Making it Last: A Randomized, Controlled Trial of a Home Care System to Promote Persistence in PrEP Care
Phase: NA
Conditions: HIV/AIDS
Sponsor: Emory University

 
 
 
 
 
 
 
 
Making it last: A randomized, controlled trial of a home care system 
to promote persistence in  
PrEP care 
NCT03569813 
 
 
Date: August 08, 2024 
IRB00096594 

1
PrEP@Home Protocol v2.8
Full title:
Making it last: A randomized, controlled trial of a home care system to promote persistence in 
PrEP care
Short Title:
PrEP@Home
Principal Investigators: 
, PhD 
, MD
Co-Investigators:
, MD 
, MD 
, PhD
, MD MPH 
, MD, MPH 
, MD
, DVM PhD 
, PhD
Sponsor’s Name:
National Institutes of Health, National Institute of Mental Health
Trial Registration:
NCT03569813
Date:
August 08, 2024
Version:
2.8

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PrEP@Home Protocol v2.8
TABLE OF CONTENTS
LIST OF ABBREVIATIONS AND ACRONYMS........................................................................5
PROTOCOL TEAM ROSTER .......................................................................................................6
1. INTRODUCTION.......................................................................................................................8
2. METHODS................................................................................................................................10
3. STUDY OVERVIEW ...............................................................................................................11
3.1 Study Design .......................................................................................................................11
3.2 Study Schedule...................................................................................................................11
3.4 Study Locations...................................................................................................................13
3.5 Study Population .................................................................................................................13
3.5.1 Sample .........................................................................................................................13
3.5.2 Participant Eligibility.................................................................................................13
3.5.3 Inclusion Criteria........................................................................................................14
3.5.4 Exclusion Criteria.......................................................................................................14
3.6 Recruitment Procedures.......................................................................................................15
3.6.1 Primary recruitment methods...................................................................................15
3.6.2 Secondary recruitment methods ...............................................................................15
3.7 Participant Retention ...........................................................................................................15
3.8 Participant Withdrawal / Early Termination .......................................................................16
4. STUDY INTERVENTION .......................................................................................................16
5. TRIAL DESIGN........................................................................................................................17
5.1 Study Arms..........................................................................................................................17
5.2 Randomization.....................................................................................................................17
6. STUDY Procedures...................................................................................................................17
6.1 Visit Procedures...................................................................................................................17
6.1.1 Scheduling ...................................................................................................................17
6.1.2 Visit Reminders ..........................................................................................................18
6.2 Baseline Visit.......................................................................................................................18

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PrEP@Home Protocol v2.8
6.3 Follow-up Visits .................................................................................................................19
6.4 Referrals .............................................................................................................................19
6.5 Measures.............................................................................................................................20
6.5.1 Surveys.........................................................................................................................20
6.5.2 Outcome Measures .....................................................................................................20
6.6 Training..............................................................................................................................20
7. LABORATORY SPECIMENS AND PROCEDURES ............................................................20
7.1 HIV Testing.........................................................................................................................20
7.2 STI Testing ..........................................................................................................................21
7.3 Safety Labs ..........................................................................................................................21
7.4 Dried Blood Spots ...............................................................................................................21
7.5 Biohazard Containment.......................................................................................................21
7.6 Future Storage .....................................................................................................................21
8. SAFETY MONITORING AND ADVERSE EVENT REPORTING.......................................21
8.1 Data Safety Monitoring Board (DSMB) .............................................................................21
8.2 Adverse Events....................................................................................................................22
9. STATISTICAL CONSIDERATIONS......................................................................................22
9.1 Primary Outcome.................................................................................................................22
9.2 Power to detect effects in primary outcomes ..................................................................23
9.3 Exploratory analyses ...........................................................................................................23
9.4 Mathematical modeling.......................................................................................................23
9.5 Qualitative ...........................................................................................................................24
9.6 Cost-effectiveness and cost-utility analyses........................................................................25
9.6.1 Costing the intervention and standard of care arms...............................................25
9.6.2 Determining the health effect ....................................................................................26
9.6.3 Cost-effectiveness and cost-utility analysis ..............................................................26
10. HUMAN SUBJECTS CONSIDERATIONS ..........................................................................26
10.1 Informed Consent..............................................................................................................26
10.2 Risks to participation.........................................................................................................27
10.3 Benefits to the subject or future benefits...........................................................................27
10.4 Compensation....................................................................................................................27

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PrEP@Home Protocol v2.8
10.5 Participant Privacy and 
Confidentiality.............................................................................27..............................................
10.6 Communicable Disease Reporting Requirements.............................................................28
11. ADMINISTRATIVE                                                                                       
PROCEDURES. .............................................................................2811.1 Data Collection, Entry
and Management ...........................................................................................................................28
11.2 Quality Assurance .............................................................................................................29
11.3 Regulatory Requirements..................................................................................................29
11.4 Institutional Review Board................................................................................................29
12. REFERENCES........................................................................................................................30

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PrEP@Home Protocol v2.8
LIST OF ABBREVIATIONS AND ACRONYMS
AE
Adverse Event
CDC
Centers for Disease Control and Prevention
CDMS
Clinical Data Management System
CFR
U.S. Code of Federal Regulations
CITI
Collaborative Institutional Training Initiative
CLIA
Clinical Laboratory Improvement Amendments
DBS
Dried Blood Spots
DSMB
Data Safety Monitoring Board
eCRF
Electronic Case Report Form
FDA
U.S. Food and Drug Administration
GCP
Good Clinical Practice
GLMM
Generalized Linear Mixed Model
GSN
Geosocial network
HBsAg
Hepatitis B surface antigen
HIPAA
Health Insurance Portability and Accountability Act
HIV
Human Immunodeficiency Virus
ICF
Informed Consent Form
ICH
International Conference on Harmonization
IRB
Institutional Review Board
ISO
International Organization for Standardization
LGBT
Lesbian, Gay, Bisexual, and Transgender
MMS
Mobile messaging service
MSA
Metropolitan Statistical Area
MSM
Men who have sex with men
NIH
National Institutes of Health
OHRP
Office for Human Research Protections
PCR
Polymerase chain reaction
PEP
Post Exposure Prophylaxis

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PrEP@Home Protocol v2.8
PrEP
Pre-Exposure Prophylaxis
RPR
Rapid plasma reagin
SMS
Standard messaging service
STI
Sexually Transmitted Infection 
TAF/FTC
Tenofovir alafenamide/emtricitabine
TDF/FTC
Tenofovir disoproxil fumarate/emtricitabine 
TFV-DP
Tenofovir diphosphate
YBMSM
Young Black Men who have sex with men 
FTC-TP
Emtricitabine triphosphate
PROTOCOL TEAM ROSTER
Trial Sponsor
 NIH Program Official
Phone: 2
Email: s
Lead Investigators 
, PhD 
Principal Investigator
Associate Professor, Department of 
Behavioral Sciences and Health 
Education
Emory University
 
Phone: 
Email: 
 
Chairman, Department of 
Population Health Science
John D. Bower School of Population Health 
University of Mississippi Medical Center 
Phone: 
Email: l

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PrEP@Home Protocol v2.8
, MD 
Principal Investigator 
Medical Director of Research
Fenway Community Health Center, Inc 
 
PhD
Co- 
Investigator
Assistant Professor, Department of 
Epidemiology
Emory University
Rollins School of Public Health 
 
 DVM, PhD Co- 
Investigator
Professor, Department of Epidemiology 
Emory University
Rollins School of Public Health 
 Site Investigator 
Assistant Professor of Medicine 
University of Mississippi Medical Center 
 MD MPH 
Co-Investigator
Assistant Professor, Department of Medicine 
Washington University
 
MD
MPH
Co- 
Investigator
Assistant Professor, Department of 
Medicine
Emory University 
School of Medicine 
 
 
 Co-Investigator 
Assistant Professor, Department of
Epidemiology
Emory University
Rollins School of Public Health 
 MD Site Investigator 
Assistant Professor, Department of Medicine 
Washington University
 
, MD Site Investigator 
Division of Infectious Diseases 
MetroHealth Medical Center
 
 

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PrEP@Home Protocol v2.8
1. INTRODUCTION
Background and Rationale
Pre-exposure prophylaxis (PrEP) has demonstrated high effectiveness and efficacy for HIV 
prevention for men who have sex with men (MSM),1-3 who are disproportionally impacted by HIV. 
The US Centers for Disease Control and Prevention (CDC) estimates that approximately 1.2 
million US adults are eligible for PrEP, including 492,000 MSM.4 PrEP prescriptions are growing 
exponentially, with over 79,000 prescriptions between 2012 and 2015 in the US,5 yet the benefits 
of PrEP protection are accruing inversely to HIV acquisition risk,6 with young and minority MSM 
less likely to access PrEP despite higher risk.
Studies indicate expanding PrEP access would be both cost-effective7 and feasible for MSM, 
including MSM of color.8 Modeling indicates that if PrEP were scaled to cover 40% of behaviorally 
eligible MSM in the United States, approximately 25% of new HIV infections among all MSM would 
be averted over the next ten years.9
Scale-up of PrEP may be limited by the burden to the healthcare system. Guidance issued by 
CDC10 and by WHO11 calls for quarterly follow-up visits for those on PrEP, to include behavioral 
and laboratory assessments and intervention as needed. The burden of quarterly visits for MSM, 
if PrEP was brought to scale at an 80% level among those eligible, would be 1,576,000 annual 
patient visits.4 We estimate such visits would entail over 3 million hours of patient time, with an 
opportunity cost of $68 million annually, in addition to the millions spent on clinician time and clinic 
facilities.
In 2015, MSM continue to account for two-thirds of new HIV cases in the United States.12 Within 
this elevated risk group, Black MSM (10,315/26,645, 39%) and young MSM aged 20-34 
(15,381/26,645, 58%) bear disproportionate burdens,12 and represent appropriate populations for 
intervention. As PrEP is being brought to scale, it has been shown to have high effectiveness: in 
international settings the PROUD study1 found 86% reduction in anticipated infections, and the 
IPERGAY13 study’s open-label extension found 95% reduction. In domestic settings, an 
observational assessment of Bay Area Kaiser HMO patients found no new cases of HIV among 
their PrEP users, despite common bacterial STI, with 855 person years of follow-up.3
Implementation data from Washington D.C., San Francisco, and Miami have found that at 
12months post-PrEP initiation, persistence in PrEP care was 79%, and similarly found PrEP 
adherence among those maintained in care at 80%.14 Given low adherence among US MSM in 
the iPrEX RCT (56%),15 higher levels of adherence can likely be attributed to patient awareness 
of using an active medication with documented efficacy, as opposed to the blinded RCT 
participants not knowing if the medication was protective, or whether they were receiving a 
placebo that couldn’t work. Interventions that promote improved persistence in PrEP care are an 
essential part of optimizing the impact of PrEP.
Our theoretical model regarding a PrEP care continuum, as retrospectively applied to a cohort of 
young, Black MSM (YBMSM), indicates that a key to achieving high PrEP efficacy will be 
persistence in PrEP care,16 yet persistence has been suboptimal in studies among YBMSM. In a 
cohort study of YBMSM with PrEP offered as standard of care, 38/110 participants accepted, but 
within 6 months of initiation 16% (n=6) ceased PrEP. Of three observed seroconversions, two 
were among those who had started but subsequently ceased PrEP. In ATN 113, 60% of 
participants had protective PrEP dosing at 4 weeks follow-up, but only 23% maintained at 36 
weeks follow-up.17 Minimizing the participant burden of PrEP while supporting persistence in care 
could reduce PrEP cascade drop-off.

