Abstract
Background
Opioid agonist therapies (OAT) for people with opioid use disorders (OUD) have been available in Ukraine since 2004. This study assessed the effect of 2014 Russian invasion of Ukraine on OAT re-enrollment and retention in conflict areas.
Methods
We analyzed the Ukraine national registry of OAT patients containing 1,868 people with OUD receiving OAT as of January 2014 in conflict areas (Donetsk, Luhansk, and the Autonomous Republic [AR] of the Crimea). We developed logistic regression models to assess the correlates of re-enrollment of OAT patients in government-controlled areas (GCA) from conflict areas and retention on OAT at 12 months after re-enrollment.
Results
Overall, 377 (20.2%) patients were re-enrolled at an OAT site in a GCA from confict areas, of whom 182 (48.3%) were retained on OAT through 2021. Correlates of re-enrollment were residing in Donetsk (adjusted odds ratios (aOR)=7.06; 95% CI: 4.97–10.20) or Luhansk (aOR=6.20; 95% CI: 4.38–8.93) vs. AR Crimea; age 18–34 (aOR=2.03; 95% CI: 1.07–3.96) or 35–44 (aOR=2.09; 95% CI: 1.24–3.71) vs. ≥55 years, and being on optimal (aOR=1.78; 95% CI: 1.33–2.39) or high OAT dosing (aOR=2.76; 95% CI: 1.93–3.96) vs. low dosing. Correlates of retention were drug use experience 15–19 years (aOR=3.69; 95% CI: 1.47–9.49) vs. <14 years of drug use; take-home (aOR=3.42; 95% CI: 1.99–5.96) vs. daily on-site dosing, and optimal (aOR=2.19; 95% CI:1.05–4.72) vs. low OAT dosing.
Conclusion
Our study showed that one-fifth of patients were re-enrolled at sites in GCA areas, less than half of re-enrolled patients were retained. Disruption of OAT has implications for drug-, HIV-, and HCV-related morbidity and mortality.
Keywords: buprenorphine, methadone, military conflict, opioid agonist therapies (OAT), people with opiod use disorder (OUD), war, Ukraine
Background
Opioid agonist therapies (OAT) are an effective means of HIV prevention among people who inject opioids (Bruce, 2010). OAT have been available in Ukraine beginning in 2004 with buprenorphine and evolved into a large-scale national program in 2008 when methadone became available. Providing OAT has been a critical harm reduction strategy for people with opioid use disorder (OUD) in Ukraine, and is considered one of the most cost-effective approaches to reducing HIV infection in this population (Fairley et al., 2021). Retention in OAT has also been associated with lower mortality risk (Pearce et al., 2020). In February 2014 - the onset of the first stage of the Russian invasion of Ukraine – 8,614 patients were receiving OAT at 167 sites countrywide, with 572 and 557 patients in Donetsk and Luhansk oblasts, respectively, and 739 patients in the Autonomous Republic of the Crimea (AR Crimea) (Public Health Center, 2022).
After the Euromaidan, a series of escalating protests in late 2013 and early 2014 related to membership in the European Union (Chayinska et al., 2019), Ukraine entered a period of intense conflict. In February 2014, Russian forces invaded AR Crimea, and by March, Russia had occupied the peninsula. Starting in April 2014, pro-Russian activists supported by Russian troops in Donetsk and Luhansk oblasts occupied certain territories which were subsequently recognized by Russia (Haroz et al., 2019). By October 2015, 1.5 million people had been internally displaced (Cheung et al., 2019).
A limited literature has examined the effects of war, conflict, and displacement on treatment for drug use disorders among non-combatants. Greene et al. conducted a scoping review of the literature through October 2018 and found 14 publications (nine among refugees and five in conflict-affected populations) describing substance misuse interventions among conflict-affected populations (Greene et al., 2018). Only two of the publications reviewed focused on medication for opiod use disorder (MOUD), specifically examining OAT in Northeast India, a region experiencing a longstanding insurgent conflict and high burden of injection opioid use (Armstrong et al., 2010). Kumar et al. described drop-in centers for OAT with sublingual buprenorphine run by local non-governmental organizations, three of which had to seek and obtain support from underground militants in order to implement the program (Kumar et al., 2009). Armstrong et al. evaluated the drop-in centers and found that the program had high retention and reduced HIV risk behaviors, even in such a highly constrained environment (Armstrong et al., 2010). To our knowledge, no other studies have explicitly studied OAT in the context of war or conflict.
