Measuring sustainability of opioid agonist therapy programs in the context of transition from global fund support.

BACKGROUND: Programmatic and financial sustainability of health responses dependent on donor funding has risen as a major concern. In the HIV field in particular, it generated a number of instruments and assessments on sustainability and processes related to donor transition planning. The authors aimed to develop an instrument specific to opioid agonist therapy (OAT) programs as they were addressed only marginally by the HIV-specific assessments. METHODS: The development of the OAT sustainability instrument used desk review of existing HIV sustainability concepts and tools, an International Advisory Board, and piloting to validate the instrument. RESULTS: The new OAT sustainability instrument is comprised of the three parts: the conceptual framework, methodological guidelines and a practical implementation tool for assessing the degree of OAT sustainability at the country level. It measures sustainability in the three broad areas for sustainability measuring-Policy & Governance; Finance & Resources; and Services. The selection of indicators and their composites for the three sustainability areas extensively used the United Nations and World Health Organization's guidance on health system building blocks, on care and HIV and viral hepatitis prevention among people using opioids and for opioid dependence, and the definition of access to health framed by the United Nations Convent on Economic, Social and Cultural Rights. The instrument's methodological guidelines require the engagement of a national consultant to conduct desk review, key informant interviews and focus groups for measuring discrete milestones and adding qualitative information for interpretation of the data, progress and opportunities. The guidelines advise engaging a country-specific multi-stakeholder advisory group for planning, validation and follow-up of the assessment. The pilot of the instrument in 3 countries in 2020 validated it and required minor adjustments in the instrument. By mid-2023, the instrument has been successfully applied in 5 countries. CONCLUSIONS: The developed instrument enables a comprehensive review of the resilience of OAT programs and their ability to scale up and to inform a roadmap for improved sustainability. While developed in the context of Eastern Europe and Central Asia, it has been reviewed by a global advisory panel and could be easily adapted outside this regional context.

A scalable, integrated intervention to engage people who inject drugs in HIV care and medication-assisted treatment (HPTN 074): a randomised, controlled phase 3 feasibility and efficacy study.

BACKGROUND: People who inject drugs (PWID) have a high incidence of HIV, little access to antiretroviral therapy (ART) and medication-assisted treatment (MAT), and high mortality. We aimed to assess the feasibility of a future controlled trial based on the incidence of HIV, enrolment, retention, and uptake of the intervention, and the efficacy of an integrated and flexible intervention on ART use, viral suppression, and MAT use. METHODS: This randomised, controlled vanguard study was run in Kyiv, Ukraine (one community site), Thai Nguyen, Vietnam (two district health centre sites), and Jakarta, Indonesia (one hospital site). PWID who were HIV infected (index participants) and non-infected injection partners were recruited as PWID network units and were eligible for screening if they were aged 18-45 years (updated to 18-60 years 8 months into study), and active injection drug users. Further eligibility criteria for index participants included a viral load of 1000 copies per mL or higher, willingness and ability to recruit at least one injection partner who would be willing to participate. Index participants were randomly assigned via a computer generated sequence accessed through a secure web portal (3:1) to standard of care or intervention, stratified by site. Masking of assignment was not possible due to the nature of intervention. The intervention comprised systems navigation, psychosocial counselling, and ART at any CD4 count. Local ART and MAT services were used. Participants were followed up for 12-24 months. The primary objective was to assess the feasibility of a future randomised controlled trial. To achieve this aim we looked at the following endpoints: HIV incidence among injection partners in the standard of care group, and enrolment and retention of HIV-infected PWID and their injection partners and the uptake of the integrated intervention. The study was also designed to assess the feasibility, barriers, and uptake of the integrated intervention. Endpoints were assessed in a modified intention-to-treat popualtion after exclusion of ineligible participants. This trial is registered on ClinicalTrials.gov, NCT02935296, and is active but not recruiting new participants. FINDINGS: Between Feb 5, 2015, and June 3, 2016, 3343 potential index participants were screened, of whom 502 (15%) were eligible and enrolled. 1171 injection partners were referred, and 806 (69%) were eligible and enrolled. Index participants were randomly assigned to intervention (126 [25%]) and standard of care (376 [75%]) groups. At week 52, most living index participants (389 [86%] of 451) and partners (567 [80%] of 710) were retained, and self-reported ART use was higher among index participants in the intervention group than those in the standard of care group (probability ratio [PR] 1·7, 95% CI 1·4-1·9). Viral suppression was also higher in the intervention group than in the standard of care group (PR 1·7, 95% CI 1·3-2·2). Index participants in the intervention group reported more MAT use at 52 weeks than those in the standard of care group (PR 1·7, 95% CI 1·3-2·2). Seven incident HIV infections occurred, and all in injection partners in the standard of care group (intervention incidence 0·0 per 100 person-years, 95% CI 0·0-1·7; standard of care incidence 1·0 per 100 person-years, 95% CI 0·4-2·1; incidence rate difference -1·0 per 100 person-years, 95% CI -2·1 to 1·1). No severe adverse events due to the intervention were recorded. INTERPRETATION: This vanguard study provides evidence that a flexible, scalable intervention increases ART and MAT use and reduces mortality among PWID. The low incidence of HIV in both groups impedes a future randomised, controlled trial, but given the strength of the effect of the intervention, its implementation among HIV-infected PWID should be considered. FUNDING: US National Institutes of Health.