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PrEP@Home Protocol v2.8
Young persons in urban areas,18,19 and Black persons in urban areas,18,19 have lower access to 
transportation by car, and are therefore more likely to rely on transit methods requiring larger 
amounts of time.18,19 This is important because urban transportation has been identified as a 
potential barrier to PrEP access.20
As effectiveness of PrEP is already established, PrEP@Home could be beneficial to bringing 
PrEP to scale in a variety of care settings. For large PrEP clinics, home care would enhance 
capacity for PrEP scale-up given limited space and personnel resources. For instance, 
Magnet@Strut Clinic in San Francisco has initiated over 1,900 patients on PrEP (close to 2% of 
total PrEP prescriptions in the United States),21 and Callen-Lorde in New York has initiated PrEP 
for over 2,000 PrEP. In the past, Magnet has at times been limited in accepting new PrEP patients, 
attributing this problem to lack of available provider time and clinic space, the bulk of which was 
occupied by PrEP visits. Similarly, other common venues of PrEP provision have limited “brick 
and mortar” space to add substantial numbers of new patient visits, an issue that home care could 
address.
Electronic communication, such as that used by PrEP@Home surveys and patient portal, is now 
the predominant mode of communication for young people. Male adolescents send or receive 
over 2800 mobile messages (MMS and SMS) a month on average,22 96% of MSM teens use 
Facebook,23 and the predominant final activity immediately prior to sleep for 69% of adolescents 
involves electronic media.24 Simply put, mobile and electronic interactions are now the dominant 
means of communication and interaction for young men. Moreover, 75% of young MSM use 
geosocial network (GSN) websites, and 60% use GSN apps, with a majority reporting frequent 
use and reporting an intended use for “meet(ing) guys for sex.”23 Smartphone ownership is 
particularly high among YBMSM, with ownership higher in groups identifying as Black (70%) or 
under age 30 (85%) than ownership in the general US (63%).25 Moreover, smartphone ownership 
is increasing as sub-$100 smartphones proliferate.
Relative to clinic-based STI tests, mail-in tests have been shown to improve rescreening rates, 
cost-effectiveness, and acceptability. Home-based, self-collected test kits for chlamydia increased 
rescreening rates by over 20% in one study.26 Another study found home-based testing for 
chlamydia and gonorrhea to be more cost-effective than clinic-based testing.27 Moreover, a 
majority of MSM prefer home-based HIV/STI tests to clinic-based tests, with 75% willing to 
undergo routine home screenings with no monetary incentive.28,29
A home-based PrEP support system could address some patient concerns regarding PrEP 
uptake. One limitation of PrEP is the heavy burden of follow-up visits borne by patients, including 
indirect cost (i.e. absence from paid work, need for child-care) and direct cost (i.e. transport, 
copayments)30 that could lead to problems with PrEP adherence.31,32 The home care system for 
PrEP is comprised of inexpensive, commonly available laboratory supplies such as finger prick 
devices, swabs, and microtubes. Patient self-completion surveys that simulate clinician visit 
typical questions may allow for clinicians to have a higher volume of patients due to time savings. 
Given these inputs, the home care system has the potential to be cost saving, depending in part 
on the level of human resources required to maintain patients in home care.
A home-based monitoring approach could facilitate PrEP prescription by non-HIV specialist 
doctors. Expanding access to PrEP will involve providing services to HIV-negative MSM who 
frequently do not visit HIV specialist providers. Provider type and current care models may pose 
limitations to PrEP scale-up.31,33 A survey of providers found that generalist physicians, relative to 
HIV specialists, were more likely to rate time required for counseling (19% and 6%, respectively) 
and time for clinical monitoring (23% and 10%) as barriers to providing PrEP.33 A qualitative study 
found that providers believe their current care models are poorly suited to PrEP, particularly

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PrEP@Home Protocol v2.8
surrounding extensive follow-up and monitoring required. In a pilot test that replaced a regular 
clinician visit with a PrEP@Home visit, 55/58 participants successfully renewed their PrEP 
prescriptions without an in-person provider visit. Forty percent (22/55) indicated they would have 
a greater likelihood of remaining on PrEP if the home care system was made available and 87% 
(48/55) indicated they would like to use PrEP@Home again.
A home-based PrEP monitoring and support system could decrease provider and patient burden, 
increase patient willingness to initiate or remain on PrEP, facilitate the provision of PrEP by 
primary care practitioners who are less experienced in counseling to prescribe PrEP, and might 
be cost-saving. This study will be the first to assess the feasibility of home-based PrEP support 
among providers.
The purpose of this study is to assess the maintenance in PrEP care, not to study the 
effectiveness of PrEP medication. Adherence to follow-up visits will be assessed through 
several methods. PrEP will be prescribed according to standard of care practices.
2. METHODS
Aim 1. Assess protective levels of emtricitabine triphosphate (TFV-DP) for the intervention relative 
to the control arm.
Hypothesis: Participants randomized to PrEP@Home will have higher levels of protection 
against HIV infection as determined by levels of TFV-DP than standard of care controls. Drug 
levels are an indication of maintenance in PrEP care throughout the study.
Aim 2. Conduct additional assessments to contextualize trial results and facilitate appropriate 
scale-up:
Aim 2.1 Adjusted analyses of the primary outcome that control for potential residual 
confounding, and analyses of secondary outcomes including retention in PrEP care.
Aim 2.2. Exploratory analyses of intervention effectiveness across subgroups, and 
analysis of potential mediators of persistence in PrEP care across both study arms, such 
as medication self-efficacy.
Aim 2.3. Mathematical modeling to determine population-level impact for different scaleup 
scenarios.
Aim 2.4. Interviews and survey assessments among clinicians, healthcare managers, and 
patients involved in PrEP care to inform roll out of home care, should the intervention 
demonstrate efficacy.
Aim 3. Conduct cost-effectiveness and cost-utility analyses of the PrEP@Home intervention.

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PrEP@Home Protocol v2.8
3. STUDY OVERVIEW
3.1 Study Design
The study is a stratified randomized, controlled trial comparing PrEP@Home intervention care to 
standard of care control (i.e. patients being seen quarterly in clinic with a provider), with primary 
outcome of having protective levels of TFV-DP (700 fmol/ml or greater) and secondary outcome 
of retention in PrEP care, as measured by photo of dated prescription label. 
A screening will be conducted online and involve a screening consent and questions to determine 
initial eligibility. This will be followed by a full consent (if eligible), a baseline survey, and the return 
of self-collected specimens for testing to determine clinical PrEP eligibility. Those eligible for the 
study will be enrolled into the trial and randomized to either intervention (PrEP@Home) or control 
(standard of care). Participants assigned to the PrEP@Home intervention will have a baseline 
teleconsultation with a site study clinician who will be responsible for prescribing PrEP as 
indicated. Intervention participants enrolled prior to May 2022 will be offered telemedicine 
consultations at 1, 3, 6, 9 and 12 months, and will complete quarterly home specimen collection 
for laboratory tests recommended by CDC at each time period. Individuals enrolled after May 
2022 will be offered telemedicine consultations at 1, 3, and 6 months, and will complete quarterly 
home specimen collection for laboratory tests recommended by CDC at each time period. The 
study virtual visits consist of surveys, specimen collection, and telemedicine consultation. Those 
assigned to the control condition will be referred to a publicly available website that geolocates 
the nearest PrEP provider, www.PrEPLocator.org. Both conditions will have identical TFV-DP kit 
collection for primary outcome assessments at month 6 (and 12 months for those enrolled before 
May 2022) and app-based surveys for secondary outcomes assessments at baseline, 3, 6, (and 
9 and 12 months for those enrolled before May 2022).
Study sites in Atlanta, GA, Boston, MA, Jackson, MS, St. Louis, MO, and Cleveland, OH, will allow 
for recruitment to focus on MSM known to be at highest risk of acquisition and with documented 
lower levels of persistence in PrEP care. The sample of 396 will be composed of at least 50% 
Black and 50% younger (aged 18-34) participants, including at least 25% YBMSM.
Prior to the RCT starting, a small pilot with 5-10 participants will be conducted to test and verify 
logistics of lab processing procedures. Included in the pilot will be shipping lab specimens, 
tracking the specimen samples through processing and testing the app systems shipping and lab 
results components.

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PrEP@Home Protocol v2.8
3.2 Study Schedule
Figure 1: Study Design or Schema for 12 Months of Follow Up

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PrEP@Home Protocol v2.8
Figure 2: Study Design or Schema for 6 Months of Follow Up

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PrEP@Home Protocol v2.8
3.3 Study Timeline
Study to complete target enrollment in 18 months of recruitment. Participants will be followed for 
6 and/or 12 months after initiating PrEP.
3.4 Study Locations
Study procedures and data collection will take place in the metropolitan areas of Atlanta, GA, 
Boston MA, Jackson, MS, St. Louis, MO, and Cleveland, OH. The sites where the study will be 
conducted include PRISM Health Research Center (Atlanta), The Fenway Institute (Boston), 
UMMC with clinic space at Open Arms Health Care Center and Express Personal Health 
(Jackson), The Infectious Disease Clinic at Washington University (St. Louis), and MetroHealth 
(Cleveland). Each site will have a study clinician prescribing PrEP to site patients and site staff to 
support study conduct. Study participants will be completing the PrEP support kits in their homes 
or another private location of their selection.
3.5 Study Population
3.5.1 Sample
The study population includes born males, ages 18 to 49 years, who have sex with men. Eligible 
men will be residents of metropolitan areas of Atlanta, Georgia; Boston, Massachusetts; Jackson, 
Mississippi; St. Louis, Missouri, or Cleveland, Ohio. Total sample size will be 396, with 50% 
minority and 50% age 18-34.
3.5.2 Participant Eligibility
After recruitment, we will use a three-stage process to screen participants for eligibility. For Stage 
1, a screener will be used to determine study visit eligibility. The screener will be conducted in 
Alchemer, self-completed by all participants excepting those that require a phone call, in which 
case the screener form will be filled by study staff. The initial eligibility criteria include (1) male at 
birth, (2) age 18-49, (3) live in the metro area of a study site, (4) self-report HIV negative status,
(5) own a smartphone, (6) not currently taking PrEP or <3 months of PrEP use in lifetime or 
stopped taking PrEP >6 months ago, (7) not enrolled in an HIV prevention trial, (8) willing to use 
study-provided PrEP navigation services to obtain PrEP, and (9) willing to use a home test kit. 
Those eligible for a visit based on the screener results will be shown the full study consent to 
review and sign. Consented participants will be called to confirm consent and for further eligibility 
determination. This step may take up to two weeks.
Stage 2 of eligibility assessment will be participant visit with study staff, either conducted in clinic 
or via telehealth consultation over Zoom. Decision will be made depending on clinic ability to 
conduct in-person visits and participant preference. Participants will complete a more detailed 
behavioral screening (based on CDC and WHO guidelines for PrEP initiation) and screened for 
clinical eligibility for PrEP and other study eligibility criteria: (1) report anal sex with a man in the 
past 6 months, (2) provide at least 2 means of alternate contact, (3) willing to take a photo of PrEP 
prescription label, (4) ability to complete English-language forms, (5) willing to take and adhere to 
PrEP daily dosing, (6) willing to obtain PrEP for a year, even if financial assistance is not available,
(7) HIV-negative rapid and laboratory test or 4th gen HIV test only, (8) no symptom(s) that could 
indicate acute HIV infection, (9) creatinine clearance ≥60 ml/min, (10) no contraindications to 
taking Tenofovir Disoproxil Fumarate/ Emtricitabine (TDF/FTC) or Tenofovir Alafenamide/ 
Emtricitabine (TAF/FTC), (11) no history of hemophilia and (12) successful completion of a 
selffinger prick at study site or home. Participants will be called by the study staff with lab results. 
Participants who are Stage 2 eligible for the study will be provided a prescription by the site study 
clinician. PrEP prescription can be called in or given to participant while waiting for 4th gen HIV

