Behavioral Procedures: 
• Locator information (if location has changed) 
• Behavioral risk, risk perceptions, and health assessment 
o 30-day timeline follow-back [TLFB] (sex acts and PrEP use) 
o substance use 
o mental health 
o anticipated and experienced PrEP-related stigma 
o anticipated and experienced HIV-related stigma 

 
 
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o gender norms 
• PrEP use assessment 
• HIV risk reduction counseling 
 
Clinical Procedures: 
• Symptom-driven physical examination 
• Blood collection 
• Urine collection 
 
Laboratory Procedures: 
• HIV rapid antibody testing 
• Syphilis RPR & reflex TPPA if appropriate 
• CT/NG (if >2 weeks since testing conducted at PrEP visit) 
• Plasma storage 
• Urine storage 
• DBS storage 
 
*A subset of participants will also have a visit at Weeks 39 and 52, if the window of study 
follow-up allows. Participants enrolled in the first 13 weeks of recruitment will be 
followed for 52 weeks and those enrolled during the first 26 weeks of recruitment will be 
followed for 39 weeks. The remaining participants will be followed for 26 weeks total 
follow-up. 
 
Identical procedures will occur at Weeks 13, 26, 39, and 52, with the notable exception 
that a subset of participants will be asked to engage in an in-depth interview during their 
final visit (Week 26, 39, or 52).  
 
6.4 
PROCEDURES FOR PARTICIPANTS WITH SUSPECTED OR CONFIRMED HIV 
INFECTION  
 
The following sections relate specifically to HIV seronegative participants initiating 
PrEP.  
 
6.4.1 Enrollment  
HIV testing will be performed to identify persons with HIV infection prior to enrollment, 
in line with Malawi PrEP eligibility and HIV testing guidelines (Section 4.3). Individuals 
who have one or more reactive/positive HIV tests at eligibility assessment (prior to 
enrollment) are not eligible to participate in this study as PrEP participants. Per current 
Malawi PrEP eligibility criteria (Section 4.1), PrEP should not be offered to persons with 
signs or symptoms consistent with acute (pre-seroconversion) HIV infection. All enrolled 
HIV-seronegative participants will be screened for acute HIV infection with HIV RNA 
testing (Section 9.1), regardless of signs or symptoms, as part of study procedures. 
Persons with detectable HIV RNA from enrollment visit will be linked to appropriate 
HIV care and followed as described in Section 6.1.   

 
 
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6.4.2 After study enrollment 
Participants will be tested for HIV at all follow-up PrEP visits prior to distribution of 
PrEP medication, per Malawi standards. Participants will be tested for HIV at all study 
visits, regardless of HIV testing results from PrEP visits. Participants who have any 
reactive/positive HIV test result during follow-up visits will be referred for care. These 
participants will have further testing to confirm infection and will be followed quarterly 
up to approximately 26 weeks to assess viral suppression. In all cases, confirmation of 
infection requires testing samples collected on two different dates. 
  
6.5 
OTHER STUDY PROCEDURES  
 
6.5.1 Sexually transmitted infections  
Testing for CT/NG and syphilis will occur throughout the study. Testing will be 
performed at LL. Intervention arm participants who have been tested within the two 
weeks prior to a study visit as part of their PrEP care will not be re-tested for CT/NG. 
Syphilis testing may be repeated as the PrEP clinic uses POC tests that are not entered 
into Laboratory information systems and thus cannot be captured other than self-
report/paper medical record. POC test results documented in participant records may be 
extracted using case report forms, however, all CT/NG and syphilis results performed at 
LL will be entered into appropriate study databases, extracted from existing laboratory 
information systems. Results will not be returned same day, however, participants who 
test positive for an STI at study visits will be informed of their result and be referred for 
treatment as per local guidelines.  
 
6.5.2 HIV and risk reduction counseling 
PrEP visits: Participants randomized to the standard of care arm who remain engaged in 
PrEP care will receive HIV testing and counseling, as well as any risk reduction 
counseling, from MoH staff and PrEP nurses (respectively) in accordance with local 
policy and guidelines. Participants randomized to the intervention arm will similarly 
receive HIV testing and counseling and PrEP counseling from MoH staff, as well as 
relevant counseling through systems navigation.  
 
Study visits: Standard pre- and post-test counseling will be provided as part of HIV 
testing conducted at each study visit (see Section 6.3). All participants will be offered 
condoms.  
 
6.6 
QUALITATIVE DATA COLLECTION 
To assess the acceptability of the intervention, individual semi-structured interviews will 
be conducted with stakeholders, including enrolled participants (during final study visit), 
and other clinic-based key stakeholders who will be engaged during the final stages of 
intervention follow-up. Stakeholders include key personnel as described in Section 4.1. 
 
Participation of all stakeholders will be entirely voluntary. The subset of PrEP user 
participants will assent and/or consent to participate in their enrollment consent, but can 

 
 
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opt out upon being approached for an interview. If other stakeholders choose not to 
participate, he/she will experience no penalty or loss of employment or benefits. 
Procedures will be undertaken to ensure that no penalties are incurred nor pressure 
exerted by supervisors. The informed consent process for interviews will be conducted in 
a location that assures adequate privacy and confidentiality.  
 
All interview transcripts will be stripped of personal identifiers. Reports and publications 
will be thoroughly redacted to confirm that no identities can be discerned. 
 
Semi-structured interviews will follow a standard guide that includes probes and queries 
specific to stakeholders. They will explore experiences with the intervention, perceived 
barriers to persistent PrEP engagement among the target population, and potential 
barriers or facilitators to scaling or sustaining the intervention. Specifically, interviews 
will explore how the intervention successfully or unsuccessfully addresses barriers or 
enhances facilitators of PrEP uptake and persistent effective use. Barriers will be also 
assessed through the barrier questionnaire with the participant systems navigators’ data 
forms/log books, and interviews with additional stakeholders.   
 
All interviews will be audio-taped, translated, and transcribed by qualified personnel, 
with any identifiable information redacted from transcripts prior to dissemination for 
analysis.  
 
6.7 
COST AND RESOURCE DATA COLLECTION  
We will embed empirical costing into study procedures. Costs will be collected 
prospectively in two ways: micro costing and time-and-motion logs. Micro-costing 
involves “direct enumeration” for consumed inputs, an ingredients-based approach. We 
will quantify resources associated with the development and implementation of our 
intervention. We will also extract data from project expenditure and management records, 
including purchase logs and human resource records. Time-and-motion assessments 
record how involved parties (navigators) divide time among navigation-related tasks, 
reliably apportioning effort relevant to implementing the intervention. This includes time 
for trainings, counseling, tracing, and other related tasks. No formal modeling is proposed 
as part of this protocol. 
 
6.8 
VISIT WINDOWS 
 
For each required study visit, there is an allowable visit window specifying on which 
study days (post-enrollment) the visit is "allowed" to be completed. The allowable visit 
windows are contiguous from visit to visit, and do not overlap. Within each allowable 
visit window, there is a target visit window and study visits should ideally be conducted 
within this window. These windows are outlined in the table below. If more than one visit 
is necessary to complete all visit procedures, these could be completed during multiple 
days within the allowable visit window.  
 
Table 1. Visit Window Schedule 

 
 
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Visit 
Target Visit 
Day 
Target Visit 
Window 
Target Visit 
Window Days 
Allowable Visit 
Window 
Eligibility 
Determination  
-- 
-- 
Up to 7 days 
before 
enrollment 
-- 
Enrollment  
Day 0 
-- 
0 
0 
Week 13  
Day 91 
-21/+21 
Day 70 – 112 
Day 70 - 153 
Week 26  
Day 182 
-21/+21 
Day 161 - 203 
Day 154 - 244 
Week 39 (optional) 
Day 273 
-21/+21 
Day 252 - 294 
Day 245 - 336 
Week 52 (optional) 
Day 365 
-21/+21 
Day 344 - 386 
Day 337 – 427 
 
6.9 
INTERIM CONTACTS AND VISITS  
 
Interim contacts and visits (those between regularly scheduled follow up visits) may be 
performed at participant request or as deemed necessary by the IoR or designee at any 
time during the study. All interim contacts and visits will be documented in participants’ 
study records and on applicable CRFs.  
 
Some interim visits may occur for administrative reasons. For example, the participant 
may have questions for study staff. Interim visits at which no data are collected are not 
documented on CRFs. Other interim contacts and visits may occur in response to social 
harms experienced by study participants. When interim contacts or visits are completed 
in response to participant reports of social harms, study staff will assess the reported 
event, record the event on the CRF, and provide or refer the participant to appropriate 
medical care. 
  
7.0 
MONITORING AND ADVERSE EVENT REPORTING  
 
7.1 
ADVERSE EVENT REPORTING  
 
As this study only involves low-risk activities (recruitment activities; testing for HIV and 
STIs; questionnaires; support for linkage-to-PrEP, PrEP engagement, and PrEP 
adherence) and contains no biomedical intervention or clinical care (PrEP prescription or 
other medical treatment), standard adverse event reporting and monitoring will not be 
undertaken. Any product related to this study (i.e. PrEP) is not being offered or 
administered directly by the study staff. All drugs used by participants in this study (i.e., 
PrEP, STI treatment) for the prevention of HIV or management of STIs, have regulatory 
approval for this purpose in Malawi and have well-established safety profiles. All safety 
monitoring of these approved drugs will be at the discretion of Malawi Ministry of 
Health.  

 
 
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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. 
 
7.2 
MONITORING AND CLINICAL DATA REVIEW  
 
The study site investigators are responsible for the initial evaluation and reporting of 
safety information at the participant level, and for alerting the protocol team if 
unexpected concerns arise. Sites are required to have detailed SOPs describing methods 
for social harms reporting to ensure that social harms are reported and managed in 
accordance with the protocol and for alerting the Protocol Team if unexpected concerns 
arise. Study participants will be provided a 24-hour telephone number and contact 
information and instructed to contact the study clinician to report any social harms they 
may experience. For life-threatening events, they will also be instructed to seek 
immediate emergency care. Where feasible and medically appropriate, participants will 
be encouraged to seek evaluation where the study clinician is based, and to request that 
the clinician be contacted upon their arrival. 
 
The SDMC will prepare routine study conduct and social harms reports for the Study 
Monitoring Committee (SMC), which will meet by conference call approximately every 
6 months. More frequent or ad hoc reviews may be conducted by the SMC as needed. A 
recommendation to stop the trial may be made by the SMC, if warranted.  
 
7.3 
SOCIAL IMPACT REPORTING  
 
It is possible that participants’ involvement in the study could become known to others, 
and that a social harm may result (i.e., because participants could be perceived as having 
HIV or at increased likelihood for HIV acquisition). For example, participants could be 
treated unfairly, or could have problems being accepted by their families and/or 
communities. Although self-identification as heterosexual is an inclusion criterion, it is 
possible that cisgender male participants may disclose having sex with other men or 
transgender individuals, including naming men as recent partners. Given the fact that 
homosexuality is illegal in Malawi, extensive care will be taken to preserve 
confidentiality and safety of all participants. All staff, including systems navigators, will 
be informed of the sensitive nature of all disclosed sexual activities and will be trained in 
the appropriate conduct of clinical research to treat all participants fairly and 
professionally. Reporting of any participant-reported homosexual activity is not required 
of research studies. 
 
Research staff will be trained to recognize, collect, and report social impacts, and provide 
referrals for counseling and social service support, if necessary. Any social harm that is 
reported by the participant and judged by the IoR/designee to be serious or unexpected 
will be reported to the site’s IRBs at least annually, or according to their individual 
requirements. Participants could also benefit from the study in various ways. Therefore, 

 
 
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both social harms and benefits due to participation in the study will be collected and 
reported on CRFs during regular visits. In the event that a participant reports a social 
harm, 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. The site will provide such care and counseling in accordance with locally-
available resources. While maintaining participant confidentiality, study staff may engage 
the CAB in exploring the social context surrounding instances of social impacts, to 
minimize the potential occurrence of such an impact. 
 
8.0 
STATISTICAL CONSIDERATIONS  
 
8.1 
REVIEW OF STUDY DESIGN 
This is a single site, two-arm, randomized pilot study. Two-hundred eligible participants 
will be randomized to the intervention or standard of care arms in a 2:1 ratio. 
Randomization will be stratified by age (15-25, >25), and a permuted blocks design will 
be used to ensure balanced treatment assignments within each stratum. Age-based 
stratification was selected due to expected differences in effect of intervention and base-
case PrEP persistence among younger compared to older cisgender men. We have opted 
for a 2:1 randomization to facilitate evaluation of our acceptability outcomes, which are 
only examined among persons randomized to the intervention arm.  
 
 
8.2 
OBJECTIVES AND ENDPOINTS  
 
Further details on how these endpoints are defined and measured are included in the 
statistical analysis plan (SAP). Of note, we aim to use validated instruments whenever 
feasible. 
 
8.2.1 Primary Objective(s) and Endpoints  
 
8.2.1.1 
To assess the effect of a systems-navigator facilitated HIV 
prevention package on PrEP persistence among heterosexual 
cisgender men seeking STI clinical services in Lilongwe, Malawi at 
26 weeks. 
Consistent with this primary study objective, the following endpoint(s) 
will be assessed: Persistent PrEP use across all three modalities (LAI, 
daily oral, or event-driven PrEP), where persistence is defined as 
adherence to any PrEP modality through 26 weeks, comparing 
proportions in intervention and control arm participants.  
 
o (LAI) receive on-time injections (+/- 7-day window for the first 
injection and 14-day window thereafter) 
o (Daily Oral) have protective PrEP concentration detected at 
designated study follow-up visits, based on intraerythrocytic TFV-
DP collected as DBS; TFV-DP concentrations associated with ≥4 
doses/week will be classified as adherent. 

 
 
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o (Event-driven) self-reported PrEP adherence (2+1+1), in the past 
30 days, assessed through self-report of PrEP use and sex acts at 
study follow-up visits, and intraerythrocytic TFV-DP 
concentrations.   
 
8.2.1.2 
To assess acceptability and barriers of implementing a systems-
navigator delivered HIV prevention package among key 
stakeholders in the clinic and heterosexual cisgender men initiating 
PrEP at STI clinics.   
 
