Preparing for Pre-exposure Prophylaxis Implementation in Central-Eastern European Countries With Low Access to Biomedical Prevention
Phase: NA
Conditions: Human Immunodeficiency Virus
Sponsor: Columbia University

 
 
 
 
 
Preparing for Pre-exposure Prophylaxis Implementation 
in Central-Eastern European Countries With Low Access 
to Biomedical Prevention 
 
 
 
NCT05323123 
 
July 10, 2024 
 
 

BACKGROUND 
 
Abstract 
Despite the effectiveness of pre-exposure prophylaxis (PrEP) in preventing HIV 
acquisition, PrEP is not currently medically prescribed in Romania, although demand is rapidly 
growing. Evidence-based knowledge is urgently needed to guide PrEP’s effective rollout in 
Romania. First, Romania has the 2nd highest increasing HIV incidence of 15 Central-Eastern 
European (CEE) countries, with gay and bisexual men (GBM) being one of the few epidemic-
driving groups; however, there is no national HIV programming for GBM. Second, in a large 2019 
GBM report, Romania was the 8th of 44 European countries with the largest gap between PrEP 
use (1%) and demand (70%). Third, Romania displays some of the highest homophobic attitudes 
in CEE, keeping GBM in hiding and underutilizing healthcare. Consequently, many Romanian 
GBM obtain PrEP on their own and use it without medical guidance, thereby increasing their HIV 
and other health risks. To address the unmet HIV-prevention needs of Romanian GBM, the US-
Romanian research team proposes to introduce a culturally-responsive pre-exposure prophylaxis 
(PrEP) program in Romania. The intervention consists of two tools that the team developed and 
tested in the US and adapted for Romania in a prior study: 1) SPARK, an in-person motivational 
intervention for uptake of and adherence to PrEP using an empowering sexual health approach; 
and 2) P3 (Prepared, Protected, emPowered), a PrEP adherence support app that utilizes engaging 
social networking and game-based elements, with an in-app portal for individualized live 
adherence counseling. PrEP Romania’s feasibility, acceptability and early efficacy will be tested 
across two aims. 
Aim 1. Any necessary adjustments to PrEP Romania based on a prior trial will be made. 
Then, 120 PrEP-eligible gay and bisexual men in two Romanian cities (Bucharest and Cluj) will 
be randomized to receive either 1) PrEP Romania or 2) a PrEP education condition. Differences 
across arms in PrEP uptake, adherence, persistence (self-reported and biomarker verified) at 3- and 
6-mos post-PrEP initiation will be examined. 
Aim 2. Individual and institutional barriers and facilitators of implementing PrEP Romania 
will be investigated by examining Aim 2 feasibility and acceptability data, and via research staff, 
and GBM interviews to inform a future hybrid effectiveness-implementation trial. 
 

Study Purpose and Rationale 
Despite evidence of the effectiveness of pre-exposure prophylaxis (PrEP) in preventing 
HIV acquisition, PrEP is often hardest to access in global regions and populations most at risk. In 
Romania, for instance, PrEP is not currently medically prescribed, yet there is urgency around its 
rollout. First, Romania has the 2nd highest increasing HIV incidence of 15 Central-Eastern 
European (CEE) countries, with gay and bisexual men (GBM) being one of the few epidemic-
driving groups; yet, there is no national HIV programming for GBM. Second, in a large 2019 GBM 
report, Romania was the 8th of 44 European countries with the largest gap between PrEP use (1%) 
and demand (70%). Third, Romania displays some of the highest homophobic attitudes in CEE, 
keeping GBM in hiding and underutilizing healthcare. Consequently, many Romanian GBM 
obtain PrEP on their own and use it without medical guidance, thereby increasing their HIV and 
other health risks. To address the unmet HIV-prevention needs of Romanian GBM, this study 
proposes to introduce a culturally-responsive PrEP program to the country of Romania. 
Specifically, PrEP Romania is a hybrid in-person + mobile health (mHealth) program that 
facilitates PrEP uptake and adherence by providing knowledge, motivation, and support. mHealth 
is an ideal HIV-prevention strategy for Romanian GBM given its private accessibility in 
stigmatizing locales. The study will integrate and adapt for Romania two tools we developed and 
tested in the US 1) SPARK, an in-person intervention for uptake of and adherence to PrEP using 
brief sex-positive motivational counseling; and 2) P3 (Prepared, Protected, emPowered), a PrEP 
adherence support app that utilizes engaging social networking and game-based elements, while 
an in-app portal allows for individualized live text-based adherence counseling to heighten GBM’s 
sense of accountability, enhance their motivation, and address specific adherence needs. These 
goals will be accomplished in collaboration with a Romanian Partner Consortium of GBM-
competent health providers, including: infectious disease physicians (IDPs), whom we trained in 
GBM-affirmative practice; community-based organizations (CBOs); and the National Institute of 
Infectious Diseases (NIID) and Romanian Association against AIDS (ARAS), prominent HIV-
focused medical institutions. This study has two aims. 
Aim 1. Conduct a randomized controlled trial (RCT) to test the early efficacy of PrEP 
Romania. The US team will make necessary adjustments to PrEP Romania with the Romanian 
Partner Consortium. These adjustments are based on a pilot study conducted prior to the award of 
the current study by NIH, between September 2020 and March 2022. Then, 120 PrEP-eligible 