After the occupation of AR Crimea, Russia eliminated OAT on the peninsula since OAT is prohibited by Russian legislation. At the time, the United Nation’s special envoy for HIV and AIDS in Eastern Europe and Central Asia, reported that 11 treatment programs had closed which had served approximately 806 OAT patients; by May 2014 an estimated 80 to 100 of these patients had died (Hurley, 2015; Kazatchkine, 2014). Moreover, treatment programs in non-Ukrainian government-controlled areas (GCAs) of Donetsk and Luhansk experienced disruptions and eventual closures as a result of the occupation in those oblasts. The list of OAT sites closed at non-GCAs and time of closure are presented at Table 1. Little is known about the impact of the military conflict on OAT patients in these regions of Ukraine.
Table 1.
Opioid Agonist Therapies (OAT) Sites That Were Closed in Donetsk, Luhansk Regions and AR Crimea Due to Invasion
| Site | The latest OAT patients’ enrollment date | Closure date* |
|---|---|---|
|
| ||
| The Autonomous Republic of the Crimea | ||
|
| ||
| Yevpatoria Hospital No.2 | February 2014 | May 2014 |
| Armiansk OAT Site | November 2013 | May 2014 |
| Crimean Republican Drug Addiction Center | March 2014 | May 2014 |
| Crimean Republican TB Clinic | February 2014 | May 2014 |
| Dzhankoy Central Hospital | October 2013 | May 2014 |
| Feodosia OAT Site | March 2014 | May 2014 |
| Kerch Narcology Center | February 2014 | May 2014 |
| Krasnoperekopsk OAT Site | February 2014 | May 2014 |
| Saki OAT Site | October 2013 | May 2014 |
| Yalta City Hospital No.1 | March 2014 | May 2014 |
|
| ||
| Donetsk Region | ||
|
| ||
| Donetsk City Mental Hospital No.2 | November 2014 | March 2015 |
| Donetsk Regional TB Clinic | June 2014 | March 2015 |
| Donetsk Regional Drug Addiction Clinic | November 2014 | June 2016 |
| Gorlivka Drug Addiction Center | January 2015 | June 2015 |
| Gorlivka TB Clinic | Sepember 2014 | March 2015 |
| Makeevka Drug Addiction Clinic | May 2014 | December 2015 |
|
| ||
| Luhansk Region | ||
|
| ||
| Antratsyt City Drug Addiction Clinic | September 2014 | December 2014 |
| Luhansk Regional AIDS Center | December 2014 | December 2014 |
| Luhansk Regional Drug Addiction Center | December 2014 | December 2014 |
| Perevalsk OAT Site | November 2014 | December 2014 |
| Stakhaniv OAT Site | July 2014 | June 2015 |
Information reported by the Chief Narcologist [main Drug Addiction Specialist] of each of the oblasts
On February 24, 2022, Russia launched a full-scale invasion of Ukraine. Since the onset of Russian invasion, nearly 12.8 million people are estimated to have been displaced in Ukraine, most of whom have not left the country. As of May 2022, 7.7 million people were internally displaced as a result of the conflict, which is equivalent to 17.5% of the entire population of the country (UNHCR, 2022). The number of internally displaced OAT patients is about 1,800 which constitutes over 10% of all OAT patients (Morozova et al., 2023; Public Health Center, 2022). At the time of this writing, men between 18 and 60 years of age cannot cross the border. Patients have to re-enroll in OAT in receiving countries (Altice et al., 2022).
The objective of this analysis is to assess the effect of the first stage of Russian invasion of Ukraine among people with OUD receiving OAT. We focused on patients who had been on OAT in January 2014 for at least six months in the non-GCAs of Donetsk and Luhansk and in AR Crimea through December 2021, just two months before the country-wide invasion of Ukraine by Russia. We describe patients’ transitions from OAT sites in non-GCAs to GCAs in Donetsk and Luhansk and other oblasts following the 2014 invasion. We then explore two outcomes of interest: (1) re-enrollment of OAT patients from the conflict areas to the OAT sites in GCAs and (2) retention on OAT after re-enrollment at OAT sites in GCAs as of the end of 2021.
Methods
Source of data and study sample
For this study we analyzed data from a national registry of all OAT patients in Ukraine (N=16,478) from 242 OAT sites in 25 regions. Figure 1 presents a flowchart illustrating the sampling process for the study. The OAT database contained 3,140 records of patients’ who received OAT services before 2014 in Donetsk oblast, Luhansk oblast and AR Crimea. Next, we excluded patients whose OAT was interrupted before 2014 because the military conflict would not have influenced their decision to discontinue OAT (n=808). Additionally, we excluded patients from OAT sites in GCA of Donetsk and Luhansk as OAT services remained functional there after 2014. All patients who received OAT services as of January 2014 in non-GCAs of Donetsk and Luhansk and in all of AR Crimea were classified as conflict-affected and were included in the study sample (n=1,868).
