Uptake and Persistent Use of HIV Preexposure Prophylaxis Among Key Populations: Results From Ukraine’s Scaled National Preexposure Prophylaxis Program

Abstract

Background:

Ukraine has implemented ambitious HIV-prevention programs since 1999 and began offering preexposure prophylaxis (PrEP) in 2017. Little is known about PrEP uptake and persistence in this setting.

Setting:

We analyzed data from 40 facilities providing PrEP in 11 oblasts (regions) of Ukraine between October 2020 and February 2022.

Methods:

We estimated the time between PrEP visits and conducted Kaplan–Meier analyses to estimate retention on PrEP stratified by sex, age, and key populations (KPs): men who have sex with men (MSM), people who inject drugs (PWID), sex workers (SW), discordant couples, and others vulnerable to HIV acquisition (DC/other). We used Cox regression to estimate the risk of PrEP discontinuation by KP group and sex, adjusting for age.

Results:

Overall, 2033 clients initiated PrEP across regions; the majority (51%) were DC/other, 22% were MSM, 22% were PWID, and 5% were SW. The overall 3-month persistence was 52.3% (95% confidence interval [CI]: 49.9% to 54.8%) and was lowest among MSM (46.7%; 95% CI: 41.9% to 52.2%) and SW (25.9%; 95% CI: 18.2% to 36.9%) (P < 0.05 for differences by KP group). After adjusting for age, PrEP discontinuation was not statistically significantly different across groups, although female PWID tended to have the lowest discontinuation risk (adjusted hazard ratio [aHR] 0.59; 95% CI: 0.31 to 1.11) while male SW tended to have the highest risk (aHR 1.87, 95% CI: 0.57 to 6.11) compared with females in the DC/other group.

Conclusion:

Three-month PrEP persistence was low across KP groups, especially in SW. Further research examining the barriers and enablers of persistence by KPs is needed.

INTRODUCTION

Central and Eastern Europe (CEE) have experienced a growing epidemic of HIV infection in recent years.¹ Ukraine has observed a drop in incidence in the past decade. Yet, as of 2021, there were still 245,000 people living with HIV (PLWH),² the second largest population of PLWH in Eastern Europe.¹ Historically, HIV primarily affected people who inject drugs (PWID), mainly men in Ukraine³; however, heterosexual transmission has been the main driver of Ukraine’s epidemic since 2008.⁴ As of 2021, the epidemic in Ukraine was largely concentrated in several key population (KP) groups: HIV prevalence was 3.1% among sex workers (SW) (2700 PLWH), 3.9% among men who have sex with men (MSM) (7000 PLWH), 20.9% among PWID (73,200 PLWH), 8.2% among prisoners (3400 PLWH) and 1.7% among transgender people (200 PLWH).² Ukraine formally committed to the Joint United Nations Programme on HIV/AIDS (UNAIDS) 95–95-95 targets for HIV epidemic control and has launched multiple large-scale projects to accelerate HIV prevention and control efforts, many funded by the United States President’s Emergency Plan for AIDS Relief (PEPFAR).^5,6

One core approach of Ukraine’s HIV prevention strategy is preexposure prophylaxis (PrEP), which is highly effective at preventing infections when used with high adherence.⁷ PrEP was introduced in Ukraine in 2017 as part of a 2-year pilot project for 100 MSM and transgender people.³ In 2021, more than 5700 people received PrEP in Ukraine.² Ukraine’s clinical guidelines for PrEP support daily oral PrEP using a combination of tenofovir disoproxil fumarate (TDF 300 mg) and emtricitabine (FTC 200 mg), as well as on-demand, or event-driven PrEP (ie, taking 2 pills within 24 hours of a sexual encounter, followed by 1 pill per day the next 2 days) using a similar formulation.

The International Training and Education Center for Health (I-TECH) is a PEPFAR partner funded by the US Health Resources and Services Administration that has been working in Ukraine since 2011 to support the Government of Ukraine in improving HIV prevention and treatment. Before 2023, PEPFAR prioritized HIV-related services in 12 oblasts, or regions, with the highest burden of HIV, either in prevalence rates or absolute numbers of PLWH. These oblasts accounted for 75% of estimated PLWH before the war launched in February 2022 by the Russian Federation.⁶ I-TECH began providing technical assistance to 40 hospitals and clinics in 11 out of 12 priority oblasts in 2020, to help them scale and improve their PrEP programs (Fig. 1). PrEP has consistently been provided free of cost to all clients, with emphasis on serving SW, MSM, PWID, discordant couples, and other individuals vulnerable to HIV acquisition (DC/other).