HIV, Drug Injection, and Harm Reduction Trends in Eastern Europe and Central Asia: Implications for International and Domestic Policy.

PURPOSE OF REVIEW: Scaling up evidence-based HIV prevention strategies like opioid agonist therapies (OAT), syringe services programs (SSPs), and antiretroviral therapy (ART) to mitigate the harms of drug injection is crucial within Eastern Europe and Central Asia (EECA), the only region globally where HIV incidence and mortality are increasing. RECENT FINDINGS: Though the proportion of new HIV cases directly attributable to drug injection has recently declined, it remains a critical driver of HIV, especially to sexual partners. Concurrently, scale-up of OAT, SSPs, and ART has remained low, contributing to a volatile HIV epidemic among people who inject drugs (PWID). Despite evidence that drug injection contributes to an evolving HIV epidemic in EECA, coverage of evidence-based harm reduction programs remains substantially below needed targets. Due to a combination of punitive drug laws, ideological resistance to OAT among clinicians and policymakers, and inadequate domestic and international funding, limited progress has been observed in increasing the availability of these programs.

The perfect storm: incarceration and the high-risk environment perpetuating transmission of HIV, hepatitis C virus, and tuberculosis in Eastern Europe and Central Asia.

Despite global reductions in HIV incidence and mortality, the 15 UNAIDS-designated countries of Eastern Europe and Central Asia (EECA) that gained independence from the Soviet Union in 1991 constitute the only region where both continue to rise. HIV transmission in EECA is fuelled primarily by injection of opioids, with harsh criminalisation of drug use that has resulted in extraordinarily high levels of incarceration. Consequently, people who inject drugs, including those with HIV, hepatitis C virus, and tuberculosis, are concentrated within prisons. Evidence-based primary and secondary prevention of HIV using opioid agonist therapies such as methadone and buprenorphine is available in prisons in only a handful of EECA countries (methadone or buprenorphine in five countries and needle and syringe programmes in three countries), with none of them meeting recommended coverage levels. Similarly, antiretroviral therapy coverage, especially among people who inject drugs, is markedly under-scaled. Russia completely bans opioid agonist therapies and does not support needle and syringe programmes-with neither available in prisons-despite the country's high incarceration rate and having the largest burden of people with HIV who inject drugs in the region. Mathematical modelling for Ukraine suggests that high levels of incarceration in EECA countries facilitate HIV transmission among people who inject drugs, with 28-55% of all new HIV infections over the next 15 years predicted to be attributable to heightened HIV transmission risk among currently or previously incarcerated people who inject drugs. Scaling up of opioid agonist therapies within prisons and maintaining treatment after release would yield the greatest HIV transmission reduction in people who inject drugs. Additional analyses also suggest that at least 6% of all incident tuberculosis cases, and 75% of incident tuberculosis cases in people who inject drugs are due to incarceration. Interventions that reduce incarceration itself and effectively intervene with prisoners to screen, diagnose, and treat addiction and HIV, hepatitis C virus, and tuberculosis are urgently needed to stem the multiple overlapping epidemics concentrated in prisons.

Why People Who Inject Drugs Voluntarily Transition Off Methadone in Ukraine.

Methadone maintenance therapy (MMT) treats opioid use disorder among people who inject drugs (PWID). To understand why PWID may voluntarily discontinue MMT, we analyzed data from 25 focus groups conducted in five Ukrainian cities from February to April 2013 with 199 participants who were currently, previously, or never on MMT. Using constant comparison method, we uncovered three themes explaining why PWID transition off MMT: (a) purposeful resistance to rigid social control associated with how MMT is delivered and to power asymmetries in provider-patient relationships, (b) self-management of a PWID's "wounded identity" that is common in socially stigmatized and physically sick persons-MMT serves as a reminder of their illness, and (c) the quest for a "normal life" uninterrupted by daily MMT site visits, harassment, and time inefficiencies, resources, and social capital. Focusing on holistic principles of recovery would improve addiction treatment and HIV prevention in Ukraine and globally.