Figure 1. Flowchart of opioid agonist therapies (OAT) patients affected by the military conflict in Donetsk, Luhansk and the Autonomous Republic of the Crimea, 2014–2021.
GCA = government-controlled area
Data collection
The data were collected from all 242 OAT sites on a quarterly basis. The database contains patient-level data on basic demographics, history of injection drug use, and clinical data related to OAT (e.g., dosing, entry/termination dates, services received), HIV (e.g., status, awareness of status, linkage to antiretroviral therapy [ART], viral load), and HCV (e.g., status, treatment). All data in the dataset are deidentified, and the study protocol was approved by the Institutional Review Board at the Alliance for Public Health (APH). Also, this project was reviewed in accordance with CDC human research protection procedures and was determined to be non-research, i.e. secondary data analysis.
Measures
The two outcomes were: (1) re-enrollment from a non-GCA OAT program in a conflict region to a GCA program following the beginning of the conflict in 2014 and, among those re-enrolled, (2) retention in OAT following re-enrollment through the end of 2021. Re-enrollment was indicated if a patient was receiving OAT at a non-GCA site within one of the three conflict areas in January 2014 and then subsequently received OAT at a GCA site after their original treatment location closed. For this study, we defined retention as being on OAT at 12 months after re-enrollment. Patients were classified as having been retained in OAT following re-enrollment if they were still receiving treatment at an OAT program as of the end of 2021. Among those re-enrolled at a GCA program, we also tracked and visualized the location of the new OAT program (oblast). These variables are measured at the end of observation (dropout date or 12 months after re-enrollment).
Explanatory variables included sex (male and female), categorized age in years (18–34 years, 35–44 years, 45–54 years, and ≥55 years), and years of drug use experience before OAT initiation (≤14 years, 15–19 years, and ≥20 years). Other potential correlates of re-enrollment from OAT program were type of OAT medication (buprenorphine and methadone, which are still the only available options in Ukraine), and OAT dosage per day (low: methadone <40 mg, buprenorphine <6 mg;, moderate: methadone 40–85 mg, buprenorphine 6–15 mg; or, and high: methadone>85 mg, buprenorphine>16 mg) (“Guidelines for the Psychosocially Assisted Pharmacological Treatment of Opioid Dependence,” 2009). Additionally, we used the latest HIV test result (negative and positive) before the conflict started and after the re-enrollment. Other potential correlates of OAT retention after re-enrollment were OAT method of dispensing (take-home dosages from OAT sites, daily use at OAT sites, and other, including OAT dispensing in pharmacies and hospice care).
Statistical analyses
We performed all the analyses using R version 4.1.3 (2022–03-10). We assessed the descriptive characteristics of OAT patients stratified by conflict area (Donetsk, Luhansk, AR Crimea). Pearson’s χ2 test was used to assess bivariable associations between the outcomes and all study variables. We used unadjusted and adjusted logistic regression to estimate the magnitude of the association between outcomes and covariates. In the multivariable analyses, we applied a backward selection approach to remove all variables that were not significant at the level of p<0.05 to construct parsimonious models. We used the Akaike Information Criteria (AIC) to assess model fit and the variation inflation factor (VIF) to test for collinearity. We excluded collinear variables.
To assess correlates of re-enrollment from a program in a non-GCA to a GCA, we used variables that represented patients’ information right before the time of their re-enrollment or when the conflict in their region started. Covariates include region of the OAT site in 2014 (non-GCA Donetsk, non-GCA Luhansk, AR Crimea), sex, age, years of drug use before OAT initiation, time on OAT, the latest type of OAT medication and dosage, and the latest available HIV status. In the adjusted model, to avoid collinearity, we included the OAT patients’ age variable into the model instead of time on OAT before re-enrollment or duration of drug use experience. We made this choice based on the assumption that some age groups (e.g., young and middle-aged people) would be more likely to be mobile and move to GCAs.
Retention in OAT services at 12 month after re-enrolment was assessed among the group of patients who were re-enrolled at an OAT site in a GCA (n=377). The covariates included the region of the patient’s OAT site before the re-enrollment, sex, age, years of drug use before OAT initiation, time on OAT after re-enrollment, the current type of OAT medication and dosage, the current method of OAT dispensing, and the latest available HIV status. In the adjusted model, to avoid collinearity, we used 12 month on OAT after the re-enrollment rather than age or duration of drug use experience before OAT, assuming that long-term OAT treatment would improve retention in the program.