FIGURE 1.

Eleven oblasts in Ukraine targeted for PrEP scale-up in 2020 (shown in grey), with the number of participating health facilities per oblast (n = 40 total).

Previous studies of PrEP persistence are concentrated in the United States and Africa and encompass diverse patient populations with analyses stratified by SW, MSM, PWID, and DC. Across these regions and patient populations, research consistently illustrates limited PrEP persistence, with typically more than 50% of users discontinuing within 6–12 months, and demonstrates that younger PrEP users are more likely to discontinue PrEP than older users.^8–16

Although existing scientific reports have shown steady uptake of PrEP in Ukraine since 2017,^2,17,18 there are no published reports or studies on PrEP persistence, which is important for understanding effectiveness of programs. We sought to estimate PrEP persistence in KPs in Ukraine and assess associations by sex and age.

METHODS

Study Design and Setting

We analyzed data from Ukraine’s scaled PrEP program from October 1, 2020, when I-TECH began providing technical assistance to scale up PrEP, through February 23, 2022, when Russia launched a full-scale war on Ukraine. The University of Washington Human Subjects Division gave an expedited review of the study protocol, determined that there were minimal risks to human subjects based on its secondary use of deidentified client data, and approved the study. This observational study involved a secondary analysis of medical record data. Figure 1 shows a map of the 40 health facilities that were included in our analysis.

The standard operating procedure (SOP) for Ukraine’s PrEP program follows international guidelines and requires clients to be screened for HIV infection and complete other standard World Health Organization–recommended PrEP screening procedures before being eligible to initiate PrEP.¹⁹ PrEP client education typically covers issues such as risk reduction, importance of sexually transmitted infection testing, PrEP adherence and adherence strategies, detecting acute infection, PrEP side effects, and family planning methods. PrEP administration is oral, with either daily or event-driven dosing. The SOP recommends a 30-day supply of PrEP to be prescribed at initiation, 60-day supply at the first follow-up visit, and 90-day supply at all subsequent follow-up visits. In practice, subsequent follow-up visits were scheduled according to amount of medication dispensed at each visit. HIV testing (through rapid test), PrEP adverse effects assessments, PrEP adherence counseling, and other sexually transmitted infection and health assessments are conducted at each follow-up visit. If the patient shows symptoms of acute HIV infection (eg, fever, mouth ulcers, lymphadenopathy) at follow-up visits, they are tested for HIV through rapid test, and PrEP is delayed by 4 weeks. When they return, the patient is reassessed for acute HIV infection and retested for HIV before receiving a PrEP refill.

All client and visit information are recorded on the client’s medical card and in the Information System for Socially Significant Diseases (IS-SSD), Ukraine’s electronic health record system. The IS-SSD is fully integrated across facilities, meaning if patients relocate to a different facility after PrEP initiation, details of their care continue to be captured in the IS-SSD. When clients are diagnosed with HIV, they are referred for HIV antiretroviral therapy.

Study Participants

We included clients who were newly prescribed PrEP at any of the 40 program facilities during the time frame of interest. Participants were 18–70 years old and were eligible for PrEP based on their ongoing behavioral risk for exposure to HIV.

Data Collection

Birthdate, sex at birth, and KP group (including SW, PWID, MSM, and other people vulnerable to HIV acquisition [DC/other]) were collected by health facility staff for all clients upon program entry. Gender identity was not collected, so it was not possible to disaggregate sex at birth from gender identity or separate transgender clients as a distinct KP group. The dates of visits with infectious disease specialists for PrEP initiation and refills were included in the medical record and used to define PrEP persistence. The data set was constructed by I-TECH Ukraine staff using biweekly data extracts from the IS-SSD provided by the Public Center of the Ministry of Health of Ukraine (Public Health Center) and facility-level PrEP program registers developed by the I-TECH team to monitor complementary services.

