Conditions: Human Immunodeficiency Virus
Keywords: PrEP HIV MSM Men Having Sex With Men Episodic PrEP Adherence Episodic HIV Risk
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 54
Healthy volunteers: yes

Brief summary:
This study is designed to investigate the acceptability, perceived need and uptake of short-term episodic Pre-Exposure Prophylaxis (PrEP) for HIV prevention among men who have sex with men (MSM). The overall objective is to determine the feasibility of a clinic-based Epi-PrEP implementation pilot project for 50 MSM (25/each of the 2 study sites) who report occasional condomless sex and who anticipate a period of high-risk while away from home (e.g. vacation) during the study period.

Detailed description:
This proposed study is designed to investigate the acceptability, perceived need and uptake of short-term episodic Pre-Exposure Prophylaxis for HIV prevention among men who have sex with men (MSM). Long-term PrEP may be unnecessary for the many HIV-uninfected men who have episodic contextually defined high-risk periods, particularly when away from their home setting. Alternative dosing strategies, such as short-term fixed-interval episodic PrEP (Epi-PrEP), may be a more realistic, feasible, acceptable, and useful option with high public health impact for the majority of MSM. The overall objective is to determine the feasibility of a clinic-based Epi-PrEP implementation pilot project for 50 MSM (25/each of the 2 study sites) who report occasional condomless sex and who anticipate a period of high-risk while away from home (e.g. vacation) during the study period.

Arms:
arm 1: Given emtricitabine/tenofovir for 2-3 weeks. Brief CBT-based counseling to promote PrEP adherence

Interventions: intervention 1: emtricitabine/tenofovir intervention 2: CBT-based counseling
Intervention descriptions: intervention 1: Short-term episodic use for 2-3 weeks. intervention 2: Brief CBT-based counseling to promote adherence

Protocol document:
Prot_SAP_000.pdf: 
Feasibility of Short-Term PrEP Uptake for MSM With Episodic High-Risk for HIV 
NCT02495779 
06/02/16 


Epi-PrEP Detailed Protocol – Intervention v1.0 
EpiPrEP_DetailedProtocol_1 
Epi-PrEP: Detailed Protocol 
 
 
Co-Principal Investigators 
 
Ronald D Stall  
 
 
 
 
Kenneth H Mayer 
Professor and Vice Chair 
 
 
 
Medical Research Director and Co-Chair 
Dept. Behavioral and Community Health Sciences 
The Fenway Institute 
Graduate School of Public Health 
 
 
1340 Boylston Street, Boston, MA 02215 
University of Pittsburgh             
 
 
617-927-6400, kmayer@fenwayhealth.org 
130 DeSoto Street, Pittsburgh, PA 15261 
 
 
412-624-7933, rstall@pitt.edu 
 
 
1. 
BACKGROUND AND SIGNIFICANCE 
 
1.1 
ABSTRACT 
This proposed study is designed to investigate the acceptability, perceived need and uptake of short-term 
episodic Pre-Exposure Prophylaxis (PrEP) for HIV prevention among men who have sex with men 
(MSM). Long-term PrEP may be unnecessary for the majority of HIV-negative men who do not have 
sustained periods of high-risk sex, but rather episodic, contextually defined, high-risk periods, particularly 
when away from their home setting. Alternative dosing strategies, such as short-term fixed-interval 
episodic PrEP (Epi-PrEP), may be a more realistic, feasible, acceptable and useful option with high public 
health impact for the majority of high-risk MSM whose risk behaviors may be best described as 
occasional, episodic, but non-random. 
 
1.2 
BACKGROUND 
Current approaches to HIV prevention are not controlling the HIV/AIDS epidemic among MSM. After 30 
years of experience in fielding behaviorally-based interventions, high HIV incidence rates among MSM 
continue to be reported, a situation that is attributable to limited HIV prevention impact. Of the 1.2 million 
people living with HIV in the U.S., MSM continue to be disproportionately impacted accounting for 61% of 
all incident U.S. HIV infections in 2009 [2, 3]. Stall, et. al., in a systematic review of HIV incidence rates 
among MSM in the post-HAART era calculated an overall community-based HIV incidence rate of 2.4% 
among MSM (with 4% for Black MSM). Assuming an annual incidence rate of 2.4%, prevalence rates in a 
cohort of 18 year-old HIV-negative men would increase to 41% by age 40 [4], thereby reproducing the 
AIDS epidemic across generations. Combined, these findings highlight both the contributions and 
shortcomings of current HIV prevention practice: although behavioral interventions reduce risk, they are 
unable in and of themselves to achieve the sustainable risk reductions necessary to control the HIV 
epidemic among MSM.  
 
PrEP, in combination with behavioral interventions, is a promising approach to increasing the 
effectiveness of HIV prevention efforts. Biomedical advances have created the opportunity to increase the 
effectiveness of biobehavioral HIV interventions. According to one model, with sufficient coverage, 
available biobehavioral interventions could prevent a quarter of new infections [5]. For example, 
combination prevention [6, 7] approaches attempt to reduce HIV transmission through multiple methods 
including ARV treatment to decrease individual and community viral load (CVL), structural change, and 
behavioral interventions. ARV treatment has proven effective in decreasing individual plasma HIV RNA 
(viral load) thereby reducing the risk of sexual transmission of HIV [8]. Furthermore, reductions in plasma 
HIV RNA at the individual level have resulted in reducing levels of viral load at the community level [9-11]. 
PrEP is the next step in the use of ARVs to both prevent HIV and be part of combination packages to 
reduce CVL. Daily tenofovir-emtricitabine (TDF/FTC) use among at risk HIV-uninfected individuals in 
decreased HIV transmission by 44% in an RCT in MSM (iPrEX) and retrospective analyses found that 
participants who had blood levels consistent with daily use achieved a 99% level of protection [12] and 
was recently FDA approved for use as PrEP [13].  
 


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EpiPrEP_DetailedProtocol_2 
PrEP can be taken on a short-term basis to achieve optimal protection. The overall intent-to-treat 
protective effect of TDF/FTC for MSM was 44% in iPrEX [1], but drug was detected in only about 50% of 
the samples tested among participants randomized to receive the active medication. In the post-hoc 
analysis of the iPrEX data [12] although blood levels consistent with daily PrEP use were associated with 
a greater than 99% protection rate, drug levels consistent with every-other-day usage (i.e. 4 times a 
week) were associated with 96% protection, and studies of intermittent PrEP are underway. TDF/FTC 
needs to be phosphorylated intracellularly to inhibit HIV reverse transcriptase and it is estimated that at 
least 4 daily doses are needed to begin to achieve steady state concentrations consistent with 90% 
protection [12, 14-16]. The iPERGAY study of French and Quebecois MSM is evaluating peri-event 
dosing, and HPTN 067 (Project Adapt) which is comparing peri-event dosing, fixed interval (e.g. weekend 
focused) dosing, and daily dosing among MSM in Bangkok and Harlem and women in South Africa. 
However, neither of these trials are focused on a population of individuals who may have discrete but 
intense periods of risk, in which daily dosing would be preferable. 
 
Risk among MSM is often episodic, contextual and predictable [17, 18]. We have known for a quarter of a 
century that few MSM report consistent high-risk sex over time [4]. Sexual risk reductions among most 
MSM are unlikely to be permanent, but rather characterized by episodic lapses [4]. Evidence of increased 
behavioral risk associated with travel/vacation has been found in studies of circuit parties. In two recent 
studies, circuit party-goers reported increased substance use, condomless sex anal sex with more 
partners and more serodiscordant condomless sex anal sex during party weekends away from home 
compared to MSM attending circuit parties at home and MSM during typical home weekends. This 
suggests an increased risk both from the party atmosphere and from being away from home [17, 19]. 
Benotsch, et al., found that vacation risk behaviors significantly contributed to HIV acquisition among 
MSM vacationers in Key West [20]. More recently, our group completed a survey on a sexual networking 
site, with more than 9,000 respondents, and found that 76% went on a vacation in the prior year; and 
19.4% of those who vacationed anticipated UAS while away. The median duration of vacations was 7 
days (IQR: 4-10), with 69% reported going on vacation more than once per year. Only 1.9% of those who 
planned UAS during vacation had ever used PrEP. MSM who reported increased UAS on vacation had 
greater odds of indicating that they would take PrEP if it were helpful for short periods (aOR=1.83, 95% CI 
1.49-2.25) [21]. These data support our approach of investigating the feasibility of developing protective 
strategies for one particular time-limited period of episodic risk and that HIV-negative men who take 
vacations in high-risk settings might be a particularly promising group for whom Epi-PrEP is indicated and 
for whom data on Epi-PrEP adherence would prove valuable to guide future combination prevention 
practice.  
 