Results
The list of OAT sites closed at non-GCAs, time of closure as well as the date the last patient was enrolled at each OAT site are presented at Table 1. It is worth noting, that the largest OAT site in Donetsk oblast (in the city of Donetsk, the administrative capital of the oblast) continued working for over a year after city’s occupation on moral and volitial efforts of the staff of Donetsk Regional Narcological Dispensary where the OAT site was based.
At the beginning of military conflict, there were 1,868 patients enrolled in the OAT program sites in the conflict areas: 30.6% in Donetsk, 29.8% in Luhansk, and 39.6% in AR Crimea. Among them, 377 (20.2%) patients were re-enrolled at an OAT site in a GCA, of whom 182 (48.3%) were retained on OAT through 2021 (Figure 1). The remaining 1,491 patients were lost to follow-up. Characteristics of OAT patients stratified by conflict region are presented in Table 2. In all conflict areas, the largest proportion of OAT patients were 35–44 years old (58.0%, 64.1% and 43.6% in non-GCA Donetsk, non-GCA Luhansk, and AR Crimea, respectively) and the majority were male (86.0%, 88.2% and 78.9%), although patients were somewhat older and a larger proportion female in AR Crimea compared to the other regions (p<0.001). Most patients in Donetsk region (70.6%) and AR Crimea (74.0%) had been injecting for over 20 years prior to OAT initiation, while in Luhansk region less than half of the patients (44.7%) had over 20 years of injecting experience (p<.001), although information on years of drug use prior to OAT initiation was missing for almost one-fifth of patients in Luhansk (19.4%). Over 70% of OAT patients in three regions had been recieving OAT for over 12 months, and this did not differ significantly by region (p=.300). Over 90% were recieving methadone, instead of buprenorphine, with the highest proportion recieving methadone in Luhansk compared to the other regions (98.0%, p<.001). About half of OAT patients were reciveing moderate OAT dosing (51.7%, 47.2%, and 53.6% in non-GCA Donetsk, non-GCA Luhansk, and AR Crimea, respectively), with more recieving lower dosing in Donetsk and Luhansk and more recieving higher dosing in AR Crimea (p<.001). The highest prevalence of HIV positive was observed among OAT patients from Donetsk (49.8%) vs. Luhansk (14.4%) and AR Crimea (35.5%, p<.001), although 21.4% of patients were missing information on HIV status in Luhansk. At some point during the military conflict, approximately 29% of OAT patients in non-GCA Donetsk and non-GCA Luhansk were re-enrolled at an OAT site in a GCAs, while among the patients from AR Crimea, this proportion was only 6.6% (p<.001). The approximate median time to re-enrollment was one month for Donetsk and Luhansk regions and 16 months for AR Crimea (p<.001). Of those patients re-enrolled (n=377), the retention rates on OAT at 12 months after re-enrollement were 70.5%, 75.2% and 65.3% (p=.279) for Donetsk, Luhansk and the AR Crimea respectively.
Table 2.
Characteristics of opioid agonist therapies (OAT) patients from Donetsk, Luhansk regions and the Autonomous Republic of the Crimea during the military conflict, 2014-2021 (N=1,868)
| Region (non-GCA), N=1,868 |
||||
|---|---|---|---|---|
| Characteristic | Donetsk | Luhansk | AR Crimea | p-value |
| (N=572), n (%) | (N=557), n (%) | (N=739), n (%) | ||
|
| ||||
| Sex | <0.001 | |||
| Male | 492 (86.0) | 491 (88.2) | 583 (78.9) | |
| Female | 80 (14.0) | 66 (11.8) | 156 (21.1) | |
| Age (years) | <0.001 | |||
| 18–34 | 47 (8.2) | 68 (12.2) | 43 (5.8) | |
| 35–44 | 332 (58.0) | 357 (64.1) | 322 (43.6) | |
| 45–54 | 140 (24.5) | 112 (20.1) | 270 (36.5) | |
| ≥55 | 53 (9.3) | 20 (3.6) | 104 (14.1) | |
| Drug use experience before OAT initiation | <0.001 | |||