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PrEP@Home Protocol v2.8
and creatinine clearance results as long as rapid HIV test is documented negative and participant 
meets other eligibility criteria. Participants who are ineligible will be linked to care as needed. If 
more than four weeks pass since initial visit, then participants will need to rescreen for PrEP 
eligibility, including a repeat HIV test. Participants may be able to rescreen if symptoms of acute 
HIV infection are no longer present and HIV infection is ruled out per local protocol.
Stage 3 screening will be verification that HIV 4th generation and creatinine clearance tests 
indicate eligibility and a PrEP prescription has been filled. Using our electronic software (described 
below) the survey will prompt participants to use their smartphone to take a photo of their 
prescription label that identifies their name, date of prescription, and the medication name. We 
anticipate this to occur within one week of receiving the prescription. Once this brief process is 
completed, participants will be enrolled into the trial.
3.5.3 Inclusion Criteria
•
Male at birth
•
Age 18-49
•
Report anal sex with a man in the past 6 months
•
Are able to complete survey instruments in English
•
Live in the metropolitan area of a study site
•
Are willing to provide at least 2 means of alternate contact
•
Willing to not enroll in another HIV prevention trial
•
HIV-negative (self-reported and lab confirmed)
•
Own and willing to use a smart phone for the duration of the study
•
Willing to download study app
•
Willing to take a photo of a PrEP prescription label
•
Behaviorally indicated for PrEP (per CDC guidance, Appendix 3) or if sexually 
active African American MSM 34
•
PrEP naïve or < 3 months lifetime experience of PrEP use or stopped taking PrEP
>6 months ago
•
Willing to take PrEP including adherence to daily dosing
•
Willing to use study-provided PrEP navigation services to obtain coverage for PrEP 
medication
•
Able to work with study site to develop a plan to cover financial cost of PrEP if not 
covered through insurance or Gilead financial assistance
•
Willing to use a home kit that will include self-administered collection of urine, rectal 
and pharyngeal swabs, and finger prick blood.
3.5.4 Exclusion Criteria
•
Not male sex at birth
•
Reports having genital reassignment surgery
•
HIV positive
•
<18 or ≥ 50 years of age
•
Currently enrolled in another HIV prevention trial
•
Symptoms of acute HIV infection, or being evaluated for acute infection because 
of recent high risk exposure
•
Currently taking PEP
 Based on WHO Guidelines of including populations at “substantial risk”

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PrEP@Home Protocol v2.8
•
Creatinine clearance <60 ml/min
•
Contraindications to taking tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) 
or tenofovir alafenamide/emtricitabine (TAF/FTC)
•
History of hemophilia
•
Unable to conduct finger prick at study site
•
Health Insurance with Kaiser Permanente (unable to prescribe PrEP through the 
study)
•
Investigator discretion to exclude anyone whose best interest is not to participate
•
Evidence of fraudulent participation, such as duplicate IP address, multiple 
screening attempts, duplicate emails, etc
3.6 Recruitment Procedures
For participants who meet eligibility criteria, we will ask for a first name, e-mail and phone number. 
For participants who do not screen eligible for the study, we will ask them if they want to provide 
their contact information for future studies for which they might be eligible. If they indicate interest 
in being contacted for future studies, we will request their contact information. These data will be 
stored in the secure, HIPAA-compliant servers of Alchemer.
Participants will have the opportunity to indicate that they prefer to be called by a study staff 
member and screened over the phone rather than completing the full study screener online. 
Participants will be asked to read an informed consent form and indicate consent prior to 
completing the online screening survey or to verbally indicate consent if being screened on the 
phone by a study staff.
Venue-based recruitment strategies may be used, in which staff attend known MSM venues or 
events to recruit for the study. Possible venues include bars, malls, clubs and events such as Gay 
Pride. During venue-based recruitment, study staff will obtain verbal consent and then administer 
screener questions using a handheld device. Flyers and similar forms of visual advertisement 
may also be posted in public and private venues such as clinics, bars, clubs, churches, stores, 
restaurants, colleges, coffee shops, public transit venues, etc.
3.6.1 Primary recruitment methods
Primary recruitment methods include targeted online recruitment strategies, venue-based 
recruitment, and flyers and visual advertisements reviewed by the Emory IRB. Links to the 
screener survey will be advertised through banners or electronic messages on social media 
platforms such as Facebook, Grindr, or Instagram.
3.6.2 Secondary recruitment methods
Other recruitment methods will be used if recruitment targets are not being met. These additional 
strategies may include recruiting individuals who have recently been prescribed PrEP but are not 
established in a follow-up routine. This recruitment strategy would require a change to the 
exclusion criteria to allow for individuals recently prescribed PrEP to enroll.
3.7
Participant Retention
Once a participant enrolls in the study, study staff will seek to retain the participant throughout the 
follow-up period in order to minimize possible bias associated with loss-to-follow-up. Study staff 
will be responsible for developing and implementing standard operating procedures to target this 
goal. Retention efforts include an explanation of the study and procedural requirements during 
the informed consent process and re-emphasis throughout the study. Detailed contact information

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PrEP@Home Protocol v2.8
will be collected at the study baseline visit, with active review and updating of this information 
throughout the study. Reminder mechanisms will be used through the application, including 
notifications and messaging. Staff will use electronic messages, telephone calls, or emails to 
serve as reminders prior to scheduled consultation visits. Missed visits will be immediately 
followed up, with rescheduling. Staff will attempt to reengage participants who have been 
unresponsive to scheduling attempts through the duration of the study.
3.8
Participant Withdrawal / Early Termination
Participants may voluntarily withdraw from the study for any reason at any time. The study 
investigators also may withdraw participants from the study in order to protect participant or staff 
safety. Study staff will record the reasons for all withdrawals. Early study termination may occur 
for the following reasons:
•
Participants who have a confirmed HIV-positive test.
•
Participants also may be withdrawn if the study is terminated prior to its planned end date.
•
Participants will be withdrawn from the study if the physician determines it is in the 
participant’s best interest to discontinue participation in the study.
4. STUDY INTERVENTION
The PrEP@Home System is a fully remote system for conducting PrEP care with the goal to serve 
as a virtual visit and to allow providers to renew PrEP prescriptions without an in-person visit. To 
allow this to happen, relevant study data will be provided to participants’ PrEP-prescribing 
physicians. Data that would be collected as part of a standard quarterly PrEP follow-up visit10, 
including all lab results and relevant participant behavioral survey results, will be shared with 
providers. Participants will need to sign a release form allowing us to share these test and 
behavioral survey results with their provider. The release form is uploaded to eIRB.
The PrEP@Home System includes the participant facing app, the clinician dashboard and the 
administrative system. Participants will be able to track their study schedule through an application 
and message study staff if needed. All participants will download the app in order to access the 
quarterly surveys and to be able to track the home testing kits. To manage study logistics, control 
participants will receive the same management system as the intervention.
PrEP@Home System: Home Care Kit
Participants will receive the home care kit as a plain box via standard mail. The box includes self- 
collection components and specimen return shipping. Each specimen collection component has 
its own bag containing instructions and materials for the specimen collection along with biohazard 
sealable bags for specimen return. The instructions are optimized to facilitate quality specimen 
collection and ease of use. The shipping is tracked through the study management system.
Laboratory results and the survey results will be collated and uploaded to an electronic interface 
for study clinicians, the clinician dashboard. If laboratory and behavioral survey results do not 
show contraindications to PrEP continuation, the study clinician will have the choice to renew the 
prescription without a visit by the patient. If there is a laboratory or behavioral result that the study 
clinician wants to discuss with the participant, then a telemedicine appointment will be scheduled. 
For positive laboratory results, participants will be referred to care for follow-up.

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PrEP@Home Protocol v2.8
5. TRIAL DESIGN
5.1 Study Arms
The Intervention group will be assigned to using the PrEP@Home system for 6 months and/or 
one year of follow-up PrEP care, including telemedicine visits if needed and home test kits. 
Participants in the Intervention group will have full access to the application. All PrEP 
consultations will be conducted via telemedicine unless there is a clinical need to be seen in- 
clinic. Participants will have the option of coming to the clinic for in-person linkage to care at the 
end of study, if clinics are open.
The Control group will be actively linked to a local PrEP provider for standard of care follow-up. 
Participants in the Control group will see portions of the study app pertinent to their participation 
in the study, including electronic surveys and kit tracking for the mail DBS card for TFV-DP. 
Partner institutions at each site are already implementing PrEP as standard of care in their 
community, and participants will be referred to these institutions for PrEP care. Each study site 
will have designated local clinics that have agreed to provide standard PrEP care to control arm 
patients.
5.2 Randomization
Upon completion of stage 3 eligibility assessment (successful initiation of PrEP as determined by 
photo of prescription label), participants will be randomized to either intervention (PrEP@Home, 
n=264) or control (standard of care, n=132). Participants will be randomized using an electronic 
data system, DFexplore. We will implement a stratified randomization scheme using categories 
of age (18-34, 35-49) and study site to decreases the likelihood of Type I error due to the expected 
association between covariates and study outcome. An uneven allocation ratio of 2:1 (Intervention
: Control) will facilitate subgroup analyses and modeling for Aims 2 and 3 by allowing for larger 
intervention group size.
All randomization will be accomplished within the study data management platform; within each 
stratum, the data system will produce a sequential block randomization list. This list, not viewable 
by study PI’s or the study statistician, will automatically populate the appropriate study arm 
assignment in the electronic data system at the time each new participant is randomized at any 
of the four study sites.
6. STUDY PROCEDURES
Visits include screening, baseline, and follow-up for months 1, 3, 6, 9, and 12 for those enrolled 
prior to May 2022, and months 1, 3 and 6 for those enrolled after May 2022. Procedures outlined 
in Appendix 2. A cross-sectional survey will be sent out to all participants to collect information on 
behavior and PrEP changes due to COVID-19 pandemic and distancing regulations.
6.1 Visit Procedures
6.1.1 Scheduling
Once recruited respondents have completed the online screening, study site staff will contact the 
eligible participants, and schedule a baseline visit for either at the local study site or via Zoom. 
Participants will be seen at the research clinical space at their local study site or via Zoom 
telehealth consultation.
After baseline procedures are completed (Section 6.2) and participants are randomized, study 
staff will schedule telemedicine appointments with intervention arm participants via electronic