Risk is also influenced by environmental/structural factors. Millett’s findings that African-American MSM 
experience disproportionate HIV burden not due to individual risk behaviors but because of the 
epidemiological context within which they find sexual partners [22, 23] may be germane to considering 
the consequences of episodic risks among MSM in new contexts. Millett’s analyses highlight the 
importance of the prevalence of uncontrolled HIV replication among the members of a network (CVL) in 
explaining excess HIV burden among African-American MSM, and show that it is the social network in 
which men meet partners that contributes to high HIV infection rates. Several other recent studies also 
suggest complex interactions between neighborhood environments and individual-level identity 
expression and behavior [24-30] that function to raise levels of risk. Sexual scripting (finding sex 
partners/behavior during sex) is also greatly impacted by environment (e.g. space/place, socio-sexual 
networks, perceived norms).  
 
There is evidence suggesting that some MSM may already be identifying periods of risk and self-initiating 
context-specific risk reduction including PrEP. For example, 76% of men in iPrEx who reported URA sex 
had detectable drug levels compared to 36% who had not [31], possibly suggesting a link between self-
identified need (i.e. risk) and use (i.e. adherence) of PrEP. Others have documented PrEP self-initiation 
and ARV sharing [32-36]. Providers in both Pittsburgh and Boston have reported men requesting PrEP to 
use during upcoming vacations [37]. These observations suggest that a program of education about how 
to optimally use episodic PrEP might result in optimal uptake and adherence at a time when 
chemoprophylaxis is most needed.  


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EpiPrEP_DetailedProtocol_3 
 
While promising, there are many barriers and unanswered questions to Epi-PrEP uptake among MSM. 
For Epi-PrEP to succeed, MSM must successfully navigate a set of barriers [38] for which there are no 
intervention protocols. These barriers include: 1) Risk Identification: Men must be able to accurately self-
identify when they are appropriate candidates for Epi-PrEP and then be willing and able and to access it 
through their provider. There are likely several individual (e.g., self-awareness of and stigma associated 
with high-risk behavior, being ‘out’ to providers) and structural (e.g. non-HIV provider awareness of PrEP 
and sexual risk behavior) barriers to achieving this goal. 2) Acceptability/Uptake: Much remains unknown 
about how MSM will respond to Epi-PrEP as a prevention option. The few studies that have been 
conducted have found low levels of PrEP awareness [32-36] and initiation [33, 35]. The limited number of 
studies that have examined interest in PrEP as a prevention option cite affordability [32] and effectiveness 
[36] as major barriers to uptake. Even less is known of attitudes about medication-taking (e.g. 
unwillingness to take any medicine, stigma associated with having “HIV medication”) and dosing 
preferences (e.g. everyday vs. event-based) among high-risk MSM. 3) Cost: Yearly HIV treatment with 
TDF/FTC is costly (≈$1000/month) [39]. PrEP also incurs additional costs such as safety lab monitoring 
(i.e. renal function), HIV/STI testing, adherence/risk counseling and other ancillary services. Current 
cost/effectiveness data suggest that without increased efficacy or a reduction of medication cost, PrEP is 
unlikely to be a cost neutral intervention [40] and is likely to be beyond the means of men who would have 
to cover these costs without insurance. 4) Adherence: Adherence is a key predictor of developing 
successful protection [8, 11, 41] and likely to be one of the largest barriers to effective implementation. 
For community-level PrEP dissemination to have a significant impact on decreasing HIV incidence among 
MSM, an efficacious bio-behavioral intervention will need to address adherence-related issues. Without a 
combined bio-behavioral approach to uptake and adherent use, PrEP will be unable to achieve its full 
promise as an effective tool for HIV prevention.  
 
Several of these challenges may be addressed by shorter-term episodic PrEP. Epi-PrEP could be highly 
effective for HIV prevention [42, 43] while also decreasing medication burden and costs [44], avoiding 
long term drug side effects and adherence fatigue. Furthermore, understanding how to get Epi-PrEP to 
effectively work among MSM will likely have implications on how to better implement PrEP for other key 
populations. A contextually specific frame may help to introduce MSM and the larger community to this 
new prevention technology in a tangible fashion thereby creating a bridge to longer-term interventions for 
those with greater need. The proposed project represents one of the steps on the behavioral PrEP 
agenda.  
 
The Need for Epi-PrEP Biobehavioral HIV Prevention Interventions: PrEP cannot achieve its promise as a 
HIV prevention tool if MSM do not access it or are insufficiently adherent while using it. For some, PrEP 
may be unsuitable for use as a long-term prevention strategy, not only because of the episodic nature of 
risk, but also because of cost issues and concerns about the biological consequences of long-term 
medication use. Thus the development of protocols to support effective PrEP use should begin by 
developing interventions to support appropriate uptake and adherence to Epi-PrEP among men entering 
a temporary period of their life in which their risks for HIV infection are increased. Studying the facilitators 
and barriers to Epi-PrEP use among high-risk MSM is a necessary first step to understanding how to 
support Epi-PrEP uptake. Similarly, MSM who are entering high-risk episodes are an appropriate 
population to study short-term barriers and facilitators to adherent use of Epi-PrEP. By basing the 
creation of new intervention strategies on data that measure both Epi-PrEP uptake and adherence among 
high-risk MSM, we can help ensure that PrEP strategies will reduce HIV transmission among the risk 
group that accounts for nearly two-thirds of all new HIV infections in the U.S. 
 
 
1.3 
SIGNIFICANCE 
This study proposes one of the first attempts to measure the feasibility of episodic context-specific PrEP to 
reduce HIV transmission among MSM. Long term PrEP regimens may be untenable for most MSM, the 
largest (by far) risk group for HIV in the U.S., for reasons having to do with cost, possible drug side effects 
and the fact that many MSM have recurrent but short-term periods in their lives when they are at high-risk. 
Relatively few MSM manifest patterns of very high-risk for long periods of time, thereby making long-term 


Epi-PrEP Detailed Protocol – Intervention v1.0 
EpiPrEP_DetailedProtocol_4 
PrEP unnecessary. Shorter-term dosing for those periods when men are likely to be at high-risk will help 
control toxicity and costs and so be more appealing to MSM. However, whether high-risk MSM are able to 
achieve high-level adherence to medications during periods in their lives when their normal routines are 
disrupted remains unknown. This study will pave the way for the development of an intervention combining 
both pharmacological and behavioral components that would work to lower risk of HIV infection for men who 
are entering a time-limited high-risk period in their lives.  
 
This proposal suggests a novel study to identify the psychosocial characteristics of MSM who report episodic 
high-risk sexual behavior and the likely barriers they will experience to achieve appropriate Epi-PrEP 
presentation. For Epi-PrEP to succeed as an effective public health tool, high-risk MSM will need to do more 
than adhere to the regimen. They will need to be able to self-diagnose the need for Epi-PrEP and to present 
for treatment before entering into a high-risk period. Currently we know surprisingly little about the 
characteristics of men who report episodic risk. This gap in our knowledge also extends to the barriers that 
high-risk men are likely to experience in presenting for Epi-PrEP. This study will pave the way for public 
health campaigns that will help men understand how to appropriately determine when they might use episodic 
PrEP and address barriers they may experience accessing it from health care providers.  
 
HIV behavioral literature has largely emphasized variables at the individual level. This study proposes an 
emphasis on the context within which individuals operate, how a change in context increases levels of risk 
and how episodic PrEP could be used to make movement to unknown or known-risky contexts less risky. 
Although increasing evidence is being produced to highlight the importance of contexts as drivers of HIV risk 
[22, 23], the study of how to intervene in high-risk contexts remains underdeveloped in the HIV prevention 
literature. The use of a combination prevention approach to intervene at the contextual level to lower HIV risk 
adds to the innovation of this research design. By studying whether men can achieve the necessary levels of 
adherence to TDF/FTC during contextually driven high-risk episodes, we will learn a great deal about how to 
field efficacious combination prevention interventions in high-risk contexts. To the best of our knowledge, this 
will be the first study of HIV risk and Epi-PrEP adherence defined to highlight context-specific drivers of risk 
behaviors and drug adherence. 
 
Creating biobehavioral combination prevention approaches may lower HIV incidence among high-risk MSM. 
We have seen that, while effective, behavioral intervention potency may be limited in reducing HIV incidents 
thereby creating demand for additional tools to significantly control the epidemic among MSM. Epi-PrEP 
offers an exciting new tool to reduce HIV infections within the risk group that accounts for nearly two out of 
every three new infections in the U.S. However, Epi-PrEP cannot achieve its promise if men who need to use 
it don’t present for treatment and if they don’t adhere to TDF/FTC during high-risk phases of their lives. 
Unfortunately, our knowledge about how to achieve these necessary goals with this new biomedical 
innovation is limited. This proposed study represents a first step in developing a new bio-behavioral 
innovation to support this new technology in a way that combines clinical (effects of short course medical 
regimens), behavioral (how to optimize short-term adherence), community (assessment of norms related to 
acceptability and patterns of uptake), and cost-effectiveness (optimum length of treatment dependent on risk) 
considerations. 
 