"Bureaucracy & Beliefs": Assessing the Barriers to Accessing Opioid Substitution Therapy by People Who Inject Drugs in Ukraine.

AIMS: Opioid substitution therapy (OST) is an evidence-based HIV prevention strategy for people who inject drugs (PWIDs). Yet, only 2.7% of Ukraine's estimated 310,000 PWIDs receive it despite free treatment since 2004. The multi-level barriers to entering OST among opioid dependent PWIDs have not been examined in Ukraine. METHODS: A multi-year mixed methods implementation science project included focus group discussions with 199 PWIDs in 5 major Ukrainian cities in 2013 covering drug treatment attitudes and beliefs and knowledge of and experiences with OST. Data were transcribed, translated into English and coded. Coded segments related to OST access, entry, knowledge, beliefs and attitudes were analyzed among 41 PWIDs who were eligible for but had never received OST. FINDINGS: A number of programmatic and structural barriers were mentioned by participants as barriers to entry to OST, including compulsory drug user registration, waiting lists, and limited number of treatment slots. Participants also voiced strong negative attitudes and beliefs about OST, especially methadone. Their perceptions about methadone's side effects as well as the stigma of being a methadone client were expressed as obstacles to treatment. CONCLUSIONS: Despite expressed interest in treatment, Ukrainian OST-naïve PWIDs evade OST for reasons that can be addressed through changes in program-level and governmental policies and social-marketing campaigns. Voiced OST barriers can effectively inform public health and policy directives related to HIV prevention and treatment in Ukraine to improve evidence-based treatment access and availability.

Lost-to-care and engaged-in-care HIV patients in Leningrad Oblast, Russian Federation: barriers and facilitators to medical visit retention.

Sixty-nine percent of the 1.5 million Eastern Europeans and Central Asians with HIV live in the Russian Federation. Antiretroviral therapy (ART) is effective but cannot help those who leave treatment. Focus groups with patients who dropped out of ART for ≥12 months (lost-to-care, LTCs, n = 21) or continued for ≥12 months (engaged-in-care; EICs; n = 24) were conducted in St. Petersburg. Structural barriers included stigma/discrimination and problems with providers and accessing treatment. Individual barriers included employment and caring for dependents, inaccurate beliefs about ART (LTC only), side-effects, substance use (LTCs, present; EICs, past), and depression. Desire to live, social support, and spirituality were facilitators for both; EICs also identified positive thinking and experiences with ART and healthcare/professionals. Interventions to facilitate retention and adherence are discussed.

Preferences and decisional considerations relating to opioid agonist therapy among Ukrainian people who use drugs: A conjoint analysis survey.

Scaling up opioid agonist therapies (OAT) is the most effective strategy to control combined HIV and opioid epidemics, especially in Eastern Europe and Central Asia (EECA), where HIV incidence and mortality continue to increase. Patient concerns about OAT, however, have undermined scale-up. The objective of this study is to understand Ukrainian opioid use disorder patient preferences about OAT to guide the development of an evidence-informed decision aid for clinical decision-making. We conducted a conjoint-based choice (CBC) survey. Participants were asked to about their preferences relating to 7 attributes of OAT (cost, dosing frequency, concerns about withdrawal symptoms, adverse side effects, improvements in quality of life, precipitation of withdrawal and legislative requirements to be registered as a drug dependent person) and 20 attribute levels for receiving OAT under differing potential treatment constraints. Data were analyzed using Hierarchical Bayesian models. Using respondent-driven sampling and random sampling, we recruited 2,028 people who inject drugs with opioid use disorder. Relative importance (RIS) and partial-worth utility scores (PWUS) were used to assess preferences for attributes and thresholds within each attribute. Cost and dosing frequency were the most important attributes (RIS = 39.2% and RIS = 25.2%, respectively) to potential patients, followed by concerns about withdrawal symptoms (RIS = 10.8%), adverse side effects (RIS = 9.0%), quality-of-life improvement (RIS = 7.5%), precipitation of euphoria (5.2%) and requirement to be registered as a drug- dependent person (RIS = 3.1%). The monthly cost-threshold for willingness-to-pay was 1,900 UAH ($70 USD). In Ukraine, where both governmental and private OAT clinics have emerged and provide markedly different delivery strategies, preferences are mostly driven by out-of-pocket expenses, despite many patients being willing to pay for OAT. Programmatic demands (flexibility and ease of acquiring medications) remain an important consideration while for a minority, clinical concerns about withdrawal symptoms, adverse side effects and OAT impact on life play a smaller role.