Consistent with this primary study objective, the following endpoint(s) 
will be assessed among participants in the intervention arm only: 
• 
Engagement with system navigators: 
o Overall: Proportion of intervention arm participants 
engaged by systems navigator within 7-days of enrollment 
visit (defined as any contact, i.e. text exchange, in-person 
communication) 
o Overall: Proportion of intervention arm participants 
engaged by systems navigators at least once after the initial 
engagement during the first 26 weeks following initiation of 
PrEP.  
o Overall: Proportion of intervention arm participants with 
attempted engagement by systems navigators at least once 
after the initial engagement during the first 26 weeks 
following initiation of PrEP. 
o Overall: Mean (standard error) number of contacts (text, 
telephone call, home visit, other) with intervention arm 
participants made with systems navigators (mean contacts 
per participant) during first 26 weeks following initiation of 
PrEP. 
• 
Uptake of self-test/pill pack (“re-start” kit) among those to whom it 
is distributed (through end of study participation): 
o Proportion who self-report use of HIV self-test 
o Proportion who self-report use of PrEP pill pack 
o Proportion who self-report use of HIV self-test in 
conjunction with/prior to initiation of PrEP pill pack 
• 
Acceptability and barriers among key stakeholders, including 
participants enrolled as seronegative PrEP initiators and other key 
stakeholders: 
o Acceptability based on quantitative surveys (participants 
enrolled as seronegative PrEP initiators only) 
o Perceived facilitators and barriers to implementation of the 
intervention will be assessed through individual semi-
structured interviews. 
 
8.2.2 Secondary Objective(s) and Endpoints  

 
 
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8.2.2.1 
To assess the feasibility of a future randomized controlled trial.  
 
Consistent with this secondary study objective, the following 
endpoint(s) will be assessed, considering all enrolled HIV seronegative 
participants: 
• Calendar time to enroll 200 participants  
• Proportion of participants retained at each [eligible] study visit 
• Complete all study visits through 26 weeks, 39 weeks, and 52 
weeks (among participants eligible for longer follow-up)  
• Proportion of PrEP visits on the same day as study visits, by 
PrEP modality 
• Proportion of participants completing 30-day TLFB at 
quarterly study visits  
• Time to complete each study visit 
• Additional time (at PrEP visits) engaging with systems 
navigators 
 
8.2.3 Exploratory Objectives and Endpoints  
 
8.2.3.1 
To assess prevention-effective PrEP use among heterosexual 
cisgender men initiating PrEP at STI clinics 
Prevention-effective PrEP use evaluates PrEP use in the context of 
ongoing HIV risk, exploring the alignment between periods with 
evidence of ongoing HIV risk and protective PrEP levels. This will be 
assessed for participants by evaluating self-reported HIV risk 
behaviors, observed incident STI or HIV, and PrEP use during 
quarterly study follow-up visits: 
o Proportion of PrEP initiators with incident STI/HIV  
o Proportion of PrEP initiators who report HIV risk during study 
follow-up, including self-reported sexual behaviors, and HIV 
status of partners 
o Proportion of PrEP initiators who have target PrEP 
concentrations (oral) or on-time receipt (LAI) during periods of 
potential HIV risk based on incident HIV/STI, self-reported 
sexual behaviors, and HIV status of partners.  
o Proportion of PrEP initiators who discontinue PrEP (based on 
self-report or medical record review)  
o Proportion of sex acts with appropriate PrEP dosing (before 
and after each act) in 14- and 30-day recall periods, among 
PrEP initiators endorsing event-driven PrEP use  
 
8.2.3.2 
To assess PrEP modality preferences among heterosexual cisgender 
men initiating PrEP at STI clinics. 

 
 
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We will assess proportion of cisgender men selecting each of the 
available PrEP options at enrollment, and examine any changes in PrEP 
modality selection during study follow-up. 
 
8.2.3.3 
To assess the effect of a systems-navigator facilitated HIV 
prevention package on PrEP persistence among heterosexual 
cisgender men seeking STI clinical services in Lilongwe, Malawi, at 
39 and 52 weeks. 
Consistent with this exploratory objective, we will assess all PrEP use 
outcomes described in Section 8.2.2 for subset of participants who are 
eligible for extended follow-up based on enrollment date, extending to 
39 weeks or 52 weeks. 
 
8.2.3.4 
To quantify costs and resources necessary to develop and integrate a 
systems-navigator delivered HIV prevention package into an urban 
STI clinic, informing future cost-effectiveness model development. 
Consistent with this exploratory study objective, the following 
endpoint(s) will be assessed: 
• cost quantification following an ingredients-based micro-costing 
approach, including costs associated with training and time-and-
motion evaluation of systems navigation activities including 
counseling and tracing. 
 
8.2.3.5 
To perform laboratory assessments that may include evaluation of 
factors related to HIV infection or other STIs; characterization of 
HIV in participants who acquire HIV; characterization of the host 
response to antiretroviral drugs; and evaluation of virologic, 
pharmacologic, or STI-based laboratory assays. 
 
8.2.3.6 
To evaluate event-driven PrEP drug concentrations within the 
context of TLFB reported PrEP use and sex acts. 
 
8.2.3.7 
To explore the perceived and experienced PrEP related stigma and 
potential influence of perceived gender norms on PrEP persistence 
among heterosexual cisgender men initiating PrEP at the STI clinic. 
This exploratory objective will be assessed using a combination of 
quantitative surveys as well as the qualitative interviews with cisgender 
male participants.  
 
8.3 
SAMPLE SIZE  
 
For our HIV seronegative PrEP initiation participant population, we expect to enroll 
approximately 200 heterosexual cisgender males. We assume 10% loss to follow-up 
through 26 weeks. As a pilot study, the sample size is chosen to provide reasonable 
precision for assessing the primary endpoints and informing future studies. We chose a 

 
 
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2:1 randomization to intervention and SOC to maximize our ability to assess acceptability 
of the intervention.  
 
Based on previous studies, we expect persistent PrEP use under standard of care (SOC) is 
40% at 26 weeks. The targeted difference in persistent PrEP use at 26 weeks between the 
intervention and the standard of care arm is 15%-35%. Table 1 gives the two-sided 95% 
confidence intervals for the true proportions of persistent PrEP use (a binary endpoint) 
separately for two arms. This is a pilot study seeking to rapidly evaluate indication of an 
effect signal that would suggest potential benefit of systems navigation to inform a future 
larger study. Our sample size, selected to quickly enroll and answer this important and 
timely knowledge gap, will be sufficient to identify a minimum detectable RD of 0.22 
assuming 80% power and 5% alpha level, and RD of 0.25 assuming 90% power and 5% 
alpha level. 
 
Table 2: 95% confidence intervals for the true proportions of persistent PrEP use at 
26 weeks separately for two arms, given the total sample size of 200 and assuming 
10% loss to follow-up (a working sample size of 180)   
Proportion 
of persistent 
PrEP use 
under SOC 
 Proportion of persistent PrEP use under intervention with varying risk 
difference (RD) 
 
  
 RD=0.15 
RD=0.2  
RD=0.25 
RD=0.3 
RD=0.35 
(0.28, 0.52) 
(0.46, 0.64) 
(0.51, 0.69) 
(0.56, 0.74) 
(0.62, 0.78) 
(0.67, 0.83) 
 
8.4 
ACCRUAL AND RETENTION  
 
A total of approximately 200 HIV seronegative PrEP initiating participants will be 
enrolled in approximately 39 weeks and followed for at least 26 weeks but up to 52 
weeks. An overall retention rate of 90% will be targeted.  
 
8.5 
STATISTICAL ANALYSIS  
 
8.5.1 Primary Analyses  
 
Effect of intervention on persistent PrEP use 
 
Comparison of persistent PrEP use will be performed on all enrolled participants during 
the first 26 weeks of study follow-up. Participants may choose to switch PrEP modalities 
during study follow-up; persistence to each modality will be assessed during the follow-
up time when the participant reports using that modality, using a combination of self-
report and clinic records. Only those who are retained on study at the end of 26 weeks 
will be considered to have reached the persistence endpoint. Data will be presented in a 
two-by-two table in which each participant is classified as persistent/non-persistent to 
PrEP. A Z-test based on asymptotic normality will be used to compare persistent PrEP 
between the intervention and the SOC arm. 

 
 
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Acceptability and barriers  
 
For binary endpoints, the number will be tabulated, its specified proportion will be 
calculated, with variance calculated under binomial distribution. For continuous 
endpoints, its mean, median, standard deviation, quantiles and range will be calculated. 
Qualitative analyses are described separately (Section 8.6) 
 
8.5.2 Secondary Analyses  
 
Feasibility of a future randomized controlled trial 
 
Secondary data analysis will tabulate the number of each endpoint observed during the 
study. For binary endpoints, its percentage of the total enrolled participants will be 
calculated, with variance calculated under binomial distribution. For continuous 
endpoints, its mean, median, standard deviation, quantiles and range will be calculated. 
Z-tests will be used to compare endpoints between arms. 
 
8.6 
QUALITATIVE ANALYSES 
 
Acceptability and feasibility of the systems navigation component will also be assessed 
through administration of brief behavioral surveys and qualitative interviews with 
approximately 20 study participants. The surveys will include, but not be limited to, 
questions about participants’ attitudes/beliefs towards their interactions with the systems 
navigator, as well as other related topics such as their perceived risk for HIV. 
Approximately 15 other key stakeholders will also be interviewed regarding the adoption 
and implementation of systems navigation as a strategy to improve HIV prevention 
integration in the STI clinic. 
 
Participant in-depth interviews (IDI) will be scheduled to attempt to correspond with their 
final study visit (week 26, 39, or 52). When conducting a qualitative exploration, the 
sampling method should be designed to include a range of possible perspectives on the 
phenomenon under study, thus ideal qualitative samples are purposive in nature. For this 
study, we will utilize a purposive sampling strategy, which will allow for consideration of 
the concepts of range, saturation/redundancy, and stratification in the sampling frame. 
We will ask site staff to identify potential participants who would be interested in and 
comfortable with sharing their experiences in the study. Data on acceptability and factors 
affecting adherence will be collected during the IDI, including questions that explore the 
use and the acceptability of the systems navigation component. Additional interview 
topics will include challenges to study participation as well as risk perception. These 
interviews will be conducted by a trained study interviewer and will follow a semi-
structured questionnaire guide. They will be approximately 60 minutes in duration and 
will be conducted in an area that maximizes participant privacy and confidentiality. 
Participants may be compensated for the completion of the in-depth interview. These 
interviews will be recorded for analysis and transcribed. Recording storage, tracking, and 

 
 
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management details will be described in the site’s SOPs. These recordings will be stored 
in accordance with the longest requirement of any applicable regulations. 
 
After transcription, all qualitative interviews will be translated into English (as needed), 
and then uploaded into a qualitative software analysis program (such as NVivo 12). The 
HPTN 112 Qualitative Team will follow a process of reading, coding, data display and 
data reduction in order to explore in greater depth participants’ attitudes towards and 
experiences with the intervention. Data coding and analysis will be both iterative and 
interactive processes. The team will first read all interview transcripts in order to increase 
familiarity with the data. Next, the team will assign a priori codes and create emergent 
codes. Transcripts will then be re-read to create pattern codes that connect subsequent 
concepts under larger headings. Consistent patterns in meaning, concepts, and themes 
across all interviews will be identified, and detailed memos/data matrices will be 
developed to examine how participants’ perceptions related to the intervention (i.e., ease 
of use, interactions with systems navigators, perceived efficacy) and to risk perception 
(i.e., motivations for participation, impact on partner or other social relationships) 
influence acceptability and interest in future use of a systems navigation component 
embedded in the clinic. Comparative analyses will be conducted to clarify differences 
that may exist for any subgroups of participants. Coding and analytic activities will be 
discussed during qualitative data analysis meetings, and discrepancies in coding and 
interpretation will be resolved through consensus.  
 
See Appendix II for timing of interviews.  
 
9.0 
LABORATORY SPECIMENS AND BIOHAZARD CONTAINMENT  
 
Laboratory procedures are described below and in Appendix II and Section 6.2.1; tests to 
be performed at a subsequent visit for participants who have a reactive or positive HIV 
test interpretation are described in Appendix III. 
 
9.1 
LOCAL LABORATORY SPECIMENS  
 
As described in Section 6, the following types of specimens will be collected at the local 
laboratory (LL): 
• Blood 
• Urine 
 
As described in Section 6, the following types of testing will be performed at the local 
laboratory (LL):  
• HIV rapid antibody testing  
• HIV RNA (Enrollment) 
• STI testing for syphilis (RPR and reflex to TPPA, if appropriate) 
• STI testing for CT/NG 
 

 
 
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LLs will perform HIV and STI testing as indicated in Appendices II-IV. All STI test 
results obtained through study visits, including POC STI testing through systems 
navigators, will be returned to HIV seronegative participants. Some results will not be 
returned same day, however, participants who test positive for an STI at study visits will 
be informed of their result and be referred for treatment as per local guidelines. For HIV 
seronegative participants, HIV RNA testing will typically be tested within 7-10 days of 
enrollment. Participants will be informed if this result is consistent with HIV infection, 
despite negative rapid antibody testing at enrollment. 
 
The study site must adhere to the HPTN Manual of Operations (MOP), the SSP Manual, 
and local SOPs, for proper collection, processing, labeling, transport, and storage of 
specimens to the LL. Non-US laboratories performing these tests will be monitored by an 
External Quality Assurance (EQA) provider or specified quality assurance contractor. In 
addition, each study site must adhere to the Requirements for Laboratories in Performing 
Testing for DAIDS-Supported and/or Sponsored Clinical Trials policy (DAIDS-OD-A-
POL-00002) as outlined in the DAIDS SCORE Manual and the DAIDS Good Clinical 
Laboratory Practice (GCLP) as appropriate. Laboratories must also follow the DAIDS 
Clinical Research Laboratory and Specimens Management policies at 
https://www.niaid.nih.gov/research/daids-clinical-research-laboratory-specimens-
management. Specimen collection and storage at the local laboratory will be documented 
using the Laboratory Center Specimens Management System (LDMS) as described in the 
SSP Manual. 
 
9.1.1 Specimen Storage at Study Site  
 
Sites will provide short-term storage of blood (plasma, DBS) and urine to facilitate 
batched testing. Stored samples will be shipped to the HPTN LC (located in the US) for 
Quality Assurance (QA), as well as measurement of antiretroviral drugs from DBS or 
plasma.  Stored samples may also be used for characterization of HIV in participants who 
acquire HIV, additional testing of STI pathogens, and evaluation of laboratory assays 
related to the study objectives. Specifically, these tests are conducted to characterize 
factors associated with HIV and STI infection, and virologic, pharmacologic and 
immunologic responses among men initiating PrEP at Bwaila STI clinic. Testing on 
stored samples will be performed by the HPTN LC or another laboratory selected and 
approved by the HPTN LC. Samples stored at study sites may not be used for LL testing 
not otherwise specified in the protocol without written approval by the HPTN LC and 
appropriate regulatory body prior to use.  
 
Stored samples may be maintained at the site until the study is complete.  The HPTN LC 
will communicate with sites when samples can be destroyed; sites will follow LL policies 
for sample destruction. A list of samples to be destroyed will be provided by the SDMC, 
which will be reviewed and reconciled by the site as part of the sample destruction 
process. 
 

 
 
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9.1.2 Virology  
 
HIV testing will be performed by local laboratories and will follow Malawi Ministry of 
Health algorithms. 
 