KP Group Classification

Registration procedures at Ukrainian clinics are likely inaccurate in identifying clients as members of stigmatized groups, such as MSM or PWID. A prior study of HIV risk group classification in Ukraine demonstrated that only two-thirds of patients that self-reported injection drug use, and less than half of those with hepatitis C virus markers, had injection drug use listed as a mode of HIV transmission in their medical record. Only about half of men self-reporting having sex with men (who did not report injection drug use) had this listed in their medical record and, in turn, the proportion of heterosexual HIV transmission was overestimated by almost 75%.²⁰

Because modes of transmission are substantially misclassified within the medical record, we classified people into KPs based on both group type (as assigned by health workers in a specific PrEP program register) and examination code representing the client’s reason for HIV testing (as assigned in the official medical record), to use all transmission data available to increase accuracy of classification. Group types SW, DC, MSM, PWID, and risky behavior (heterosexual relationships) were assigned by health workers at PrEP enrollment. Examination codes included more granular categories than the group type, including people who were pregnant, had heterosexual contacts with PLWH, had symptoms of STIs, had unprotected sexual contacts with casual sexual partners, and those released from prison or experiencing homelessness. We considered both data elements and upcoded clients to PWID, MSM, or SW categories (groups assumed to have descending risk of HIV acquisition based on HIV prevalence estimates) if there was evidence for such classification in either of the 2 variables. We merged DC and risky behavior groups together because of anecdotal data showing that health workers frequently misclassified DC to the risky heterosexual behavior category. Exam code was not available for 1.1% of clients (n = 23), whereas the group code was available for all clients, so no clients had missing information about KP membership. For most clients, the group type guided group assignment, and 15 individuals’ key groups per the IS-SSD were reclassified or upcoded when determining KPs (those in the DC and risky heterosexual behavior categories grouped into the DC/other KP were not included as part of this count).

PrEP Persistence Outcome

PrEP persistence was defined as the duration that a client continued to fill PrEP prescriptions without a discontinuation event. PrEP discontinuation was defined as the first instance of a 75-day or greater gap between recorded prescription refills, or new diagnosis with HIV. We established the 75-day time frame assuming a 60-day refill window plus a 15-day buffer period. We based our definition on a 60-day PrEP supply (rather than a 30- or 90-day supply) to account for the possibility that some PrEP users would be given 90-day supplies of PrEP, whereas others would be given 30- or 60-day supplies. For clients who discontinued PrEP, time on PrEP was calculated as the number of days between their first prescription and their last refill plus 37 days (the midpoint of the expected 75-day return window). We conducted sensitivity analyses with failure definitions using a gap greater than 45 days and a gap greater than 105 days, using a similar approach of considering the failure date as the midpoint of the expected return window. For clients newly diagnosed with HIV, the date of the first positive test was their discontinuation date. For clients who did not discontinue, observation time was the number of days between the initial prescription and the administrative censor date of February 23, 2022.

Data Analysis

KP group (MSM, PWID, SW, and DC/other) was our primary exposure, and persistence on PrEP was our primary outcome. To understand visit frequencies, we constructed a Sankey diagram to visualize the number and percentage of clients returning 0–45, 46–75, 76–105, >105 days after their prior PrEP visit or not returning at all.

We examined persistence by sex (male and female) and age (18–25, 26–45, and 46–70 years). A time-to-event analysis was used to estimate the proportion of the population persisting on PrEP 3 months following initiation. We constructed Kaplan–Meier curves stratified by KP, sex, and age categories and used Cox regression to compare the probability of discontinuing PrEP for KPs while adjusting for sex and age. We considered models which clustered the data at the healthcare facility level, for appropriate variance estimation for hierarchical data. We tested the proportional hazards assumption based on weighted residuals.²¹ Analyses were completed in R version 4.2.3,²² and the Sankey diagram was made using SankeyMATIC.²³

RESULTS

Study Population

We included 2033 first-time PrEP users, of whom 65% were males (Table 1). Men had a median age of 35 years (interquartile range [IQR] = 29–42 years), and women had a median age of 37 years (IQR = 31–43 years). Overall, 51% were DC/other, 22% MSM, 22% PWID, and 5% SW. A larger share of MSM and SW were 18–25 years old (35% and 26%, respectively), compared with DC/other and PWID groups (10% and 6%, respectively).

TABLE 1.