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PrEP@Home Protocol v2.8
messages. Control arm participants will receive an active linkage to care scheduled visit to study 
identified standard of care clinics, or to the participant’s preferred local provider, for the PrEP 1 
month follow-up visit.
6.1.2 Visit Reminders
Electronic reminder mechanisms for intervention participants will be sent, including app 
notifications and/or electronic messages. Staff will use electronic messages, telephone calls, or 
emails to serve as reminders for scheduled consultation visits.
6.2 Baseline Visit
All baseline procedures are identical for both intervention and control participants and occur after 
participant provides consent. Participants will be directed to download the study app, P@H, and 
will be able to take the baseline survey through the app. Participants will be called and scheduled 
for a baseline visit and instructed to have materials necessary for enrollment in PrEP financial 
assistance programs. Study consent will be reviewed with participants at the clinic visit and 
eligibility will be confirmed for stage 1 and assessed for stage 2 (section 3.5.2). Participants will 
talk with a healthcare provider about initiating PrEP and any concerns they have regarding PrEP. 
The baseline survey will assess domains including demographics, healthcare, HIV/STI knowledge 
and testing history, PrEP knowledge and interest, sexual history including overall and detailed 
partner-level data, substance use history including injection drug use, and scientifically validated 
scales for depression, anxiety, resilience, self-efficacy, experience of racism, and stigma.
Participants will conduct self-finger prick rapid HIV test either at the clinic or from home test kit. If 
negative, they will proceed to have specimens collected to be tested for creatinine, HIV AbAg (4th 
gen), Hepatitis B (HBsAg), Hepatitis C antibody (anti-HCV), syphilis (EIA with reflexive RPR), and 
oral, pharyngeal, and rectal gonorrhea/chlamydia (NAAT). Laboratory testing will be conducted 
by CLIA-certified laboratories at each site’s locally contracted laboratory. If a participant has 
completed these labs as part of PrEP initiation at the clinic in the past 3 months, only the HIV 
AbAg (4th gen) test will need to be repeated along with the self-finger prick. Other tests may be 
repeated at clinician discretion. Participants unable to come to the clinic for the baseline visit, will 
be sent a home test kit for self-collected specimens. The kit will contain instructions on specimen 
collection for urine, throat and rectal swabs, and finger prick for dried blood spot and microtainer. 
The participant will mail the specimens back, using pre-paid mailer, to the lab for testing.
All participants will receive a follow-up call to receive lab results. Participants with low creatinine 
clearance (<60 ml/min) or who are positive for HIV will be ineligible, and referred to local clinical 
care, independent of study participation. Participants testing positive for STI, Hepatitis B, or 
Hepatitis C will be referred to local clinics that can provide treatment options for those with and 
without insurance, with clinic referrals provided by study staff experienced in providing linkage to 
care services. Participants who test positive for Hepatitis B will be counselled on the need to 
contact study staff if they plan on stopping PrEP.
Eligible participants will have a three-month prescription for PrEP sent to the pharmacy of their 
choice. The study will recommend pharmacies that can send prescriptions through the mail for 
participants interested in receiving their prescriptions in this manner. Participants will be reminded 
to submit a photo of their prescription label once they have received their prescription.
To optimize external generalizability, all participants will be provided standard of care PrEP 
navigation services. Navigation services will be delivered by study staff experienced in PrEP 
navigation with the goal of assisting patients in financial access to PrEP. The navigation will use

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PrEP@Home Protocol v2.8
Gilead medication assistance and co-pay access programs, in addition to state-specific programs, 
to facilitate access to PrEP at low or no cost to participants. All study participants will be provided 
with identical PrEP navigation services that will assist with covering the costs of PrEP medication.
Participants will be randomized after all Baseline Visit procedures are complete and the participant 
has initiated PrEP. PrEP will not be provided to the participants as part of the study. The study 
purpose is to evaluate maintenance in PrEP care, using standard of care PrEP guidelines.
6.3 Follow-up Visits
Follow-up visits (visits are defined as any interaction with the study data system) will be conducted 
at Months 1, 3, 6, 9, and 12 for those enrolled prior to May 2022 and 1, 3 and 6 Months for those 
enrolled after May 2022. The month 1 visit will consist of a brief survey for control participants, 
and a brief survey and clinical check-in for intervention participants. For intervention participants, 
home specimen kits for HIV and STI testing will be sent at months 3 and 6 for those enrolled after 
May 2022 as well as Months 9 and 12 for those enrolled prior to May 2022. Creatinine will be 
tested at month 3 for all participants as well as Month 9 for those enrolled prior to May 2022. 
Participants enrolled prior to May 2022 will complete surveys at months 3, 6, 9, and 12, and will 
use home specimen kit for DBS collection, TFV-DP testing, at months 6 and 12. Participants 
enrolled after May 2022 will complete surveys at months 3 and 6, and will use home specimen kit 
for DBS collection, TFV-DP testing at Month 6.
Home Care Kits:
For the intervention, the home care kits will consist of a self-collection of the following specimens: 
urine sample, rectal swab, pharyngeal swab, microtube blood collection, and dried blood spot 
collection. Instructions for self-collection of specimens will be available on the app and included 
in the kit. There will also be available to participants a call-in line to receive help with any 
unexpected problems in completing the kit during normal business hours. The kits will be tailored 
to the tests needed for each specific visit.
In collecting home specimens, participants will conduct 1-3 self-administered finger pricks, each 
one similar to the practice someone with diabetes might follow on a regular basis. The finger prick 
device will be spring-loaded and encased in a plastic shell, so participants will not see or 
manipulate the needle. Following the finger pricks, participants will collect 4-6 drops of blood by 
blotting their finger on collection paper, and by using a gravity-fed microtube. Participants will mail 
their biological specimens using pre-paid mailers included in the home kit. If an insufficient sample 
is collected at home, participants will be given an option to resend their sample or to take their lab 
tests at their provider’s office.
Biological tests routinely performed at PrEP follow-up visits will be conducted on the mailed 
specimens from the home kit. Gonorrhea and Chlamydia tests will be performed on the urine 
sample and on the rectal and pharyngeal swabs. Syphilis testing and creatinine level will be 
performed using whole blood samples. HIV AbAg (4th gen) testing will be conducted from DBS 
cards. These tests will be conducted at a CLIA-certified laboratory.
Communication will be sent to participants through the app to confirm kit receipt and to remind 
participants to return their kit in a timely fashion.
Communication of results with providers will be accomplished through the secure clinician portal 
dashboard. Participants will be counselled as needed during follow-up visits regarding results and 
PrEP adherence.
Authorization for Release of Information:

21
PrEP@Home Protocol v2.8
All participants, in both intervention and control arms, will be contacted during the study period to 
fill out an optional Authorization for Release of Information form. This form will provide study staff 
with permission to contact each participant’s pharmacy where they fill their current PrEP 
prescription. Participants will be asked to sign the form and provide contact information for their 
pharmacy (i.e. pharmacy name and number, address, and/or phone number). Study staff and 
clinicians will contact pharmacies to collect information on prescription fill dates and quantities. 
This information will be used to better understand study outcomes, particularly the primary 
adherence outcome for participants who have not returned their DBS cards.
6.4 Referrals
During Study: Treatment referrals will be provided to participants for positive STI laboratory 
results. Staff will work with local resources to facilitate access to care at free or low cost. In the 
case of a positive HIV test, participants will cease PrEP dosing, be discontinued from the study, 
and be linked to care the next business day. For positive STI tests, participants will have PrEP 
prescriptions initiated or renewed, and be referred to STI treatment at a local agency. Site study 
staff will follow-up with participants testing positive for STI to ensure they have sought appropriate 
care. In cases of participant-opted discontinuation of PrEP, the participant’s rationale for 
discontinuing PrEP will be documented.
End of Study: Participants in the intervention arm will be linked to PrEP care by study staff. Control 
arm participants will continue with their regular care.
6.5 Measures
6.5.1 Surveys
As part of the PrEP@Home kit, participants will also complete an electronic survey through the 
app hosted on Alchemer.com. These surveys will include domains that physicians usually assess 
at quarterly PrEP follow-up visits, including sexual risk, illicit substance use risk, self-reported 
PrEP adherence, and any PrEP-related side effects. This information will be marked clearly in the 
survey as being shared with providers. Another section of the survey will involve research 
assessment and will not be transmitted to providers. This will include factors relevant to PrEP 
experience such as length of time on PrEP, as well as assessing participant experiences with and 
perceptions of the home kit. An additional cross-sectional survey will be emailed to participants to 
complete via Alchemer as a general assessment, PrEP, and behavior changes due to COVID19 
public health restrictions.
6.5.2 Outcome Measures
Measurement of TFV-DP levels will be conducted for participants in both arms using liquid 
chromatography/tandem mass spectrometry methods on DBS samples. The primary outcome is protective 
levels of PrEP, as indicated by TFV-DP levels.  TFV-DP level can be translated to an interpretation that 
indicates mean number of days per week PrEP is ingested over a time period of approximately 1-month 
preceding specimen collection.  The cutpoint used for the primary outcome measure will be TFV-DP levels 
considered to be a surrogate for substantial protection: 
>700 fmol/punch, a level indicating >4 doses/wk. 
6.6 Training
Recruiters and personnel staffing study data collection will complete CITI ethical conduct of 
research training, and also training on recruitment procedures and use of study instruments. 
Documentation of study staff training will be kept at each study site.

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PrEP@Home Protocol v2.8
7. LABORATORY SPECIMENS AND PROCEDURES
Baseline labs will be tested at each sites local laboratory. All study lab tests will be conducted at 
CLIA-certified laboratories using FDA-approved tests. Testing methods are specified for each site 
in Appendix 5.
7.1 HIV Testing
HIV testing will be done for each study visit. All HIV testing will be conducted using a 4th generation 
Antibody Antigen (AbAg) test. An additional rapid HIV test may be used at the in-person baseline 
visit prior to determining eligibility to continue with the study. The HIV testing at follow-up visits for 
the intervention participants will be done using a self-finger prick collection and DBS card. 
Specimens with a reactive result will undergo confirmatory testing per CDC algorithm (Appendix
4) and participant will be asked to stop taking PrEP. If confirmed, results will be returned to 
participants by study staff experienced in HIV care linkage.
7.2 STI Testing
All participants will be tested for Hepatitis B (HBsAg), Hepatitis C (anti-HCV), syphilis (EIA and 
RPR), and pharyngeal, urethral, and rectal gonorrhea and chlamydia at Baseline. Intervention 
participants will be tested for syphilis, gonorrhea, and chlamydia (pharyngeal, urethral and rectal) 
at quarterly follow-up visits.

23
PrEP@Home Protocol v2.8
7.3 Safety Labs
Creatinine will be checked at baseline as part of eligibility and repeated at months 3 and 9 for 
safety. Creatinine will be tested using CLIA-certified FDA-approved tests. The creatinine 
clearance will be calculated using the Cockcroft and Gault equation and the participant’s weight 
at baseline.
If creatinine clearance <60 ml/min on follow-up testing, the participant may need repeat testing 
and/or PrEP hold as per the prescribing physician’s assessment and recommendation. Participant 
will be referred for further testing and management if needed.
7.4 Dried Blood Spots
DBS cards will be collected from participants at months 6 and 12 for TFV-DP testing. The CLIA- 
xcertified UNC Kashuba Lab will perform testing on the DBS to assess TFV-DP levels, which will 
allow us to gain an understanding of participant adherence to their PrEP regimen. Participants 
will be informed of expectations regarding specimen collection at baseline. If we find higher rates 
of non-return of specimen cards for those who report cessation of PrEP care, we will consider 
increasing incentive payments to allow for collection of outcome data.
7.5 Biohazard Containment
General (Baseline): each site has staff trained in biohazard handling who will be responsible for 
collecting specimens and preparing them for transport to the local laboratory for testing.
Home care: After collecting specimen(s) for testing, participants place the specimen collected in 
the provided packaging, which meets all federal regulations for shipment of Biological 
Substances, Category B (UN3373). Participants will ship their collected specimens in pre-paid 
mailers. Staff trained in biohazard handling will store specimens or ship them to the appropriate 
laboratory.
7.6 Future Storage
Participants will be asked during the consenting process if they give permission to have samples 
stored for future research. DBS specimens collected from participants who agree to have samples 
stored for future use will be stored at Emory University or contracted laboratory. Personal 
identifying information will not be kept with the samples. These samples could assist with other 
research, such as DBS validation measures. Participants who do not agree to have specimens 
stored will have specimens discarded after lab tests are conducted.
8. SAFETY MONITORING AND ADVERSE EVENT REPORTING
8.1 Data Safety Monitoring Board (DSMB)
A DSMB will conduct interim monitoring of accumulating study data. The DSMB will receive 
standard data reports on a quarterly basis, with all serious adverse events reported in real time. 
The chair of the DSMB will lead biannual calls to discuss study progress, and the chair will 
convene additional DSMB meetings as needed based on interim reporting. Although the 
intervention is using an FDA-approved product for an approved indication, and care will be 
provided in line with guidance from the US Public Health Service using a CLIA-certified laboratory, 
a DSMB will be to provide several areas of oversight. The DSMB will be tasked with stopping the 
study if the intervention proves to be significantly outperforming the standard of care, or if the 
inverse occurs. The DSMB will monitor a number of factors, including HIV seroconversion, 
behavioral disinhibition, medication adherence, persistence in PrEP care, and differential loss to 
follow-up. The DSMB, comprised of experts on HIV prevention and PrEP, will incorporate the 
most current scientific advances in the rapidly changing field of PrEP in their study oversight. Prior 
to study launch, the DSMB will review all study protocols and manuals of operation.