Additional virologic assays may be performed to address study objective 2.3.5 at the 
HPTN LC or a laboratory designated by the HPTN LC. This testing may include the 
following tests for participants who acquire HIV infection: HIV viral load, HIV 
resistance testing, HIV subtyping, and other tests to characterize HIV viruses and/or the 
host response to HIV infection. Further, the HPTN LC may perform HIV RNA testing at 
study visits with stored samples from individuals who do not acquire HIV during the 
study. Results will not be returned to the sites or study participants, except for HIV 
diagnostic testing (if results obtained at the HPTN LC do not agree with site results).  
 
Resistance testing may be performed at the HPTN LC or a laboratory selected by the  
HPTN LC.  Results of this testing will not be returned to study sites.  
 
9.1.3 Pharmacology  
 
To address study objective 2.3.5, plasma and DBS samples for pharmacology testing will 
be collected throughout the study from all participants. Pharmacology testing will be 
performed at the HPTN LC or a laboratory designated by the HPTN LC. The primary 
pharmacologic assessments will be performed using assays that have been appropriately 
validated and approved. Results will not be returned to the study participants.  
Interpretation of pharmacologic results, including pharmacokinetic modeling, will be led 
by the HPTN LC Pharmacology Core, in collaboration with other groups, as needed. 
 
Stored plasma may also be tested for the presence of other antiretroviral drugs or other 
concomitant medications. 
 
9.1.4 Other HPTN LC testing  
 
STI testing (syphilis, CT/NG) will be performed at the LL. Stored urine may be used for 
the following to inform objective 2.3.5: additional characterization of STIs, including 
CT/NG, M. genitalium, T. vaginalis; evaluation of laboratory assays for identification of 
STIs.  Deidentified samples may also be used to evaluate incidence and prevalence of 
other STIs. 
 
9.2 
QUALITY CONTROL AND QUALITY ASSURANCE PROCEDURES  
 
HPTN LC staff will conduct periodic visits to the study site to review the implementation 
of on-site laboratory quality control (QC) procedures, including proper maintenance of 
laboratory equipment and use of appropriate supplies and reagents. HPTN LC staff will 
follow up directly with site staff to resolve any QC or QA problems identified through 
proficiency testing or on-site visit reviews. Throughout the course of the study, the HPTN 

 
 
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LC will perform QA testing for HIV infection on stored samples. HPTN LC staff will 
follow-up directly with site staff to resolve any QA problems identified through this 
process.  
 
Samples will be shipped to the HPTN LC on a routine basis throughout the study.  Site 
staff will be informed by the HPTN LC on when to ship stored samples.  
 
9.3 
HIV DIAGNOSTIC TESTING  
 
Eligibility HIV testing (to determine PrEP eligibility) will be conducted per Malawi 
Ministry of Health guidelines.  
 
Additional testing at scheduled study visits will be conducted by LL. HIV infection status 
will be confirmed at study sites using local HIV testing guidelines or following the advice 
of the HPTN LC. In addition, if a participant has signs or symptoms consistent with acute 
HIV infection, or expresses a concern about recent HIV acquisition, testing will be 
performed following in-country recommendations.  The HPTN LC may characterize 
seroconversion events using additional HIV testing approaches.  
 
9.4 
HIV RNA TESTING  
 
Quantitative HIV RNA (viral load) testing will be performed at LLs at enrollment for 
HIV seronegative participants. For HIV seronegative participants who acquire HIV 
infection during study follow-up, viral load testing will be performed at the visit when 
HIV infection is confirmed and at subsequent study visits. LLs must participate in a 
DAIDS-contracted EQA program, with results that are deemed satisfactory by the HPTN 
LC.  
 
9.5 
BIOHAZARD CONTAINMENT  
 
As the transmission of HIV and other blood-borne pathogens can occur through contact 
with used needles, blood, and blood products containing HIV, appropriate blood and 
secretion precautions will be employed by all personnel in the drawing of blood and 
shipping and handling of all specimens for this study, as currently recommended by the 
United States Centers for Disease Control and Prevention. All specimens will be shipped 
using packaging that meets requirements specified by the International Air Transport 
Association Dangerous Goods Regulations for UN 3373, Biological Substance, Category 
B, and Packing Instruction 650.  
 
10.0 
HUMAN SUBJECTS CONSIDERATIONS  
 
10.1 
ETHICAL REVIEW  
 

 
 
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The HPTN Ethics Working Group developed the HPTN Ethics Guidance for Research, a 
network-wide ethical principles document, which is suitable for further elaboration and 
tailoring for each study.  
 
This protocol and the template informed consent forms (ICFs) contained in Appendices 
III and IV were reviewed and approved by the HPTN Scientific Review Committee with 
respect to scientific content and compliance with applicable research and human subjects 
regulations.  
 
The protocol, ICFs, participant education and recruitment materials, 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 the study site.  
 
Subsequent to initial review and approval, the responsible IRBs/ECs will review the 
protocol at least annually. The Investigator will make safety and progress reports to the 
IRBs/ECs at least annually, and within three months of study termination or completion. 
These reports will include the total number of participants enrolled in the study, the 
number of participants who completed the study, all changes in the research activity, and 
all unanticipated problems involving risks to human subjects or others. The study site will 
submit documentation of continuing review to the DAIDS Protocol Registration Office 
(PRO), in accordance with the current DAIDS Protocol Registration Policy and 
Procedures Manual. 
 
10.2 
INFORMED CONSENT  
 
Written informed consent will be obtained from each study participant. Study ICF(s), 
based on the template in Appendices III and IV, describes the purpose of the study, the 
procedures to be followed, and the risks and benefits of participation, in accordance with 
all applicable regulations. ICFs will be translated into local language and the accuracy of 
the translation verified by performing an independent back-translation. 
 
Literate participants will document their provision of informed consent by signing their 
ICF(s). Non-literate participants will be asked to document their informed consent by 
marking their ICF(s) (e.g., with an X, thumbprint, or other mark) in the presence of a 
literate third-party witness. Further details regarding DAIDS requirements for 
documenting the informed consent process with both literate and non-literate participants 
are provided in the DAIDS SCORE Manual. Any other local IRB/EC requirements for 
obtaining informed consent from non-literate persons also will be followed.  
 
Participants will be provided with a copy of their ICF if they are willing to receive it.  
 
Consistent with prior PrEP research at the Bwaila STI clinic as conducted by HPTN 112 
investigators, this study proposes to enroll adolescents aged 15 to 17 years old.15 All 
minors (under the age of 18) will be required to provide assent with parental consent. 
Malawi guidelines allow those aged 15 and above to initiate PrEP if they meet other 

 
 
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eligibility requirements. Adolescents are often excluded from research studies largely 
because of confusion about whether they should be regarded as children or as adults, and 
because of uncertainty regarding who has the right and ability to give consent for 
adolescents to participate in research. However, such exclusion potentially deprives 
research of the important and unique perspective of the adolescent to which the 
adolescent may themselves benefit.22 As such, this trial will enroll adolescents using the 
above procedures.  
 
 We will provide adequate protection in the confidentiality of all study activities, 
including receipt of care, participation in interviews, tracing, and referrals for services if 
needed (see Section 10.6). 
 
10.3 
RISKS  
 
It is not expected that this trial will expose participants to unreasonable risk. Blood draws 
may lead to discomfort, feelings of dizziness or faintness, and/or bruising, swelling 
and/or infection. Participants may become embarrassed, worried, or anxious when 
completing their HIV risk assessment and/or receiving risk reduction and PrEP 
counseling. They also may become worried or anxious while waiting for their HIV test 
results. Trained counselors will be available to help participants deal with these feelings. 
Although the site will make every effort to protect participant privacy and confidentiality, 
it is possible that participants' involvement in the study could become known to others, 
and that social harms may result (i.e., because participants could be thought of as 
vulnerable for HIV infection because of their participation in a PrEP study).  
 
Study procedures also address the potential risk of field-based tracing for missed study or 
PrEP visits (by study staff and systems navigators, respectively). All tracing efforts are 
conducted consistent with the stated preferences and locator information provided and 
updated regularly by participants or their parent/guardians. Community sensitization and 
CAB involvement are cornerstones in maintaining the safety of participants and those 
conducting tracing activities. Additional measures to mitigate risk to persons conducting 
tracing activities include working in pairs or teams, bringing phones to facilitate 
communication, using flexible transportation (i.e. not relying on availability of public 
transport), and extensive training regarding immediate departure if any hostility is 
perceived. Any such event is generally reported back to the community representative.  
 
10.4 
 BENEFITS  
 
There may be no direct benefits to participants in this study, however, participants and 
others may benefit in the future from information learned from this study. Specifically, 
information learned in this study may lead to improved HIV prevention services for 
heterosexual cisgender men. In addition, participants will receive HIV and STI 
counseling and testing as part of the study process. Participants also will be referred for 
treatment if applicable. Participants may benefit from the potentially improved use of 

 
 
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PrEP agents, as facilitated through systems navigation, which are known to protect 
against getting HIV if taken as directed.  
 
10.5 
INCENTIVES  
 
Pending IRB/EC approval, participants will be compensated for their time and effort in 
this study, and/or be reimbursed for travel to study visits and time away from work. Site-
specific reimbursement amounts will be specified in the study ICF(s). 
 
10.6 
CONFIDENTIALITY  
 
All study-related information will be stored securely at the study site. All participant 
information will be stored in locked file cabinets in areas with access limited to study 
staff. All laboratory specimens, reports, study data collection, process, and administrative 
forms will be identified by a coded number only to maintain participant confidentiality. 
All local databases will be secured with password-protected access systems. Forms, lists, 
logbooks, appointment books, and any other listings that link participant ID numbers to 
other identifying information will be stored in a separate, 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 the NIAID and/or its contractors; 
representatives of the HPTN LOC, SDMC, and/or LC; other government and regulatory 
authorities, and/or site IRBs/ECs.  
 
10.6.1 Certificate of Confidentiality  
 
Research participants in Network protocols are protected by a Certificate of 
Confidentiality (CoC) from the US NIH, which can prevent disclosure of study 
participation even when that information is requested by subpoena. However, CoCs 
may not be effective for data held outside of the US. 
 
10.7 
COMMUNICABLE DISEASE REPORTING REQUIREMENTS  
 
Study staff will comply with all applicable local requirements to report communicable 
diseases identified among study participants to local health authorities. Participants will 
be made aware of all reporting requirements during the study informed consent process. 
 
10.8 
STUDY DISCONTINUATION  
 
The study also may be discontinued at any time by NIAID, the HPTN, and/or site 
IRBs/ECs.  
 
11.0 
ADMINISTRATIVE PROCEDURES 
 

 
 
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11.1 
PROTOCOL REGISTRATION  
 
Initial Registration of the protocol by the DAIDS PRO is required prior to the 
implementation of this protocol. As part of this process, each site must have the protocol 
and protocol ICF(s) approved, as appropriate, by their IRB/EC and any other applicable 
regulatory entity (RE). 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 ICFs WILL be reviewed and approved by the DAIDS PRO. Sites will 
receive an Initial Registration Notification from the DAIDS PRO that indicates 
successful completion of the protocol registration process. A copy of the Initial 
Registration Notification should be retained in the site's regulatory files. 
 
Upon receiving final IRB/EC and any other applicable RE approval(s) for an amendment, 
sites should implement the amendment immediately. Sites are required to submit an 
amendment registration packet to the DAIDS PRO at the RSC. The DAIDS PRO will 
review the submitted protocol registration packet to ensure that all the required 
documents have been received. Site-specific ICF(s) WILL NOT be reviewed and 
approved by the DAIDS PRO. 
 
For additional information on the protocol registration process and specific documents 
required for initial and amendment registrations, refer to the current version of the 
DAIDS Protocol Registration Manual, which can be found at: 
https://www.niaid.nih.gov/sites/default/files/prmanual.pdf. 
 
11.2 
STUDY ACTIVATION  
 
Pending successful protocol registration and submission of all required documents, the 
HPTN LOC staff will “activate” the 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 
DAIDS SCORE Manual will outline procedures for conducting study visits; data and 
forms processing; and other study operations. 
  
Study CRFs and other study instruments will be developed by key members of the 
protocol team and HPTN SDMC. Data will be submitted to the HPTN SDMC for data 
cleaning, reporting and analysis. Data management and coding queries will be generated 

 
 
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and applied to the data by HPTN SDMC staff on a routine basis for verification and 
resolution by site staff.   
 
Close coordination between protocol team members will be necessary to track study 
progress, respond to queries about proper study implementation, and address other issues 
in a timely manner. Rates of accrual, adherence, follow-up, and visit completion rates 
will be monitored closely by the team as well as the HPTN SMC. Select members of the 
Protocol Team will address issues related to individual study eligibility and any other 
issues as needed to assure participant safety, consistent case management, 
documentation, and information-sharing across sites. 
 
11.4 
STUDY MONITORING  
 
Study monitoring will be performed in accordance with DAIDS policies. Study monitors 
will: 
 
• 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. 
• Confirm the quality and accuracy of information collected at the study site and 
entered into the study database. 
• Verify compliance with GCLP 
 
Monitoring visits may be conducted on-site or remotely. Remote visits may include 
remote source document verification using methods specified for this purpose by NIAID. 
Remote monitoring visits may be performed in place of or in addition to onsite visits to 
ensure the safety of study participants and data integrity.18 The site will make available 
study documents for study monitors to review utilizing a secure platform that is HIPAA 
and 21 CFR Part 11 compliant. Potential platform options include: Veeva SiteVault, site-
controlled SharePoint or cloud-based portal, direct access to Electronic Medical Record 
(EMR), and Medidata Rave Imaging Solution. Other secure platforms that are 21 CFR 
Part 11 compliant may be utilized, as allowed by the DAIDS Office of Clinical Site 
Oversight (OCSO). 
 
For on-site visits, site investigators will also allow study monitors to inspect study 
facilities and documentation (e.g., ICFs, clinic and laboratory records, other source 
documents, paper or electronic CRFs), as well as observe the performance of study 
procedures. Investigators also will allow inspection of all study-related documentation by 
authorized representatives of the HPTN LOC, HPTN SDMC, HPTN LC, NIAID, site 
IRBs/ECs, and US regulatory authorities (Office for Human Research Protections 
(OHRP) and US FDA or other regulatory agencies). A site visit log will be maintained at 
each study site to document all visits. 
 

 
 
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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)/EC(s) and the RSC prior to implementing the amendment. 
 
11.6 
INVESTIGATOR’S RECORDS  
 
The Investigator will maintain, and store in a secure manner, complete, accurate, and 
current study records throughout the study. Under the US Department of Health and 
Human Services (DHHS) regulations, the Investigator is required to retain all study 
records relating to research for at least three [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 (e.g., when 
all subjects are off study);  
• 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 each participant enrolled in the study, including ICFs, locator 
forms, CRFs, and notations of all contacts with the participant; and all other source 
documents. 
 
11.7 
USE OF INFORMATION AND PUBLICATIONS  
 
Publication of the results of this study will be governed by the HPTN Manual of 
Operations. Any presentation, abstract, or manuscript will undergo review by the HPTN 
Manuscript Review Committee, and DAIDS prior to submission. 
 