Characteristics of Clients Aged 18–70 Years Enrolled in PrEP Program From October 1, 2020, Through February 23, 2022, in 40 Health Facilities in 11 High HIV-Burden Oblasts in Ukraine

	DC/Other, N = 1042 (51%)	MSM, N = 453 (22%)	PWID, N = 437 (22%)	SW, N = 101 (5%)	Total, N = 2033
Males	486 (47%)	453 (100%)	364 (83%)	9 (9%)	1312
Age (yr) median [IQR]	37 [32–45]	30 [23–38]	36 [32–41]	35 [30–40]	35 [29–42]
18–25 yrs	45 (4%)	157 (35%)	18 (4%)	1 (1%)	221
26–45 yrs	328 (31%)	235 (52%)	301 (69%)	6 (6%)	870
46–70 yrs	113 (11%)	61 (13%)	45 (10%)	2 (2%)	220
Females	556 (53%)	NA (0%)	73 (17%)	92 (92%)	721
Age (yr) median [IQR]	37 [32–43]	NA	35 [31–39]	34 [25–44]	37 [31–43]
18–25 yrs	58 (6%)	NA (0%)	4 (1%)	25 (25%)	87
26–45 yrs	395 (38%)	NA (0%)	64 (15%)	47 (47%)	506
46–70 yrs	103 (10%)	NA (0%)	5 (1%)	20 (20%)	128

IQR, interquartile range; NA, no individuals in this group.

Frequency of PrEP Prescription Refills

In practice, there were variations in SOP compliance across facilities, with providers prescribing 30–90-day supplies of medication even at the first PrEP visit. Ninety-five percent of intervals between all visits fell within 14–134 days. Among clients returning for their first PrEP follow-up visit, 81% returned within 45 days after initiation, whereas the largest share with a second PrEP follow-up visit returned within 46–75 days after their first follow-up visit (45% among those with a second follow-up visit) (Fig. 2). A small percentage of clients discontinued PrEP and then reinitiated after more than 105 days (3%, 8%, 11% after visits 1–3, respectively). Among 52 people returning for a sixth follow-up visit, 71% completed this visit within 1–45 days, 6% within 46–75 days, and 8% within 76–105 days of the prior visit (results not shown).

FIGURE 2.

Number and percentage of clients in Ukraine by timing of return since their prior PrEP visit. Legend for horizontal lines (“nodes”) and connections between nodes (“links”): 1–45 days: clients who returned within 45 days (from previous visit) for visit indicated. 46–75 days: clients who returned within 46–75 days (from previous visit) for visit indicated. 76–105 days: clients who returned within 76–105 days (from previous visit) for visit indicated. >105 days: clients who returned after >105 days (from previous visit) for visit indicated. HIV-positive and did not return: clients who returned for visit indicated and tested HIV positive (therefore not receiving PrEP), and clients who did not return (from previous visit) for visit indicated. Clients who returned for follow-up visits received a PrEP prescription at the indicated visits. Clients who returned but tested HIV positive were only included in the HIV-positive node. Those who returned >105 days after the prior visit likely stopped and then restarted PrEP. Clients that did not return were broken down by those with <75 days observation time and those with ≥75 days before administrative censoring. Percentages shown are calculated from the total number of clients returning for that visit (eg, excluding those that did not return at all from the percentage calculation).

Persistence Estimates and Hazard Ratios

Overall persistence at 3 months was 52.3% (95% confidence interval [CI]: 49.9% to 54.8%), assuming a 75-day refill window (Fig. 3a). In sensitivity analyses, the Kaplan–Meier estimate of 3-month persistence was 11.8% (95% CI: 10.2% to 13.6%) for the 45-day refill window and 74.1% (95% CI: 72.0% to 76.3%) for the 105-day refill window (see Figure 1, Supplemental Digital Content, http://links.lww.com/QAI/C277).

FIGURE 3.

Kaplan–Meier PrEP persistence curves for clients in Ukraine, for all clients (A) and by KP (B). Number at risk values are zero when all participants have failed or been administratively censored by the time point of interest. Curves are truncated at 250 days, after which there are fewer than 17 total individuals at risk.