2 4
Pr E P @ H o m e Pr ot o c ol v 2. 8
8. 2 A d v er s e E v e nt s
A d v er s e e v e nt s will b e r e c or d e d u si n g st a n d ar di z e d f or m s a n d r e p ort e d t o t h e st u d y cli ni ci a n at 
e a c h sit e; i n a d diti o n, q u art erl y r e p ort s will b e pr o vi d e d t o t h e st u d y D S M B a n d m or e a s n e e d e d 
i n t h e e v e nt of u n e x p e ct e d a d v er s e e v e nt s, s u c h a s e v e nt s t h at ar e n ot k n o w n a n d c o m m o nl y 
d o c u m e nt e d si d e eff e ct s of Pr E P. Alt h o u g h n o s eri o u s a d v er s e e v e nt s ar e a nti ci p at e d, t h e s e will 
b e r e p ort e d t o t h e I R B, t h e st u d y D S M B, a n d NI H wit hi n 2 4 h o ur s of t h e M PI b e c o mi n g a w ar e of 
t h e m. F oll o wi n g NI H g ui d eli n e s, a d v er s e e v e nt s will b e d efi n e d a s “ a n y u nt o w ar d or u nf a v or a bl e 
m e di c al o c c urr e n c e i n a h u m a n st u d y p arti ci p a nt.” S eri o u s a d v er s e e v e nt s will b e a d v er s e e v e nt s 
t h at r e s ult i n d e at h, ar e lif e t hr e at e ni n g, r e q uir e s or pr ol o n g s h o s pit ali z ati o n, c a u s e s di s a bilit y, or 
p o s e s ot h er si g nifi c a nt h a z ar d s. S e v erit y of A E s will b e cl a s sifi e d a s f oll o w s: mil d, m o d er at e, a n d 
s e v er e. Mil d A E s will b e e v e nt s t h at d o n ot r e q uir e m e di c al att e nti o n a n d ar e e a sil y t ol er at e d. 
M o d er at e A E s will b e e v e nt s t h at r e q uir e si m pl e a n d r o uti n e m e di c al tr e at m e nt a n d m a y c a u s e 
s o m e i nt err u pti o n t o d ail y lif e. S A E s will b e d efi n e d a s a b o v e. A E s will al s o b e c at e g ori z e d a s 
d efi nit el y, p o s si bl y, or n ot r el at e d t o t h e st u d y. A E s t h at ar e d efi nit el y r el at e d will f oll o w a l o gi c al 
c a u s al s e q u e n c e fr o m a st u d y a cti vit y. P o s si bl y r el at e d e v e nt s will f oll o w a l o gi c al c a u s al 
s e q u e n c e fr o m a st u d y a cti vit y b ut m a y al s o b e d u e t o n o n- st u d y a cti viti e s. N ot r el at e d e v e nt s will 
b e e v e nt s t h at d o n ot f oll o w a l o gi c al c a u s al s e q u e n c e fr o m a n y st u d y a cti vit y.
9. S T A TI S TI C A L C O N SI D E R A TI O N S
9. 1 Pri m ar y O ut c o m e
A s s e s s m e nt of T F V- D P will b e c o n d u ct e d at 6 a n d 1 2- m o nt h f oll o w- u p s. Diff er e n c e s i n t h e 
pr o p orti o n of p arti ci p a nt s wit h pr ot e cti v e l e v el s of T F V- D P b et w e e n t h e i nt er v e nti o n ar m a n d t h e 
c o ntr ol ar m will b e t e st e d u si n g t w o- pr o p orti o n z-t e st s wit h p o ol e d v ari a n c e s, b a s e d o n i nt e nt- 
t otr e at a s si g n m e nt. T h e p er c e nt a g e of p arti ci p a nt s wit h pr ot e cti v e l e v el s of T F V- D P at m o nt h s 6 
a n d 1 2 will b e c o m p ar e d u si n g a G e n er ali z e d Li n e ar Mi x e d M o d el ( G L M M) l o gi sti c r e gr e s si o n 
m o d el t h at a c c o u nt s f or wit hi n- p arti ci p a nt c orr el ati o n o v er ti m e, of t h e f or m: : l o git ￿[￿ij] =  ￿ +  ￿0 ￿ 
+
￿(￿r m￿￿) +  ￿(tim e ij) +  ￿(￿r m￿￿ ×
 tim e ij), w h er e ￿
￿j r e pr e s e nt s t h e o ut c o m e at ti m e j o n p arti ci p a nt i, 
￿0 ￿ r e pr e s e nt s a r a n d o m i nt er c e pt f or p arti ci p a nt i, a n d fi x e d eff e ct d u m m y v ari a bl e s ar e i n cl u d e d f or 
i nt er v e nti o n ar m, ti m e, a n d t h e i nt er a cti o n b et w e e n ar m a n d ti m e. 3 5 T h e st ati sti c al m o d el will b e 
u s e d t o e sti m at e t h e pr o p orti o n of p arti ci p a nt s wit h pr ot e cti v e l e v el s of T F V- D P ( pl u s 9 5 % 
c o nfi d e n c e i nt er v al s) b y i nt er v e nti o n a s si g n m e nt a n d ti m e o n st u d y. T h e st ati sti c al t e st f or 
i nt er a cti o n b et w e e n ar m a n d ti m e will b e t h e pri m ar y o v er all t e st t o d et er mi n e w h et h er Pr E P
pr ot e cti o n c h a n g e d i n si g nifi c a ntl y diff er e nt w a y s d uri n g f oll o w- u p ( at  = 0. 0 5). If a si g nifi c a nt 
ti m e*i nt er v e nti o n i nt er a cti o n i s d et e ct e d, w e will t e st diff er e n c e s b et w e e n t h e m o d el- b a s e d a d h er e n c e 
e sti m at e s at e a c h ti m e p oi nt. If pr ot e cti v e l e v el s of Pr E P r at e s ar e c o n si st e ntl y diff er e nt or si mil ar 
(i. e., n o i nt er a cti o n) t h e n t h e m ai n eff e ct t e st f or i nt er v e nti o n a s si g n m e nt will b e u s e d t o e v al u at e 
i nt er v e nti o n effi c a c y.
9. 2 P o w er t o d et e ct eff e ct s i n pri m ar y o ut c o m e s
A t ot al of 3 9 6 p arti ci p a nt s will b e e nr oll e d at b a s eli n e t o a c c o u nt f or a 1 0 % e x p e ct e d l o s s t o 
f oll o w u p d uri n g 1 2- m o nt h s of st u d y f oll o w- u p. Wit h t hi s s a m pl e si z e a n d a s s u mi n g = 0. 5  a n d t w o- 
si d e d si g nifi c a n c e, t h er e will b e 8 0 % p o w er t o d et e ct a b s ol ut e diff er e n c e s b et w e e n t h e 
i nt er v e nti o n a n d c o ntr ol ar m s i n t h e pr o p orti o n of s u bj e ct s wit h pr ot e cti v e l e v el s of T F V- D P of > 
1 5. 8 % w h e n t h e a v er a g e pr o p orti o n i n t h e c o ntr ol gr o u p i s 0. 5 0. P o w er c al c ul ati o n s w er e 
p erf or m e d u si n g P A S S v. 1 3 s oft w ar e ( N C S S, L L C. K a y s vill e, Ut a h). H y p ot h e si s i s p arti ci p a nt s 
r a n d o mi z e d t o Pr E P @ H o m e will h a v e hi g h er l e v el s of pr ot e cti o n a g ai n st HI V i nf e cti o n a s 

25
PrEP@Home Protocol v2.8
determined by levels of emtricitabine triphosphate (TFV-DP) than standard of care controls.

26
PrEP@Home Protocol v2.8
9.2.1 Adjusted analyses
GLMM models will control for potential confounding for factors such as medication self-efficacy 
and motivation to take PrEP. (1) Adjusted analyses will be conducted to control for changes in 
PrEP eligibility over time for participants in each trial arm, per CDC guidelines, using an additional 
interaction term between eligibility and treatment arm. (2) Per protocol assessments will be 
conducted that account for potential changes in intervention as delivered; for instance, this would 
account for participants assigned to the intervention condition opting to instead receive standard 
of care PrEP from their local clinician.
A number of secondary analyses will be conducted using GLMM models. (3) Intervention impact 
on the secondary outcome of PrEP prescription persistence will be determined using analogous 
logistic regression models. (4) Secondary analysis will be conducted to model log10 (TFV-DP 
levels), using a linear mixed model. Other specific and aggregate measures of safety include: 
renal function, HIV incidence, and incident bacterial STI across study arms.
9.3 Exploratory analyses
Exploratory analysis of intervention effectiveness across subgroups, and analysis of potential 
mediators of persistence in PrEP care across both study arms
Heterogeneity of the intervention effects across subgroups, including those stratified upon (city, 
age), 
and 
socioeconomic 
indicators, 
using 
unadjusted 
proportion 
tests 
and 
subgroups*intervention arm interaction variables in GLMM models. We will examine expected 
mediators of primary and secondary study outcomes. Possible mediators are variables 
hypothesized to be on the causal pathway between the intervention and study outcomes (e.g. 
medication adherence self-efficacy, perceived benefits of PrEP, perceived ease of use of PrEP). 
For participants who seroconvert during the study, we will analyze levels of TFV-DP, PrEP 
persistence, and other clinically-relevant study data.
9.4 Mathematical modeling
Mathematical modeling will be used to estimate the potential impact of scaling-up PrEP@Home 
for MSM across the United States.36 This will be done by using a robust model that simulates HIV 
transmission across dynamic sexual partnership networks,37 which we have used to predict the 
impact and efficiency of CDC’s PrEP guidelines for MSM.38 Model parameters related to PrEP 
persistence and adherence will be based on the efficacy results in Aims 1-2.1. Sensitivity analyses 
will vary levels of and heterogeneity in PrEP access, PrEP@Home uptake, and time-varying PrEP 
adherence. The aim of these models will be to address the question of how PrEP@Home could 
reduce HIV incidence in the population by improving persistence above levels currently observed 
in clinic-based PrEP demonstration projects.14 Modeling activities will also include extending our 
web-based 
PrEP 
forecasting 
tool 
for 
public 
health 
policymakers 
(https://prism.shinyapps.io/cdcprep-guidelines) to incorporate new parameter data and sensitivity 
analyses. Model outputs such as the cumulative number of infections averted (a measure of 
impact) and the number needed to treat to prevent one new infection (a measure of efficiency) 
will be fed into the cost-effectiveness analyses (Aim 3) as input parameters.
9.5 Qualitative
Interviews and survey assessments among clinicians, healthcare managers, and patients 
involved in PrEP care to inform roll out of home care, should the intervention demonstrate efficacy. 
Qualitative interviews will be conducted with approximately 40 participants.
To inform future research with the PrEP home care system and to contextualize study results, we 
will conduct in-depth interviews (IDI) and key informant interviews (KII).