11.8 
CLINICALTRIALS.GOV  
 
This protocol is not an FDAAA “applicable clinical trial.” However, this study is subject 
to the NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information. A 
description of this clinical trial will be available on http://www.ClinicalTrials.gov. 
 

 
 
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12.0 
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Fonner VA, Dalglish SL, Kennedy CE, et al. Effectiveness and safety of oral HIV 
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Ong JJ, Fu H, Baggaley RC, et al. Missed opportunities for sexually transmitted 
infections testing for HIV pre-exposure prophylaxis users: a systematic review. J Int 
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Rutstein SE, Matoga M, Chen JS, et al. Integrating Enhanced HIV Pre-exposure 
Prophylaxis Into a Sexually Transmitted Infection Clinic in Lilongwe: Protocol for a 
Prospective Cohort Study. JMIR Res Protoc. 2022;11(12):e37395. 
15. 
Bandura A. Social Cognitive Theory and Exercise of Control over HIV Infection. In: 
DiClemente R. J PJL, ed. Preventing AIDS: Theories and Methods of Behavioral 
Interventions. Springer US; 1994:25-59. 
16. 
Turner JC, J. OP. The significance of the social identity concept for social psychology 
with reference to individualism, interactionism and social influence. British Journal of 
Social Psychology 1986;25(3):237-252. 

 
 
HPTN 112, FINAL Version 2.0                           Page 55 of 91                                    19 December 2023 
 
 
17. 
Underhill K, Guthrie KM, Colleran C, Calabrese SK, Operario D, Mayer KH. Temporal 
Fluctuations in Behavior, Perceived HIV Risk, and Willingness to Use Pre-Exposure 
Prophylaxis (PrEP). Arch Sex Behav. 2018;47(7):2109-2121. 
18. 
Food and Drug Administration (FDA). Conduct of Clinical Trials of Medical Products 
During the COVID-19 Public Health Emergency: Guidance for Industry, Investigators, 
and Institutional Review Boards, March 2020, Updated on January 27, 2021. In: 
https://www.fda.gov/media/136238/download. 
22.  
Ozer EJ, Piatt AA. Adolescent Participation in Research: Innovation, rationale and next 
steps. UNICEF Office of Research- Innocenti, Florence. 2017. 
23.  
United Nations Committee on the Rights of the Child. Convention on the Rights of the 
Child: General comment No. 20 (2016) on the implementation of the rights of the child 
during adolescence. 6 Dec 2016. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
HPTN 112, FINAL Version 2.0                           Page 56 of 91                                    19 December 2023 
 
 
 
 
 
 
 
13.0 
APPENDICES I-VII 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 HPTN 112, FINAL Version 2.0                           Page 57 of 91                                           19 December 2023 
 
 
13.1 
APPENDIX I: CLINIC FLOW 
 
Figure 1a: Recruitment to first study visit 
 
 
 
 
Figure 1b:  Follow-up PrEP visits, as determined by Ministry of Health guidelines. 
 

HPTN 112, FINAL Version 2.0                           Page 58 of 91                                        19 December 2023 
 
13.2 
APPENDIX II: SCHEDULE OF EVALUATIONS FOR HIV-UNINFECTED PARTICIPANTS 
 
 
Eligibility 
Determination 
Enrollment 
Weeks 
Early 
termination2 
 
13 
26 
391 
521 
Administrative and Behavioral Evaluations/Procedures3  
Informed consent 
Randomization 
Demographics 
 
 
X 
X 
X 
X 
 
 
 
 
 
HIV risk factors 
X 
X 
 
 
 
 
X 
Locator information 
 
X 
X 
X 
X 
X 
 
Behavioral risk 
assessment 
 
X 
X 
X 
X 
X 
X 
PrEP use assessment 
Mental health status 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Substance use 
 
X 
X 
X 
X 
X 
X 
Perceived HIV & 
PrEP Stigma 
 
X 
X 
X 
X 
X 
X 
Gender norms 
HIV risk reduction 
counseling 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
 
In-depth interviews5 
 
 
 
X 
X 
X 
 
Clinical Evaluations/Procedures 
Symptom-driven 
physical exam 
 
X 
X 
X 
X 
X 
 
Venous blood draw  
 
X 
X 
X 
X 
X 
X 
Urine collection 
 
X 
X 
X 
X 
X 
X 
STI management 
referral4  
 
X 
X 
X 
X 
X 
X 
Laboratory Evaluations/Procedures 
Rapid HIV testing 
X6 
X6 
X 
X 
X 
X 
X 
HIV RNA7 
 
X 
 
 
 
 
 
STI testing8 
 
X 
X 
X 
X 
X 
X 
Plasma (storage) 
 
X 
X 
X 
X 
X 
X 
DBS (storage) 
 
X 
X 
X 
X 
X 
X 
Urine (storage) 
 
X 
X 
X 
X 
X 
X 
1 all participants will be followed at least 26 weeks; persons enrolled in the first 13 weeks will be followed up to 
52 weeks;  
2 extent of procedures, including surveys and specimen collection, at early termination visit will be determined 
depending on reasons for termination and ongoing safety/ability to obtain consent of the participant; 
3 Systems navigation occurs at the participant’s clinic PrEP visits, and not the study visits for this study. Therefore, 
systems navigation provided by the study is not included in this Schedule of Evaluations; 
4 referral for management in the event of new or persistent STI symptoms/complaints;  
5 in-depth interviews will be conducted with a subset of participants at their final visit (week 26, week 39, or 
week 52);  
6 HIV testing for PrEP eligibility determination will be conducted by Malawi Ministry of Health personnel 
7 HIV RNA will be tested at LL on enrollment; HIV RNA testing may be performed on stored plasma collected at 
follow-up visits at the HPTN LC;  
8 STI testing, including Neisseria gonorrhea  (NAAT), Chlamydia trachomatis (NAAT), and syphilis (RPR) will 
be collected at study visits unless results of these tests are documented within 2-weeks in review of record. 
 
 
 

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13.3 
APPENDIX III: SCHEDULE OF EVALUATIONS FOR PARTICIPANTS WHO 
SEROCONVERT ON STUDY 
 
 
Weeks post seroconversion 
Early termination 
13 Weeks 
26 Weeks 
 
Administrative and Behavioral Evaluations/Procedures 
Locator information 
X 
X 
 
Clinical Evaluations/Procedures 
Venous blood draw 
X 
X 
X 
HIV management 
referral1 
X 
X 
X 
Laboratory Evaluations/Procedures 
HIV RNA 
X 
X 
X 
Plasma (storage) 
X 
X 
X 
DBS (storage) 
X 
X 
X 
1 HIV management referral will only occur if participant is not already in care.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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13.4 
APPENDIX IV: SAMPLE ENROLLMENT INFORMED CONSENT 
 
HPTN 112: Improving HIV prevention among heterosexual cisgender men seeking STI 
services in Malawi: examining the benefits, acceptability, and associated costs of a systems-
navigator- delivered integrated prevention package 
 
SAMPLE ENROLLMENT ICF 
Version 2.0  
19 December 2023 
DAIDS Document ID: 39057  
 
Sponsored by: Division of AIDS (DAIDS), US National Institute of Allergy and Infectious 
Diseases (NIAID), US National Institutes of Health (NIH).  
 
PRINCIPAL INVESTIGATOR (US): Sarah Rutstein, MD, PhD 
PRINCIPAL INVESTIGATOR (MALAWI): Mitch Matoga, MBBS, MSc 
Study contact phone: +265 1 755 056 
Study contact email: mmatoga@unclilongwe.org 
 
 
CONCISE SUMMARY: This is a research study. Taking part in this research study is voluntary 
(your choice). You do not have to participate, and you can leave the study at any time. No matter 
what you decide, any other care that you get at this site will not change. 
 
This study is testing whether adding a systems navigator (similar to a coach or guide) to pre-
exposure prophylaxis (PrEP) care, a medicine that can help prevent HIV, improves PrEP use 
among heterosexual men, compared to the current standard PrEP care.  
 
The study will take about 15-months total. If you choose to enroll in the study, you will be 
followed on the study for at least 6 months and up to 12 months. You will be asked to give blood 
and urine specimens for HIV, STI, and other tests. You do not need to remain on PrEP to continue 
participation in this study.  
There are very limited risks involved with this study, including (but not limited to) risk of 
discomfort, dizziness/faintness, and/or bruising, swelling and/or infection from your blood being 
taken. You may also feel feelings of embarrassment or worry when answering questions about your 
own behaviors and/or receiving HIV counseling, or become worried while waiting for your HIV 
test results. Finally, there is the potential that some of your information may become known to 
others, even though the study will do everything possible to prevent that.  
There may be no direct benefits to you for being in this study, but others may benefit in the future 
from information learned from this study. Specifically, information on how to improve HIV 
prevention services for heterosexual men. In addition, you will receive HIV and STI counseling 
and testing as part of the study process and will be referred for treatment as needed.  
More information about this study is described in the rest of this form. We will help you 
understand the information and answer all your questions. You should feel that you understand the 
study before deciding whether you will participate. If you agree to join the study, you will be asked 

HPTN 112, FINAL Version 2.0                           Page 61 of 91                                        19 December 2023 
 
to sign your name or make your mark on this form. We will offer you a copy of this form to keep. 
 
What are some general things you should know about research studies? 
You are being asked to take part in a research study. To join the study is voluntary. You may 
choose not to participate, or you may withdraw your consent to be in the study, for any reason, 
without penalty. 
 
Research studies are designed to obtain new knowledge. This new information may help people in 
the future. You may not receive any direct benefit from being in the research study. There also may 
be risks to being in research studies. Deciding not to be in the study or leaving the study before it is 
done will not affect your relationship with the researcher or the health care provider.  If you are a 
patient with an illness, you do not have to be in the research study in order to receive health care. 
Details about this study are discussed below. It is important that you understand this information so 
that you can make an informed choice about being in this research study. 
 
You will be given a copy of this consent form. You should ask the researchers named above, or 
staff members who may assist them, any questions you have about this study at any time. 
 
What is the purpose of this study? 
The main purpose of this research study is to understand if it is helpful to use a systems navigator 
(coach or guide) to support the use of PrEP to prevent HIV. The overall goal of this study is to 
collect data that will inform future research, helping men from STI clinics reduce risk of getting 
HIV by taking PrEP. 
 
This study is for adult and adolescent cisgender men who: 
o are age 15 years or older, 
o are seeking services at Bwaila STI Clinic, and 
o have tested HIV negative 
Are there any reasons you should not be in this study? 
You should not be in this study if you are taking part in another study of drugs or medical devices. 
You are asked to tell the study staff about any other studies you are taking part in or thinking of 
taking part in. This is very important for your safety. 
 
How many people will take part in this study? 
About 200 HIV-seronegative heterosexual men will participate in this study from Lilongwe, 
Malawi.  
 
How long will your part in this study last? 
Participants who choose to join the study will be in the study for at least 6 months and up to 12 
months total.

 
HPTN 112, FINAL Version 2.0                           Page 62 of 91                                        19 December 2023 
 
What will happen if you take part in the study? 
During this study, you will be in one of 2 study groups. Researchers will "randomize" you into one 
of the study groups described here. 2 out of every 3 persons enrolled will be assigned to the 
intervention group and 1 out of every 3 persons enrolled will be assigned to the standard of care 
group. Random assignment means that you are put into a study group by chance, like flipping a 
coin. Neither you nor the study staff can choose your study group. The table below indicates what 
services each group will receive.  
 
Standard of 
Care Group 
Standard PrEP services, including HIV testing and risk reduction counseling  
 
Intervention 
Group 
Standard PrEP services, including HIV testing and risk reduction counseling. 
You will also be assigned a systems navigator (coach), respond to a brief 
questionnaire about your sexual activities, and be tested for STIs at any PrEP 
visit you attend. This coach may also attempt to contact or trace you for any 
missed PrEP visit (~7 days late), using information you provide regarding 
your preferred tracing time, method (phone or in-person), and location. 
 
PrEP visits: If you continue on PrEP, the timing of PrEP visits will be decided by the PrEP nurse at 
the clinic, according to the Malawi guidelines for PrEP. These visits typically occur every 2-3 
months, depending on the kind of PrEP you are taking.  
 
This study is using a Standard of Care Group (also known as a “Control Group”) because we do 
not yet know whether the intervention being tested in this study improves PrEP use. This kind of 
intervention has not previously been tested in PrEP care among men in Malawi. Using a Standard 
of Care Group will allow researchers to assess whether providing the additional intervention 
resources improves PrEP use. That information can be used to make recommendations to health 
care providers and leaders about what services should be offered in the future.  
 
All participants will complete the study visit procedures outlined below, regardless of which group 
they are assigned.  
 
Study visits: The study has at least 3 visits (including the enrollment visit today). Besides this first 
visit, you will be asked to come back for a visit ~3 months and ~6 months from now. If you enroll 
early in the study, you may also be asked to come back for study visits ~9 months and ~12 months 
from now. At each visit, you will be asked a series of questions about your behaviors and be tested 
for HIV and other STIs. You may also be asked to participate in a one-on-one interview. You 
should attend these study visits even if you have decided to stop taking PrEP. 
 
Enrolling in the Study  
If you decide to take part in the study, the Enrollment visit will last about 1-2 hours. During the 
Enrollment Visit, we will: 
 
• 
Obtain full written informed consent for the study 
• 
Ask you where you live and how to contact you 
• 
Ask you to answer questions in a survey about your sexual activities and overall health 

 
HPTN 112, FINAL Version 2.0                           Page 63 of 91                                        19 December 2023 
 
• 
Ask you about your previous and current PrEP use 
• 
Provide brief HIV risk reduction counseling 
• 
Conduct a symptom-driven physical exam 
• 
Collect ~10 to 20 mL (about 2 to 4 teaspoons) of blood to make sure you do not have a 
very early infection with HIV that may not be detected by the standard HIV tests you’ve 
received in clinic. If you have not been tested for syphilis (another STI) at any recent PrEP 
visits, this blood will also be used to test you for syphilis. 
• 
Collect ~ 10mL of your urine to test for STI testing (Chlamydia and Gonorrhea)  
• 
Store blood (plasma, dried blood spots) and urine samples for study-related testing  
• 
If you are assigned to the intervention group, study staff will connect you to your coach to 
discuss next steps in your PrEP care 
 
Additional Visits: 2 to 4 additional visits over the next 6 to 12 months. 
If you decide to join the study, after your Enrollment Visit, you will be asked to come to this 
location for follow up visits. Participants will be followed for at least 6 months and up to 12 
months depending on the time of enrollment.  
 
Each visit will last about 1 hour.  
 