GBM in two cities (Bucharest and Cluj-Napoca) will be randomized to receive either 1) PrEP 
Romania (counseling, self-directed app use, and in-app text-based adherence support for 6 months) 
or 2) a PrEP education condition. We will examine differences across arms in PrEP uptake, 
adherence, persistence (self-reported and via dried blood sample biomarkers), and mediators (self-
efficacy, mental health) at 3- and 6-months post-PrEP initiation. 
Aim 2. Explore implementation outcomes to prepare for a future multi-city effectiveness 
trial. The team will identify individual and institutional barriers to and facilitators of implementing 
PrEP Romania by applying Proctor et al.’s implementation framework to the analysis of RCT’s 
feasibility and acceptability data, and PrEP counselor, IDP, clinic administrator, and GBM 
interviews. Results will inform a future effectiveness-implementation hybrid trial of a scaled-up 
PrEP Romania across several cities. 
 
Research Aims & Abstracts 
Hypotheses: Compared to control arm (education only), PrEP Romania participants 
(counseling, self-directed app use, and in-app text-based adherence support for 6-mos) will be 
more likely to accept PrEP (H1); evince better adherence (H2); and sustain PrEP use across 6-mos 
(H3). 
 
STUDY DESIGN 
 
One hundred and twenty GBM will enroll in a 2-arm pilot to test PrEP Romania’s (a) 
feasibility (medical visit attendance), (b) acceptability (intervention staff and GBM interviews 
about counseling and app usability), and (c) PrEP uptake (filled prescriptions), adherence (self-
reported and DBS) and persistence (still on PrEP) at 3- and 6-month follow-ups. 
Study Sites: Two of Romania’s primary infectious disease (ID) centers in Bucharest and 
Cluj-Napoca will serve as the study sites. Their IDPs are involved in our ongoing research and 
treat GBM who test positive for HIV/STIs through our study. They, together with their site 
psychologists, were part of the team's pilot study for the current RCT, which ended in March 2022. 
The National Institute of Infectious Diseases (NIID) Bucharest Clinic. The largest ID 
university hospital in Romania, NIID is one of 9 regional centers monitoring HIV. NIID monitors 
all HIV/AIDS cases in Romania, and oversees the other 8 regional centers. 

The Cluj-Napoca Clinic. The Regional Center of Evidence and Monitoring of HIV 
Infection Cluj-Napoca (CREM Cluj) covers 5 jurisdictions in northern Romania. A total of 706 
HIV/AIDS patients are registered in CREM Cluj, with 668 being on ART. 
Inclusion Criteria. Men will be eligible based on criteria for GBM PrEP candidates: 1) male 
sex at birth and current male identity; 2) age 18 years old; 3) 1 acts of condomless anal sex with 
an HIV-positive or status-unknown male partner or diagnosis of bacterial STI in past 6 mos; 4) 
confirmed to be HIV-negative upon study testing; 5) own a mobile device (smartphone, tablet, 
laptop); 6) will reside in Romania for the following 6 months; and 7) are not currently participating 
in other research studies or related projects. 
Exclusion Criteria. Children <18 years old will be excluded as Romanian law that prohibits 
prescribing medication to minors without parental consent, which may jeopardize wellbeing if 
youth are “outed” to unsupportive families. 
 