| ≤14 years | 37 (6.5) | 83 (14.9) | 56 (7.6) | |
| 15–19 years | 131 (22.9) | 117 (21.0) | 134 (18.1) | |
| ≥20 years | 404 (70.6) | 249 (44.7) | 547 (74.0) | |
| Missing | 0 (0.0) | 108 (19.4) | 2 (0.3) | |
| Time on OAT before conflict | 0.300 | |||
| <12 months | 145 (25.3) | 164 (29.4) | 200 (27.1) | |
| ≥ 12 months | 427 (74.7) | 393 (70.6) | 539 (72.9) | |
| OAT medication | <0.001 | |||
| Buprenorphine | 54 (9.4) | 11 (2.0) | 56 (7.6) | |
| Methadone | 518 (90.6) | 546 (98.0) | 683 (92.4) | |
| OAT dosage§§ | <0.001 | |||
| Low | 214 (37.4) | 176 (31.6) | 101 (13.7) | |
| Moderate | 296 (51.7) | 263 (47.2) | 396 (53.6) | |
| High | 62 (10.8) | 118 (21.2) | 242 (32.7) | |
| HIV status | <0.001 | |||
| Negative | 275 (48.1) | 358 (64.3) | 472 (63.9) | |
| Positive | 285 (49.8) | 80 (14.4) | 262 (35.5) | |
| Unclear | 12 (2.1) | 0 (0.0) | 4 (0.5) | |
| NA | 0 (0.0) | 119 (21.4) | 1 (0.1) | |
| Re-enrollment | <0.001 | |||
| No | 406 (71.0) | 395 (70.9) | 690 (93.4) | |
| Yes | 166 (29.0) | 162 (29.1) | 49 (6.6) | |
| Retained on OAT at 12 months (n=377) | ||||
| No | 49 (29.5) | 40 (24.7) | 17 (34.7) | 0.279 |
| Yes | 117 (70.5) | 122 (75.3) | 32 (65.3) | |
GCA = government-controlled area
§§ Low: Methadone<40 mg; Buprenorphine <6 mg
Moderate: Methadone 40–85 mg; Buprenorphine 6–15 mg
High: Methadone>85 mg; Buprenorphine >15mg
The results of regression analysis of re-enrollment from OAT sites in non-GCAs to GCAs among the 1,868 internally displaced OAT patients affected by the military conflict are presented in Table 3. In the adjusted, parsimonious model, greater odds of re-enrollment were noted among patients residing in non-GCA Donetsk (aOR=7.06; 95% CI: 4.97–10.20) or non-GCA Luhansk (aOR=6.20; 95% CI: 4.38–8.93) vs. AR Crimea, younger vs. older patients (≤34 years old: aOR=2.03; 95% CI: 1.07–3.96; 35–44 years old: aOR=2.09; 95% CI: 1.24–3.71 vs. ≥ 55 years older), and recieving moderate (aOR=1.78; 95% CI: 1.33–2.39) or high OAT drug dosing (aOR=2.76; 95% CI: 1.93–3.96) as compared to low dosing.
Table 3.
Results of the bivariable and multivariable logistic regression: re-enrollment adjusted for key characteristics among internally displaced opioid agonist therapies (OAT) patients affected by the military conflict in Donetsk, Luhansk regions and the Autonomous Republic of the Crimea, 2014–2021 (N=1,868)
| Covariables | Crude OR (95% CI) | Adjusted OR (95% CI)╪ |
|---|---|---|
|
| ||
| Region (non-GCA) of re-enrollment | ||
| Donetsk | 5.76 (4.12–8.17)*** | 7.06 (4.97–10.20)*** |
| Luhansk | 5.78 (4.13–8.21)*** | 6.20 (4.38–8.93)*** |
| AR Crimea | ref. | ref. |
| Sex | ||
| Male | 1.37 (0.99–1.92) | - |
| Female | ref. | |
| Age (years) | ||
| 18–34 | 2.88 (1.57– 5.47)*** | 2.03 (1.07–3.96)* |
| 35–44 | 2.88 (1.76– 5.02)*** | 2.09 (1.24–3.71)** |
| 45–54 | 1.86 (1.10– 3.32)* | 1.71 (0.99–3.13) |
| ≥55 | ref. | ref. |
| Drug use experience before OAT initiation | ||
| ≤14 years | ref. | |
| 15–19 years | 0.90 (0.59–1.39) | - |
| ≥20 years | 0.74 (0.51–1.10) | - |
| NA | ||
| Time on OAT before conflict | ||
| < 12 months | ref. | |
| ≥ 12 months | 1.00 (0.77–1.29) | - |
| OAT medication | ||
| Buprenorphine | ref. | |
| Methadone | 0.83 (0.54–1.31) | - |
| OAT dosage§§ | ||
| Low | ref. | ref. |
| Moderate | 1.29 (0.98–1.72) | 1.78 (1.33–2.39)*** |
| High | 1.43 (1.03–1.99)* | 2.76 (1.93–3.96)*** |
| HIV status | ||
| Negative | ref. | |
| Positive | 1.09 (0.85–1.40) | - |
AR = Autonomous Republic
OR = odds ratio
CI = confidence interval
Low: Methadone<40 mg; Buprenorphine <6 mg
Moderate: Methadone 40–85 mg; Buprenorphine 6–15 mg
High: Methadone>85 mg; Buprenorphine >15 mg
Variables that were excluded from the adjusted model using backward selection method: sex, OAT medication, HIV-status.