Persistence at 3 months was highest among PWID (59.9%; 95% CI: 54.8% to 65.4%) and DC/other (54.4%; 95% CI: 51.1% to 57.9%) (see Table 1, Supplemental Digital Content, http://links.lww.com/QAI/C279). Among MSM, 3-month persistence was moderate (46.7%; 95% CI: 41.9% to 52.2%) and steadily declined to 0 people on PrEP at 189 days, much faster than DC/other, SW, and PWID, which still had 11.6%–28.9% of people on PrEP at this time, respectively (Fig. 3b). Persistence at 3 months was lowest among SW (25.9%; 95% CI: 18.2% to 36.9%) and then decreased slowly thereafter.

In unadjusted analyses, individuals in the age group of 25–70 years (52.8%; 95% CI: 50.1% to 55.4%) were more likely to persist on PrEP at 3 months than those <25 years (49.7%; 95% CI: 43.6% to 55.8%). Women (53.2%; 95% CI: 49.3% to 57.4%) were slightly more likely to persist on PrEP at 3 months than men (51.8%; 95% CI: 48.8% to 54.9%). Differences by KP (P < 0.0001) and age (P = 0.025) were statistically significant, whereas differences by sex were not (P = 0.34).

In our multivariable Cox regression model including KP, sex, and age, age was not associated with persistence (adjusted hazard ratio [aHR] 1.00, 95% CI: 0.99 to 1.01) (Table 2). Adjusted for age, PrEP persistence did not vary significantly by KP and sex, although female PWID tended to have the highest estimated persistence, followed by male PWID, female DC/other, and then male DC/other. The proportional hazards assumptions test revealed strong evidence of nonproportional hazards for the group variable and global test, meaning the aHRs varied over time and should be interpreted as average estimates over time (see Supplemental Methods, Table 2, Figure 2, Supplemental Digital Content, http://links.lww.com/QAI/C313, http://links.lww.com/QAI/C280, http://links.lww.com/QAI/C278). aHRs for age did not vary significantly over time.

TABLE 2.

Cox Proportional Hazard Models of PrEP Discontinuation for Clients in Ukraine, by KP Group, Sex, and Age

N = 2033	Adjusted Hazard Ratio (95% CI)	P
Key population, sex
DC/other, female	REF	REF
DC/other, male	1.06 (0.90–1.25)	0.480
MSM, male	1.33 (0.86–2.06)	0.207
SW, female	1.29 (0.58–2.87)	0.537
SW, male	1.88 (0.58–6.11)	0.297
PWID, female	0.59 (0.31–1.12)	0.104
PWID, male	0.75 (0.45–1.25)	0.268
Age	1.00 (0.99–1.01)	0.743

DC, discordant couples; MSM, men who have sex with men; SW, sex worker; PWID, persons who inject drugs.

DISCUSSION

PrEP uptake in Ukraine increased steadily from program inception in 2017, reaching 5711 clients in 2021,² a substantial increase in uptake from the 200 people who had access in 2017 and 2018.³ The effectiveness of PrEP hinges on not only uptake but also persistent use of PrEP for clients with ongoing risk of exposure to HIV.²⁴ Clients in Ukraine had low persistence on PrEP, consistent with the global literature. Across different countries and settings, PrEP persistence was generally short, with 50% or more of users discontinuing within 6–12 months.^8–10 Our study found this level of discontinuation after just 3 months. Our estimates of PrEP persistence in Ukraine contribute to the limited amount of literature on PrEP program results in routine care settings in CEE countries.

Our exploratory analysis identified potential characteristics of clients most likely to discontinue PrEP use in Ukraine, among those already disproportionately vulnerable to HIV acquisition. Overall, PWID had the highest persistence compared with other KP groups. The low observed persistence in MSM was disappointing given that MSM have been a primary focus of PrEP and other HIV prevention campaigns in Ukraine.^3,25,26 Intense stigma and discrimination facing sexual minorities in Ukraine is likely a barrier to consistency of health services for MSM.²⁷ Another explanation for the low observed persistence may be that they adhered to event-driven regimens, which required less frequent refills.