2. SPECIFIC AIMS 
The specify aims and hypotheses to be tested in this research project include: 
 
2.1 Epi-PrEP Trial: Determine the feasibility of clinic-based Epi-PrEP implementation pilot project for up 
to 50 MSM (approximately 25 at each of the two study sites) who report occasional condomless sex and 
who anticipate that they will have a period of high-risk while away from home (e.g. vacation) during the 
study period. To accomplish this we will assess adherence to Epi-PrEP via self-report and drug level 
assessments for the entire period they are prescribed PrEP. Hypothesis: MSM who use Epi-PrEP will 
have varying levels of adherence as measured by self-report and drug levels, and those who are not 
adherent to Epi-PrEP will have multiple psychosocial health problems that will warrant additional 
adherence support. 
 


Epi-PrEP Detailed Protocol – Intervention v1.0 
EpiPrEP_DetailedProtocol_5 
2.2 Qualitative. Identify specific adherence-related contexts and problems, as well as resiliencies that will 
inform the intervention design of a larger scale trial of the efficacy of Epi-PrEP. To do this we will conduct 
qualitative interviews to compare perspectives and experiences of Epi-PrEP adherent (n≈10) and non-
adherent (n≈10) MSM from the implementation pilot. Hypothesis: Adherent and non-adherent men will 
report different themes regarding adherence vulnerabilities (e.g. substance use, lack of schedule). 
 
3. SUBJECT SELECTION 
 
3.1 Inclusion/Exclusion Criteria 
 
3.1.1 Epi-PrEP Trial 
 
INCLUSION CRITERIA 
1. Self-identify as MSM: (1) born male who (2) has sex with men 
2. Age: 18 or older  
3. Sexual Risk: has had condomless anal sex with 2 or more men or any transactional sex with 
a man within the past 12-months.  
4. Vacation: identified an upcoming period of episodic risk away (i.e. vacation) from their home 
city that will last at least 7 but not more than 14 days during which they anticipate having at 
least one high-risk sexual event. 
5. Able and willing to provide informed consent 
 
EXCLUSION CRITERIA  
1. HIV positive 
2. Glomerular filtration rate < 60 mL/min (calculated using the Cockcroft-Gault formula) 
3. Hepatitis B surface antigen positive 
4. Symptoms suggestive of acute HIV seroconversion at screening or enrollment 
5. Have used PrEP or PEP within the previous 3 months 
6. Currently enrolled in another study involving medications, investigational drug, or medical 
device 
7. Has other conditions (based on opinion of investigator or designee) that would preclude 
informed consent, make the study unsafe, complicate interpretation of study outcome data, or 
otherwise interfere with study procedures 
 
3.1.2 Qualitative Interviews 
All participants for the qualitative interviews will be recruited from men who enrolled in the Epi-PrEP trail. 
 
3.2 Source of Subjects and Recruitment Methods 
 
3.2.1 Recruitment.  
 
3.2.1.1 Epi-PrEP Trial 
Participants will be recruited through 1) research assistants (RAs) and study coordinators working with 
treatment providers and 2) advertisements. We will use recruitment techniques previously employed in 
Fenway and University of Pittsburgh studies, including venue outreach (bar, club, cruising areas), community 
outreach, word of mouth from past or present participants in studies, and advertising (print, clinic flyers and 
electronic media). Recruitment for the present study will be done in conjunction with recruitment for other, 
ongoing studies and health promotion activities. Our recruitment efforts, in line with our previous recruitment 
initiatives, will include targeted recruitment of people of color, by adapting our recruitment materials, and 
conducting recruitment drives in minority communities. We have budgeted time for study staff to encourage 
and insure adequate recruitment.  
 
3.2.1.2 Qualitative 
Participants will be recruited from the men enrolled in the Epi-PrEP trial and will be purposively sampled based on 
self-report or biological adherence outcomes. Men will be equally enrolled into a balanced design as adherent 


Epi-PrEP Detailed Protocol – Intervention v1.0 
EpiPrEP_DetailedProtocol_6 
(n≈10) or non-adherent (n≈10). Our goal is to divide interviews as equally as possible between University of 
Pittsburgh and Fenway Health.  
 
 
3.2.2 
Retention.  
The study coordinators will track participant retention, which will be reviewed weekly by the PI or co-PI. As has 
been successful in previous trials with this population, we will collect extensive locator information (such as 
information regarding at least two significant others with whom the participant is in regular contact and 
involvement with AIDS service organizations) for participants. To facilitate retention, if necessary we will meet with 
participants at their homes or any confidential location that is comfortable for them for study assessment visits. 
Additionally, we have budgeted for appropriate financial incentives for participants which correspond to clinical 
visits.  
 
To reduce non-response to the follow-up assessments, we will send text messages and emails, and make phone 
calls prior to the scheduled assessment. At enrollment, participants will be asked to identify individuals to serve as 
locators. Participants will be asked to sign a form letter addressed to each of the locators, which explains that the 
participant is participating in a research project with Fenway Health or the University of Pittsburgh and that they 
have named this person as a locator. Locators will be contacted only if all efforts to reach the participant with the 
provided information failed. Weekly case review meetings will be held among investigators to discuss ways to 
complete contact with the participants when necessary. 
 
4 Subject Enrollment 
 
4.1  
Referral is described above under section 3.2.1.  
4.2 
Screening. Initial screening will be done by the research assistants or other study administrative 
staff. The initial screening will occur either over the telephone or in person using attached phone screen. 
If the participant appears to be eligible and is interested, he will be scheduled for an informed consent 
and screening visit. 
4.3 
Informed Consent. Informed consent will be obtained by the interventionist or other study staff. 
Every participant will read or have read to them a statement of informed consent which includes all of the 
study procedures, information about potential risks and benefits of participation, and information 
regarding who they can contact for further questions. Before any other study procedures take place, each 
participant will read and review the Informed consent with study staff and allowed time to ask any 
questions they have before signing the form. After completion of the informed consent form, the 
participant undergoes the screening diagnostic evaluation. At the end of the diagnostic assessment, the 
participant is asked again about study participation. 
5.0 Study Procedures 
 
 
5.1 
Study Visits 
 
Schedule of Study Visits 
Time Period 
Type of Visit  
Assessment 
Compensation 
Pre-Trip 
2+ weeks pre-trip 
Phone 
Screening 
Establish basic eligibility requirements 
NA 
At least 2 weeks 
pre-trip 
Clinical 
Baseline 
Full assessment battery, safety labs, 
STI screening. Online behavioral 
interview 
$25  
At least 1 week 
pre-trip 
Epi-PrEP 
enrollment 
Review labs, dispense Epi-PrEP, 
counseling 
$25  


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EpiPrEP_DetailedProtocol_7 
Trip 
7-14 days away 
NA 
NA 
NA 
Post-Trip 
1-3 days post-trip 
Clinical Post-
Trip Follow-up 
TFV concentrations, STI screening, 
safety labs, online behavioral 
interview.  
$25  
3 months post-
trip 
Final Clinical 
Safety labs, STI testing if 
symptomatic, online behavioral 
interview. 
$25  
6 months post-
trip 
Final Survey 
Online behavioral interview emailed to 
participant to be completed outside 
the context of an office visit.   
NA 
 
5.1.1 
Phone Screening 
Phone screening to determine eligibility will be completed by study coordinator or recruiter. 
 
FORMS TO COMPLETE 
1. Phone screener  
 
5.1.2 
Visit 1: Clinical Screening 
1. Informed Consent: prior to any research-related activities, subjects must read or have read to 
them a statement of informed consent. Subjects must understand and sign this statement.  
2. Medical History: general medical history including pre-existing medical conditions, prior 
hospitalizations, current medications (including over-the-counter medications and nutritional 
supplements), any known medication allergies or intolerances. 
3. Physical examination:  this will include: vital signs (temperature, blood pressure, pulse rate 
and respiration rate) and a symptom-directed examination, i.e., examination of body systems 
in which the subject reports active symptoms. 
4. Questionnaire: See Section 8 for more detail. 
5. HIV risk reduction counseling:  will include a discussion of how HIV antibody and antigen 
testing is conducted, the “window period” of seronegativity following HIV exposure, methods 
of HIV transmission and means for avoiding exposure and/or transmission (“safer sex”).  
6. Laboratory Testing: 
a. Mandatory: 
o 
4th generation HIV-1 ELISA 
o 
Hepatitis B Panel: Hepatitis B surface antigen (only if not done within the past 
month) 
o 
Creatinine (calculate creatinine clearance estimated by Cockcroft-Gault equation) 
o 
STI Testing 
o 
Syphilis serology 
o 
CT/GC Urine NAAT 
o 
CT/GC Cx - Anal 
7. Refer to Mental Health provider on call if appropriate (e.g. suicidality, severe depression) 
8. Make appointment for Visit 2 
9. Obtain Locator Information 
    
FORMS TO COMPLETE 
1. Consent Form 
2. Locator Form 
3. Medical Release Form  
4. Medical History Form 
5. ROS/Physical Exam Form(s) 
6. Con Medication Log 


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EpiPrEP_DetailedProtocol_8 
7. Eligibility Checklist 
8. Creatinine clearance log 
9. Clinical Screening Checklists: RA and clinician 
 
5.1.3 
Visit 2: Epi-PrEP Enrollment  
1. Disclosure of results from Visit 1; exclusion from study if HIV-infected and referral to primary 
care/infectious diseases 
2. Review of systems (symptom-directed physical exam if indicated) 
3. Review concomitant medications 
4. Medications dispensed. Participants will receive TDF 300 mg/FTC 200 mg in fixed dose 
combination (Truvada®), to be taken once daily. Subjects will be given 30 tabs in the original 
bottle and will be asked to return any unused tabs to study staff at their 3 month visit.  
5. Refer for Hepatitis B Vaccination if seronegative; excluded from study if there is evidence of 
current Hepatitis B infection  
6. If participant consents, send provider letter indicating TDF/FTC prescription. 
7. Adherence intervention session  
8. Make appointment for Visit 3. 
 