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PrEP@Home Protocol v2.8
IDI: Interviews will seek to explore the experiences of home care users and standard of care 
participants over time. We will use a timeline, activity-based approach, prompting participant 
memories and creating an interactive discussion between moderator and participant regarding 
PrEP care experiences. PrEP care visits will be plotted on the timeline, with participants adding 
surrounding life and PrEP care-related events. IDI topics will include: (1) barriers and facilitators 
to PrEP care, (2) problems with and benefits of the home care or standard of care, (3) ways to 
address problems and amplify success of home care or standard of care, and (4) factors that 
influence successful persistence in or fall-off from PrEP care. IDI will be conducted until data 
saturation has been reached. Purposive sampling of study participants will include up to 15 IDI 
with participants maintained in PrEP care (10 intervention, 5 control) and up to 15 IDI with 
participants not maintained in PrEP care (10 intervention, 5 control). PrEP care is a new and 
dynamic field, and broader healthcare system changes also may occur, so we anticipate that 
conducting this qualitative exploration among intervention and control participants is warranted. 
Participants who seroconvert during the study will also be asked to participate in IDI to assess 
their experience using PrEP and follow-up care, including app use, during their time on the study.
Stigma IDI: In addition to the interviews which will explore the experiences of home care users 
and standard of care participants over time, a second set of IDI will be conducted. In August 
2020, the PrEP@Home parent grant was awarded a minority research supplement, which will 
allow a junior faculty-level scientist, Dr. Allysha Maragh-Bass with Family Health International 
(FHI 360), to conduct research as part of PrEP @Home. This supplemental qualitative research 
seeks to explore the relationship of stigma and resilience, and their role as potential barriers and 
facilitators to healthcare engagement among men who have sex with men (MSM). Interviews 
will be via ZOOM, given the current social distancing measures required for continuation of the 
study and to protect participants. Interviews will explore sexual and PrEP stigma, individual, 
social, and neighborhood/community level access to resilience resources, and the role of these 
factors as barriers and facilitators of PrEP@Home and healthcare engagement. Because some 
individuals may not develop resilience to sexual stigma and/or PrEP stigma, and others do even 
with lower levels of PrEP stigma and sexual stigma, qualitative inquiry will be critical in exploring 
these constructs among both White MSM and MSM of color. IDI will be conducted with 
participants after their 6-month visits by ZOOM, and should not take longer than 60 minutes.
Participants will be paid $60 for their participation. Participants in the parent study who agreed 
to be contacted for future research will be recruited for interviews. Approximately six interviews 
will be conducted per site (i.e., four in intervention, three in control). At least two-thirds of 
participants will be MSM of color, and at least half will be ages 18 to 34 (informed by the parent 
grant’s sampling frame; N=up to 25 interviews total).
Injectable PrEP IDI: In addition to the interviews which will explore the relationship of stigma 
and resilience in healthcare engagement, a third set of IDI will be conducted. In December 
2020, the FDA approved a new injectable medication for PrEP called cabotegravir. It works for 
PrEP just like Truvada® or Descovy®. The difference is that it’s given intramuscularly (in the 
buttocks) every 2 months instead of taking a daily pill. We are preparing a new project where we 
would integrate the administration of this medication into the PrEP@Home model. In other 
words, we would come to participant’s homes to give them their shots every 2 months and we 
would also draw blood. This qualitative research seeks to explore PrEP@Home participant’s 
opinions and preferences regarding home-based injectable PrEP to inform our future study. We 
are not adding the at-home injectable PrEP to this study, but only conducting interviews to 
assess subjects’ opinions on it. Interviews will be via ZOOM, given the current social distancing 
measures required for continuation of the study and to protect participants. Each IDI should not 
take longer than 30 minutes. Participants will be paid $75 for their participation. Participants in

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PrEP@Home Protocol v2.8
PrEP@Home who are currently enrolled at the Emory site and between the ages of 18 and 29 
will be recruited for interviews. Approximately fourteen interviews will be conducted.
KII: Key informant interviews will be conducted with the intervention and standard of care control 
clinicians (n=6), as well as PrEP-prescribing clinicians and managers at institutions interested in 
scaling up PrEP (n=20). For the three intervention clinicians (one per site) and three comparable 
standard of care clinicians, KII will explore the experience of providing PrEP care to participants 
over the course of the clinical trial, focusing on areas for potential improvement of PrEP@Home 
or standard of care provision. KII with members of up to 10 institutions interested in scaling up 
PrEP will focus on how scale-up of PrEP@Home would influence their institution, and exploring 
desired/required adaptations of the system for each care setting. This set of KII will sample from 
PrEP care settings such as: STI/county public health clinics, Health Maintenance Organization 
(HMO), hospital teaching clinics, and Federally Qualified Health Centers. Depending on data 
saturation, we will conduct up to 20 interviews with members of these care settings, half with 
clinicians and half with managers at these institutions. KII will include a briefing regarding the 
home care system, and the results of the clinical trial. The interviews will then explore: (1) How 
would expanding PrEP home care impact each system of care provision, (2) What are areas of 
the system that would need to be adapted or developed, and (3) how home care can best be 
leveraged in their setting to promote their institution’s goal of scaling up PrEP.
Analysis for IDI and KII: Transcriptions and interviewer notes will be entered into maxQDA 
qualitative software to facilitate data management and analysis. Analysis of the data will be led 
by MPI 
and will begin with classification efforts to code data, conducted concurrently with 
data collection, in line with the constant comparison analysis method39. This method leverages 
the ability of qualitative research to quickly identify main themes, and then explore them in further 
depth among subsequent participants. To ensure consistency, coding will be verified by multiple 
study members trained in analysis. Final analysis will compare data within and across codes and 
themes, developing theoretical models based on grounded theory principles to answer study 
questions regarding PrEP@Home adaptation, scale-up considerations, and future research 
directions.
In-depth interviews will be conducted during and after the trial using either telephone or 
videobased systems and will be facilitated by Emory University.
9.6 Cost-effectiveness and cost-utility analyses
We will conduct an economic analysis from both the payer perspective (the cost to the party 
implementing the program) and societal perspective (the payer costs plus the cost to the 
participant for participating in the program) to estimate the cost, cost-effectiveness, and cost-utility 
of the intervention relative to standard of care. Including the societal perspective accounts for 
costs to all parties, acknowledges the value of competing uses for societies’ resources, and 
maximizes comparability with other cost-effectiveness analyses. The cost analysis will calculate 
the overall cost of implementing the program, the cost per participant, and the cost per person 
contacted.
9.6.1 Costing the intervention and standard of care arms
Comprehensive cost analysis will be conducted to assess the cost of developing and 
implementing the PrEP@Home intervention. A micro-costing approach will be used along with 
the standard literature practice of itemizing the intervention components and attaching a dollar 
value to them. Two categories of costs will be defined: developmental costs (the initial or start-up

29
PrEP@Home Protocol v2.8
costs involving the time spent in developing the intervention) and implementation costs (on-going 
costs of delivering the intervention). The development costs will include costs from the first phase 
of the research including salaries and fringe benefits for intervention development staff, pilot 
testing of the intervention, study recruitment, screening, consenting, enrollment, and mailing 
systems; and piloting lab procedures. Implementation costs will include recruitment, salary and 
fringe benefits for an intervention coordinator, kit component, production and laboratory testing 
costs, drug costs (not paid by the study), and the as-needed cost of consultants and technical 
support, self-reported time participants spend adhering to the PrEP@Home intervention or 
standard of care, data management, and clinical costs. Participant’s self-reported time spent 
involved in study activities will be translated into an opportunity cost, where participation 
incentives will be taken as a proxy of the cost of patient time and we will also use income data 
from study participants.
Costing analysis for the standard of care arm within the cost-effectiveness analysis will be based 
on secondary literature estimating the health care and societal costs associated with PrEP for 
MSM in the US.7,40 To calculate personnel costs, we will multiply these hours by wage rates 
gathered from the Bureau of Labor Statistics and calculate an average cost per man receiving 
care in the standard of care arm. We will carefully track these ongoing costs during the 12 months 
of implementation (the time period of the analysis) using standardized data collection tools. Cost 
data will be collected by extraction from accounting records, budget records, external contracts, 
study case report forms, PrEP prescription receipt data; interviews with program implementers; 
and self-report from participants. Data will be entered into a standardized excel spreadsheet with 
embedded formulas to calculate the cost. These methods have been used by our research team 
for economic analyses for a variety of HIV prevention interventions including PrEP interventions. 
7,40,41 Costs will be discounted at an annual rate of 3%.
9.6.2 Determining the health effect
The health effect is defined as the projected reduction in HIV incidence over time associated with 
adopting the intervention relative to standard of care. This will be estimated in our dynamic 
modeling activities and quantified by two key model outcomes: the number of infections averted 
per unit person-time on the intervention and the number needed to treat on PrEP@Home to 
prevent one new infection. The base, standard of care, model will estimate the number of 
infections expected in the absence of the intervention, and may vary under different assumptions 
of baseline, clinic-based PrEP coverage outside of the intervention.42 Each sensitivity analysis in 
the epidemic model (varying levels of access, coverage, and adherence) may be tested as a 
unique intervention scenario for the cost-effective analysis.
9.6.3 Cost-effectiveness and cost-utility analysis
First, we will calculate the incremental cost-effectiveness ratio (ICER) for the intervention overall 
compared to standard of care as: [(CostIntervention – CostStandardofCare)] / [(Infections 
AvertedIntervention – Infections AvertedStandardofCare)]. This value will give us the cost per HIV 
infection averted. We will use bootstrapping to calculate the confidence interval around this ratio
43. If we let ΔX denote the total number of infections averted by the intervention relative to standard 
of care, the corresponding savings in averted HIV-related treatment costs equals T*ΔX, where T 
is the (discounted at an annual rate of 3%) lifetime cost of medical care averted each time an 
incident HIV infection is averted. Thus, the net cost of the intervention can be calculated as C – 
T*ΔX, where C is total costs. Similarly, the total number of QALYs saved by the intervention equals 
Q*ΔX, where Q is the number (discounted at an annual rate of 3%) of QALYs saved by preventing 
a single HIV infection. Estimates of T and Q are available in the literature. We will use the most up-
to-date values available for our analyses (current estimates of T are $330,000 and Q

30
PrEP@Home Protocol v2.8
are 5.83 44). The cost-utility ratio (the net cost per QALY saved) is thus (C – T*∆X)/Q*∆X. 45,46 The 
intervention will be considered “cost-saving” if the net cost per QALY saved is negative. The 
intervention will be considered “cost-effective” if the cost-utility ratio is less than commonly-cited
U.S. thresholds (e.g., $100,000 per QALY saved).44,47,48 One-way sensitivity analyses will be 
performed for all input variables to determine which inputs the cost-effectiveness and cost-utility 
estimates are most sensitive to. We will explore implementation scenarios including the impact of 
generic drug pricing, one of the major determinants of PrEP cost-effectiveness.40
10.HUMAN SUBJECTS CONSIDERATIONS
10.1 Informed Consent
Consent will be obtained prior to screening for study eligibility. Eligible participants will be asked 
to read and sign study consent online before any study procedures are initiated. All participants 
will be offered a copy of the informed consent form, and a study staff member will review the 
consent and key study components with the participant at the baseline visit. The participant will 
have an opportunity to ask any questions before proceeding with the visit. For those participants 
invited to an IDI, a separate informed consent process will be administered prior to the interview. 
Partial HIPAA-waiver may be used at sites with ongoing clinics to use PHI for laboratory 
specimens and results that have been collected for PrEP prescribing.
10.2 Risks to participation
While the purpose of the study is maintenance in care, this study will have study clinicians 
prescribing PrEP, in accordance with Gilead’s label indications for tenofovir disoproxil fumarate/ 
emtricitabine or tenofovir alafenamide/emtricitabine. The prescription of PrEP in the study will also 
follow guidance from the US Public Health Service and US Centers for Disease Control and 
Prevention. However, participants may experience some side effects from taking PrEP, and these 
will be monitored and assessed.
This study is considered minimal risk. While there are side effects associated with PReP, those 
would be the same regardless of how participants access PReP We anticipate that the 
intervention will enhance persistence in PrEP care, based on results from the pilot phase of this 
research that indicated high acceptability and high levels of persistence in care. By providing 
remote, as opposed to in-person, clinical care for PrEP, however, it is possible that some 
participants may be more likely to either fail to persist in PrEP care, exhibit higher levels of 
behavioral disinhibition, or have lower levels of medication adherence. Other risks include 
performing finger pricks that can cause pain, some questions we ask may make participants feel 
uncomfortable, and data security risks to be addressed through careful implementation of 
rolebased procedures, training, and use of highly secure data systems.
Participants may feel uncomfortable answering personal questions about their sexual behavior. 
Electronic survey methods are used for privacy and participants will be able to refuse to answer 
any question that makes them feel uncomfortable. Participants may also learn that they have an 
STI or HIV and this may be upsetting. Participants who receive positive HIV tests will be 
counselled and linked to care at a local clinic of their preference. Participants who have a positive 
STI test will be referred for treatment at a local clinic that provides STI treatment services to MSM 
at either low or no cost.
10.3 Benefits to the subject or future benefits
Participants will accrue protective benefits of PrEP and of regular STI testing and referrals to care 
as needed. There is the potential benefit of increased knowledge about HIV, STI, PrEP and home 
care for PrEP in the United States. The broader community may benefit in the future, if the