During these follow-up visit(s), we will: 
 
• 
Ask you where you live and how to contact you, only if the information you gave before 
has changed.  
• 
Ask you to answer questions in a survey about your sexual activities and overall health 
• 
Ask you questions about if you are still using PrEP, why, or why not 
• 
Provide HIV risk education counseling 
• 
Conduct a symptom-driven physical exam 
• 
Collect ~10 to 20 mL (about 2 to 4 teaspoons) of blood. Your blood will be used to test 
you for HIV. If you have not been tested for syphilis at any recent PrEP visits, this blood 
will also be used to test you for syphilis  
• 
Collect ~ 10mL of your urine to test for STI testing (Chlamydia and Gonorrhea) if you 
have not been tested for these infections at any recent PrEP visits 
• 
Store blood (plasma, dried blood spots) and urine samples for study-related testing 
At your final study visit, we will talk with you about the end of the study and when the results of 
the study will be available. You may also be asked to participate in a one-on-one interview around 
the time of your final study visit. Approximately 20 participants will be asked to participate in this 
type of interview. This would add 30-60 minutes to your visit time, and you would be reimbursed 
for this additional time. The interviewer will ask you questions about your understanding about 

 
HPTN 112, FINAL Version 2.0                           Page 64 of 91                                        19 December 2023 
 
HIV prevention, including PrEP, your experience being part of this study, and any challenges you 
experienced engaging in HIV prevention. If you are assigned to the intervention group, you will 
also be asked about your experience working with the PrEP coach. The interview will be 
audiotaped so that your responses can be transcribed for analysis. During transcription, any 
identifying names or places in the interview will be removed from the transcript. After 
transcription, the recording of the interview will be destroyed. Analysis will be conducted to look 
for common themes in all interviews conducted. You can decline participation in this interview.  
 
If you test positive for HIV at any point in the study, you will be referred for HIV care and 
encouraged to start treatment for HIV immediately and you will have an additional approximately 
6-months of study follow-up time from the time you test positive. During this time, you will have 
blood collected twice – once at 3 months and once at 6 months – to make sure that your body is 
responding appropriately to HIV treatment. During these visits, we will draw 10-20 mL (about 2-4 
teaspoons) of blood to check the amount of HIV in your body. We will ask you about any 
medications you are taking. If you have not started HIV treatment yet, we will encourage you to 
start. We will also update your contact information. This could happen at a final visit if you want to 
stop the study early. 
 
If you stop taking PrEP, we will ask you to stay in the study. 
If you permanently stop taking PrEP during the study for any reason, we will ask you to continue to 
come for your regular study visits, but you will no longer have to undergo certain procedures, like 
answering questions about taking PrEP, etc. Similarly, if you or miss doses of PrEP or miss PrEP 
visits, we will ask you to continue to come for your regular study visits as scheduled.  
 
If you get HIV during the study, we will help you get care and support.  
We will test your blood for HIV during this study. If you get HIV while you are in the study, you 
will stop taking PrEP, and we will help you find the care and support you need.  
 
Use of stored samples 
In addition to the laboratory testing performed at each study visit, further study-related testing may 
be performed on blood and urine samples. This will include testing related to HIV and other 
infections, including testing for anti-HIV medications and for quality control testing (to confirm 
results obtained in laboratories). If you are found to have a very early phase of HIV or get infected 
with HIV during the study, some blood may also be used to learn more about HIV viruses, the 
body’s response to HIV infection, and how HIV is spread in the community. The samples used for 
this testing will be labeled with your study number and will be tested at special laboratory facilities 
that may be located in the US and other countries outside of Malawi. The laboratory doing the 
testing will not know who you are. Only approved researchers will have access to your samples. 
Results of this specialized testing will not be returned to the study site or you. Your samples will 
not be sold or directly used to produce commercial products or for commercial gain. No host 
genetic testing will be tested from these samples. Host testing means genetic testing derived from 
you. 
 
What are the possible benefits from being in this study? 
There may be no direct benefits to participants in this study, however, participants and others may 
benefit in the future from information learned from this study. Specifically, information learned in 
this study may lead to improved HIV prevention services for heterosexual men in Malawi and the 

 
HPTN 112, FINAL Version 2.0                           Page 65 of 91                                        19 December 2023 
 
African region. In addition, participants will receive HIV and STI counseling and testing as part of 
the study process. Participants also will be referred for treatment if needed. Participants who 
choose to continue PrEP may benefit from the use of PrEP medicines which are known to protect 
against getting HIV if taken as directed.  
 
If you choose not to be in the study, what other treatment options do you have? 
Your participation is voluntary. You do not have to take part in any of the tests or procedures in the 
study. You should also know that: 
 
• 
If you decide not to join the study, you will not lose your regular medical care. 
• 
If you join this study and later decide to leave, you will not lose your regular medical care. 
• 
You do not have to join the study to receive HIV prevention medications.  
• 
If you decide not to join the study, you will still be able to join another study at a later time 
if there is one available and you qualify. 
Can I change my mind about participating in this study? 
Yes, you can change your mind at any time. Your participation in this study is completely up to 
you (voluntary). Your decision to leave the study will not lead to any penalty, or loss of benefits or 
rights that you would normally have otherwise. 
 
What are the possible risks or discomforts involved from being in this study? 
It is not expected that this study will expose you to unreasonable risk. Blood draws may lead to 
discomfort, feelings of dizziness or faintness, and/or bruising, swelling, and/or infection. You may 
become embarrassed, worried, or anxious when completing their HIV risk assessment and/or 
receiving HIV counseling. You also may become worried or anxious while waiting for their HIV 
test results. Trained counselors will be available to help you deal with these feelings. Although the 
site will make every effort to protect your privacy and confidentiality, it is possible that your 
involvement in the study could become known to others, and that social harms may result. Social 
harms could occur if you are perceived as having HIV or at increased likelihood of getting HIV. 
Examples of social harms are when you are treated unfairly or have problems being accepted by 
your families and/or communities (i.e., because you could become known as vulnerable to HIV). 
 
What if we learn about new findings or information during the study? 
You will be told any new information learned during this study that might affect your willingness 
to stay in the study. For example, if information becomes available that shows that the PrEP coach 
may have bad effects, you will be told about this. You will also be told when the results of the 
study may be available, and how to learn about them.  
 
How will information about you be protected? 
Every effort will be made to keep your personal information confidential, but we cannot guarantee 
absolute confidentiality. To keep your information private, your samples will be labeled with a 
code that can only be traced back to the study clinic. The results of any tests done on these samples 
will not be included in your health records. Your name, where you live, and other personal 
information will be protected by the study clinic. You will be identified by a code, and personal 
information from your records will not be released without your written permission. Any 

 
HPTN 112, FINAL Version 2.0                           Page 66 of 91                                        19 December 2023 
 
publication of this study will not use your name or identify you personally. Your personal 
information may be disclosed if required by law. 
 
Clinic staff will have access to your study records. Your records may also be reviewed, under 
guidelines of the US Federal Privacy Act, by: 
 
The Malawi National Health Science Research Committee (NHSRC) 
The University of North Carolina at Chapel Hill (UNC) Institutional Review Board (IRB) 
The sponsor of the study (US National Institutes of Health [NIH]), its contractors, and its study 
monitors 
The US Office for Human Research Protections (OHRP) 
Other local, US, or international regulatory authorities/entities  
The HPTN (HIV Prevention Trials Network) that is conducting this study 
 
The study staff will also use your personal information, if needed, to verify that you are not taking 
part in any other research studies. This includes other studies conducted by Bwaila STI Clinic and 
studies conducted by other researchers that study staff know about. 
 
Malawi regulations require study staff to report the names of people who get HIV to the local 
health authority. Outreach workers from the health authority may then contact you about informing 
your partners, since they also should be tested. If you do not want to inform your partners yourself, 
the outreach workers will offer to contact them, according to the confidentiality guidelines of the 
Malawi Ministry of Health. 
 
A description of this clinical trial will be available on http://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 study results. You can search this Web site at any time. 
 
What will happen if you are injured by this research? 
If you get sick or injured during the study, contact us immediately. 
 
It is unlikely that you will be injured as a result of study participation. If you are injured, the 
Bwaila STI Clinic will give you immediate necessary treatment for your injuries. You 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. 
 
If you think you have been injured from taking part in this study, call the Principal Investigator at 
the phone number provided on this consent form. They will let you know what you should do. 
 
What if you want to stop before your part in the study is complete? 
You can withdraw from this study at any time, without penalty.  The investigators also have the 
right to stop your participation at any time. This could be because you have had an unexpected 
reaction, or have failed to follow instructions, or because the entire study has been stopped. If you 
decide to withdraw, we will ask you to come in for a final visit for collection and storage of blood 
and urine and STI testing and referral 

 
HPTN 112, FINAL Version 2.0                           Page 67 of 91                                        19 December 2023 
 
 
Will you receive anything for being in this study? 
You will receive the equivalent of approximately 12USD for your time, effort, and travel to and 
from the clinic at each scheduled study visit. 
 
Will it cost you anything to be in this study? 
There will be no cost to you for study related visits, physical examinations, laboratory tests, or 
other procedures. 
 
Who is sponsoring this study? 
This research is funded by Family Health International (FHI 360) through a grant from the US 
National Institutes of Health (NIH). This means that the research team is being paid by the 
sponsor for doing the study. The researchers do not, however, have a direct financial interest with 
the sponsor or in the final results of the study.  
 
What if you have questions about this study? 
 If you ever have any questions about the study, want to report a social harm, or if you have a 
research- related injury, you should contact Dr. Mitch Matoga at +265 999 511 726.  
 
If you have questions about your rights as a research participant, you should contact the Head of 
Secretariat at the National Health Science Research Committee, Dr Collins Mitambo, at +265 999 
397 913.  
 
By mail: 
The Head of Secretariat 
Malawi National Health Science Research Committee (NHSRC) 
Ministry of Health 
Phone: +265 726 422 
or by email: mohdoccentre@gmail.com 
 
What if you have questions about your rights as a research participant? 
All research on human volunteers is reviewed by a committee that works to protect your rights 
and welfare. If you have questions or concerns about your rights as a research subject, or if you 
would like to obtain information or offer input, you may contact the Institutional Review Board 
at 919-966-3113 or by email to IRB_subjects@unc.edu.

 
 
 HPTN 112, FINAL Version 2.0                           Page 68 of 91                                           19 December 2023 
 
SAMPLE ENROLLMENT CONSENT SIGNATURE PAGE 
 
 If you have read this consent form, or had it read and explained to you, you understand the information, 
and you voluntarily agree to join the study, please sign your name or make your mark below.  
 
____ I agree to take part in this study. 
____   I do not agree to take part in this study 
 
 If selected for an interview:  
____ If selected, I agree to participate in an interview where I will be asked questions about this 
research, and the interview will be recorded. 
____ If selected, I do not agree to participate in an interview where I will be asked questions about this 
research.  
 
________________________________ 
_____________________________________ 
Participant Name (print) 
Participant Signature and Date 
 
 
________________________________ 
_____________________________________ 
Study Staff Conducting Consent Discussion (print) 
Study Staff Signature and Date 
 
 
________________________________ 
_____________________________________ 
Witness Name (print) (As appropriate) 
 
      Witness Signature and Date 

 
 HPTN 112, FINAL Version 2.0                           Page 69 of 91                                           19 December 2023 
 
13.5 
APPENDIX V: SAMPLE KEY STAKEHOLDER INFORMED CONSENT FOR SELECTED 
SYSTEM NAVIGATORS AND CLINIC STAFF AT BWAILA STI CLINIC, OR OTHER 
STAKEHOLDERS 
   
HPTN 112: Improving HIV prevention among heterosexual cisgender men seeking STI 
services in Malawi: examining the benefits, acceptability, and associated costs of a systems-
navigator- delivered integrated prevention package 
   
SAMPLE KEY STAKEHOLDER INTERVIEW INFORMED CONSENT 
Version 2.0  
19 December 2023 
DAIDS Document ID: 39057 
   
Sponsored by: Division of AIDS (DAIDS), US National Institute of Allergy and Infectious 
Diseases (NIAID), US National Institute of Health (NIH).  
   
PRINCIPAL INVESTIGATOR (US): Sarah Rutstein, MD, PhD 
PRINCIPAL INVESTIGATOR (MALAWI): Mitch Matoga, MBBS, MSc 
Study contact phone: +265 1 755 056 
Study contact email: mmatoga@unclilongwe.org 
 
CONCISE SUMMARY 
Things you should know about: 
• 
This interview is part of a larger research study. 
• 
Taking part in this research study is voluntary (your choice). You do not have to participate, 
and you can leave the study at any time. 
• 
The larger study is testing whether adding a systems navigator (similar to a coach or guide) 
to pre-exposure prophylaxis (PrEP) care, a medicine that can help prevent HIV, improves 
PrEP use among heterosexual men, compared to the current standard PrEP care.  
• 
You are being asked to be a part of this interview because we would like to talk with you 
about your experiences as someone working in areas related to the study, like as a systems 
navigator, a care provider, a clinic manager, or a policy or program developer. 
• 
There will only be one interview and it will take about an hour. 
• 
There are very limited risks involved with this study, including (but not limited to) risk of 
discomfort, embarrassment, or worry when answering questions. There is the potential that 
some of your information may become known to others, even though the study will do 
everything possible to prevent that.  
• 
There may be no direct benefits to you for being part of this interview, but others may 
benefit in the future from information learned as part of this interview, specifically, 
information on how to improve HIV prevention services for heterosexual men.  
More information about this interview is described in the rest of this form. We will help you 
understand the information and answer all your questions. You should feel that you understand the 

 
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study before deciding whether you will participate. If you agree to join the study, you will be asked 
to sign your name or make your mark on this form. We will offer you a copy of this form to keep. 
 
INTRODUCTION TO PARTICIPATE 
 
What is the key information I should know about this study? 
You have been invited to participate in a research study which includes an interview to discuss 
your perceptions of and experience with the intervention exploring use of a systems navigator to 
improve PrEP care for heterosexual men. You are being invited because you are: 1) a provider or 
supervisor of providers offering STI or HIV care or prevention services; 2) a systems navigator for 
participants in the study; or 3) involved in the development or implementation of HIV prevention 
policy or programming at the local or national level in Malawi. This “Key Stakeholder Interview” 
is an individual discussion about a specific set of topics. 
  
Why is the study being done? 
We would like to learn about perceived barriers to persistent pre-exposure prophylaxis (PrEP ) use 
among heterosexual cisgender male STI clinic patients, and potential barriers or facilitators to 
scaling or sustaining the systems navigation intervention studied during this trial.  
 
What will happen during the study? 
The interview will be led by an individual that is not directly a member of our research team here at 
Bwaila clinic but is affiliated with our overall research organization. The individual will not be 
someone who has a supervisory role for your position. 
 
How many participants will be in this study? 
Approximately 15 participants will participate in these interviews, conducted approximately 6-12 
months after the intervention has first been implemented at the clinic. The information from these 
interviews will help us better understand how the intervention successfully or unsuccessfully 
addresses barriers or enhances facilitators of PrEP uptake and persistent PrEP use for men 
accessing care through the STI clinic. We hope the information we learn will help us promote PrEP 
use among men from STI clinics, reducing the risk of HIV. The information obtained from these 
interviews will be combined with the rest of the information that is collected during this research 
study. Approximately 20 participants from the main study will also be interviewed.   
 