Design and implementation of a Type-2 hybrid, prospective randomized trial of opioid agonist therapies integration into primary care clinics in Ukraine.

INTRODUCTION: Ukraine has high HIV prevalence, concentrated among people who inject drugs (PWID), mostly of opioids. Maintenance on opioid agonist therapies (OAT) is the most effective evidence-based treatment for opioid use disorder. As PWID experience high morbidity and mortality from preventable and treatable non-communicable diseases, international agencies recommend integrating OAT into primary care centers (PCC). METHODS: A randomized, type-2 hybrid implementation trial was carried out to compare outcomes of OAT integration in PCC to OAT delivery at specialty treatment centers (STC) - standard-of-care. Tele-education supporting PCC providers in managing OAT, HIV, tuberculosis and non-communicable diseases along with pay-for-performance incentives were used to facilitate implementation. Consenting patients underwent 1:2 randomization to either STC or PCC. Quality health indicators (QHIs), a composite percentage of recommended primary and specialty services accessed by patients (blood/urine tests, cancer screenings, etc.), were defined as efficacy outcomes and were assessed by participant self-report at baseline and every 6 months over 24 months and electronic chart reviews after the completion of the follow-up. The primary outcome is defined as the difference in composite QHI scores at 24 months, in which a repeated measures likelihood-based mixed model with missing at random assumptions will be used. Providers at PCC completed surveys at baseline, 12 and 24 months to assess implementation outcomes including changes in stigma and attitudes towards OAT and PWID. PRELIMINARY RESULTS: Among the 1459 participants allocated to STC (N = 509) or PCC (N = 950), there were no differences in clinical and demographic characteristics. Self-reported prevalences were available for HIV (42 %), HCV (57 %), and prior tuberculosis (17 %). Study retention at 6, 12, 18, and 24 months was as 91 %, 85 %, 80 %, and 74 %, respectively. CONCLUSION: PWID have a high prevalence of medical comorbidities and integrating OAT into primary care settings has the potential to improve the health of PWID. Findings from this study can help guide implementation of integrated care in Ukraine and throughout similar low-resource, high-burden countries in the Eastern European and Central Asian region.

High rates of deferring antiretroviral treatment for patients with HIV and substance use disorders: Results from a national sample of HIV physicians in Ukraine.

BACKGROUND: HIV incidence and mortality are increasing in Ukraine despite their reductions globally, in part due to suboptimal antiretroviral therapy (ART) coverage in key populations of people with HIV (PWH) where the epidemic is concentrated. As physicians are gatekeepers to ART prescription, stigma and discrimination barriers are understudied as a key to meeting HIV treatment targets in key populations. METHODS: A national sample (N = 204) of ART-prescribing physicians in Ukraine were surveyed between August and November 2019. Participants underwent a series of randomized, hypothetical HIV clinical scenarios and decided whether to initiate or defer (or withhold) ART. Scenarios varied based on 5 distinct CD4 counts (CD4: 17, 176, 305, 470, or 520 cells/mL) and 10 different PWH key populations. Z scores and McNemar's test for paired samples were used to assess differences between key populations and CD4 count. Feeling thermometers were used to assess stigma-related measures toward key populations among physicians. RESULTS: Physicians were highly experienced (mean = 19 years) HIV treaters, female (80.4%), and trained in infectious diseases (76.5%). Patients who drink alcohol (range: 21.6%-23.5%) or use (PWUD range: 16.7%-20.1%) or inject (PWID range: 15.5%-20.1%) drugs were most likely to have ART deferred, even at AIDS-defining CD4 counts. PWID maintained on methadone, however, were significantly (p<0.001) less likely to have ART deferred compared with those who were not (range: 7.8%-12.7%) on methadone. Men who have sex with men (range: 5.4%-10.8%), transgender women (range: 4.9%-11.3%), sex workers (range: 3.9%-10.3%),and having an HIV-uninfected sex partner (range: 3.9%-9.3%) had the lowest likelihood of ART deferral. Increasing levels of stigma (i.e., feeling thermometers) towards a key population was correlated with ART deferral (i.e., discrimination). CONCLUSIONS: Despite international and Ukrainian guidelines recommending ART prescription for all PWH, irrespective of risk or CD4 count, ART deferral by experienced HIV experts remains high in certain key populations, especially in PWH and substance use disorders. Strategies that initiate ART immediately after diagnosis (i.e., rapid start antiretroviral therapy), independent of risk group, should be prioritized to truly mitigate the current epidemic.

