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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Regional differences between people who inject drugs in an HIV prevention trial integrating treatment and prevention (HPTN 074): a baseline analysis.

INTRODUCTION: People who inject drugs (PWID) experience high HIV incidence and face significant barriers to engagement in HIV care and substance use treatment. Strategies for HIV treatment as prevention and substance use treatment present unique challenges in PWID that may vary regionally. Understanding differences in the risk structure for HIV transmission and disease progression among PWID is essential in developing and effectively targeting intervention strategies of HIV treatment as prevention. METHODS: We present a baseline analysis of HIV Prevention Trials Network (HPTN) 074, a two-arm, randomized controlled trial among PWID in Indonesia (n = 258), Ukraine (n = 457) and Vietnam (n = 439). HPTN 074 was designed to determine the feasibility, barriers and uptake of an integrated intervention combining health systems navigation and psychosocial counselling for the early engagement of antiretroviral therapy (ART) and substance use treatment for PWID living with HIV. Discordant PWID networks were enrolled, consisting of an HIV-positive index and their HIV-negative network injection partner(s). Among the enrolled cohort of 1154 participants (502 index participants and 652 network partners), we examine regional differences in the baseline risk structure, including sociodemographics, HIV and substance use treatment history, and injection and sexual risk behaviours. RESULTS: The majority of participants were male (87%), with 82% of the enrolled females coming from Ukraine. The overall mean age was 34 (IQR: 30, 38). Most commonly injected substances included illegally manufactured methadone in Ukraine (84.2%), and heroin in Indonesia (81.8%) and Vietnam (99.5%). Injection network sizes varied by region: median number of people with whom participants self-reported injecting drugs was 3 (IQR: 2, 5) in Indonesia, 5 (IQR: 3, 10) in Ukraine and 3 (IQR: 2, 4) in Vietnam. Hazardous alcohol use, assessed using the Alcohol Use Disorders Identification Test - Alcohol Consumption Questions (AUDIT-C), was prominent in Ukraine (54.7%) and Vietnam (26.4%). Reported sexual risk behaviours in the past month, including having two or more sex partners and giving/receiving money or drugs in exchange for sex, were uncommon among all participants and regions. CONCLUSIONS: While regional differences in risk structure exist, PWID particularly in Ukraine need immediate attention for risk reduction strategies. Substantial regional differences in risk structure will require flexible, tailored treatment as prevention interventions for distinct PWID populations.

Opioid Agonist Treatment and Improved Outcomes at Each Stage of the HIV Treatment Cascade in People Who Inject Drugs in Ukraine.

BACKGROUND: The HIV treatment cascade is a crucial tool to guide HIV prevention and treatment strategies. The extent to which opioid agonist treatments (OATs) such as methadone and buprenorphine influence this cascade was examined in a nationwide study of people who inject drugs (PWID) in Ukraine. SETTING: Cross-sectional stratified survey of PWID followed by HIV and hepatitis C virus testing in 5 Ukrainian cities. METHODS: Opioid-dependent PWID (N = 1613) were sampled from January 2014 to March 2015. Analysis was confined to 520 participants with HIV, with 184 (35.4%) prescribed OAT. Weighted logistic regression models were used to assess independent factors associated with the 5 steps in the HIV treatment cascade. RESULTS: Compared with PWID not on OAT (N = 336), participants who prescribed OAT (N = 184) were significantly more likely to be diagnosed (91% vs. 71%), linked (81% vs. 52%), and retained (69% vs. 35%) in HIV care, and prescribed (56% vs. 31%) and optimally (>95% of doses) adherent to antiretroviral therapy (41% vs. 22%). Receiving OAT contributed most as an independent factor with every step of the cascade. Other steps in the HIV treatment cascade were influenced by age, depression, and geographical variability. CONCLUSIONS: OAT remains an essential and effective strategy to not only treat patients with opioid use disorder, but also a crucial strategy to engage PWID in care to meet UNAIDS 90-90-90 targets. Geographical differences suggest local structural impediments. With low OAT coverage prescribed for 2.9% of the estimated 347,000 PWID in Ukraine, OAT expansion requires strategic interventions that target the individual, clinical care settings, policies, and funding.

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.

Concurrent drug injection during opioid agonist treatment among people who inject drugs in Ukraine.

Ongoing drug use during opioid agonist treatment (OAT) negatively affects treatment and health outcomes, and increases treatment dropout. This study aimed to examine correlates of concurrent illicit drug use among OAT patients in Ukraine. A random sample of 434 patients currently on OAT receiving buprenorphine (BMT) or methadone maintenance treatment (MMT) from five cities in Ukraine were assessed for factors associated with self-reported concurrent illicit drug use during OAT using a multivariable logistic regression. Among 434 OAT patients, 100 (23%) reported concurrent drug injecting in the previous 30 days; 28% of these were injecting ≥20 days. While 100 (100%) of these injected opioids, 24 (24%) injected stimulants; 40 (40%) met criteria for polysubstance use disorder that included opioids, stimulants and alcohol. Independent correlates of concurrent drug injection included: being on MMT vs. BMT (aOR = 2.8, 95%CI = 1.4-5.8), lower OAT dosage (aOR = 1.7, 95%CI = 1.1-2.7), more severe addiction severity (aOR = 2.3, 95%CI = 1.4-3.8), younger age of injection initiation (aOR = 2.3, 95%CI = 1.3-3.9), and presence of alcohol use disorder (aOR = 2.1, 95%CI = 1.3-3.5); participants living with parents were negatively associated with concurrent drug injection. Concurrent drug use was prevalent among OAT patients in Ukraine indicating the urgent needs for tailored interventions and changes in OAT program design and implementation. Results highlight the importance of prescribing an adequate OAT dosage, and discrepancies between MMT and BMT programs in Ukraine addressing needs of OAT patients with specific characteristics such as severe opioid and alcohol dependence.

A qualitative assessment of attitudes about and preferences for extended-release naltrexone, a new pharmacotherapy to treat opioid use disorders in Ukraine.

Numerous individual barriers, including negative attitudes toward opioid agonist therapies (OAT), have undermined HIV prevention efforts in Ukraine where the epidemic is concentrated in people who inject drugs (PWID). The recent availability of extended-release naltrexone (XR-NTX), an opioid antagonist, provides new opportunities for treatment and prevention, but little is known about patient preferences. We conducted qualitative analysis using focus groups (FG) of PWID recruited based on OAT experience: currently, previously, and never on OAT in five Ukrainian cities. FG included 199 PWID in 25 focus groups. Focus group transcripts were coded and analyzed using a modified grounded theory approach to identify common themes and domains related to attitudes about and preferences for XR-NTX, relative to other treatments. Interest in XR-NTX was supported if supervised opioid withdrawal and psychological support were assured. Other factors supporting XR-NTX included a focus on younger PWID early in their injection career and motivated for recovery. Perceptions of recovery included not receiving psychoactive medications like methadone or buprenorphine. With more information, XR-NTX could be a viable option for PWID in Ukraine, especially if concerns regarding withdrawal and psychological support are adequately addressed.