FORMS TO COMPLETE 
1. ROS 
2. Update Con Med log 
3. Dispensation log 
4. Enrollment Visit Checklists: RA and Clinician 
  
 
5.1.4 
Visit 3: Clinical Post-Trip Follow-up 
1. Recording of adverse events and concomitant medications 
2. Review of systems (symptom-directed physical exam if indicated) 
3. Questionnaire: See Section 8 for more detail. 
4. Laboratory Testing: 
a. Mandatory: 
i. Kinetic drug level assay  
1. Collect samples for both PBMC and plasma analyses 
ii. 4th generation HIV-1 ELISA 
iii. Creatinine (calculate creatinine clearance estimated by Cockcroft-Gault equation) 
5. Make appointment for visit 4. 
6. Refer to Medical Department for STD testing if symptomatic 
 
 
FORMS TO COMPLETE 
1. ROS 
2. Update Con Med log 
3. Update AE log 
4. Update creatinine clearance log 
5. Visit 3 Checklists: RA and Clinician 
 
5.1.5 
Visit 4: 3 Month Follow-up study visit 
1 
Recording of adverse events and concomitant medications 
2 
Review of systems (symptom-directed physical exam if indicated) 
3 
Questionnaire: See Section 8 for more detail. 
4 
Laboratory Testing: 
a. Mandatory:   
o 4th generation HIV-1 ELISA  
o Creatinine (calculate creatinine clearance estimated by Cockcroft-Gault equation) 
5 
–Refer to Medical Department for STD testing if symptomatic 
a.  


Epi-PrEP Detailed Protocol – Intervention v1.0 
EpiPrEP_DetailedProtocol_9 
 
FORMS TO COMPLETE 
1. ROS 
2. Update Con Med log 
3. Update AE log 
4. Update creatinine clearance log 
5. Visit 4 Checklists: RA and clinician  
 
5.1.6 
6 Month: Final Online Survey 
Participants will be emailed a link to complete a final online survey. This survey will be implemented 
using the Qualtrics system allowing participants to log in and complete the survey from anywhere with 
Internet connectivity, including desktop and laptop computers and mobile devices. The electronic survey 
will be designed to take approximately 20 minutes. Data will be submitted anonymously through a secure 
system developed for previous collaborations accessible only to the PIs and study staff. Participants will be 
given a unique link which will allow us to link responses to study PTID. 
 
5.1.7 
Qualitative interview Visit 
 
To minimize participant burden, the qualitative interview visit can be either a standalone visit or 
added to the three month study visit. This in-depth qualitative interview will last approximately 90 min. For 
information on selection of participants for the qualitative interview see Section 3.2.1.2. For detail on 
content see attached interview guide as well as Section 8.2. 
 
5.1.8 
Interim Visits 
Interim visits may occur at any time during the study. Interim visits may occur for the following reasons: 
(1) for operational reasons, e.g., a participant may request to reschedule, or to ask questions; (2) for 
product-related reasons, e.g., a participant may need additional study product or want to discuss 
problems with adherence to product use; (3) for AE-related reasons. When interim contacts or visits are 
completed in response to participant reports of AEs, study staff will assess the reported event clinically 
and provide appropriate medical care or make appropriate referrals; (4) for interim STI counseling and 
testing in response to STI symptoms. (5) if a participant presents to the study site after having missed a 
scheduled visit (e.g., in response to locator/tracing efforts) on a day that does not fall within a scheduled 
visit window; (6) if a participant is experiencing symptoms suggestive of acute HIV infection; or, (7) for 
other reasons at participant request. Subjects with symptoms consistent with acute HIV infection 
syndrome will receive diagnostic testing to attempt to elucidate the cause of the syndrome, including rapid 
testing for HIV RNA and additional tests as medically indicated. Subjects will be taken off of study drug if 
they have any reactive rapid HIV antibody test. All interim contacts and visits will be documented in 
participants' study records and on applicable CRFs. 
 
5.1.9 
HIV Seropositive Visits 
Men who are found to have a reactive HIV antibody test during the study will be instructed to stop the 
study drug immediately. After confirmatory HIV serology, individuals with confirmed HIV infection will be 
referred for HIV care.  
 
5.1.10 Participant Replacement policy 
If a participant does not complete the post-vacation visit (within 7 days of returning from vacation), they 
will be considered lost to follow up and may be replaced in the study with another participant. Those who 
enroll but do not go on vacation may also be replaced. Participants who are unable to attend an 
enrollment visit and acquire study product at least 7 days prior to their vacation will be excluded and 
replaced. 
 
5.1.11 Reimbursements 
Participants will receive a monetary remuneration in the amount of $25 at the end of each scheduled 
office visit including: Visit 1: Clinical Baseline; visit 2: Epi-PrEP Enrollment; visit 3: Post Trip; and visit 4: 3 
Month Follow-up. A light snack and refreshment may be provided. Participants will not be compensated 
for completing the online survey emailed to them at the 6 month time point (see Section 5.3.6). To 


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EpiPrEP_DetailedProtocol_10 
encourage participants to take this survey, we will enter all participants who complete this survey in a 
drawing to win a $50 Amazon.com gift card. The drawing will take place at least 7 months after the last 
active participant’s enrollment date. Each site will have its own drawing for participants who completed 
study visits at that site; two drawings in total will occur.   
 
Participants who are selected for the qualitative interview and complete that interview will be 
compensated $50 for their time. If the qualitative interview occurs the same day as an existing visit, this 
compensation will be in addition to the compensation the participant was otherwise entitled to.  
 
5.1.12 Interface with Electronic Medical Record – Fenway only 
For participants who are seen at Fenway Health, after obtaining bi-directional Medical Record release, 
study staff will interface with the Electronic Medical Record. Study staff will review the participant’s EMR 
at screening to obtain concomitant medications and pre-existing conditions. Study staff will alert the 
participant’s provider of participation and that the patient has been prescribed Truvada. Study staff will 
also notify the participant’s provider of laboratory results.  
 
5.1.13 Interface with outside providers   
With their consent and a signed medical release, patients will have a letter sent to their primary care 
provider discussing their involvement in the study. The letter to providers will alert the physician to their 
patient’s new prescription: Truvada™. The letter will state that involvement does not preclude any regular 
HIV risk reduction strategies they may have been working on. In our prior work, sending this letter has not 
adversely affected study outcomes. Study staff will notify the participant’s provider of clinically relevant 
laboratory results. 
 
6.0 Study Agents and Pharmacy 
 
6.1 
Truvada™ 
Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) is a fixed-dose co-formulation of FTC and TDF 
prescribed for daily administration. Each FTC/TDF tablet contains of 200 mg of FTC and 300 mg of TDF 
(equivalent to 245 mg of tenofovir disoproxil). All study products will be supplied by Gilead Sciences (Foster 
City, Ca). More detail about Truvada provided in the most recent package insert for the drug, attached. 
 
6.2 
Pharmacy Facility  
Fenway Health: The pharmacy facilities will be located at the study site and staffed by credentialed 
pharmacists. The pharmacy will have adequate space to store sufficient quantities of study agent to assure 
access to all study participants. The study drug will be stored in accordance with the drug manufacturer’s 
recommendations. The study pharmacy will be locked by a secure door and will be accessed only by the 
pharmacy staff. The pharmacy is a climate-controlled environment, with temperature controlled to remain 
within limits allowed by the manufacturer for drug storage. 
 
University of Pittsburgh: Investigational Drug Service Pharmacy (IDS):  The main IDS pharmacy, used 
primarily for ACTG studies, is located in UPMC Presbyterian University Hospital (PUH), approximately 
one block from the research clinic, connected by an interior walkway.  The IDS has two offices for staff, 
each with computers, printers, desks, shelves, and a fax machine for IDS employees.  The main 
pharmacy room is approximately 22 X 17 feet.  An additional pharmacy room and storage space are 
located at Montefiore University Hospital Pharmacy, located one block from UPMC-PUH and connected 
by an interior walkway.  The investigational drug storage area is maintained at a temperature of 72°F. A 
continuous temperature monitoring system for the ambient temperature and relative humidity is in 
operation at all times. The unit is on battery back-up.   All refrigerators and freezers have temperature 
sensor alarms that are monitored 24 hours daily. 
 