Integrating methadone into primary care settings in Ukraine: effects on provider stigma and knowledge.

INTRODUCTION: Stigma has undermined the scale-up of evidence-based HIV prevention and treatment. Negative beliefs influence clinicians' discriminatory behaviour and ultimately have wide-ranging effects across the HIV prevention and treatment continuum. Stigma among clinicians can be mitigated in several ways, including through interpersonal contact. In this study, we test whether interactions with people who inject drugs (PWID) influence attitudes of both direct and indirect providers of opioid agonist therapies (OATs) within the same primary care clinics (PCCs) where OAT is newly introduced. METHODS: In a cluster randomized controlled trial integrating OAT and HIV care into PCCs in Ukraine, clinicians at 24 integrated care sites (two sites in 12 regions) from January 2018 to August 2022 completed a structured survey at baseline, 12 and 24 months. The survey included feeling thermometers and standardized scales related to clinician attitudes towards patients and evidence-based care. Nested linear mixed-effects models were used to examine changes in mean scores over three timepoints for both direct and indirect clinicians. RESULTS: There were fewer significant changes in any of the scales for direct providers (n = 87) than for indirect providers (n = 155). Direct providers became less tough-minded about substance use disorders (p = 0.002), had less negative opinions about PWID (p = 0.006) and improved their beliefs regarding OAT maintenance (p<0.001) and medical information (p = 0.004). Indirect providers reported improvements in most stigma constructs, including a significant decrease in prejudice (p<0.001), discrimination (p = 0.001), shame (p = 0.007) and fear (p = 0.001) towards PWID. CONCLUSIONS: Integrating OAT services within primary settings was associated with significantly reduced stigma constructs and improved attitudes towards PWID, possibly through increased intergroup contact between PWID and general clinical staff. Unlike most stigma reduction interventions, re-engineering clinical processes so that PWID receive their care in PCCs emerges as a multilevel stigma reduction intervention through the integration of specialized services in PCCs. Integration influences different types of stigma, and has positive effects not only on health outcomes, but also improves clinician attitudes and efficiently reduces clinician stigma.

Aligning public health and public safety: Probation as a touchpoint to identify and link patients with opioid use disorder to opioid agonist treatment.

BACKGROUND: People in criminal justice settings (CJS) have high rates of opioid use disorder (OUD) and HIV. Probation is part of the CJS and congregates many individuals with high rates of mental health and substance use disorders relative to the general population; nevertheless, probation remains a major improvement to incarceration. As a steppingstone to full decarceration efforts, community supervision settings like probation can be leveraged as "touchpoints" to identify and link people with OUD (and other co-morbid conditions) to treatment and reduce criminal activity. METHODOLOGY: To determine the feasibility of a modified screening, brief intervention and referral to treatment (SBIRT) strategy to link probationers to opioid agonist therapies (OAT) in the newly created probation system in Ukraine, we conducted a single-arm SBIRT intervention in eight probation centers in four Ukrainian administrative regions. For those screening positive for OUD, interest in OAT was assessed before and after a brief intervention. Those interested in OAT were referred to community OAT services. Participants with OUD also underwent HIV testing. PRINCIPAL FINDINGS: Of the 1,298 consecutive individuals screened, 208 (16.0%) met criteria for opioid dependence. Of these, 122 (58.7%) enrolled in brief intervention, of which 54 (44.3%) had HIV and 14 (25.9%) of these were newly diagnosed. After the brief intervention, interest in starting OAT increased significantly from a median of 7.0 to 8.0 (P = <0.001) using a 10-point scale. Thirty (N = 30; 24.6%) of the enrolled participants initiated OAT and 21 of these (70%) were retained in treatment for 6 months. SIGNIFICANCE: The prevalence of OUD (and HIV) is high among people in probation in Ukraine. SBIRT can identify a large number of people eligible for OAT, many of whom were willing to initiate and remain on OAT. Integrating SBIRT into probation can potentially assist with OAT scale-up and help address HIV prevention efforts.

Design, implementation and preliminary results of a type-2 hybrid cluster-randomized trial of integrating screening and treatment for major depressive disorder into specialty clinics providing opioid agonist therapies in Ukraine.