31
PrEP@Home Protocol v2.8
information we learn results in improved HIV/STI prevention services for MSM in the United 
States.
10.4 Compensation
All participants will receive compensation of $125 for completing all baseline procedures ($25 for 
initial visit, $75 for completing labs, and $25 after completing all eligibility requirements). 
Participants in both the Intervention group and the Control group will receive $10 for Month 1 
survey and $25 for quarterly survey completion and $75 for DBS collection for TFV-DP testing. 
An additional bonus compensation of $50 will be given to participants at the end of study for 
completing all of their study visits. In addition, participants enrolled after May 2022 will be eligible 
for another bonus incentive of $125 if they have completed all prior study procedures. This will 
allow compensation to be equal between the two groups with varied follow-up schedules. The 
expected total compensation is $435 for all participants. Participants who participate in an in- 
depth interview following completion of participation in the trial will be compensated an additional
$50. For unscheduled follow-up procedures, participants will receive $20 incentive if travel is 
required or $10 incentive if online only. Participants will receive an additional $20 compensation 
for completing the COVID-19 survey.
10.5 Participant Privacy and Confidentiality
The privacy of participants and confidentiality will be protected through several means: study 
procedures, training, and data management practices.
Study Procedures: We will collect multiple means of contact for participants during recruitment. 
We will ask permission to leave a generic message on phone/email/ and cell phone numbers. 
Standardized scripts for phone and email contact will be used (uploaded in the eIRB system).
Training: All study staff will have completed CITI training and a 1-hour training related to 
recruitment, data collection and confidentiality. Staff will sign a confidentiality agreement before 
having access to any confidential data.
Data management practices: Personally identifying information will be stored in a separate 
dataset from participant data where able. Access to the identifying information will be restricted, 
so that persons who are responsible for scheduling can view contact information and next study 
visit due date, but no other study data.
The PrEP@Home System is HIPAA compliant. Data at rest and in transit are encrypted and 
transferred over a secure channel. The database is stored on a central SQL server that is secure 
and accessed via secured website that requires login and password for each user. The mobile 
application requires user authentication and requires login for access. The app will have an 
automatic logout every time the user closes the app on their mobile phone and after 15 minutes 
if inactive. No survey information will be stored in the mobile app. The app will be downloaded via 
app stores, either Google Play or Apple Store, and the user must be authenticated with a code 
sent to their phone and email before being able to log in.
For the telemedicine visits, the study will rely on the Zoom platform. Participants will use Zoom 
to communicate with their study clinician in face-to-face video chat. Zoom is HIPAA-compliant 
and offers the Business Associate Agreement (BAA), where Zoom agrees to be responsible for 
keeping all patient information secure and to immediately report any breach of personal health 
information. Zoom includes the following functions to protect users: End-to-End encryption and 
connects automatically using udp and tcp port 8801, 8802, and 8804 or HTTPS (port 443/TLS). 
The encryption used Advance Encryption Standard (AES) 256-bit algorithm. Session keys are

32
PrEP@Home Protocol v2.8
generated with device unique hardware ID to avoid data being read from other devices. This 
ensures that the session cannot be eavesdropped or tampered with.
The only linkage of identifying information to the study data will be a simple set of items regarding 
whether participant completes study procedures, needs to be re-contacted, refuses participation, 
or other similar recruitment information directly relevant to a participant’s study involvement. This 
information will be stored in a secure and encrypted database. Access to that table will be limited 
to study staff on the role-based system described above.
10.6 Communicable Disease Reporting Requirements
All relevant local reporting procedures will be followed, as required by law, for laboratory testing 
for HIV and STI. Each site will be responsible for reporting positive results to the State Department 
of Health according to each state’s guidelines.
11.ADMINISTRATIVE PROCEDURES
11.1 Data Collection, Entry and Management
Data will be stored in password-protected, encrypted files and on secure Alchemer servers. BAA 
between Alchemer and Emory University ensures HIPAA compliance. Databases of participant 
identifying information (contact information such as names, emails, and phone numbers) will not 
be linked to databases with participant data. Participant identifying information will only be linked 
to whether the participant completes study procedures, needs to be re-contacted, or refuses to 
participate. The name, e-mail, and phone number of screened men who decline to be scheduled 
for participation will be removed from the study database after we have asked them questions 
about why they have a lack of interest in proceeding, unless they request to be contacted for 
future studies. Access to the identifying information will be on a role-based system: access to 
identifying information will be restricted to those who need access to perform their work function. 
Thus, access to identifying information will be restricted to the Project Coordinator, study staff 
providing counseling/referral services, and 2-3 work study students charged with data entry and 
scheduling tasks.
Paper forms will be stored in a secure filing cabinet in a locked office at each site. Electronic CRFs 
will be used for data capturing through DFexplore. Access to the records will be limited to study 
staff as necessary. CRF data will be stored in a cloud-based LINUX Microsoft Azure server 
managed by DF/net, the company of that manages DFexplore. The data will then be downloaded 
onto secure Emory servers. Emory has BAA with DF/net and data will only be accessible to 
persons who have been provided with login and passwords.
11.2 Quality Assurance
Site Investigators are responsible for ensuring the quality of activities conducted at their own site. 
Monitoring visits will be made periodically by the principal investigator during the study to ensure 
that all aspects of the current, approved protocol/amendment(s) are followed. The study may also 
be subject to a quality assurance audit by the sponsor or its designees, as well as inspection by 
appropriate regulatory authorities.
Site clinicians will follow CDC recommendations for PrEP guidelines.
11.3 Regulatory Requirements
Clinical trial best practice will be followed in accordance with NIH guidance, including early trial 
registration at clinicaltrials.gov, investigators and relevant staff completing appropriate training in 
Good Clinical Practice (GCP), and adherence to guidance regarding timely dissemination of

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PrEP@Home Protocol v2.8
clinical trial results. We will report any protocol violations to IRB and the DSMB within three days 
of the principal investigator becoming aware of the violation.
The clinical trial will be registered at clinicaltrials.gov.
11.4 Institutional Review Board
The protocol, informed consent form(s), recruitment materials, and all subject materials will be 
submitted to the IRB for review and approval. Approval of both the protocol and the consent form 
must be obtained before any subject is enrolled. Any amendment to the protocol will require 
review and approval by the IRB before the changes are implemented in the study.
12. REFERENCES
1.
McCormack S, Dunn DT, Desai M, et al. Pre-exposure prophylaxis to prevent the 
acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a 
pragmatic open-label randomised trial. Lancet. 2016;387(10013):53-60.
2.
Grant RM, Anderson PL, McMahan V, et al. Uptake of pre-exposure prophylaxis, sexual 
practices, and HIV incidence in men and transgender women who have sex with men: a 
cohort study. The Lancet Infectious diseases. 2014;14(9):820-829.
3.
Volk JE, Marcus JL, Phengrasamy T, et al. No New HIV Infections With Increasing Use of 
HIV Preexposure Prophylaxis in a Clinical Practice Setting. Clinical infectious diseases : 
an 
official 
publication 
of 
the 
Infectious 
Diseases 
Society 
of 
America. 
2015;61(10):16011603.
4.
Smith DK, Van Handel M, Wolitski RJ, et al. Vital Signs: Estimated Percentages and 
Numbers of Adults with Indications for Preexposure Prophylaxis to Prevent HIV 
Acquisition--United States, 2015. MMWR Morb Mortal Wkly Rep. 2015;64(46):1291-1295.
5.
Mera R, McCallister S, Palmer B, Mayer G, Magnuson D, Rawlings K. Truvada (TVD) for 
HIV pre-exposure prophylaxis (PrEP) utilization in the United States (2013-2015). 
International AIDS Conference (IAS) 2016; 2016; Durban, South Africa.
6.
Bush S, Magnuson D, Rawlings M, Hawkins T, McCallister S, Mera Giler R. Racial 
Characteristics of FTC/TDF for Pre-exposure Prophylaxis (PrEP) Users in the US. Paper 
presented at: ASM Microbe2016; Boston, MA.
7.
Juusola JL, Brandeau ML, Owens DK, Bendavid E. The cost-effectiveness of preexposure 
prophylaxis for HIV prevention in the United States in men who have sex with men. Annals 
of internal medicine. 2012;156(8):541-550.
8.
Hosek S, Siberry G, Bell M, et al. The Acceptability and Feasibility of an HIV Pre-Exposure 
Prophylaxis (PrEP) Trial with Young Men who Have Sex with Men (YMSM). J Acquir 
Immune Defic Syndr. 2012.
9.
Sullivan PS, Carballo-Diéguez A, Coates T, et al. Successes and challenges of HIV 
prevention in men who have sex with men. The Lancet.380(9839):388-399.
10.
Centers for Disease Control and Prevention. US Public Health Service preexposure 
prophylaxis for the prevention of HIV infection in the United States–2014 clinical practice 
guideline. http://wwwcdcgov/hiv/pdf/prepguidelines2014pdf. 2014.
11.
World Health O. Guidance on oral pre-exposure prophylaxis (PrEP) for serodiscordant 
couples, men and transgender women who have sex with men at high risk of HIV: 
recommendations for use in the context of demonstration projects, July 2012. 2012.
12.
Centers for Disease Control and Prevention. HIV Surveillance Report, 2015. In. Vol 27: 
http://www.cdc.gov/hiv/library/reports/hiv-surveillance.html; 2016.
13.
Molina JM, Capitant C, Spire B, et al. On-Demand Preexposure Prophylaxis in Men at 
High Risk for HIV-1 Infection. N Engl J Med. 2015;373(23):2237-2246.