6.3 
Study Drug Accountability 
The site pharmacist is required to maintain complete records of all study products received from Gilead 
Sciences and subsequently dispensed to study participants. The pharmacist at the study site will receive 
the study agent and store it in the pharmacy. Access will be restricted to pharmacy personnel authorized 


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EpiPrEP_DetailedProtocol_11 
by the pharmacist of record. The pharmacist will be responsible for keeping accurate records of the 
material received. At the end of the study, the pharmacist will perform the final drug accounting of unused 
study material on the proper log documents. Unused study agent will be disposed of as instructed by the 
Principal Investigator and by study agent manufacturer. 
 
6.4 
Study Drug Dispensing  
A study nurse will be responsible for dispensing the drug to each study participant. The pharmacist will 
receive the prescription that includes the participant’s ID number. For each bottle dispensed, the pharmacist 
will enter the bottle label information and date in a Drug Dispensation Log. Dispensation of all study products 
to study staff and distribution to participants will follow the institutions SOP on Study Product Chain of 
Custody. 
 
6.5 
Replacing Study Drug 
Lost or misplaced study drug will be replaced at the discretion of the site PI after the study team has 
reviewed the case with him. 
 
6.6 
Toxicity 
Per the inclusion/exclusion criteria, individuals with pre-existing renal disease (GFR <60) will not be 
enrolled in the study. Those who are hepatitis B seronegative will be referred to receive vaccination. 
Participants with chronic hepatitis B (Hepatitis B surface antigen) will be excluded from the study for their 
own safety. Any participant who develops a Grade III toxicity per the DAIDS Adverse Event Tables will 
have medication held, and only restarted after a full clinical assessment, including consultation of the 
study clinicians with the principal investigator. Participants with Grade IV or recurrent Grade III toxicities 
will have medication discontinued, and referred to primary care for follow up.    
 
7.0 Adherence Intervention 
 
7.1 
Nurse-administered adherence and sexual risk CBT. Intervention participants will undergo a 
single session CBT-based intervention at visit 2: enrollment (guide attached). The intervention will involve 
a series of cognitive-behavioral and problem-solving steps. Including the following sections: 
1. Psychosocial assessment (10 minutes) 
2. PrEP psychoeducation (10 minutes) 
3. Brief motivational interviewing (5-10 minutes) 
4. Making a plan for adherence/forgetting (5 minutes) 
5. Barriers to adherence (5-10 minutes) 
6. Closing  
 
This adherence intervention is designed to first get to know the participant through a conversation about 
general information about PrEP and the rationale for the counseling including: 
 
Daily routine. This will include a general discussion of the participant’s sexual behavior, sexual 
history, and general patterns regarding unsafe sex. 
 
Educational information about PrEP, coping with side effects. The counselor will go over a “fact 
sheet” regarding PrEP and the rationale behind adherence to PrEP. This will be basic educational 
information about PrEP adherence and will serve as a basis for motivational interviewing and 
problem solving. It will also include a discussion about taking PrEP daily versus intermittently. 
Additionally, tips for coping with side effects and information about their expected course of 
medication will be discussed. 
 
We will then turn to motivational interviewing about staying PrEP adherent. Accordingly, the nurse 
interventionist will ask about PrEP motivations, as well as complete a pros and cons exercise about PrEP 
adherence. Following motivational interviewing guidelines, the nurse will ask about the advantages and 
disadvantages of both “not adhering” as well as adhering to PrEP. The interventionist will then ask the 
participant to rate how motivated they are to be adherent to PrEP and will subsequently have a 
discussion about why the participant made the rating, and a discussion about what it would take for them 
to be even more motivated. Again, this will be a basis for the problem-solving steps to come, and the 


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EpiPrEP_DetailedProtocol_12 
interventionist will be particularly sensitive to issues regarding social capital or social roles. This step will 
address the issue of taking medication for preventative as opposed to treatment purposes, which may 
play a role in PrEP adherence for men in the study. 
 
Next, the conversation changes to focus on making a plan for adherence/forgetting. The counselor will 
work with the patient to establish a daily dosing time based on the patient’s preferences (keeping in mind 
the relationship between dosing time & side effect management), and when it can be linked to a daily-
occurring behavior. 
 
The counselor will then focus on barriers to PrEP adherence and problem solving. They will review a list 
of potential barriers to PrEP adherence. For each issue, following principles of CBT problem-solving, the 
counselor will assess what potential problems could emerge with each issue, and discuss whether the 
participant has a current plan and backup plan for each.  
 
The following preliminary list of topics will be addressed, although the relative emphasis on the different 
topic areas will be adjusted accordingly: 
 
Daily schedule and weekend schedule. This discussion will involve reviewing with the 
participant the times when PrEP can be most reliably taken, and will include a discussion, again, 
of the timing of PrEP in relation to potential sexual risk episodes. 
 
Substance use. This will involve learning about the participant’s current substance use patterns 
and how that will interact with taking PrEP. As needed, additional referrals will be made for 
detoxification or other substance abuse services. Potentially, motivational interviewing will be 
used regarding assessing the participant’s readiness to use specific services. 
 
Meeting sexual partners and pill taking. This will involve a discussion of how the participant 
meets sexual partners in general, and how to continue daily PrEP use within the context of 
sexual episodes. 
 
Reminder strategies. This will involve having a reminder strategy for PrEP, such as 
programming a reminder on a cell phone alarm, which will be based on the preference of the 
participant. 
 
Need to take PrEP even if not currently sexually active. One potential problem may occur if 
participants decide that they are not going to be sexually active and thus do not need PrEP, but 
then have episodic risky sex during a period when they have discontinued PrEP or are non-
adherent. Given that data demonstrating the efficacy of intermittent PrEP are unlikely to emerge 
for several years, in the current study, we will work with participants to make a plan for using 
PrEP on a daily basis using strategies such as motivational interviewing and planning for 
unforeseen sexual experiences. 
 
Generation of a list of potential barriers, and problem solving to overcome each barrier. 
The interventionist will query the participant for additional potential barriers to PrEP. Similar to 
steps above, a plan and backup plan will be generated for each. 
 
Finally, the counselor will: summarize the content of the session; review the adherence plan(s); 
review back-up plan(s); and review the plan should side effects emerge. The session will end with 
time for the participant to ask any further questions. 
 
8.0 Data Sources 
 
 
8.1 
Epi-PrEP Trial 
 
 
8.1.1 
Adherence 
Adherence will be measured both by self-report and from biological assays.  
 
8.1.2 
Behavioral assessments 
 
TABLE 3: Proposed Constructs, Domains, and Scales of Clinical Visit and Surveys for Implementation Pilot 
Construct 
Study Visit 
Description 


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EpiPrEP_DetailedProtocol_13 
 
8.1.3 
Clinical symptoms 
Clinical symptoms will be systematically assessed in a structured medical history at every in-person study 
visit. Clinical side effects of FTC/TDF that have been reported are primarily gastrointestinal, including 
nausea, vomiting, and flatulence. The severity of clinical symptoms will be scored using the DAIDS Table 
for Grading the Severity of Adult and Pediatric AEs, Version 2.0, November, 2014 (DAIDS AE Grading 
Table which can be found at http://rsc.tech-res.com/safetyandpharmacovigilance/gradingtables.aspx). 
 
8.1.4 
HIV-1 Antibody Testing and STI Testing 
Participants will be tested for HIV using a 4th generation HIV-1 ELISA test at Visits 1, 3, and 4. Frequent 
HIV testing is an important part of safety monitoring because the medications prescribed for PrEP would 
not be sufficient compared to the usual three-drug regimens prescribed for treatment, and the potential for 
medication resistance could emerge.  
 
8.1.7 
Creatinine 
Blood for creatinine clearance will be drawn at major study visits (visit 1, 3, and 4) to determine eligibility 
and monitor for safety.  
  
8.1.8 
Hepatitis testing and HBV management 
All participants will undergo testing for HBV virus (HBV) at the screening visit. This will include tests for 
HBV surface antigen (HBsAg). Those who are hepatitis B seronegative will receive referral to be 
vaccinated as indicated. Participants with chronic hepatitis B (HBsAg positive) will be excluded from the 
study. 
 
8.1.9 
Study agent drug level assay 
To better understand patterns of pill taking, PMBC samples will be collected at visit 3 for assays for 
intracellular levels of tenofovir. PBMC will be processed and stored off site and will be batch shipped to 
Hopkins lab for analysis. Blood serum samples will also be collected at visit 3 and frozen. These frozen 
serum samples will be stored for consideration for other drug level detection assays in the future.  
 
These samples will not be analyzed until all active study participants have concluded visit 3. 
 
 
8.2 
Qualitative Interviews 
Domains to be included in the qualitative interviews are outlined below. The full interview protocol is 
attached. 
 