Table 4 presents regression analysis of OAT retention among the 377 patients re-enrolled at a site in a GCA as of the end of 2021. OAT retention at 12 months after re-enrolment was associated with 15–19 years of injecting drug use experience (aOR=3.69; 95% CI: 1.47–9.49), receiving take-home dosing (aOR=7.42; 95% CI: 3.47–17.89) as compared to daily on-site dosing, and positive HIV status (aOR=3.04; 95% CI:1.43–7.11) dosing as compared to negative HIV status.
Table 4.
Results of the bivariable and multivariable logistic regression: Retained on opioid agonist therapies (OAT) at 12 months after re-enrollment to GCA adjusted for key characteristics among OAT patients affected by the military conflict in Donetsk, Luhansk regions and the Autonomous Republic of the Crimea (N=377)
| Covariables | Crude OR (95% CI) | Adjusted OR (95% CI)╪ |
|---|---|---|
|
| ||
| Region (non-GCA) of referral | ||
| Donetsk | 1.27 (0.64–2.47) | - |
| Luhansk | 1.62 (0.80–3.20) | - |
| AR Crimea | ref. | |
| Sex | ||
| Male | 1.15 (0.58–2.17) | - |
| Female | ref. | |
| Age (years) | ||
| 18–34 | 1.13 (0.30–3.93) | - |
| 35–44 | 1.15 (0.35–3.24) | - |
| 45–54 | 0.86 (0.25–2.58) | - |
| ≥55 | ref. | |
| Injecting drug use experience before OAT initiation | ||
| ≤14 years | ref. | ref. |
| 15–19 years | 3.22 (1.42–7.45)** | 3.69 (1.47–9.49)** |
| ≥20 years | 1.88 (0.94–3.71) | 1.92 (0.89–4.18) |
| OAT medication | ||
| Buprenorphine | ref. | - |
| Methadone | 0.71 (0.25–1.72) | - |
| OAT method of dispensing | ||
| Take home from OAT site | 8.90 (4.52–19.67)*** | 7.42 (3.47–17.89)*** |
| Other | 2.71 (0.96– 9.71) | 2.62 (0.86–9.94) |
| Daily on site | ref. | ref. |
| OAT dosage§§ | ||
| Low | ref. | ref. |
| Moderate | 0.86 (0.45–1.63) | 0.57 (0.29–1.16) |
| High | 2.49 (1.21–5.13)* | 1.51 (0.67–3.43) |
| HIV status | ||
| Negative | ref. | ref. |
| Positive | 4.28 (2.16–9.49)*** | 3.04 (1.43–7.11)** |
GCA = government-controlled area
AR = Autonomous Republic
OR = odds ratio
CI = confidence interval
Low: Methadone<40 mg; Buprenorphine <6 mg
Moderate: Methadone 40–85 mg; Buprenorphine 6–15 mg
High: Methadone>85 mg; Buprenorphine >15 mg
Variables that were excluded from the adjusted model using backward selection method: region of referral, sex, OAT medication, OAT method of dispensing, HIV status.
Transition of internal displacement of OAT patients from sites in Donetsk, Luhansk oblasts, and AR Crimea are presented as Alluvial plots in Figures 2 (from non-GCA Donetsk oblast), 3 (from non-GCA Luhansk oblast), and 4 (from AR Crimea). In 2014, OAT patients from non-GCA Donetsk oblast (Figure 2), were re-enrolled at OAT sites in Zaporizhzhia oblast (19.4%), GCAs of Donetsk (11.3%) and Dnipro (16.1%), and as well as to the City of Kyiv (11.3%), and other oblasts not bordering the conflict areas. In 2015, most of OAT patients moved to OAT sites located in GCAs of Donetsk (53.5%) and Dnipro (11.6%); we observed a similiar trend in 2016. Since 2017, internal displacement has slowed down, with most patients re-enrolled at oblasts that do not border the conflict areas (30.8%) and few re-enrolled at GCAs in Donetsk and Luhansk. In non-GCA Luhansk (Figure 3), most of OAT patients were re-enrolled at OAT sites in Dnipro (28.0%), Zaporizhzhia (13.4%), and Kharkiv oblasts (13.4%); GCAs in Luhansk (4.9%); and the City of Kyiv (15.9%) in 2014. In 2015, a large proportion of OAT patients moved to sites in the GCAs in Luhansk (60.9%) and Kharkiv (17.4%) oblasts. As for AR Crimea (Figure 4), where OAT has not been available since the annexation of the peninsula in May 2014, most OAT patients were re-enrolled at OAT sites in Dnipro oblast (41.7%) and the City of Kyiv (33.3%). In 2015, the largest proportion of OAT patients moved to GCAs in Donetsk (66.7%). There were re-enrollments observed in 2016 and in later years; however, they were not as numerous as in 2014–2015.