What other choices do I have? 
Your participation is voluntary. You do not have to take part in this interview. You should also 
know that: 
 
• 
If you decide not to join the study, you will not lose your employment or any benefits. 
• 
 Your decision to participate or not participate in this study is confidential and we will not 
inform other people about whether or not you participated.   
• 
If you join this study, you may refuse to answer any of the questions, or stop your 
participation completely, at any time, for any reason. 
 
Can I change my mind about participating in this study? 

 
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Yes, you can change your mind at any time.  Your participation in this study is completely up to 
you (voluntary). Your decision to leave the study will not lead to any penalty, or loss of benefits or 
rights that you would normally have otherwise. 
 
BEING IN THE STUDY 
 
Enrolling in the study. 
If you decide to take part in the study, the interview will last about 1 hour.  
 
During the interview: 
 
• We will obtain full written informed consent for the study. 
• 
The interview will be conducted in a location that assures adequate privacy and 
confidentiality. The study team will talk with you about this so you know where to go for 
the interview.   
• We will ask you questions that will help us better understand how the intervention 
successfully or unsuccessfully addresses barriers or enhances facilitators of PrEP uptake 
and persistent effective use for men accessing care through the STI clinic. 
 
To help assure that we get the best understanding possible from the interview, your answers will be 
recorded. After the interview is finished, the recording will be typed (called a transcript) and 
translated by qualified personnel. All identifying information will be removed from the 
transcript. Your name will not be included on the transcript. The recording will be destroyed after 
all analysis is completed.     
 
RISKS OF THE STUDY 
 
There may be risks to being in this study. 
As noted, to minimize discomfort and to protect your privacy, the interview will be conducted in a 
private area that will allow you to speak comfortably without being overheard. The greatest risk 
may involve your privacy and confidentiality. The steps that the study team has taken to protect 
your privacy are described below.     
 
BENEFITS OF THE STUDY 
 
There may be no direct benefit to you by participating in the study.   
You may not receive any other direct benefit from participating in this interview; however, the 
information gathered during this study may help to provide better access to effective PrEP for 
heterosexual men in Malawi and the African region.     
    
OTHER INFORMATION ABOUT THE STUDY 
 
There is no cost to you to be in this study.  
There will be no cost to you for your participation.  
 
We will give you about 12USD equivalent for each study visit. 
You will receive the equivalent of approximately 12USD for your time, effort, and any associated 
travel for this interview. 
 

 
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We will do our best to protect your private information.  
Every effort will be made to keep your personal information confidential. Your personal 
information (name, position) will be protected by the study team. Your name, or anything else that 
might identify you personally, will not be used in any publication of information about this 
study. Every effort will be made to keep your personal information confidential, but we cannot 
guarantee absolute confidentiality. Because there are only a few staff at your site working on this 
study, researchers may know your identity and the information you share.   
 
To keep your information private, your interview will be labeled with a code that can only be 
traced back to the study clinic. Your name, where you live, and other personal information will be 
protected by the study clinic. Any publication of this study will not use your name or identify you 
personally. Your personal information may be disclosed if required by law. 
 
People who may have access to your interview, under guidelines of the US Federal Privacy Act, 
include: 
 
The Malawi National Health Science Research Committee (NHSRC) 
The University of North Carolina at Chapel Hill (UNC) Institutional Review Board (IRB) 
The sponsor of the study (US National Institutes of Health [NIH]), its contractors, and its study 
monitors 
The US Office for Human Research Protections (OHRP) 
Other local, US, or international regulatory authorities/entities  
The HPTN (HIV Prevention Trials Network) that is conducting this study 
Study team members working on this interview portion of the study 
 
A description of the larger clinical trial will be available on http://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 study results. You can search this Web site at any time. 
 
Contact us at any time if you have questions or problems. 
If you ever have any questions about the study, want to report a social harm, or if you have a research-
related injury, you should contact Dr. Mitch Matoga at +265 999 511 726.  
 
If you have questions about your rights as a research participant, you should contact the Head of 
Secretariat at the National Health Science Research Committee, Dr Collins Mitambo at +265 999 
397 913.  
 
By mail (site to complete): 
The Head of Secretariat 
Malawi National Health Science Research Committee (NHSRC) 
Ministry of Health 
Phone: +265 726 422 
or by email: mohdoccentre@gmail.com    
 
 
 
 

 
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 SIGNATURE PAGE: Sample Key Stakeholder Interview Informed Consent for Selected 
System Navigators and Clinic Staff at Bwaila STI clinic, or Other Stakeholders  
   
HPTN 112: Improving HIV prevention among heterosexual cisgender men seeking STI 
services in Malawi: examining the benefits, acceptability, and associated costs of a systems-
navigator- delivered integrated prevention package 
   
Version 2.0  
19 December 2023 
   
SAMPLE ENROLLMENT CONSENT SIGNATURE PAGE 
 
If you have read this consent form, or had it read and explained to you, you understand the 
information, and you voluntarily agree to join the study, please sign your name or make your mark 
below.  
 
____ I agree to take part in this interview, where I will be asked questions about this research, and 
the interview will be recorded. 
 
________________________________ 
_____________________________________ 
Participant Name (print) 
Participant Signature and Date 
 
 
________________________________ 
_____________________________________ 
Study Staff Conducting Consent Discussion (print) 
Study Staff Signature and Date 
 
 
________________________________ 
____________________________________ 
Witness Name (print) (As appropriate) 
 
      Witness Signature and Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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13.6 
APPENDIX VI: SAMPLE ADOLESCENT (AGE 15-17) ASSENT  
   
HPTN 112: Improving HIV prevention among heterosexual cisgender men seeking STI 
services in Malawi: examining the benefits, acceptability, and associated costs of a systems-
navigator- delivered integrated prevention package 
   
SAMPLE ADOLESCENT (AGE 15-17) ASSENT 
Version 2.0  
19 December 2023 
DAIDS Document ID: 39057 
   
Sponsored by: Division of AIDS (DAIDS), US National Institute of Allergy and Infectious 
Diseases (NIAID), US National Institute of Health (NIH).  
   
PRINCIPAL INVESTIGATOR (US): Sarah Rutstein, MD, PhD 
PRINCIPAL INVESTIGATOR (MALAWI): Mitch Matoga, MBBS, MSc 
Study contact phone: +265 1 755 056 
Study contact email: mmatoga@unclilongwe.org 
 
 CONCISE SUMMARY: This is a research study. Taking part in this research study is voluntary 
(your choice). You do not have to be in the study, and you can leave the study at any time. No 
matter what you decide, any other care that you get here will not change. 
 
This study is about systems navigators for PrEP for HIV (Human Immunodeficiency Virus).  
• PrEP is short for Pre-Exposure Prophylaxis.  
• Pre-exposure means before coming into contact with HIV. Prophylaxis is the way people 
prevent a disease from infecting them. 
• A Systems Navigator is like a coach or guide to help with access and use of PrEP. 
• With PrEP for HIV, medications are used to prevent people from getting HIV if they are 
exposed to it.  
 
The study will take about 15 months total. If you choose to be in the study, you will be followed on 
the study for at least 6 months and up to 12 months. You will be asked to give blood and urine 
specimens for HIV, sexually transmitted infections (STI), and other tests. You do not need to 
remain on PrEP to continue being in this study.  
There are very few risks with this study, including (but not limited to) risk of feeling 
uncomfortable, dizziness/faintness, and/or bruising, swelling and/or infection from your blood 
being taken. You may also feel feelings of embarrassment or worry when answering questions 
about your own behaviors and/or getting HIV counseling, or become worried while waiting for 
your HIV test results. Finally, it is possible that some of your information may become known to 
others, even though the study will do everything possible to prevent that.  
There may be no direct benefits to you for being in this study, but others may benefit in the future 
from information learned from this study. Information on how to improve HIV prevention services 
for men. In addition, you will receive HIV and STI counseling and testing as part of the study 
process and will be referred for care as needed.  

 
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More information about this study is found in the rest of this form. We will help you understand the 
information and answer all your questions. You should feel that you understand the study before 
deciding whether you will participate. If you agree to join the study, you will be asked to sign your 
name or make your mark on this form. Your parent or guardian will also need to sign a form saying 
that it is ok for you to join the study. We will offer you a copy of this form to keep. 
 
What are some basic things you should know about research studies? 
You are being asked to take part in a research study. To join the study is your choice. You may 
choose not to be in the study, or you may leave the study at any time, for any reason, without 
punishment. 
Research studies are designed to obtain new information. This new information may help people in 
the future. You may not receive any direct benefit from being in the research study. There also may 
be risks to being in research studies. Deciding not to be in the study or leaving the study before it is 
done will not affect your relationship with the researcher or the health care provider.  If you are a 
patient with an illness, you do not have to be in the research study in order to receive health care. 
More information about this study is discussed below. It is important that you understand this 
information so that you can make the best choice for you about being in this research study. 
 
You will be given a copy of this consent form. You should ask the researchers named above, or 
staff members who may assist them, any questions you have about this study at any time. 
 
Why are we doing this study? 
The main reason for this research study is to understand if it is helpful to use a systems navigator 
(coach or guide) to help in the use of PrEP to keep someone from getting HIV. The overall goal of 
this study is to gather information that will help us in future research, helping men from STI clinics 
lower their chances of getting HIV by taking PrEP. 
 
This study is for adult and adolescent men who: 
o are age 15 years or older, 
o are seeking services at Bwaila STI Clinic, and 
o have tested HIV negative 
 
Are there any reasons you should not be in this study? 
You should not be in this study if you are taking part in another study of drugs or medical medical 
tools or equipment. You are asked to tell the study staff about any other studies you are in or 
thinking of being in. This is very important for your safety. 
 
How many people will take part in this study? 
About 200 men who do not have HIV will participate in this study from Lilongwe, Malawi.  
 
How long will your part in this study last? 
Men who choose to join the study will be in the study for at least 6 months and up to 12 months 
total.

 
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What will happen if you take part in the study? 
During this study, you will be in one of 2 study groups. Researchers will "randomize" you into one 
of the study groups described below. 2 out of every 3 persons in the study will be part of the group 
with the coach/guide (intervention group) and 1 out of every 3 persons in the study will be part of 
the regular care (standard of care group). Random assignment means that you are put into a study 
group by chance, like flipping a coin. Neither you nor the study staff can choose your study group. 
The table below indicates what services each group will receive.  
 
Standard of 
Care Group 
Regular PrEP services, including HIV testing and counseling to help you 
lower your chance of getting HIV  
 
Intervention 
Group 
Regular PrEP services, including HIV testing and counseling to help you 
lower your chance of getting HIV. You will also be assigned a systems 
navigator (coach), answer a brief questionnaire about your sexual activities, 
and be tested for STIs at any PrEP visit you attend. This coach may also 
attempt to contact or trace you for any missed PrEP visit (~7 days late), using 
information you provide regarding your desired tracing time, type (phone or 
in-person), and location. 
 
PrEP visits: If you stay on PrEP, the timing of PrEP visits will be decided by the PrEP nurse at the 
clinic, according to the Malawi directions for PrEP. These visits usually occur every 2-3 months, 
depending on the kind of PrEP you are taking.  
 
This study is using a Standard of Care Group (also known as a “Control Group”) because we do 
not yet know whether adding the coach  for PrEP care, which is the intervention in this study, 
improves PrEP use. This kind of intervention has not been tested in PrEP care among men in 
Malawi before. Using a Standard of Care Group will allow researchers to tell whether providing 
the extra intervention resources improves PrEP use. That information can be used to improve 
instructions for health care providers and leaders about what services should be offered in the 
future.  
 
All people in this study will finish the study visit activities given below, no matter which group 
they are in.  
 
Study visits: The study has at least 3 visits (including this enrollment or first visit today). Besides 
this first visit, you will be asked to come back for a visit ~3 months and ~6 months from now. If 
you enroll early in the study, you may also be asked to come back for study visits ~9 months and 
~12 months from now. At each visit, you will be asked a series of questions about your behaviors 
and be tested for HIV and other STIs. You may also be asked to participate in an interview with 
one other person asking you questions. You should come to these study visits even if you have 
decided to stop taking PrEP. 
 
Enrolling in the Study  
If you decide to be in the study, the Enrollment (first) visit will last about 1-2 hours. During the 
Enrollment Visit, we will: 
 
• 
Ask you if you agree to be in the study and ask you to sign this form 
• 
Ask you where you live and how to contact you 

 
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• 
Ask you to answer questions in a survey about your sexual activities and overall health 
• 
Ask you about your PrEP use now and in the past 
• 
Provide short counseling to help keep you from getting HIV 
• 
Conduct an  exam of your body if you have any issues 
• 
Collect ~10 to 20 mL (about 2 to 4 teaspoons) of blood to make sure you do not have a 
very early infection with HIV that we might not see with  the regular HIV tests you’ve 
gotten in clinic. If you have not been tested for syphilis (another STI) at any recent PrEP 
visits, this blood will also be used to test you for syphilis. 
• 
Collect ~ 10mL (about 2 teaspoons) of your urine to test for STI testing (Chlamydia and 
Gonorrhea)  
• 
Store blood (plasma, which is part of your blood, and dried blood spots) and urine for 
study testing  
• 
If you are in the intervention (coach) group, study staff will connect you to your coach to 
talk about next steps in your PrEP care 
 
Additional Visits: 2 to 4 more visits over the next 6 to 12 months. 
If you decide to join the study, after your Enrollment Visit, you will be asked to come to this 
location for more visits (called follow-up visits). You will be followed for at least 6 months and up 
to 12 months depending on when you join the study.  
 
Each visit will last about 1 hour.  
 
During these follow-up visit(s), we will: 
 
• 
Ask you where you live and how to contact you, only if the information you gave before 
has changed  
• 
Ask you to answer questions in a survey about your sexual activities and overall health 
• 
Ask you questions about if you are still using PrEP, why, or why not 
• 
Provide counseling to help keep you from getting HIV 
• 
Conduct an exam of your body if you have any issues 
• 
Collect ~10 to 20 mL (about 2 to 4 teaspoons) of blood. Your blood will be used to test 
you for HIV. If you have not been tested for syphilis (another STI) at any recent PrEP 
visits, this blood will also be used to test you for syphilis  
• 
Collect ~ 10mL (about 2 teaspoons) of your urine to test for STI testing (Chlamydia and 
Gonorrhea) if you have not been tested for these infections at any recent PrEP visits 
• 
Store blood (plasma, which is part of your blood, and dried blood spots) and urine samples 
for study testing 

 
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At your final study visit, we will talk with you about the end of the study and when the results of 
the study will be known. You may also be asked to be in an interview with one other person asking 
you questions around the time of your final study visit. About 20 people in this study will be asked 
to be in this type of interview. This would add 30-60 minutes to your visit time, and you would be 
given money for this additional time. The interviewer will ask you questions about your 
understanding about HIV prevention, including PrEP, your experience being part of this study, and 
any problems you had with HIV prevention. If you are assigned to the intervention (coach) group, 
you will also be asked about your experience working with the PrEP coach. The interview will be 
audiotaped (recorded) so that your answers can be written down in a report for review later. When 
we write down your answers, any names or places that you say in the interview will be taken out of 
the written report. After the written report is done, the recording of the interview will be deleted 
and removed from all storage. A full understanding of the written report will take place to look for 
common ideas in all interviews we have for this study. You can say no to doing this interview.  
 