34
PrEP@Home Protocol v2.8
14.
Liu AY, Cohen SE, Vittinghoff E, et al. Preexposure prophylaxis for hiv infection integrated 
with municipal- and community-based sexual health services. JAMA Internal Medicine. 
2016;176(1):75-84.
15.
Amico KR, Marcus JL, McMahan V, et al. Study product adherence measurement in the 
iPrEx placebo-controlled trial: concordance with drug detection. Journal of acquired 
immune deficiency syndromes (1999). 2014;66(5):530-537.
16.
Kelley CF, Kahle E, Siegler A, et al. Applying a PrEP Continuum of Care for Men Who 
Have Sex With Men in Atlanta, Georgia. Clinical infectious diseases : an official publication 
of the Infectious Diseases Society of America. 2015;61(10):1590-1597.
17.
Hosek S, Landovitz R, Rudy B, et al. An HIV pre-exposure prophylaxis (PrEP) 
demonstration project and safety study for adolescent MSM ages 15-17 in the United 
States (ATN 113). International AIDS Conference (IAS) 2016 2016; Durban, South Africa.
18.
McKenzie B, Rapino M. Commuting in the united states: 2009. US Department of 
Commerce, Economics and Statistics Administration, US Census Bureau; 2011.
19.
McKenzie B. Who drives to work? Commuting by automobile in the United States: 2013.
American Community Survey Reports. 2015.
20.
Smith DK, Toledo L, Smith DJ, Adams MA, Rothenberg R. Attitudes and program 
preferences of African-American urban young adults about pre-exposure prophylaxis 
(PrEP). AIDS education and prevention : official publication of the International Society for 
AIDS Education. 2012;24(5):408-421.
21.
Mera R, McCallister S, Palmer B, Mayer G, Magnuson D, Rawlings K. Truvada (TDF) for 
HIV pre-exposure prophylaxis (PrEP) utilization in the United States (2013-2015). 
International AIDS Conference; 2016; Durban, South Africa.
22.
Nielson. New Mobile Obsession U.S. Teens Triple Data Usage. December 15, 2011,.
23.
Lorimer K, Flowers P, Davis M, Frankis J. Young men who have sex with men's use of 
social and sexual media and sex-risk associations: cross-sectional, online survey across 
four countries. Sex Transm Infect. 2016.
24.
Lenhart A, Smith A, Anderson M, Duggan M, Perrin A. Teens, Technology and 
Friendships. 
In: 
Pew 
Research 
Center; 
August 
2015. 
Available 
at: 
http://www.pewinternet.org/files/2015/08/Teens-and-Friendships-FINAL2.pdf.
25.
Pew Research Center. The Smartphone Difference. In:April 2015. Available at: 
http://www.pewinternet.org/files/2015/03/PI_Smartphones_0401151.pdf.
26.
Xu F, Stoner BP, Taylor SN, et al. Use of home-obtained vaginal swabs to facilitate 
rescreening for Chlamydia trachomatis infections: two randomized controlled trials. 
Obstetrics and gynecology. 2011;118(2 Pt 1):231-239.
27.
Smith KJ, Cook RL, Ness RB. Cost comparisons between home- and clinic-based testing 
for sexually transmitted diseases in high-risk young women. Infectious diseases in 
obstetrics and gynecology. 2007;2007:62467.
28.
Wayal S, Llewellyn C, Smith H, Fisher M. Home sampling kits for sexually transmitted 
infections: preferences and concerns of men who have sex with men. Culture, Health & 
Sexuality. 2010;13(3):343-353.
29.
Sharma A, Sullivan PS, Khosropour CM. Willingness to Take a Free Home HIV Test and 
Associated Factors among Internet-Using Men Who Have Sex with Men. J Int Assoc 
Physicians AIDS Care (Chic). 2011;10(6):357-364.
30.
Eisingerich AB, Wheelock A, Gomez GB, Garnett GP, Dybul MR, Piot PK. Attitudes and 
acceptance of oral and parenteral HIV preexposure prophylaxis among potential user 
groups: a multinational study. PLoS One. 2012;7(1):e28238.

35
PrEP@Home Protocol v2.8
31.
Arnold EA, Hazelton P, Lane T, et al. A Qualitative Study of Provider Thoughts on 
Implementing Pre-Exposure Prophylaxis (PrEP) in Clinical Settings to Prevent HIV 
Infection. PLoS One. 2012;7(7):e40603.
32.
WHO. Guidance on pre-exposure oral prophylaxis (PrEP) for serodiscordant couples, men 
and transgender women who have sex with men at high risk of HIV: Recommendations 
for use in the context of demonstration projects. 2012; Geneva, Switzerland.
33.
White JM, Mimiaga MJ, Krakower DS, Mayer KH. Evolution of Massachusetts physician 
attitudes, knowledge, and experience regarding the use of antiretrovirals for HIV 
prevention. AIDS Patient Care STDS. 2012;26(7):395-405.
34.
World Health Organization. Consolidated Guidelines on the use of antiretroviral drugs for 
treating and preventing HIV infection: Recommendations for a Public Health Approach In. 
http://apps.who.int/iris/bitstream/10665/208825/1/9789241549684_eng.pdf?ua=12016.
35.
Diggle P, Liang K, Zeger S. Analysis of longitudinal data. Oxford: Clarendon Press; 1994.
36.
Cassels S, Clark SJ, Morris M. Mathematical models for HIV transmission dynamics: tools 
for social and behavioral science research. Journal of acquired immune deficiency 
syndromes (1999). 2008;47 Suppl 1:S34-39.
37.
Goodreau SM, Carnegie NB, Vittinghoff E, et al. What drives the US and Peruvian HIV 
epidemics in men who have sex with men (MSM)? PloS one. 2012;7(11):e50522.
38.
Jenness SM, Goodreau SM, Rosenberg E, et al. Impact of the Centers for Disease 
Control's HIV Preexposure Prophylaxis Guidelines for Men Who Have Sex With Men in 
the United States. The Journal of infectious diseases. 2016;214(12):1800-1807.
39.
Strauss AL, Corbin JM. Basics of qualitative research : techniques and procedures for 
developing grounded theory. 2nd ed. Thousand Oaks: Sage Publications; 1998.
40.
Paltiel AD, Freedberg KA, Scott CA, et al. HIV preexposure prophylaxis in the United 
States: impact on lifetime infection risk, clinical outcomes, and cost-effectiveness. Clinical 
infectious diseases : an official publication of the Infectious Diseases Society of America. 
2009;48(6):806-815.
41.
Jain KM, Maulsby C, Brantley M, et al. Cost and cost threshold analyses for 12 innovative 
US HIV linkage and retention in care programs. AIDS Care. 2016;28(9):1199-1204.
42.
Jenness SM, Goodreau SM, Rosenberg E, et al. Impact of the Centers for Disease 
Control's HIV Preexposure Prophylaxis Guidelines for Men Who Have Sex With Men in 
the United States. The Journal of infectious diseases. 2016.
43.
Drummond MF, Sculpher MJ, Torrance GW, O'Brien BJ, Stoddart GL. Methods for the 
Economic Evaluation of Health Care Programmes. Oxford, England: Oxford University 
Press; 2005.
44.
Farnham PG, Holtgrave DR, Gopalappa C, Hutchinson AB, Sansom SL. Lifetime costs 
and quality-adjusted life years saved from HIV prevention in the test and treat era. Journal 
of acquired immune deficiency syndromes (1999). 2013;64(2):e15-18.
45.
Pinkerton SD, Holtgrave DR. A method for evaluating the economic efficiency of HIV 
behavioral risk reduction interventions. AIDS and behavior. 1998;2:189-201.
46.
Pinkerton SD, Holtgrave DR. Assessing the cost-effectiveness of HIV prevention 
interventions: A primer. In: Holtgrave DR, ed. Handbook of Economic Evaluation of HIV 
Prevention Programs. New York: Plenum Press; 1998:33-43.
47.
Grosse SD. Assessing cost-effectiveness in healthcare: history of the $50,000 per QALY 
threshold. Expert review of pharmacoeconomics & outcomes research. 2008;8(2):165178.
48.
Walensky RP, Freedberg KA, Weinstein MC, Paltiel AD. Cost-effectiveness of HIV testing 
and treatment in the United States. Clinical infectious diseases : an official publication of 
the Infectious Diseases Society of America. 2007;45 Suppl 4:S248-254.

36
PrEP@Home Protocol v2.8
Appendix 1
Example Screening Informed Consent Form
Emory University 
Screening Consent Information Sheet
For Research Study Screening
Study Title: Making it last: A randomized, controlled trial of a home care system to promote 
persistence in PrEP care
Principal Investigators:
, PhD, MHS and 
 MD
Epidemiology Department, Rollins School of Public Health, Emory University; Medical Director, 
Fenway Community Health Center, Inc.
Funding Source:
National Institutes of Health, National Institute of Mental Health
Introduction and Study Overview
Thank you for your interest in this study. To see whether you may be a candidate for this study, 
we need to ask you for some information about yourself. But first, let me tell you about this 
screening consent and what we will do with your information.
1.
This screening questions will take about 10 minutes.
2.
You can also stop the screening interview at any time. This is completely voluntary.
3.
We can send you an information sheet about this screening, along with the screening 
questions, if you would like. We will also give you a form you can send in later if you 
change your mind and want us to remove your information from our records.
4.
We will ask you some demographic and sexual behavioral questions.
5.
The only risk to you in this phone screening is a potential loss of privacy. However your 
privacy is very important to us and we will be very careful with your information.
6.
The following persons or groups may use and/or disclose your PHI for this study:
•
The Principal Investigator and the research staff
•
National Institutes of Health who funds this Research, and people or companies they 
use to carry out the study
•
The office for Human Research Protections, the Emory Institutional Review Board 
and the Emory Office of Research Compliance.
Contact Information
If, at any time, you have questions about this screening process, your rights as a research 
participant, or if you have questions, concerns or complaints about the research you may contact 
study PI, 
 or the Emory Institutional Review Board.
 at 
Emory Institutional Review Board at 
 or toll-free at 
 or by email at 
i

37
PrEP@Home Protocol v2.8
You can also stop the screening interview at any time. This is completely voluntary.
Consent
 
I consent to being screened for this study online
     I do NOT consent to being screened for this study online
Thank you for your interest. Please answer the following questions to determine if you are eligible 
for this study. [Go to eligibility screener.]
OR
Thank you for taking the time to complete this survey. We are sorry you are not interested in our 
study. If you have any concerns or questions, or would like to be considered for our study, please 
email us at prepathome@emory.edu or call us at 404-712-9733.
Appendix 2
Study Visits and Procedures Schedule
Study Visits and Procedures
Online 
Screening
Baseline
1
Month
3
Months
6
Months
9
Months
12
Months
Screening consent
X
Obtain demographic, risk data, 
and initial eligibility
X
Study informed consent
X
Locator information (including 2 
alternative contacts)
X
HIV rapid test
X
HIV 4th gen
X
I
I
I
I
Creatinine clearance
X
I
I
Syphilis (RPR)
X
I
I
I
I
Hepatitis B and C screening
X
Urine for CT/NG
X
I
I
I
I

3 8
Pr E P @ H o m e Pr ot o c ol v 2. 8
Or al & R e ct al s w a b s f or C T/ N G
X
I
I
I
I
C o nfir m eli gi bilit y
X
D o w nl o a d a p p
X
Gil e a d fi n a n ci al s cr e e ni n g
X
Pr o vi d e Pr E P pr e s cri pti o n
X
T el e m e di ci n e vi sit
I*
I*
I*
I*
El e ctr o ni c S ur v e y
X
X
X
X
X
X
D B S c oll e cti o n f or T F V- D P
X
X
Pr o vi d e i n c e nti v e
X
X
X
X
X
X
Pr o vi d e a cti v e r ef err al
C
I
* a s n e e d e d
L e g e n d:
X
I
C
All P arti ci p a nt s
I nt er v e nti o n O nl y  
C o ntr ol O nl y
A p p e n di x 3
C D C Pr E P G ui d eli n e s
2 0 1 7 Pr E P U p d at e d Cli ni c al Pr a cti c e G ui d eli n e
Wit h o ut a c ut e or e st a bli s h e d HI V i nf e cti o n 
A n y m al e s e x p art n er s i n p a st 6 m o nt h s
N ot i n a m o n o g a m o u s p art n er s hi p wit h a r e c e ntl y t e st e d, 
HI V- n e g ati v e m a n
A N D at l e a st o n e of t h e f oll o wi n g:
S e x u al p art n er w h o i s HI V- p o siti v e
A n y S TI r e p ort e d or di a g n o s e d i n p a st 6 m o nt h s 
A n y a n al s e x wit h o ut c o n d o m s i n p a st 6 m o nt h s



A d ult m a n




M e n W h o H a v e S e x Wit h M e n

39
PrEP@Home Protocol v2.8
Appendix 4
CDC PrEP Guidelines HIV Testing Algorithm 
(https://www.cdc.gov/hiv/pdf/prepguidelines2014.pdf)