Figure 2. Re-enrollment destination for patients receiving opioid agonist therapies (OAT) in non-GCA Donetsk prior to the Russian invasion in 2014 (n=166).
GCA = government-controlled area
Figure 3. Re-enrollment destination for patients receiving opioid agonist therapies (OAT) in non-GCA Luhansk prior to the Russian invasion in 2014 (n=162).
GCA = government-controlled area
Figure 4. Re-enrollment destination for patients receiving opioid agonist therapies (OAT) in Autonomous Republic of Crimea prior to the Russian invasion in 2014 (n=49).
GCA = government-controlled area
Discussion
The 2014 military conflict between Ukraine and Russia resulted in the displacement of up to 1.5 million people from AR Crimea and occupied areas of Donetsk and Luhansk oblasts. Of the OAT patients who had been affected by the military conflict, only one-fifth were re-enrolled into other OAT treatment programs throughout the country, mostly in neighboring oblasts and Kyiv; the large majority were lost-to-follow-up. Those who were lost-to-follow-up could have moved to another country and reenrolled in OAT, moved to another country or oblast and not reenrolled in OAT, stayed in non-GCA Donetsk or Luhansk or occupied AR Crimea without access to OAT, or died. Worth mentioning that the largest OAT site in Donetsk oblast (in the city of Donetsk, the administrative capital of the oblast) continued working for over a year after city’s occupation on moral and volitial efforts of the staff of Donetsk Regional Narcological Dispensary where the OAT site was based.
The odds of re-enrollment were greater for younger patients, who may be more mobile and have greater ability to move to GCAs in the context of the conflict, and for those not in AR Crimea, which was annexed by Russia, likely making re-enrollment more difficult. Re-enrollment was also more likely among those recieving moderate or high OAT dosing as compared to low dosing, which may be explained by the fact that those patients recieving higher OAT doses are more likely to be retained in the program in general (Farnum et al., 2021). Of those who were re-enrolled, less than half were retained in OAT program. Despite the significant associations observed between take-home dispensing, higher medication dosing, and 12-month retention, we cannot infer causality because both variables are associated with time in treatment. Take home dispensing was scaled-up significantly in Ukraine since 2015, which may also confound the association.
OAT medication logistics within Ukraine became difficult after the all-out Russia’s invasion started. The two plants that produce OAT in Ukraine had been closed, and there was only enough stock to cover patients through October 2022. Since March 2022, the Public Health Center of the Ministry of Health of Ukraine, together with partnering organizations, were doing their best to organize logistics and deliver OAT medication, even to the occupied territories (Public Health Center of the Ministry of Health of Ukraine, 2022b). As of May 2023, the program has completely closed in Luhansk region which resulted in closing 15 OAT sites countrywide due to the Russian invasion, which is about 5% of all OAT sites in the country (Public Health Center, 2022; Public Health Center of the Ministry of Health of Ukraine, 2022a). The end and outcome of the current war in Ukraine is difficult to predict (McKee & Nagyova, 2022), but the humanitarian situation is likely to get worse. The current study highlights the substantial, negative impact the Russian invasion is likely to have on OAT patients specifically. The results of this study are subject to some limitations. This was a secondary data analysis of the OAT patient registry maintained for programmatic purposes. First, the SyrEx database ID is not completely unique due to the limited number of symbols it uses however, programmatic experience demonstrates that the share of duplicates is as low as <1%. Secondly, there is no information on what happened to those patients who were lost to follow-up as well as no their basic demographic information such as material status, family status, presence of elderly parents in occupied territories, availability of relatives outside of occupied territories, type of employment etc. There was a cohort of OAT patients who appeared at GCA sites in 2015–2021. Authors’ best guess is that they had probably been out of treatment since 2014 since the authors could monitor only Ukrainian patients’ records and we know that OAT wasn’t available on non-GCA or in Russia. OAT is not available in Russia, and therefore currently there is no access to OAT for people with opioid use disorders in AR Crimea and occupied areas of Donetsk and Luhansk oblasts. It is worth noting that our results were based on OAT patients who had complete data on the variables of our interest. The reasons for patients being lost to follow-up may impact the study results in an unexpected direction. During the conflict, like most of residents the affected areas, OAT patients may have moved away, been too sick to reach out for help, joined the army, or died. Hence, after the OAT sites were closed, very limited information regarding patients’ OAT experiences were available and still are not available unless they re-entered the OAT program in Ukraine. Patients who stayed alive in the conflict areas were unlikely to receive OAT because these Russian occupied areas provided no OAT. A few patients may have moved to other countries where anecdotal information suggests that some received OAT; unfortunately there is currently no systematic data collection on Ukrainian OAT patients receiving treatment elsewhere.