Only one-third of the clients in our analysis were women, indicating that they may have had lower PrEP uptake, although the absolute numbers, prevalence, and incidence rates of HIV among women and men in Ukraine are very similar.² This may be because sex work is illegal in Ukraine, so SW are reluctant to provide their information to initiate PrEP. As campaigns in Ukraine have primarily focused on MSM and PWID, women have not been included in many PrEP information campaigns. This may result in less awareness about PrEP among women generally; a study on barriers to PrEP in Ukraine and other countries in Europe found that a general lack of information about PrEP was the main barrier to PrEP use among women.²⁸ Furthermore, research shows that gender-specific and subpopulation-specific HIV prevention approaches among women PWID are needed to be effective.⁴ Ukraine’s HIV index testing program consistently refers sexual and needle-sharing partners of clients newly diagnosed with HIV to PrEP services, with an even balance by gender in partners who test negative for HIV and could be appropriate candidates for PrEP. However, other efforts may be needed to expand access to PrEP for women.²⁹

Our study points to the need to reduce barriers to PrEP uptake and persistence in Ukraine. Although we did not directly measure barriers in Ukraine, published studies from Ukraine and other settings are instructive. Studies of barriers to PrEP uptake and persistence in the United States identify structural barriers, including difficulty in accessing services for reasons such as high cost and insurance issues, long wait times for visits, and lack of medication in some health units, which were intensified with the COVID-19 pandemic.^15,30 Logistical barriers include lack of proximity to the clinic, frequency of follow-up visits or having to take time off of work, and difficulty taking a medication (especially for the daily regimen).^8,30 Medication side effects and perceptions of toxicity are also frequently mentioned across studies.^16,30 Reconciling other needs (eg, personal life and work routine) can interfere with the ability to take PrEP consistently and attend routine appointments. Daily adherence can be especially challenging for drug users who already experience higher levels of economic insecurity and housing instability; for them, meeting basic survival needs and maintaining psychoactive substance use often takes priority over regular PrEP use. Lack of education about PrEP is also a major barrier to uptake, especially among vulnerable populations, and is exacerbated by misinformation or limited information received from health professionals. In turn, low perceived HIV risk leads many to have poor compliance or discontinue PrEP altogether.³⁰ A study in adolescent girls and young women in Kenya noted relocation of PrEP users, limited screening and medication monitoring, and limited number of qualified health care workers for PrEP distribution and administration to be some of the biggest barriers to persistence in this setting.³¹

HIV-related stigma is also a primary barrier, and many communities associate PrEP use with promiscuity or with HIV treatment due to similar appearances of pills and packaging. Across multiple studies, DC reported constant fear of their partner’s HIV-positive status being revealed within their family or community. Criminalization of sex work most often prevents SW, as well as MSM, transgender, and gender-nonconforming individuals, from seeking PrEP. Many PrEP users additionally noted perceived stigma from their health providers.³⁰

There are multiple interventions that might increase both PrEP uptake and PrEP persistence in Ukraine. Because access and stigma are barriers to PrEP uptake in Ukraine, offering PrEP through primary care health facilities that do not focus solely on HIV care, a model that has been successful in other countries,²⁴ is worth studying. In recent years, Ukraine embarked on an ambitious reform of the healthcare system to make previously hard-to-access specialized care accessible through primary care. Starting in 2019, family physicians began screening for HIV as part of basic primary health care.⁵ Family doctors are an existing touch point in the medical system for many potential PrEP clients, and expanding this model by allowing them to prescribe PrEP would streamline linkages to care. It may even provide an entry into the medical system for some.³² This model has been successful in other countries.²⁴ PrEP uptake and adherence may also be improved through telemedicine approaches, with delivery locations integrated within organizations and venues KPs already frequent. The addition of mobile healthcare clinics offering PrEP has increased PrEP coverage and persistence in other countries,²⁴ and it may be effective in Ukraine, perhaps among populations that might have poor access to telemedicine. The Public Health Center of the Ministry of Health of Ukraine plans a small-scale pilot of long-acting injectable cabotegravir for PrEP to be launched by the end of 2023, which may solve issues pertaining to adherence.³³ Further study of each of these interventions, as well as of the role of visit frequency in PrEP persistence, is recommended.