INTRODUCTION: Ukraine has a high prevalence of co-occurring disorders (COD), defined as having both substance use (SUD) and psychiatric disorders. Major depressive disorder (MDD) is the most prevalent psychiatric disorder among people with SUD. People with COD experience poor health outcomes, and international agencies propose integrated COD care. In Ukraine, treatment for SUD is delivered in specialized substance use clinics, without providing any other medical services for comorbidities, including MDD. Here we present the protocol, along the with the preliminary results of the MEDIUM project, including observations over the first 6 months. METHODS: A cluster-randomized type-2 hybrid trial was conducted to integrate MDD treatment into specialty clinics providing opioid agonist therapies (OAT) in Ukraine. Twelve clinics in four regions underwent randomization to control (N = 1) vs experimental arms (N = 2) in each region. Clinicians at experimental sites received tele-education through modified project ECHO using a facilitated screening, evaluation, and treatment algorithm of depression, with or without financial incentives. Service-, patient- and provider-level data were collected for the analysis every 6 months for 24 months. PRELIMINARY RESULTS: For service delivery outcomes, 4421 patients enrolled on OAT across all sites were assessed for MDD for screening (76.7%), evaluation with diagnosis (43.5%) and treatment (30.7%) for MDD; 13.8% continued treatment at least for 6 months. For patient-level outcomes, 1345 patients and 54 providers participated in serial surveys every six months. CONCLUSION: This study will be the first to explore integrated COD care in Ukraine and generate evidence on effective service integration and delivery strategies for people with COD receiving treatment at substance use clinics with broader implications for Eastern Europe and Central Asia region.

Preliminary analysis of self-reported quality health indicators of patients on opioid agonist therapy at specialty and primary care clinics in Ukraine: A randomized control trial.

International agencies recommend integrating addiction treatment into primary care for people who inject drugs (PWID) with opioid use disorder (OUD). Empirical data supporting integration that incorporates comprehensive health outcomes, however, are not known. For this randomized controlled trial in Ukraine, adult PWID with OUD were randomized to receive opioid agonist therapy (OAT) in specialty addiction treatment clinics (SATC) or to primary care clinics (PCCs). For those randomized to PCC, they were subsequently allocated to PCCs where clinicians received pay-for-performance (P4P) incentives (PCC with P4P) or not (PCC without P4P). Participating cities had one of each of the three intervention sites to control for geographic variation. Ongoing tele-education specialty training (OAT, HIV, tuberculosis) was provided to all PCCs. While the primary outcome for the parent trial focuses on patient medical record data, this preliminary analysis focuses on assessment of self-reported achievement of nationally recommended quality health indicators (QHIs) which is summed as a composite QHI score. Secondary outcomes included specialty and primary care QHI subscores. This study occurred from 01/20/2018-11/1/2020 with 818 of 990 randomized participants having complete self-reported data for analysis. Relative to SATC (treatment as usual), the mean composite QHI score was 12.7 (95% CI: 10.1-15.3; p<0.001) percentage points higher at PCCs; similar and significantly higher scores were observed in PCCs compared to SATCs for both primary care (PCC vs SATC: 18.4 [95% CI: 14.8-22.0; p<0.001] and specialty (PCC vs SATC: 5.9 [95% CI: 2.6-9.2; p<0.001] QHI scores. Additionally, the mean composite QHI score was 4.6 (95% CI: 2.0-7.2; p<0.001) points higher in participants with long term (>3 months) experience with OAT compared to participants newly initiating OAT. In summary, PWID with OUD receive greater primary care and specialty healthcare services when receiving OAT at PCCs supported by tele-education relative to treatment as usual provided in SATCs. Clinical trial registration: This trial was registered at clinicaltrials.gov and can be found using the following registration number: NCT04927091.

The development and initial validation of the Russian version of the BASIS-24.