Study procedures 
Recruitment: We will enroll a total of 120 men meeting the above criteria. GBM living in 
or within 40 miles of Bucharest (n=60) and Cluj (n=60), will be recruited and enrolled if eligible. 
Rationale: We have existing collaborations with clinics in these 2 cities, which are major 
Romanian medical infectious disease centers with a sufficiently large GBM patient load and high 
HIV risk (given their urbanicity and being international travel hubs). It is normative for Romanians 
from surrounding small urban and rural settlements to travel to these cities for medical and social 
reasons (especially GBM for whom resources are scant and urban migration is normative). Thus, 
participating from within a 40-mile radius around each city will not represent an unusual demand. 
Venues: We will follow our successful recruitment procedures from our previous studies in 
Romania with this population. First, our partner, ARAS, provides weekly free confidential 
HIV/STI testing in Bucharest and Cluj’s gay clubs at its so-called “Checkpoints.” Second, we will 
post study ads on websites of MozaiQ (NGO partner with extra outreach to the Roma community), 
ACCEPT (LGBT advocacy organization since 1996), study recruiter networks, subscriber lists, 
and key virtual venues (e.g., Facebook, Planet Romeo). In previous studies, 45% and 24% of 
participants were recruited on GBM sex-seeking apps, respectively, and 41% and 59% on 
Facebook/Instagram, respectively. Finally, enrolled participants will be encouraged to spread the 
word. 

Screening: Within the study ad, potential participants will click on a link to complete a 5-
min eligibility screener on Qualtrics, a HIPAA-compliant secure web application. The first page 
in the screener consists of the informed consent form for screening eligibility. This form is self-
administered and contains the researchers' contacts that can be used for clarification purposes. 
Once potential participants have read through the electronic consent form and agree to screen for 
eligibility, they will click "Yes" on the consent form, if still interested in taking the screener (or 
"No" otherwise, and exit). Should the consent to screen, the next screen will take them to the first 
questions of the screener. Eligible GBM will have the option to provide contact information at the 
end of the screener, in a separate survey, to be contacted for consent. 
Consent: Eligible participants will be contacted within days of screening to undergo the 
phone consent process we used successfully in other studies. Specifically, ARAS staff will send 
potential participants a link to an electronic Qualtrics-based consent form. ARAS staff and 
participants will read the electronic consent document together while on the phone (15 minutes). 
Points of confusion will be clarified and interested participants will submit the electronic consent. 
The consenting ARAS staff will submit their own version of the Qualtrics-based electronic consent 
form. 
Assessments: Upon consent, participants will be sent their unique study ID an electronic 
link to a Qualtrics-based baseline survey (30 minutes). They will complete similar 3- and 6-month 
surveys, and 20% will complete exit interviews with the PI about their intervention experiences to 
inform future PrEP Romania iterations. 
Procedures: After the baseline survey is completed, participants will be randomized 1:1 to 
receive PrEP Romania (n=60) or an Education Condition (n=60). Next, research staff will help 
participants schedule their first visit with the clinic for PrEP counseling, biological testing and 
PrEP prescription pick-up. All participants will be tested at the clinic for HIV at each visit, and, if 
positive, treated immediately. 
Intervention Arm (PrEP Romania): The intervention, named PrEP Romania, is based on 
the team’s previously tested PrEP Adherence and Counseling Protocols, delivered in-person. PrEP 
adherence is supported via an app previously tested by the team, including in Romania. To facilitate 
uptake, the Sexual Health Counseling Intervention seeks to “normalize” PrEP as part of a 
comprehensive HIV prevention/sexual health strategy chosen by the PrEP candidate. The 
intervention’s “sex-positive” approach is ideal for Romania given its focus on de-stigmatizing both 

sexual behavior and potential PrEP stigma, two drivers of negative attitudes of sexual behavior 
among men. PrEP Romania defines sexual health as physical, mental, emotional, and social 
wellbeing in the context of sexuality. Consistent with research on message framing, this 
intervention presents PrEP – and other sexual health promotion strategies– in a gain frame, 
emphasizing the positive impact of health promotion behavior, rather than the potential hazards of 
risk-taking. This is salient for Romanian GBM by allowing them to view their sexuality as natural 
and pleasurable, while minimizing stigmatizing societal discourses. PrEP Romania helps GBM 
consider PrEP as a means of sexual agency and fulfillment by asking them to reflect on their ideal 
sex life and identify sexual health priorities. SPARK is delivered in a clinic setting by a counselor 
using motivational interviewing techniques (e.g., open-ended questions, affirmations). The PrEP 
Adherence component provides behavioral support for PrEP adherence across five steps: 1) 
provision of rationale for daily dosing (e.g. blood drug concentrations); 2) creation of plans to 
integrate PrEP into daily routines (e.g., when, where, how); 3) managing side effects (e.g., over-
the-counter remedies); 4) navigating PrEP use disclosure to avoid stigma (e.g., when and whom to 
tell); and 5) anticipating circumstantial changes that can affect PrEP use (e.g., traveling). PrEP 
Romania uses US CDC guidelines for PrEP daily use. 
Prepared, Protected, emPowered (P3) App Overview: P3 is the app component that 
accompanies PrEP Romania, to support PrEP adherence and persistence. P3 is a theory-based, 
smartphone app that utilizes social networking, game-based mechanics, and evidence-based 
features to improve adherence. It was co-created by researchers, health game developers and 
GBM. P3 is versatile, allowing for customization and adaptations for diverse cultural and linguistic 
contexts, and technological advances. Within the app, users can receive information and social 
support, experience health-promoting social norms and reflective appraisals, and connectedness to 
peers, read informational articles about reducing alcohol use, achieving a healthy sex life, coming 
out, or building a supportive community. Relatedly, P3 is built for and has reduced users’ PrEP 
stigma-related concerns, which pose barriers to PrEP uptake and adherence if unaddressed. The 
gaming features of P3, such as answering short quizzes on how to use condoms, are intended to 
increase health promotion knowledge. P3 is ideal for engaging GBM in sustained behavior change 
by maintaining attention, and reducing boredom and attrition. P3 has an extensive library of facts 
on PrEP, sexual health, and relationships, from which Romanian GBM can benefit from accessing. 
Adherence counseling will be delivered via live text-based chat through the app, 2 weeks after 