SURVEYS  
Demographics 
Baseline 
Data to characterize the sample (e.g. ethnicity, age, sexual orientation) 
Implementation 
Final 
Extent to which part. received and satisfaction with key study elements  
Theory of Planned Behavior Variables 
PrEP Knowledge & 
Perceptions 
Baseline, 3M, final 
Knowledge of PrEP, how it works, how to take it, community perceptions 
PrEP Uptake Barriers 
Baseline, 3M, Final 
Willingness (e.g. stigma of HIV medication, slut stigma), Access (e.g. availability, cost, not out 
to MD, unwilling/unknowledgeable MD)  
PrEP uptake  
Baseline, post-trip 
Baseline = perceptions about using PrEP, Post-Trip = experience with PrEP 
PrEP Intentions 
Baseline, post-trip,3M,  final 
Bridge to Successive and/or Longer Term PrEP, perceptions of future use  
Syndemics Variables 
Psychosocial 
Baseline 
Syndemics and resiliency production, planned behavior  and other psychosocial measures  
Sexual Risk Behaviors 
Baseline, post-trip 
Freq. of sex and URAI/UIAI: substance use during UAI: Sexual Partners: No. of partners by 
partner type (main, casual, trading) & perceived HIV status. Serosorting. Condom use  and self-
efficacy scale (CUSES). Past 6 mos/on vacation. 
Substance Use 
Baseline, post-trip, 
Type, frequency, and self-perceived problem use. Type and frequency of substance and 
alcohol use. Past 6 months and on vacation. 
Dependent Variable 
Adherence  
Post-trip  
Self-reported number of missed doses. 
TABLE 4: Qualitative Interviews: Proposed Constructs and Sample Questions 


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EpiPrEP_DetailedProtocol_14 
 
8.3 
Audio Recordings 
 
All counseling and qualitative interview sessions will be audio-recorded and may be reviewed by study 
staff, such as, therapists who assist with the development of the intervention, or therapists who are 
learning to deliver the interventions.  This is to help insure that the interventions are designed well and 
improved upon as needed, and to insure that the each participant receives the same level of care.  
Recordings may also be transcribed onto paper and reviewed to look at potential themes or concerns 
among participants, further helping to shape future interventions.  Names mentioned on the tape will be 
removed prior to analysis.  Recordings will be identified by a study identification number only, and will be 
stored at The Fenway Institute in a secure, locked file cabinet and/or a password-protected folder on an 
electronic server.  Recordings will be retained for seven years and then destroyed.  Participants may elect 
not to have their sessions audio-recorded and still participate in the study.  Additionally, they may ask to 
turn off the recorder at any point during the sessions.  
 
9 
Biostatistical Analysis  
 
9.1 
Overview 
The primary analysis will be an assessment of feasibility as measured by self-reported and biological 
markers of adherence. While biomarkers will give a more accurate measure, the self-reported data will 
provide insight on participant perception of adherence. Inconsistencies will be followed up on during the 
qualitative interviews. Primary analysis will again begin with describing the characteristics of the men in 
the sample. The appropriate parametric or nonparametric test will then be used to compare groups. To 
the extent possible logistic regression will be used to look at predictors of adherence including the impact 
of psychosocial burden (e.g. substance use, depression) on being able to remain adherent. While the 
limited sample size will limit our ability to determine significant effect sizes, it will allow for exploratory 
analysis of trends to explore in more depth in the qualitative interviews. 
Construct 
Description 
Example Questions 
PrEP 
attitudes 
Pre-post individual attitudes 
and community norms 
about PrEP and Epi-PrEP 
In what ways has your view of PrEP changed or remained the same? How does Epi-
PrEP impact your overall opinion of PrEP? What do your friends think of PrEP? What 
will you tell them about your experience? 
PrEP 
uptake 
Epi-PrEP experience and 
pre-post barriers and 
facilitators to uptake (e.g. 
stigma, vacation activities, 
only long term option) 
What were your attitudes to using PrEP/Epi-PrEP before you enrolled? What were the 
attitudes about using PrEP/Epi-PrEP among your friends? What are some of the 
barriers to deciding to use PrEP (probe: only long term option, HIV medication stigma, 
slut stigma, vacation activities)? How have your attitudes changed since using Epi-
PrEP? What would increase the likelihood that you – or your friends – would be more 
willing to use PrEP? 
Adherence 
Barriers and facilitators to 
adherence, explore any 
inconsistencies between 
self-report and biomarkers  
What made it easy or difficult to take the pill everyday (probe: familiarity with daily 
medications, context)? How was it different taking the medication before your trip, 
during, after? What did/would have helped you maintain better adherence (probe: 
what kinds of support, technology?). Your perceived adherence was different than 
what we found in your blood, can you tell me more about what you self-reported 
(probe: real perception, wanted to look good)?  
Episodic 
Risk 
Behavior 
Behaviors at home and on 
vacation (e.g. substance 
use, partner selection, 
condom use, serosorting) 
impact of Epi-PrEP) 
Tell me about your vacation (probe: where, with whom, activities). More specifically 
now, lets talk about sex, alcohol/drugs, and HIV risk (probe: partners, activities, 
condoms). How was sex different on vacation vs. how it usually is at home (probe: 
people, places, activities)? How did being on Epi-PrEP influence your behaviors? 
How did your behaviors influence your Epi-PrEP adherence?  
Future 
PrEP 
intention 
Bridge to successive and/or 
longer term PrEP, other 
episodic risk periods 
How do you imagine using PrEP in the future? In what contexts would you/would you 
not? Other than vacations, tell me about other episodic risk periods that you or your 
friends have experienced where Epi-PrEP may have been an appropriate HIV 
prevention tool.  
Intervention 
design 
Perception/satisfaction with 
current key study elements. 
Thoughts on intervention 
design, components, 
dissemination. 
Thinking back to what you said about adherence, what thoughts do you have on 
designing an Epi-PrEP adherence intervention (probe: components, format, length, 
think about guys who may get this from their PCP – what would they need to know)?  


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EpiPrEP_DetailedProtocol_15 
 
9.2       Adherence outcomes  
As determined from biomarkers, adherence will be defined either a dichotomously including: Determined 
protective drug level (previous studies determined this to be 90% adherence) during episodic period or 
determined non-protective drug level). Or, categorically as follows: 1) Good adherence: detection of 
normal drug levels, indicating protective level of drug taken in the prior week. 2) Poor adherence: 
detection of below normal tenofivir diphosphate (TFV-DP) in PMBC. 3) No adherence: no detection of 
drug, indicating no drug taken in the prior week.  
 
 
 
9.3 
Qualitative Interviews 
Transcripts and notes will be analyzed using NVivo (v.11) to explore preexisting based on the theoretical 
contexts from which the interview guides will be developed and emergent themes. Content areas that we 
propose to address include: 1) general thoughts and feelings about PrEP and Epi-PrEP (before/after 
use); 2) an in-depth exploration of the Epi-PrEP; 3) adherence barriers/facilitators; 4) risk behaviors 
related to vacation and PrEP; 5) future PrEP intentions; 5) thoughts on intervention design/components. 
Once the interviews are transcribed, we will use two strategies, contextualizing and categorizing, to 
analyze the data [69-71]. First, the interviews will be summarized in a “digest” that identifies the major 
themes of the interview. Next, we will conduct coding, a categorizing strategy that facilitates comparisons 
within and between analytic categories that describe the data, in three steps. First, based on the 
summaries and recordings read and listened to by Stall (PI) and Egan (PD) will compose a list of analytic 
areas (code list). Second, Stall and Egan will reread the summaries and listen to the recordings and 
identify chunks of text to be given a descriptive label (either a label from the closed code list or an original 
one). Where necessary, summaries will be expanded to include data related to new codes; expansion of 
summaries may involve selective verbatim transcription of additional key segments of interviews. Next, 
the open-coded data will be organized under and integrated into the closed code list. Third, the data 
under the codes of particular interest will be re-read and recoded into sub-categories in order to refine the 
analytic categories [70]. Based on these results, we will develop a number of items, not already reflected 
in our current battery of measures. A minimum of 5 transcripts will be coded by 2 coders and compared 
for consistency. Results will be discussed with the research team and community volunteers to triangulate 
and validate the findings.  
 
9.5 
Sample Size and Power.  
The primary focus of Aim 2 is the feasibility of providing short-term fixed interval episodic PrEP (Epi-PrEP) 
as measured by adherence. With the small sample size, power is limited. To find statistical significance, 
the effect sizes would need to be large. As such, we will focus on descriptive characteristics of different 
adherence groups and predictive trends, rather than significant effect sizes, which will be explored in 
greater depth in the qualitative interviews.  
 
While there is no way to determine the necessary sample size for qualitative analysis, we feel that with 
N=20 (40% of pilot sample) we will be able to reach saturation on the key questions. As is the power of 
qualitative work, we also believe that important findings can be gained from the insight and/or 
disagreement of a small number of men. 
 