BACKGROUND: Efficient and linguistically appropriate instruments are needed to assess response to addiction treatment, including severity of addiction/mental health status. This is critical for Russian-speaking persons in Eastern Europe and Central Asia (EECA) where Medications for Opioid Use Disorder (MOUD) remain underscaled to address expanding and intertwined opioid, HIV, HCV and tuberculosis epidemics. We developed and conducted a pilot validation of a Russian version of the 24-item Behavior and Symptom Identification Scale (BASIS-24), an addiction/mental health severity instrument with six subscales, previously validated in English. METHODS: Using the Mapi approach, we reviewed, translated, and back-translated the content to Russian, pilot-tested the Russian-version (BASIS-24-R) among new MOUD patients in Ukraine (N = 283). For a subset of patients (n = 44), test-rest was performed 48 h after admission to reassess reliability of BASIS-24-R. Exploratory principal component analysis (PCA) assessed underlying structure of BASIS-24-R. RESULTS: Cronbach alpha coefficients for overall BASIS-24-R and 5 subscales exceeded 0.65; coefficient for Relationship subscale was 0.42. The Pearson correlation coefficients for overall score and all subscales on the BASIS-24-R exceeded 0.8. Each item loaded onto factors that corresponded with English BASIS-24 subscales ≥ 0.4 in PCA. CONCLUSION: Initial version of BASIS-24-R appears statistically valid in Russian. Use of the BASIS-24-R has potential to guide MOUD treatment delivery in the EECA region and help to align addiction treatment with HIV prevention goals in a region where HIV is concentrated in people who inject opioids and where healthcare professionals have not traditionally perceived MOUD as effective treatment, particularly for those with mental health co-morbidities.

The real-world impact of dosing of methadone and buprenorphine in retention on opioid agonist therapies in Ukraine.

BACKGROUND AND AIMS: Ukraine's HIV epidemic remains concentrated among opioid-dependent people who inject drugs (PWID) where opioid agonist therapies (OAT) like methadone (MMT) and buprenorphine (BMT) maintenance treatments are the most cost-effective HIV prevention strategies, but remain under-scaled. This study aimed to measure the association between dose and type of OAT prescribed and treatment retention. DESIGN: Observational longitudinal cohort study. PARTICIPANTS AND SETTING: Patients (n = 15 290) prescribed OAT throughout Ukraine from 2004 through 2016. MEASUREMENTS: Data were analyzed using time-event strategies to estimate cumulative treatment retention, defined as time to OAT discontinuation. Cumulative retention proportions at 1, 12 and 36 months were assessed for outcomes. Cox regression with log-rank likelihood assessed independent predictors of treatment discontinuation. FINDINGS: The proportion prescribed high (MMT: > 85 mg; BMT: ≥ 16 mg), medium (MMT: > 40-85 mg; BMT: > 6-15 mg) and low (MMT: ≤ 40 mg; BMT: ≤ 6 mg) dosages was 25, 43 and 32%, respectively. Retention was significantly higher for BMT than MMT both at 12 (89 versus 75%) and 36 months (80 versus 56%). Although dosing levels for BMT did not influence retention, increasing dosages for MMT were significantly associated with higher retention rates at 1 (90, 96, 99%), 12 (59, 78, 91%) and 36 (34, 59, 79%) months, respectively. Independent predictors associated with 12-month OAT discontinuation were medium [adjusted hazard ratio (aHR) = 2.23; 95% confidence limit (CL) = 1.95-2.54] and low (aHR = 4.96; 95% CL = 4.37-5.63) OAT dosage relative to high dosage, male sex (aHR = 1.27; 95% CL = 1.14-1.41), MMT relative to BMT prescription (aHR = 1.57; 95% CL = 1.32-1.87) and receiving OAT in general (aHR = 1.22; 95% CL = 1.02-1.46) or tuberculosis (aHR = 1.43; 95% CL = 1.10-1.85) hospitals, relative to specialty addiction treatment and AIDS center settings. Lower dosages contributed more to dropout especially at 1 month (aHR 3.12; 95% CL = 2.21-4.41 and aHR 7.71; 95% CL = 5.51-10.79 for medium and low dosages, respectively). Younger age was significantly associated with OAT discontinuation only at 36 months (aHR = 1.08; 95% CI = 1.02-1.15). CONCLUSIONS: Higher dosages of opioid agonist therapies, especially for methadone maintenance treatment patients, appear to be associated with higher levels of treatment retention in Ukraine.

Engaging People Who Inject Drugs Living With HIV in Antiretroviral Treatment and Medication for Opioid Use Disorder: Extended Follow-up of HIV Prevention Trials Network (HPTN) 074.