PrEP initiation, and then every 6 weeks. Participants can ask questions about PrEP and health 
through the app, which will be answered by the trained research team. The entire follow-up period 
will be 6 months. At the first 1-hr visit, the PrEP counselor will deliver the in-person component 
PrEP Romania regarding motivation for PrEP uptake, and if applicable, adherence. The counselor 
will help GBM download the app, and demonstrate each feature, answer all questions and provide 
a guided tour. Participants will be encouraged to explore all app components routinely and be told 
that the counselors will contact them periodically through the app messaging system to discuss 
adherence facilitators and barriers. Next, participants will meet for 1-hr with the IDP, who will 
discuss requisite lab results and reinforce PrEP-related facts. The IDP will next provide a 
prescription to all GBM interested in starting PrEP, to be filled at the co-located clinic pharmacy, 
provided for free through the study. A follow-up clinic visit will occur 3- and 6-months after initial 
visit. Reported PrEP side-effects will be carefully monitored and, if necessary, PrEP use will be 
discontinued. In a pilot study for this RCT by this team, no participants reported side-effects. App-
based Support. GBM will be encouraged to use the app daily for adherence reminders, information, 
and socialization. The PrEP counselor will contact GBM via the app two weeks post-PrEP 
initiation for a 15-min adherence coaching session using adapted SPARK language to reinforce 
daily adherence and trouble-shoot barriers. Participants may message their counselor with 
questions, including for technical assistance, to be answered within 24 hrs. 
Control Arm (PrEP Education Condition): Participants randomized to the control arm 
will not meet with the PrEP counselor or have access to the app. They will only meet with the 
study IDP, who will deliver PrEP education. This education content is based on previously tested 
PrEP messaging education protocol. The low PrEP knowledge among Romanian GBM suggests 
the utility of a comprehensive PrEP education intervention. The IDPs (not PrEP counselors) will 
deliver this condition and be instructed to follow it as scripted using check-lists, as to avoid cross-
arm contamination. The IDP will first review lab test results and then provide basic PrEP 
information: what it is (e.g., definition), how it works (e.g., prevents virus replication), efficacy 
(e.g., clinical trials evidence), side effects (e.g., type, duration), and importance of daily use (e.g., 
to build and sustain protective levels), and continued condom use (e.g., PrEP as an added layer of 
protection against HIV, but not STIs, unless condoms are used). IDPs will answer questions and 
provide PrEP brochures. Participants will return 3 an 6 months after the first visit, as described 
below. Follow-up Visits. Participants in both arms will receive a PrEP prescription to be filled at 

the co-located pharmacy and schedule a follow-up visit 3 months later. At that visit, participants 
will meet with their counselor and/or IDP to review past-3-month PrEP use, side effects, clarify 
questions, conduct biological testing as above, and receive a PrEP refill if desired. The same 
procedures will be used at the 6-month follow-up. Retention. For high app-based engagement and 
retention follow-up, we will apply strategies we have utilized across our NIH-funded interventions, 
two of which entailed 8 mHealth counseling sessions with >82% completion and 86% and 93% 
retention at 3- & 24-months. Study engagement will be bolstered by our GBM-affirmative research 
staff who will routinely verify and use participants’ multiple means of communication (phone calls, 
SMS, multiple social media messaging, alternate contacts). PrEP counselors will contact 
unresponsive participants. Participants will be compensated $30, $35 & $40 for BL, 3M, and 6M 
surveys, and $30 for exit interviews (20% randomly selected).