10  
Risks and Discomforts 
 
10.1 
Complications of Surgical and Non-surgical Procedures, etc. 
     
Not taking the study drug as prescribed. Because the only FDA approved indication for the use of 
TDF/FTC as PrEP is by oral daily administration, participants will be instructed to take the study drug 
daily. However, it is unclear how suboptimal adherence will affect the effectiveness of the drug. 
Participants will be told that in the iPrEx study, less adherent participants had a greater risk of becoming 
infected. 
 


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EpiPrEP_DetailedProtocol_16 
Mistakenly believing that the study drug may confer complete protection against HIV/STI: As a 
result, participants could increase their sexual risk behaviors while in the study. 
 
10.2 
Drug Side-effects and Toxicities 
As a result of taking the FTC/TDF regimen, some of the participants could experience transient nausea 
(which may last a few weeks), loss of appetite, renal dysfunction (which is almost always reversible when 
the product is stopped), accelerated bone loss after long term use, or a flare up of chronic hepatitis B 
infection when medication is suddenly discontinued. Laboratory monitoring and symptom-directed 
physical exams will detect major adverse events. Drug will be held for drug related Grade II or any new 
Grade III or IV events, and referral will be made to PCP for ongoing monitoring. 
 
10.3 
Device Complications/Malfunctions 
There are no biomedical devices used.  
 
Participants will be asked to use either their own or a provided computer to answer surveys. Reminders of 
scheduled visits will be sent both via phone and/or email.  
 
10.4  
Psychosocial (non-medical) Risks 
The interviews and assessments will involve discussions on personal matters, such as sexual behavior, 
and talking about these matters may make participants feel uncomfortable, embarrassed, upset, tired, or 
anxious. Furthermore, there is a risk of violation of confidentiality. Participants who are enrolled in the 
study will be evaluated for level of sexual risk. Those enrolled will be determined to be at higher risk for 
acquisition of HIV (i.e., have engaged in condomless sex anal intercourse receptive or insertive in the 
three months prior to enrollment). There is a potential that enrolled subjects will be stigmatized if they 
reveal their involvement with the study or in some other way become associated with the study (e.g., 
social harm). 
 
Participating in a counseling study for adherence can be difficult, because it may involve discussing 
personal matters. Another focus of the study is sexual risk-taking, which may be a difficult or 
uncomfortable topic at times. It is possible that participants will feel embarrassed or uncomfortable, 
particularly while discussing issues of a personal or sexual nature. In addition, a participant may become 
worried or uncomfortable from thinking about their non-adherent or sexual behaviors, and it is possible 
that participants may find some of the questions asked in the risk assessment to be emotionally upsetting. 
Likewise, the behavioral intervention may involve discussion of other emotionally upsetting topics. 
However, the risk to the participant is no greater than other standard counseling relationships. 
Participants are free to refuse to answer any question and may terminate participation in the study at any 
time. All information disclosed to the researcher will remain confidential if the participant chooses not to 
complete the study. Moreover, the participant can ask study staff to provide him with referrals to 
counselors or other means of support. Participants will have access to a licensed clinical psychologist and 
other Masters-level counselors who can help them deal with any feelings and/or questions they have 
which arise. 
 
With their consent and a signed medical release, patients will have a letter sent to their primary care 
physician discussing their involvement in the study. The letter will state that involvement does not 
preclude any regular HIV risk reduction strategies they may have been working on. In our previous 
studies, sending this letter to providers has not adversely affected study outcomes; however, whenever 
participant information is shared there is a risk of loss of confidentiality.  
 
As in any study, there is always risk of an inadvertent breach of confidentiality. Fenway and Pitt have 
been involved with numerous local, national, and international studies of persons with and without HIV 
and have considerable experience implementing measures to protect confidentiality. Some of these steps 
include signed confidentiality agreements, in-service trainings on confidentiality, and the assignment of 
study ID numbers. Staff at Fenway and Pitt who conduct participant recruitment, screening, enrollment, 
HIV testing, and assessments will have been trained in ethical human subjects research and screening 
and interviewing techniques to minimize participant risk as much as possible. 


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EpiPrEP_DetailedProtocol_17 
 
10.5       Radiation Risks (statement provided by Radiation Safety Committee) 
Not applicable. 
 
11  POTENTIAL BENEFITS 
 
11.1    Potential Benefits to Participating Individuals 
All participants will receive the study drug, which, if taken as prescribed, has been shown to reduce the 
risk of acquiring HIV among high-risk MSM. In addition, some participants may have the opportunity to 
access expedient treatment and decreased morbidity due to early diagnosis and treatment of 
abnormalities in biological tests. Finally, participants may appreciate the opportunity to contribute to the 
body of knowledge in the field of PrEP research.  
 
Previous interventions using behavioral skills enhancement for adherence that are individualized to 
participants’ needs have shown success in helping patients increase their adherence to medication. All 
participants will be actively tracking their adherence to the study drug, sexual behavior, substance use, 
and mental health needs by completing major assessments at visits 1,3,4, and 5.  
 
PrEP has been shown to decrease incident HIV infections, but adherence has been suboptimal, impeding 
the full benefit of the medication. This project is innovative because by combining an evidence-based 
behavioral intervention with the provision of PrEP in clinical settings, a combined biobehavioral 
intervention that targets adherence is likely to be an effective strategy to reduce new HIV infections 
among MSM, which can have public health implications insofar as it may help to curb new HIV infection 
rates among MSM. Thus, the anticipated benefits have been determined to outweigh the minimal risks 
involved with participation in this study. 
 
11.2   Potential Benefits to Society  
HIV is a serious, incurable disease that can be spread, among other behaviors, through condomless 
insertive and receptive anal sex. PrEP has been shown to reduce the risk of HIV acquisition among high-
risk MSM. However, low rates of adherence have hampered the protective effects of the medication. 
Further understanding the reasons behind low adherence rates for PrEP among high-risk MSM and 
addressing them in a tailored intervention may positively impact the rates of PrEP adherence and 
ultimately reduce the number of new HIV infections. 
 
12 
Quality Assurance 
 
12.1 
Overview of study design 
Up to 50 participants in total will be enrolled in the Epi-PrEP trial and offered PrEP for the duration of their 
upcoming vacation. All participants will complete an informed consent process before entry into the study. 
This will include completing the informed consent form and reviewing all study procedures verbally with 
the investigator or designee. During future study visits, participants will be asked about any further 
questions or concerns about informed consent. An administrative record of any informed consent issues 
that occur after the initial informed consent procedure will be maintained, and the PI or designee will 
review all informed consents within one week of their completion. Participants are provided compensation 
for all scheduled in-office visits. 
 
Because the use of TDF/FTC as PrEP has been FDA approved since July 2012, and subsequent studies 
have monitored patients for long periods of time, we do not feel a data safety and monitoring board 
necessary for this project. As outlined in this protocol, we will follow standard of care in prescribing PrEP 
and monitoring safety. 
 
12.2 
Data monitoring 
Data collection will occur in the form of: (1) diagnostic and clinical assessments, (2) self-report 
assessments administered by computer, and 3) biological tests. A quality management plan will be 
developed to specify daily quality control and monthly quality assurance measures. This will also ensure 


Epi-PrEP Detailed Protocol – Intervention v1.0 
EpiPrEP_DetailedProtocol_18 
the usability of the data. The principal investigators on the project (Drs. Mayer and Stall), working closely 
with the other investigators, will oversee all data management and analysis issues. A quality management 
plan will be developed to specify daily quality control and monthly quality assurance measures. The 
Fenway Health and University of Pittsburgh IRBs will review the data-monitoring plan along with the full 
study protocol, which will be reviewed at least annually by the IRBs. Study progress, including accrual, 
attrition and data acquisition, will be monitored regularly throughout the course of the study. Case report 
form (CRF) completion will specifically be reviewed, especially in the initial months of study 
implementation. Every effort will be made to minimize attrition, and participants who miss visits will be 
contacted using primary and secondary contact information collected at screening and confirmed at each 
follow-up visit. 
 
12.3 
Project organization 
To ensure consistency in study operations, the investigative team will have weekly team meetings to 
discuss and review study policies and procedures. During these contacts, they will address issues related 
to study recruitment, interventions, outcomes, measurement, retention and attrition, data management 
and quality control, and data analysis. There will be a study coordinator at Fenway Health and University 
of Pittsburgh  that will supervise the project staff. This individual will also participate in the weekly team 
meetings and monthly protocol team meetings with both study sites. 
 
12.4 
Training of study interventionists 
Nurse-interventionists will undergo study-specific training. The training will be led by a certified clinical 
psychologist, who has considerable experience in the delivery of behavioral adherence interventions. The 
intervention will be manualized and the nurse-interventionists will receive intensive training in the correct 
dissemination of the intervention content. 
 
12.5 
Data analysis 
For the analyses, first, all forms will be checked for any missing data following interviews and prior to data 
entry. Attrition effects will be evaluated by testing whether systematic differences exist between 
participants who complete the research versus those who drop out, as well as between the intervention 
and comparison conditions. Multiple imputation techniques will be utilized to protect against the bias that 
can occur with missing data. We will initially inspect distributions for outliers and deviations from normality 
and will perform the necessary modifications to adjust for these issues.  
 