BACKGROUND: People who inject drugs (PWID) living with HIV experience inadequate access to antiretroviral treatment (ART) and medication for opioid use disorders (MOUD). HPTN 074 showed that an integrated intervention increased ART use and viral suppression over 52 weeks. To examine durability of ART, MOUD, and HIV viral suppression, participants could re-enroll for an extended follow-up period, during which standard-of-care (SOC) participants in need of support were offered the intervention. METHODS: Participants were recruited from Ukraine, Indonesia and Vietnam and randomly allocated 3:1 to SOC or intervention. Eligibility criteria included: HIV-positive; active injection drug use; 18-60 years of age; ≥1 HIV-uninfected injection partner; and viral load ≥1,000 copies/mL. Re-enrollment was offered to all available intervention and SOC arm participants, and SOC participants in need of support (off-ART or off-MOUD) were offered the intervention. RESULTS: The intervention continuation group re-enrolled 89 participants, and from week 52 to 104, viral suppression (<40 copies/mL) declined from 41% to 29% (estimated 9.4% decrease per year, 95% CI -17.0%; -1.8%). The in need of support group re-enrolled 94 participants and had increased ART (re-enrollment: 55%, week 26: 69%) and MOUD (re-enrollment: 16%, week 26: 25%) use, and viral suppression (re-enrollment: 40%, week 26: 49%). CONCLUSIONS: Viral suppression declined in year 2 for those who initially received the HPTN 074 intervention and improved maintenance support is warranted. Viral suppression and MOUD increased among in need participants who received intervention during the study extension. Continued efforts are needed for widespread implementation of this scalable, integrated intervention.

Divergent estimates of HIV incidence among people who inject drugs in Ukraine.

BACKGROUND: Divergent estimates of HIV incidence among people who inject drugs (PWID) in Ukraine have been reported in modeling studies, longitudinal cohort studies, and recent infection assays used in cross-sectional surveys. Estimates range from 0.65 to 24.8 infections per 100 person-years with substantial regional variation. In this paper, we study the sources of this discrepancy. METHODS: We compared baseline characteristics of study subjects recruited in the cross-sectional integrated bio-behavioral surveillance surveys (IBBS) in 2011 and 2013, with those from the longitudinal network intervention trial (network RCT) conducted between 2010 - 2013, the study that found a remarkably high incidence of HIV among PWID in Ukraine. The analysis was conducted for two cities: Mykolaiv and Odesa. RESULTS: Significant differences were found in the characteristics of study subjects recruited in the IBBS surveys and the network RCT, in particular in Odesa, where the mismatch in the estimates of HIV incidence is greatest. In Odesa, recent syringe sharing was about three times as prevalent in the network RCT as in the IBBS; 39% of the network RCT and 16-18% of the IBBS participants indicated stimulants rather than opiates as their drug of choice; 97% of respondents in the network RCT and 45% in the IBBS-2013 reported injecting in a group over half of the time; and the average monthly number of injections in the network RCT was about twice that in the IBBS studies. CONCLUSIONS: Differences in study designs and sampling methodologies may be responsible for the substantial differences in HIV incidence estimates among PWID in Ukraine. The potential sources of selection bias differed between the studies and likely resulted in the recruitment of lower risk individuals into the IBBS studies compared to the network RCT. Risk stratification in the population of PWID may have implications for future surveillance and intervention efforts.

Treating opioid dependence with extended-release naltrexone (XR-NTX) in Ukraine: Feasibility and three-month outcomes.

BACKGROUND: Although opioid agonist treatments (OAT) with methadone or buprenorphine are available to treat opioid use disorders (OUD) in Ukraine, OAT acceptability and coverage remains low. Extended-release naltrexone (XR-NTX) that recently became available as another treatment option provides new opportunities for treating OUDs in this region and we aimed to test its feasibility. METHODS: Patients with OUD (N=135) and interested in treatment with XR-NTX were initiated on monthly XR-NTX injections and monitored for three months. Correlates of 3-month retention on XR-NTX and drug use at each time-point using self-reports and urine drug testing (UDT) were assessed. RESULTS: Of the 134 participants initiated XR-NTX, 101 (75%) completed three months, defined as 4 consecutive XR-NTX injections. Independent factors negatively associated with retention in XR-NTX treatment included previous maintenance with OAT (aOR=0.3; 95%CI=0.1-0.9) and extrinsic help-seeking treatment motivation (aOR=0.7; 95%CI=0.5-0.9). Of these 101 participants completing three months of treatment, opioid use markedly reduced using self-report (67%% to 22%; p>0.001) and UDT (77% to 24%; p<0.001) outcomes over time. Alcohol, marijuana and stimulant use, however, remained unchanged. Craving for opioids and symptoms of depression also significantly decreased, while health-related quality of life scores improved over time. No adverse side effects were reported during the period of observation. CONCLUSION: The first introduction of XR-NTX in Ukraine among persons with OUD resulted in high levels of retention, marked reductions in opioid use and improved quality of life. These descriptive results suggest that XR-NTX treatment is feasible and well-tolerated over a 3-month period in Ukraine.