Suggestions for future research include exploring whether persistence correlates with visit frequency. We observed a trend toward shorter intervals between visits among those who persisted longest on PrEP. It is plausible that the shorter intervals causally contributed to longer persistence because more frequent interaction with the clinic staff may have helped overcome unease about PrEP use and reinforced a new behavioral pattern of daily medication use. For example, a United States study found that more frequent interactions with providers promoted adherence in adolescents.³⁴ Future research could also assess the role of counseling and comprehensive clinical services in promoting PrEP persistence. A study among Ukrainian MSM found that across nine possible PrEP delivery programs, participants were more interested in taking PrEP if the program included safer sex counseling and intensive health assessment at the time of PrEP initiation. Authors hypothesized that the intensive services lessened some of the participants’ unease about taking PrEP.²⁵ Other groups may also prefer more thorough medical care (including more intensive and frequent consultations) as part of PrEP services, positively impacting both uptake and persistence.

Strengths of our study are inclusion of clinics from a broad geographic area in Ukraine, a large sample size, and use of existing clinical records reflecting routine, real-world clinical practice. However, our study also has several limitations. PrEP refill frequency varied greatly among clients, and information on the amount of medication clients received was not available. Persistence estimates were very sensitive to the discontinuation definition used. If we assumed that PrEP clients received a 1-month PrEP supply at initiation and at each follow-up visit (with a 45-day window for discontinuation), persistence estimates were much lower than when we assumed a 2-month PrEP supply (with a 75-day window for discontinuation). Thus, our decision to use the 75-day window for discontinuation may have overestimated persistence. Second, by clustering on healthcare facilities in the Cox model, we made a conservative assumption about the nonindependence of clients served within the same facility, which may have contributed to the lack of statistical significance of our findings. Third, we may have observed an artificially smaller proportion of clients in the SW, MSM, and/or PWID groups, as some may have registered under DC/Other groupings due to associated stigma. This may have biased the group-specific estimates of PrEP persistence in unpredictable ways. Fourth, our finding that the proportional hazards assumption was not met suggests that further research is needed on how risk of discontinuation may differ over time across KP groups. The Cox assumption of noninformative censoring independent of covariates may also have been violated. Future analyses with larger sample sizes should consider stratifying Cox models by key groups because the risk of discontinuation may differ with time.

We have several recommendations for Ukraine’s scaled PrEP program and other programs studying this topic that would enable more robust evaluation and analysis. First, our analysis considered an 18-month period with a limited sample size for some KPs. The number of SW included in this analysis was particularly low, likely because they are a closed group that is hard to reach for specialized medical care. As part of a national sample, 21.3% of SW stated that they avoid health care due to stigma and discrimination, in comparison to 10.3% of PWID and 6.3% of MSM.² Future studies of this topic should ensure that they include enough SW. Second, we measured persistence using PrEP refill dates rather than pill taking, which overestimates PrEP persistence as not all individuals who obtain a PrEP prescription take all of their pills.^9,24 In addition, our inability to distinguish event-driven PrEP could lead to underestimating persistence and overestimating discontinuation. Based on anecdotal evidence, we believe that the number of people who received event-driven PrEP was likely small because many clients faced on-going routine risk for HIV. However, prior studies on PrEP in Ukraine have demonstrated preferences for event-driven PrEP, especially among MSM,²⁵ and therefore, further study of actual demand, use, and effectiveness of event-driven PrEP in Ukraine is needed.

The Russian war has significantly affected regions with high HIV burden since 2014, and the full-scale invasion in February 2022 caused further immense challenges for HIV-related care in Ukraine.^6,35–37 Amidst the devastation caused by the war, Ukraine remains ambitious about combating HIV and continues to implement evidence-based approaches. PEPFAR expanded its support for HIV-related services in all regions of Ukraine to address the vast internal displacement of the population.³⁷ Healthcare workers have also made quick and effective adaptations to HIV-related care following the full-scale invasion, such as providing online consultations, shipping HIV medications to displaced clients, and offering greater quantities of medication dispensed per prescription.³⁵ Our findings from this study should be coupled with further study of approaches that are effective in the context of war.

We identified low PrEP persistence among KPs, notably SW. Given the limited information on PrEP persistence in Ukraine overall, we recommend in-depth qualitative studies of barriers and facilitators to persistence among MSM, SW, and DC/other to understand why PrEP persistence is low. These qualitative data, coupled with the findings in our study, may improve novel PrEP delivery strategies, such as PrEP access through family doctors and through telemedicine, and may help tailor counseling messages to groups with lower PrEP persistence. Our findings identified KPs with unmet service needs and support the expansion of HIV prevention programs across Ukraine and other countries in the CEE region with similar cultural and health systems.