13. Safety and Monitoring  
Data and safety Monitoring Plan: The conduct of this study and the protection of the enrolled subjects are 
the responsibility of the principal investigator (PI). Accrual, confidentiality, subject complaints, subject 
withdrawals, adverse events, and safety laboratories will be reviewed on an ongoing basis by the study 
nurse and by the PI and co-investigators (Co-Is) at least weekly. All local serious, expected adverse 
events; unexpected adverse events of moderate or greater intensity; or > grade 2 laboratory 
abnormalities occurring during the study will be brought to the immediate attention of the investigators 
and to the IRB. The PI will be responsible for reporting aggregate data and risk/benefit summaries to the 
IRB at the time of annual renewal unless the information contained in these reports changes the benefit-
to-risk ratio of study participation as defined in the currently approved research protocol and consent 
form, in which case a modification will be immediately submitted to the IRB. During monthly full protocol 
team calls aggregate AE will be reviewed by the respective site safety officers (Drs. Ho and 
Mayer).Concerning trends in AE will be reported to the IRB. 
 
13.1 
Definition of an Adverse Event and Serious Adverse Events: 
 
An adverse event (AE) is defined as any untoward medical occurrence in a clinical research participant who 
has been administered an investigational product, and that does not necessarily have a causal relationship 
with the investigational product. An AE can, therefore be any unfavorable and unintended sign (including 
an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a 
medicinal product, whether or not considered related to the medicinal product. All grades of AEs must be 
recorded in the participant record for all study participants throughout study participation. Study participants 


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EpiPrEP_DetailedProtocol_19 
will be provided instructions for contacting the study site to report any untoward medical occurrences they 
may experience, except for possible life-threatening events, for which they will be instructed to seek 
immediate emergency care.  
 
A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose:  
1) 
Results in death  
2) 
Is life threatening (i.e., the subject was, in the opinion of the Investigator, at immediate risk of death 
from the event as it occurred) 
3) 
Requires or prolongs inpatient hospitalization or prolongs hospitalization1.  
4) 
Results in persistent or significant disability/incapacity (i.e., the event causes a substantial 
disruption of a person's ability to conduct normal life functions)  
5) 
Results in a congenital anomaly/birth defect 
6) 
Is an important medical event that may not be immediately life threatening or result in death or 
hospitalization but may jeopardize the patient or require intervention to avoid outcomes listed 
above. 
 
Note:  The term “life-threatening” in the definition of “serious” refers to an event in which the patient was at 
risk of death at the time of the event; it does not refer to an event which hypothetically might have caused 
death if it were more severe. 
 
Note:  Overdose and cancer are classified as Serious for data collection purposes. HIV-1 infection occurring 
during the study will not be considered as an SAE, but will be reported to sponsor within 24 hours of 
diagnosis. 
 
The following types of hospitalizations do not meet the SAE definition:  
 
Any admission unrelated to an AE (administrative or social admission for temporary shelter 
placement).  
 
Protocol specified admission.  
 
Admission for a diagnosis or therapy of a pre-existing condition that has not increased in severity 
or frequency.  
 
13.2   Grading of Adverse Events 
Local and systemic signs and symptoms are assessed and graded based on The Division of AIDS Table 
for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, 
November, 2014 (available at http://rsc.tech-res.com/safetyandpharmacovigilance/gradingtables.aspx), 
except that unintentional weight loss of less than 10% in body weight from baseline is not required to be 
reported as an AE. 
 
13.3  Assessment of Relationship to Study Agent 
 
The relationship of study drug to AEs will be determined by the primary investigator or designee (M.D., 
N.P., P.A.) and will be based on the following definitions: 
o 
Not Related:  The AE is not related if exposure to study drugs has not occurred, OR the occurrence 
of the AE is not reasonably related in time, OR the AE is considered unlikely to be related to use of 
the study drugs. 
o 
Related:  The AE is possibly, probably or absolutely related to the study drug.  
 
The study agents that must be considered in determining relationships of AEs are emtricitabine and 
tenofovir disoproxil fumarate. 
 
13.4 
AE and SAE follow-up and reporting: 
                                                 
 
 


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EpiPrEP_DetailedProtocol_20 
Each study site will be responsible for the management of safety data, reporting of safety information and 
any associated regulatory reporting obligations in compliance with all applicable laws, rules and regulations.  
 
This protocol will record all adverse events on a cumulatively AE log from the period of study drug 
dispensation till participant termination from the study. All AEs will be followed until resolution, stabilization 
or participant termination from study.  
 
SAE collection begins once patient signs the informed consent and ends 30 days after discontinuation of 
dosing or completion of the patient’s participation in the Project if the last scheduled visit occurs at a later 
time. 
 
13.5  
Gilead SAE Reporting: 
 
All SAEs including any deaths, product complaints with an associated SAE or reports of medication error 
or overdose regardless of an associated SAE occurring during the study will be reported to Gilead Drug 
Safety and Public Health (DSPH) within 15 calendar days of site awareness and in accordance with 
applicable laws, rules, regulations and guidance. All reports to Gilead will be sent to the attention of:  
 
Gilead Sciences, Inc. 
Drug Safety & Public Health  
333 Lakeside Dr.  Foster City, CA 94404 
Fax: 650-522-5477  Tel: 650.522.5114  E-mail: Safety_FC@gilead.com 
 
Upon Gilead’s request the investigator will provide any additional information related to any SAEs including 
any deaths, product complaints with an associated SAE or reports of pregnancy, medication error or 
overdose regardless of an associated SAE occurring during the study.  
 
13.6  Discontinuation of study agent due to an AE 
 
An MD investigator has the authority to stop study agent for any participant due to clinical or laboratory AEs 
or at any time if it their opinion it would be in the best interest of the participant. Study product will be 
discontinued for participants with a Grade 3 or higher AE deemed related to study agent. Participants 
withdrawn from taking study product due to an AE (or for other reasons), will be followed by the investigator 
at least until a final outcome is determined (i.e., AE resolves or sequelae are considered permanent) and 
reported to BMS, Abbott and Gilead, and if possible until the study is completed.  
 
13.7  Review of  participant safety data 
Routine participant safety review occurs at the start of enrollment and then throughout the study. The 
investigator is responsible for providing periodic updates on safety information to the Fenway IRB and 
BMS. 
 
14 Participant Confidentiality 
In order to strictly protect participant confidentiality all study data will be identified by a coded number not 
participant name. The coded information will be kept in a locked file and separate from any documents 
that include participant’s name. Number coded information may become part of an electronic database, 
which is password-protected and only accessible to study staff. A list, which links participant code number 
and name, will be stored separately from both participant personally identifiable information and 
participant number coded information.  
 
Participant name will not be publicly disclosed at any time, and the records will be strictly maintained 
according to current legal requirements. This applies to any written records, visit documentation, or 
interviews. 
 
Participant records or any part thereof can only be legally obtained with written permission of the 
participant specifying what exact information is to be released or if subpoenaed by law. However, the 


Epi-PrEP Detailed Protocol – Intervention v1.0 
EpiPrEP_DetailedProtocol_21 
investigators will report cases of child or elder abuse or neglect to the authorities. Furthermore, if 
participant indicates that they are in imminent danger of hurting themselves or others, the investigators 
will need to reveal this information in order to protect the participant or that person.  
 
The University of Pittsburgh, Fenway Community Health and affiliated hospitals, researchers, health care 
providers, and physician network will make all reasonable efforts to protect the privacy of information that 
identifies the participant and relates to participant past, present, and future physical and mental health 
conditions. This is referred to as “protected health information” throughout the rest of this section.  
 
Health Information that does not contain any identifying information and cannot be connected to the 
participant is referred to as “study information”. 
 
Who may study information (which does NOT contain identifying information) be shared with? 
 
The Fenway Community Health IRB 
 
Fenway Community Health Research Staff 
 
University of Pittsburgh  IRB 
 
University of Pittsburgh  Research Staff 
 
Office of Human Research Protection 
 
National Institute of Mental Health 
 
National Institutes of Health   
 
This study information (which does not contain participant identity) may also be published. 
 
15 Regulatory Authority Approval: 
This study will be conducted in accordance with Good Clinical Practice (GCP) and all applicable regulations, 
including the Declaration of Helsinki, June 1964, as modified by the 48th World Medical Association, 
Republic of South Africa, October 1996.  
 
 
16 Institutional Review Board Approval 
The Investigator will ensure that this protocol is reviewed and approved by the Fenway Community Health 
and University of Pittsburgh IRBs.  
 
The Fenway and Pittsburgh IRBs will also review and approve the informed consent form (ICF) and any 
other written information provided to the subject prior to any enrollment of subjects, and any advertisement 
or public announcement that will be used for subject recruitment. The Investigator or his designee will 
forward to Gilead copies of the IRB approval and the approved informed consent materials, prior to the start 
of the study. 
 
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