Despite these limitations, the data used for this analysis are unique and include patient-level data managed by a non-governmental organization as well as national OAT site-level data collected by the Public Health Center of the Ministry of Health of Ukraine for all OAT patients, offering a rare opportunity to examine the impact of conflict and displacement on OAT. Additional research is imporatant for both understanding the impact of conflict on OAT outcomes and for planning for addressing the needs of this vulnerable population, particularly as the conflict in Ukraine continues with uncertain end. Further research is also needed to assess the impact of military conflict on both the HIV and HCV care cascades for OAT patients and other health related outcomes such as mental health.
To our knowledge, this is the first and the only study conducted in Ukraine on the impact of the 2014 military conflict in the East of the country and the annexation of AR Crimea on the OAT program outcomes for people with OUD. Ukraine’s health care infrastructure has been a target of Russian airstrikes (Gostin & Rubenstein, 2022) resulting in damage to facilities and medical supplies, injuries and deaths among personnel and patients, hostage taking, and disruption of routine and specialized care. OAT sites have not been spared from this, with 22 sites experiencing damage (Public Health Center of the Ministry of Health of Ukraine, 2022b). News coverage has documented the challenges of moving around certain parts of the country, particularly for civilians trying to leave areas occupied areas and areas under direct attack, convoys have been shelled and evacuees are harassed by Russian troops (Aljazeera.com, 2022; Csete et al., 2016; Human Rights Watch, 2022; Lister T, 2022). This makes it difficult and dangerous for OAT patients to move to Ukainian GCA where OAT is available.
This study provides critical insight into how conflict and displacement affect patients receiving treatment for drug use disorders. One-fifth of patients were linked to treatment sites in non-conflict areas, and approximately half of those re-enrolled were retained in treatment. Disruption of OAT has implications for drug-related, HIV-related, and HCV-related morbidity and mortality, making it an issue of critical importance to public health.
Research in context.
Evidence before this study
We searched PubMed to identify research examined the effects of war, conflict, and displacement on treatment for drug use disorders among non-combatants and found the extant literature to be limited. Greene et al. conducted a scoping review of the literature through October 2018 and found 14 publications (nine among refugees and five in conflict-affected populations) describing substance misuse interventions among conflict-affected populations. Only two of the publications reviewed focused on MOUD; specifically examining OAT in Northeast India, a region experiencing a longstanding insurgent conflict and high burden of injection opioid use. Kumar et al. described drop-in centers for OAT with sublingual buprenorphine run by local non-governmental organizations, three of which had to seek and obtain support from underground militants in order to implement the program. Armstrong et al. evaluated the drop-in centers and found that the program had high retention and reduced HIV risk behaviors, even in that highly constrained environment. We were not able to identify studies since then that explicitly studied OAT in the context of war or conflict.
Added value of this study
To our knowledge, this is the first and the only study conducted in Ukraine on the impact of the 2014 military conflict in the East of the country and the annexation of AR Crimea on the OAT program outcomes for people with OUD. Moreover, this appears to be the only paper to document what happens to OAT patients when conflict causes their programs to close.
Implications of all the available evidence
This study provides critical insight into how conflict and displacement affect patients receiving MOUD. Few patients were re-enrolled at treatment sites in non-conflict areas, but approximately half of those re-enrolled were retained in treatment. Disruption of OAT has implications for drug-related, HIV-related, and HCV-related morbidity and mortality.
Acknowledgments
Funding
AM was funded by NIH-funded grant D43TW010562; DCO was funded by the NIDA-funded Center for Drug Use and HIV|HCV Research (P30DA011041).
Footnotes
Disclaimer: The findings and conclusions of this report are those of the authors and do not necessarily represent the official position of the U.S. Centers for Disease Control and Prevention (CDC).
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