If you test positive for HIV at any point in the study, you will be referred for HIV care and 
encouraged to start treatment for HIV immediately and you will have about 6-months more of 
study follow-up time from the time you test positive. During this time, you will have blood 
collected twice – once at 3 months and once at 6 months – to make sure that your HIV treatment is 
working. During these visits, we will draw 10-20 mL (about 2-4 teaspoons) of blood to check the 
amount of HIV in your body. We will ask you about any medicines you are taking. If you have not 
started HIV treatment yet, we will encourage you to start. We will also update your contact 
information. This could happen at a final visit if you want to stop the study early. 
 
If you stop taking PrEP, we will ask you to stay in the study. 
If you stop taking PrEP for good during the study for any reason, we will ask you to continue to 
come for your regular study visits, but you will no longer have to do certain tasks, like answering 
questions about taking PrEP. Also, if you miss doses of PrEP or miss PrEP visits, we will ask you 
to continue to come for your regular study visits as scheduled.  
 
If you get HIV during the study, we will help you get care and support.  
We will test your blood for HIV during this study. If you get HIV while you are in the study, you 
will stop taking PrEP, and we will help you find the care and support you need.  
 
Use of stored (kept) samples 
In addition to the laboratory testing done at each study visit, more study testing may be performed 
on your blood and urine samples. This will include testing related to HIV and other infections, 
including testing for anti-HIV medicines and for testing to confirm answers found from your blood 
in the laboratory). If you are found to have the very beginning of HIV or get infected with HIV 
during the study, some blood may also be used to learn more about HIV viruses, how the body 
reacts to HIV infection, and how HIV is spread in the community. The samples used for this testing 
will be labeled with your study number and will be tested at special laboratories that may be 
located in the US and other countries outside of Malawi. The laboratory doing the testing will not 
know who you are. Only approved scientists will have access to your samples. Results of this 
special testing will not be returned to this clinic or you. Your samples will not be sold or directly 
used to make products for money or used to make money in general. No host genetic testing will be 
tested from these samples. Host testing means genetic testing derived from you. Genetic testing is 
when scientists look closely at your DNA (genes). 
 

 
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What are the possible benefits from being in this study? 
There may be no direct benefits to participants in this study, however, participants and others may 
benefit in the future from information learned from this study. Information learned in this study 
may lead to better HIV prevention services for men in Malawi and Africa. In addition, participants 
will receive HIV and STI counseling and testing as part of the study. Participants also will be sent 
for treatment if needed. Participants who choose to stay on PrEP may benefit from the use of PrEP 
medicines which are known to protect against getting HIV if taken the right way.  
 
If you choose not to be in the study, what other treatment options do you have? 
Your participation is your choice. You do not have to take part in any of the tests or activities in the 
study. You should also know that: 
 
• 
If you decide not to join the study, you will not lose your regular medical care. 
• 
If you join this study and later decide to leave, you will not lose your regular medical care. 
• 
You do not have to join the study to receive HIV prevention medications like PrEP.  
• 
If you decide not to join the study, you will still be able to join another study at a later time 
if there is one available and you qualify. 
 
Can I change my mind about participating in this study? 
Yes, you can change your mind at any time. Your participation in this study is completely up to 
you (voluntary). Your decision to leave the study will not lead to any punishment or loss of 
benefits or rights that you would normally have otherwise. 
 
What are the possible risks or discomforts involved from being in this study? 
We do not think that this study will expose you to too much risk. Blood being taken may lead to 
feeling uncomfortable, feelings of dizziness or faintness, and/or bruising, swelling, and/or 
infection. You may become embarrassed, worried, or nervous when answering questions about 
your chances of getting HIV and/or getting HIV counseling. You also may become worried or 
nervous while waiting for your HIV test results. Trained counselors will be available to help you 
deal with these feelings. Although the site will make every effort to keep your information safe, it 
is possible that your being in the study could become known to others, and that social harms may 
result. Social harms could occur if you are thought to have HIV or thought to have more of a 
chance of getting HIV. Examples of social harms are when you are treated unfairly or have 
problems being accepted by your families and/or communities (i.e., because you could be thought 
to have more of a chance to get HIV). 
 
What if we learn about new findings or information during the study? 
You will be told any new information learned during this study that might change whether you stay 
in the study or not. For example, if information becomes available that shows that the PrEP coach 
may have bad effects, you will be told about this. You will also be told when the results of the 
study may be available, and how to learn about them.  
 
How will information about you be kept safe? 
We won’t tell anyone else that you are in the study. We won’t share anything we find out about 
you with anyone, even your parent or guardian, without talking to you first. We will keep your 

 
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personal information safe, but we cannot be absolutely sure it will be kept safe. We use a code 
number instead of your name on all the study forms. The results of any tests done on your samples 
will not be included in your health records. Your name, where you live, and other personal 
information will be protected by the study clinic. Any written report from this study will not use 
your name or say who you are. Your personal information may be given to others if needed by law. 
 
Clinic staff will have access to your study records. Your records may also be reviewed, under rules 
of the US Federal Privacy Act, by: 
 
The Malawi National Health Science Research Committee (NHSRC) 
The University of North Carolina at Chapel Hill (UNC) Institutional Review Board (IRB) 
The sponsor of the study (US National Institutes of Health [NIH]) and its workers 
The US Office for Human Research Protections (OHRP) 
Other local, US, or international regulatory authorities/entities  
The HPTN (HIV Prevention Trials Network) that is conducting this study 
 
The study staff will also use your personal information, if needed, to make sure that you are not 
taking part in any other research studies. This includes other studies run by Bwaila STI Clinic and 
studies run by other scientists that study staff know about. 
 
Malawi rules make sure that study staff report the names of people who get HIV to the local health 
authority. If you get HIV, outreach workers from the health authority may then contact you about 
telling your partners you have HIV, since they also should be tested. If you do not want to tell your 
partners yourself, the outreach workers will offer to contact them, according to the privacy rules of 
the Malawi Ministry of Health. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov. This Web site 
will not include information about you. At most, the Web site will include an overall view of the 
study results. You can search this Web site at any time. 
 
What will happen if you are injured by this research? 
If you get sick or injured during the study, contact us immediately. 
 
It is not likely that you will be injured because of study participation. If you are injured, the Bwaila 
STI Clinic will give you immediate needed treatment for your injuries. You will not have to pay for 
this treatment. You will be told where you can get more treatment for your injuries.  
 
There is no program to pay money or give other forms of payment for such injuries either through 
this clinic or the US NIH. You do not give up any legal rights by signing this consent form. 
 
If you think you have been injured from taking part in this study, call the Principal Investigator at 
the phone number provided on this consent form. They will let you know what you should do. 
 
What if you want to stop before your part in the study is complete? 
You can leave this study at any time, without punishment.  The scientists also have the right to stop 
your participation at any time. This could be because you have had a surprising reaction, or have 
not followed instructions, or because the whole study has been stopped. If you decide to leave the 

 
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study, we will ask you to come in for a final visit for collection and storage of blood and urine and 
STI testing and referral. 
 
Will you receive anything for being in this study? 
You will receive the money that is the same as about 12 US dollars for your time, effort, and 
travel to and from the clinic at each study visit. 
 
Will it cost you anything to be in this study? 
There will be no cost to you for study related visits, physical tests, laboratory tests, or other tasks. 
 
Who is sponsoring this study? 
This research is funded by Family Health International (FHI 360) through a grant from the US 
National Institutes of Health (NIH). This means that the research team is being paid by the 
sponsor for doing the study. The researchers do not, however, have a direct money-related 
interest with the sponsor or in the final results of the study.  
 
What if you have questions about this study? 
 If you ever have any questions about the study, want to report a social harm, or if you have a 
research- related injury, you should contact Dr. Mitch Matoga at +265 999 511 726.  
 
If you have questions about your rights as a research participant, you should contact the Head of 
Secretariat at the National Health Science Research Committee, Dr Collins Mitambo, at +265 999 
397 913.  
 
By mail: 
The Head of Secretariat 
Malawi National Health Science Research Committee (NHSRC) 
Ministry of Health 
Phone: +265 726 422 
or by email: mohdoccentre@gmail.com 
 
What if you have questions about your rights as a research participant? 
All research on human volunteers is reviewed by a group of people who work to protect your 
rights and safety. If you have questions or concerns about your rights as a research subject, or if 
you would like to get or offer information, you may contact the Institutional Review Board at 
919-966-3113 or by email to IRB_subjects@unc.edu.

 
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SAMPLE ENROLLMENT CONSENT SIGNATURE PAGE 
 
If you have read this consent form, or had it read and explained to you, you understand the information, and 
you voluntarily agree to join the study, please sign your name or make your mark below.  
 
____ I agree to take part in this study. 
____   I do not agree to take part in this study. 
 
 If selected for an interview:  
____ If selected, I agree to participate in an interview where I will be asked questions about this research, 
and the interview will be audiotaped. 
____ If selected, I do not agree to participate in an interview where I will be asked questions about this 
research.  
 
________________________________ 
_____________________________________ 
Participant Name (print) 
Participant Signature and Date 
 
 
________________________________ 
_____________________________________ 
Study Staff Conducting Consent Discussion (print) 
Study Staff Signature and Date 
 
 
________________________________ 
_____________________________________ 
Witness Name (print) (As appropriate) 
 
      Witness Signature and Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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13.7 
APPENDIX VII: SAMPLE PARENTAL CONSENT FOR PARTICIPANTS AGE 15-17 
   
HPTN 112: Improving HIV prevention among heterosexual cisgender men seeking STI 
services in Malawi: examining the benefits, acceptability, and associated costs of a systems-
navigator- delivered integrated prevention package 
   
SAMPLE PARENTAL CONSENT FOR PARTICIPANTS AGE 15-17 
Version 2.0  
19 December 2023 
DAIDS Document ID: 39057 
   
Sponsored by: Division of AIDS (DAIDS), US National Institute of Allergy and Infectious 
Diseases (NIAID), US National Institute of Health (NIH).  
   
PRINCIPAL INVESTIGATOR (US): Sarah Rutstein, MD, PhD 
PRINCIPAL INVESTIGATOR (MALAWI): Mitch Matoga, MBBS, MSc 
Study contact phone: +265 1 755 056 
Study contact email: mmatoga@unclilongwe.org 
 
CONCISE SUMMARY: This is a research study. Your child taking part in this research study is 
voluntary. You and your child do not have to participate, and can leave the study at any time. No 
matter what you and your child decide, any other care that your child gets at this site will not 
change. 
 
This study is testing whether adding a systems navigator (similar to a coach or guide) to pre-
exposure prophylaxis (PrEP) care, a medicine that can help prevent HIV, improves PrEP use 
among heterosexual men, compared to the current standard PrEP care.  
 
The study will take about 15-months total. If you and your child choose to enroll in the study, your 
child will be followed on the study for at least 6 months and up to 12 months. Your child will be 
asked to give blood and urine specimens for HIV, STI, and other tests. Your child does not need to 
remain on PrEP to continue participation in this study.  
There are very limited risks involved with this study, including (but not limited to) risk of 
discomfort, dizziness/faintness, and/or bruising, swelling and/or infection from your child’s blood 
being taken. Your child may also feel feelings of embarrassment or worry when answering 
questions about their own behaviors and/or receiving HIV counseling or become worried while 
waiting for their HIV test results. Finally, there is the potential that some of your child’s 
information may become known to others, even though the study will do everything possible to 
prevent that.  
There may be no direct benefits to your child for being in this study, but others may benefit in the 
future from information learned from this study. Specifically, information on how to improve HIV 
prevention services for heterosexual men. In addition, your child will receive HIV and STI 
counseling and testing as part of the study process and will be referred for treatment as needed.  
More information about this study is described in the rest of this form. We will help you 
understand the information and answer all your questions. You should feel that you understand the 

 
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study before deciding whether your child will participate. If you agree to your child joining the 
study, you will be asked to sign your name or make your mark on this form. We will offer you a 
copy of this form to keep. 
 
What are some general things you and your child should know about research studies? 
You are being asked to allow your child to take part in a research study. To join the study is 
voluntary. You may decide to not allow your child to participate, or you may withdraw your 
permission for your child to be in the study, for any reasons, without penalty. Even if you give your 
permission, your child can decide not to be in the study or to leave the study early.  
Research studies are designed to obtain new knowledge. This new information may help people in 
the future. Your child may not receive any direct benefit from being in the research study. There 
also may be risks to being in research studies. Deciding not to be in the study or leaving the study 
before it is done will not affect your or your child's relationship with the researcher or the health 
care provider.  If your child is a patient with an illness, your child does not have to be in the 
research study in order to receive health care. 
Details about this study are discussed below. It is important that you and your child understand 
this information so that you and your child can make an informed choice about being in this 
research study. 
 
You will be given a copy of this consent form. You and your child should ask the researchers 
named above, or staff members who may assist them, any questions you have about this study at 
any time. 
 
What is the purpose of this study? 
The main purpose of this research study is to understand if it is helpful to use a systems navigator 
(coach or guide) to support the use of PrEP to prevent HIV. The overall goal of this study is to 
collect data that will inform future research, helping men from STI clinics reduce risk of getting 
HIV by taking PrEP. 
 
This study is for adult and adolescent cisgender men who: 
o are age 15 years or older, 
o are seeking services at Bwaila STI Clinic, and 
o have tested HIV negative 
Are there any reasons your child should not be in this study? 
Your child should not be in this study if they are taking part in another study of drugs or medical 
devices. Your child will be asked to tell the study staff about any other studies they are taking part 
in or thinking of taking part in. This is very important for their safety. 
 
How many people will take part in this study? 
About 200 HIV-seronegative heterosexual men will participate in this study from Lilongwe, 
Malawi.  
 
How long will your child’s part in this study last? 
Participants who choose to join the study will be in the study for at least 6 months and up to 12 

 
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months total. 
 
What will happen if your child take part in the study? 
During this study, your child will be in one of 2 study groups. Researchers will "randomize" your 
child into one of the study groups described here. 2 out of every 3 persons enrolled will be assigned 
to the intervention group and 1 out of every 3 persons enrolled will be assigned to the standard of 
care group. Random assignment means that your child is put into a study group by chance, like 
flipping a coin. Neither your child nor the study staff can choose your child’s study group. The 
table below indicates what services each group will receive.  
 
Standard of 
Care Group 
Standard PrEP services, including HIV testing and risk reduction counseling  
 
Intervention 
Group 
Standard PrEP services, including HIV testing and risk reduction counseling. 
Your child will also be assigned a systems navigator (coach), respond to a 
brief questionnaire about your sexual activities, and be tested for STIs at any 
PrEP visit you attend. This coach may also attempt to contact or trace your 
child for any missed PrEP visit (~7 days late), using information your child 
provides regarding their preferred tracing time, method (phone or in-person), 
and location. 
 
PrEP visits: If your child continues on PrEP, the timing of PrEP visits will be decided by the PrEP 
nurse at the clinic, according to the Malawi guidelines for PrEP. These visits typically occur every 
2-3 months, depending on the kind of PrEP they are taking.  
 
This study is using a Standard of Care Group (also known as a “Control Group”) because we do 
not yet know whether the intervention being tested in this study improves PrEP use. This kind of 
intervention has not previously been tested in PrEP care among men in Malawi. Using a Standard 
of Care Group will allow researchers to assess whether providing the additional intervention 
resources improves PrEP use. That information can be used to make recommendations to health 
care providers and leaders about what services should be offered in the future.  
 
All participants will complete the study visit procedures outlined below, regardless of which group 
they are assigned.  
 
Study visits: The study has at least 3 visits (including the enrollment visit today). Besides this first 
visit, your child will be asked to come back for a visit ~3 months and ~6 months from now. If your 
child enrolls early in the study, your child may also be asked to come back for study visits ~9 
months and ~12 months from now. At each visit, your child will be asked a series of questions 
about their behaviors and be tested for HIV and other STIs. Your child may also be asked to 
participate in a one-on-one interview. Your child should attend these study visits even if they have 
decided to stop taking PrEP. 
 
Enrolling in the Study  
If you and your child decide to take part in the study, the Enrollment visit will last about 1-2 hours. 
During the Enrollment Visit, we will: 
 
• 
Obtain full written informed consent for the study 
• 
Ask your child where they live and how to contact them 

 
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• 
Ask your child to answer questions in a survey about their sexual activities and overall 
health 
• 
Ask your child about their previous and current PrEP use 
• 
Provide brief HIV risk reduction counseling 
• 
Conduct a symptom-driven physical exam 
• 
Collect ~10 to 20 mL (about 2 to 4 teaspoons) of blood to make sure your child does have 
a very early infection with HIV that may not be detected by the standard HIV tests they 
have received in clinic. If your child has not been tested for syphilis (another STI) at any 
recent PrEP visits, this blood will also be used to test you for syphilis. 
• 
Collect ~ 10mL of your child’s urine to test for STI testing (Chlamydia and Gonorrhea)  
• 
Store blood (plasma, dried blood spots) and urine samples for study-related testing  
• 
If your child is assigned to the intervention group, study staff will connect your child to 
their coach to discuss next steps in their PrEP care 
 
Additional Visits: 2 to 4 additional visits over the next 6 to 12 months. 
If you and you child decide to join the study, after their Enrollment Visit, your child will be asked 
to come to this location for follow up visits. Participants will be followed for at least 6 months and 
up to 12 months depending on the time of enrollment.  
 
Each visit will last about 1 hour.  
 
During these follow-up visit(s), we will: 
 
• 
Ask your child where they live and how to contact them, only if the information your child 
gave before has changed.  
• 
Ask your child to answer questions in a survey about their sexual activities and overall 
health 
• 
Ask your child questions about if they are still using PrEP, why, or why not 
• 
Provide HIV risk education counseling 
• 
Conduct a symptom-driven physical exam 
• 
Collect ~10 to 20 mL (about 2 to 4 teaspoons) of blood. Your child’s blood will be used to 
test them for HIV. If your child has not been tested for syphilis at any recent PrEP visits, 
this blood will also be used to test your child for syphilis  
• 
Collect ~ 10mL of your child’s urine to test for STI testing (Chlamydia and Gonorrhea) if 
your child has not been tested for these infections at any recent PrEP visits 
• 
Store blood (plasma, dried blood spots) and urine samples for study-related testing 
At your child’s final study visit, we will talk with your child about the end of the study and when 
the results of the study will be available. Your child may also be asked to participate in a one-on-

 
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one interview around the time of their final study visit. Approximately 20 participants will be asked 
to participate in this type of interview. This would add 30-60 minutes to your child’s visit time, and 
your child would be reimbursed for this additional time. The interviewer will ask questions about 
your child’s understanding about HIV prevention, including PrEP, their experience being part of 
this study, and any challenges they experienced engaging in HIV prevention. If your child is 
assigned to the intervention group, your child will also be asked about their experience working 
with the PrEP coach. The interview will be audiotaped so that your child’s responses can be 
transcribed for analysis. During transcription, any identifying names or places in the interview will 
be removed from the transcript. After transcription, the recording of the interview will be 
destroyed. Analysis will be conducted to look for common themes in all interviews conducted. You 
and your child can decline participation in this interview.  
 
If your child tests positive for HIV at any point in the study, your child will be referred for HIV 
care and encouraged to start treatment for HIV immediately and your child will have an additional 
approximately 6-months of study follow-up time from the time your child tests positive. During 
this time, your child will have blood collected twice – once at 3 months and once at 6 months – to 
make sure that your child’s body is responding appropriately to HIV treatment. During these visits, 
we will draw 10-20 mL (about 2-4 teaspoons) of blood to check the amount of HIV in your child’s 
body. We will ask your child about any medications they are taking. If your child has not started 
HIV treatment yet, we will encourage them to start. We will also update your child’s contact 
information. This could happen at a final visit if your child wants to stop the study early. 
 
If your child stops taking PrEP, we will ask your child to stay in the study. 
If your child permanently stops taking PrEP during the study for any reason, we will ask your child 
to continue to come for their regular study visits, but your child will no longer have to undergo 
certain procedures, like answering questions about taking PrEP, etc. Similarly, if your child miss 
doses of PrEP or miss PrEP visits, we will ask your child to continue to come for their regular 
study visits as scheduled.  
 
If your child gets HIV during the study, we will help your child get care and support.  
We will test your child’s blood for HIV during this study. If your child gets HIV while they are in 
the study, your child will stop taking PrEP, and we will help your child find the care and support 
they need.  
 
Use of stored samples 
In addition to the laboratory testing performed at each study visit, further study-related testing may 
be performed on blood and urine samples. This will include testing related to HIV and other 
infections, including testing for anti-HIV medications and for quality control testing (to confirm 
results obtained in laboratories). If your child is found to have a very early phase of HIV or gets 
infected with HIV during the study, some blood may also be used to learn more about HIV viruses, 
the body’s response to HIV infection, and how HIV is spread in the community. The samples used 
for this testing will be labeled with your child’s study number and will be tested at special 
laboratory facilities that may be located in the US and other countries outside of Malawi. The 
laboratory doing the testing will not know who your child is. Only approved researchers will have 
access to their samples. Results of this specialized testing will not be returned to the study site or 
your child. Your child’s samples will not be sold or directly used to produce commercial products 
or for commercial gain. No host genetic testing will be tested from these samples. Host testing 
means genetic testing derived from your child.  

 
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What are the possible benefits from being in this study? 
There may be no direct benefits to participants in this study, however, participants and others may 
benefit in the future from information learned from this study. Specifically, information learned in 
this study may lead to improved HIV prevention services for heterosexual men in Malawi and the 
African region. In addition, participants will receive HIV and STI counseling and testing as part of 
the study process. Participants also will be referred for treatment if needed. Participants who 
choose to continue PrEP may benefit from the use of PrEP medicines which are known to protect 
against getting HIV if taken as directed.  
 
If your child chooses not to be in the study, what other treatment options does your child 
have? 
Your child’s participation is voluntary. Your child does not have to take part in any of the tests or 
procedures in the study. Your child should also know that: 
 
• 
If they decide not to join the study, they will not lose their regular medical care. 
• 
If they join this study and later decide to leave, they will not lose theirregular medical care. 
• 
Your child does not have to join the study to receive HIV prevention medications.  
• 
If you and your child decide not to join the study, your child will still be able to join 
another study at a later time if there is one available and your child qualifies. 
Can I change my mind about my child participating in this study? 
Yes, you and your child can change your minds at any time. Your child’s participation in this study 
is completely voluntary. You and your child’s decision to leave the study will not lead to any 
penalty, or loss of benefits or rights that you and your child would normally have otherwise. 
 
What are the possible risks or discomforts involved from being in this study? 
It is not expected that this study will expose your child to unreasonable risk. Blood draws may lead 
to discomfort, feelings of dizziness or faintness, and/or bruising, swelling, and/or infection. Your 
child may become embarrassed, worried, or anxious when completing their HIV risk assessment 
and/or receiving HIV counseling. Your child also may become worried or anxious while waiting 
for their HIV test results. Trained counselors will be available to help your child deal with these 
feelings. Although the site will make every effort to protect your child’s privacy and 
confidentiality, it is possible that your child’s involvement in the study could become known to 
others, and that social harms may result. Social harms could occur if your child is perceived as 
having HIV or at increased likelihood of getting HIV. Examples of social harms are when your 
child are treated unfairly or have problems being accepted by their families and/or communities 
(i.e., because your child could become known as vulnerable to HIV). 
 
What if we learn about new findings or information during the study? 
You and your child will be told any new information learned during this study that might affect 
your child’s willingness to stay in the study. For example, if information becomes available that 
shows that the PrEP coach may have bad effects, you and your child will be told about this. You 
and your child will also be told when the results of the study may be available, and how to learn 
about them.  
 

 
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How will information about your child be protected? 
Every effort will be made to keep your child’s personal information confidential, but we cannot 
guarantee absolute confidentiality. To keep your child’s information private, their samples will be 
labeled with a code that can only be traced back to the study clinic. The results of any tests done on 
these samples will not be included in your child’s health records. Your child’s name, where they 
live, and other personal information will be protected by the study clinic. Any tracing activities will 
be done according to you and your child’s stated preferences and will not discuss any information 
related to the study or study activities. Your child will be identified by a code, and personal 
information from their records will not be released without their written permission. Any 
publication of this study will not use your child’s name or identify them personally. Your child’s 
personal information may be disclosed if required by law. 
 
Clinic staff will have access to your study records. Your child’s records may also be reviewed, 
under guidelines of the US Federal Privacy Act, by: 
 
The Malawi National Health Science Research Committee (NHSRC) 
The University of North Carolina at Chapel Hill (UNC) Institutional Review Board (IRB) 
The sponsor of the study (US National Institutes of Health [NIH]), its contractors, and its study 
monitors 
The US Office for Human Research Protections (OHRP) 
Other local, US, or international regulatory authorities/entities  
The HPTN (HIV Prevention Trials Network) that is conducting this study 
 
The study staff will also use your child’s personal information, if needed, to verify that your child 
is not taking part in any other research studies. This includes other studies conducted by Bwaila 
STI Clinic and studies conducted by other researchers that study staff know about. 
 
Malawi regulations require study staff to report the names of people who get HIV to the local 
health authority. Outreach workers from the health authority may then contact your child about 
informing their partners, since they also should be tested. If your child does not want to inform 
their partners themselves, the outreach workers will offer to contact them, according to the 
confidentiality guidelines of the Malawi Ministry of Health. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov. This Web site 
will not include information that can identify your child. At most, the Web site will include a 
summary of the study results. Your child can search this Web site at any time. 
 
What will happen if your child is injured by this research? 
If your child gets sick or injured during the study, contact us immediately. 
 
It is unlikely that your child will be injured as a result of study participation. If your child is 
injured, the Bwaila STI Clinic will give your child immediate necessary treatment for their injuries. 
You and your child will not have to pay for this treatment. You and your child will be told where 
they can get additional treatment for their 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 and 
your child do not give up any legal rights by signing this consent form. 
 
If your child thinks they have been injured from taking part in this study, call the Principal 

 
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Investigator at the phone number provided on this consent form. They will let you and your child 
know what you should do. 
 
What if you and your child want to stop before your child’s part in the study is complete? 
You can withdraw your child from this study at any time, without penalty. The investigators also 
have the right to stop your child’s participation at any time. This could be because your child has 
had an unexpected reaction, or have failed to follow instructions, or because the entire study has 
been stopped. If you or your child decide to withdraw, we will ask you to come in for a final visit 
for collection and storage of blood and urine and STI testing and referral. 
 
Will your child receive anything for being in this study? 
Your child will receive the equivalent of approximately 12USD for their time, effort, and travel to 
and from the clinic at each scheduled study visit. 
 
Will it cost you anything for your child to be in this study? 
There will be no cost to you or your child for study related visits, physical examinations, laboratory 
tests, or other procedures. 
 
Who is sponsoring this study? 
This research is funded by Family Health International (FHI 360) through a grant from the US 
National Institutes of Health (NIH). This means that the research team is being paid by the 
sponsor for doing the study. The researchers do not, however, have a direct financial interest with 
the sponsor or in the final results of the study.  
 
What if you or your child have questions about this study? 
If you or your child ever have any questions about the study, want to report a social harm, or if 
your child has a research- related injury, you or your child should contact Dr. Mitch Matoga at 
+265 999 511 726.  
 
If you or your child have questions about their rights as a research participant, you should contact 
the Head of Secretariat at the National Health Science Research Committee, Dr Collins Mitambo, 
at +265 999 397 913.  
 
By mail: 
The Head of Secretariat 
Malawi National Health Science Research Committee (NHSRC) 
Ministry of Health 
Phone: +265 726 422 
or by email: mohdoccentre@gmail.com 
 
What if you have questions about your child’s rights as a research participant? 
All research on human volunteers is reviewed by a committee that works to protect your child’s 
rights and welfare. If there are questions or concerns about your child’s rights as a research 
subject, or if you would like to obtain information or offer input, you may contact the 
Institutional Review Board at 919-966-3113 or by email to IRB_subjects@unc.edu.

 
 
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SAMPLE ENROLLMENT CONSENT SIGNATURE PAGE 
 
If you have read this consent form, or had it read and explained to you, you understand the information, 
and you voluntarily agree to join the study, please sign your name or make your mark below.  
 
____ I agree to have my child take part in this study. 
____   I do not agree to have my child take part in this study 
 
 If selected for an interview:  
____ If selected, I agree to allow my child to participate in an interview where they will be asked 
questions about this research, and the interview will be recorded. 
____ If selected, I do not agree to allow my child to participate in an interview where they will be asked 
questions about this research.  
 
________________________________ 
_____________________________________ 
Participant Name (print) 
Participant Signature and Date 
 
 
________________________________ 
_____________________________________ 
Study Staff Conducting Consent Discussion (print) 
Study Staff Signature and Date 
 
 
________________________________ 
_____________________________________ 
Witness Name (print) (As appropriate) 
 
      Witness Signature and Date