Alcohol Use Disorder and HIV Risk in a National Survey of Men Who Have Sex with Men in Ukraine.

BACKGROUND: Problematic alcohol consumption is associated with risk behaviors associated with HIV transmission. Despite the high prevalence of problematic alcohol consumption in Ukraine, however, there are little empirical data examining its association with risk behaviors also associated with HIV transmission in men who have sex with men (MSM), a key population where HIV incidence is increasing, METHOD: Correlates of prevalent HIV infection and their association between drinking severity levels and behaviors also associated with increased likelihood of HIV acquisition were analyzed from a 2017 nationally representative survey (IBBS) of 4938 MSM in Ukraine using bivariate analyses and multivariate regression. RESULTS: Overall, 42.6% of MSM participants met screening criteria for alcohol use disorder (AUD), with 24.2%, 12.0%, and 6.3% meeting criteria for moderate, high, and severe risk of harm from alcohol consumption, respectively. Multivariate regression revealed that these risk categories were correlated with behaviors associated with increased HIV transmission risk, including reports of (1) > 5 sexual partners; (2) sex with a partner of unknown HIV status; (3) sex work; (4) any drug use; and (5) not testing for HIV (past year). HIV testing was infrequent, with only 44.1% having been tested in the previous year. CONCLUSION: The high prevalence of problematic alcohol use in Ukrainian MSM and its association with behaviors also associated with HIV transmission supports the importance of routine screening of MSM for AUD. Moreover, among those screening positive for a potential AUD, targeted HIV prevention strategies to scale-up pre-exposure prophylaxis, consistent condom use, and treatment for AUD are needed.

The impact of the 2014 military conflict in the east of Ukraine and the Autonomous Republic of the Crimea among patients receiving opioid agonist therapies.

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 1868 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. 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).

Population-level prevalence of detectable HIV viremia in people who inject drugs (PWID) in Ukraine: Implications for HIV treatment and case finding interventions.

Achievement of viral load suppression among people living with HIV is one of the most important goals for effective HIV epidemic response. In Ukraine, people who inject drugs (PWID) experience the largest HIV burden. At the same time, this group disproportionally missed out in HIV treatment services. We performed a secondary data analysis of the national-wide cross-sectional bio-behavioral surveillance survey among PWID to assess the population-level prevalence of detectable HIV viremia and identify key characteristics that explain the outcome. Overall, 11.4% of PWID or 52.6% of HIV-positive PWID had a viral load level that exceeded the 1,000 copies/mL threshold. In the group of HIV-positive PWID, the detectable viremia was attributed to younger age, monthly income greater than minimum wage, lower education level, and non-usage of antiretroviral therapy (ART) and opioid agonistic therapy. Compared with HIV-negative PWID, the HIV-positive group with detectable viremia was more likely to be female, represented the middle age group (35-49 years old), had low education and monthly income levels, used opioid drugs, practiced risky injection behavior, and had previous incarceration history. Implementing the HIV case identification and ART linkage interventions focused on the most vulnerable PWID sub-groups might help closing the gaps in ART service coverage and increasing the proportion of HIV-positive PWID with viral load suppression.

Modelling the impact and cost-effectiveness of non-governmental organizations on HIV and HCV transmission among people who inject drugs in Ukraine.

INTRODUCTION: People who inject drugs (PWID) in Ukraine have high prevalences of HIV and hepatitis C virus (HCV). Non-governmental organizations (NGOs) provide PWID with needles/syringes, condoms, HIV/HCV testing and linkage to opioid agonist treatment (OAT) and antiretroviral therapy (ART). We estimated their impact and cost-effectiveness among PWID. METHODS: A dynamic HIV and HCV transmission model among PWID was calibrated using data from four national PWID surveys (2011-2017). The model assumed 37-49% coverage of NGOs among community PWID, with NGO contact reducing injecting risk and increasing condom use and recruitment onto OAT and ART. We estimated the historic (1997-2021) and future (2022-2030, compared to no NGO activities from 2022) impact of NGOs in terms of the proportion of HIV/HCV infections averted and changes in HIV/HCV incidence. We estimated the future impact of scaling-up NGOs to 80% coverage with/without scale-up in OAT (5-20%) and ART (64-81%). We estimated the cost per disability-adjusted life-year (DALY) averted of current NGO provision over 2022-2041 compared to NGO activities stopping over 2022-2026, but restarting after that till 2041. We assumed average unit costs of US$80-90 per person-year of NGO contact for PWID. RESULTS: With existing coverage levels of NGOs, the model projects that NGOs have averted 20.0% (95% credibility interval: 13.3-26.1) and 9.6% (5.1-14.1) of new HIV and HCV infections among PWID over 1997-2021, respectively, and will avert 31.8% (19.6-39.9) and 13.7% (7.5-18.1) of HIV and HCV infections over 2022-2030. With NGO scale-up, HIV and HCV incidence will decrease by 54.2% (43.3-63.8) and 30.2% (20.5-36.2) over 2022-2030, or 86.7% (82.9-89.3) and 39.8% (31.4-44.8) if OAT and ART are also scaled-up. Without NGOs, HIV and HCV incidence will increase by 51.6% (23.6-76.3) and 13.4% (4.8-21.9) over 2022-2030. Current NGO provision over 2022-2026 will avert 102,736 (77,611-137,512) DALYs when tracked until 2041 (discounted 3% annually), and cost US$912 (702-1222) per DALY averted; cost-effective at a willingness-to-pay threshold of US$1548/DALY averted (0.5xGDP). CONCLUSIONS: NGO activities have a crucial preventative impact among PWID in Ukraine which should be scaled-up to help achieve HIV and HCV elimination. Disruptions could have a substantial detrimental impact.

Past 12-month nonfatal overdose among people who inject drugs in Ukraine: City-level estimates and risk factors from a cross-sectional study.

BACKGROUND: Nonfatal overdose contributes to high morbidity and is among the strongest proxies for the occurrence of overdose fatality - the leading cause of death among those who use opioids. In Ukraine, a majority of people who inject drugs (PWID) use opioids, but little is known about the relationship between drug market characteristics, nonfatal overdose (NFOD) prevalence, and risk factors for NFOD. METHODS: We used cross-sectional respondent-driven sampling (RDS) data to explore the variability of recent (past 12 months) NFOD among PWID across Ukrainian cities and associations with individual factors. The population-averaged -cross-sectional associations were estimated and compared using generalized linear models for the binary outcome (NFOD vs. not) with robust variance estimates. RESULTS: Recent self-reported NFOD varied between 1% and 14 % across Ukrainian cities. In adjusted analyses, overdose was associated with fewer years of injecting drugs; a higher number of types of drugs used in the past 12 months; using desomorphine, methadone, tramadol, heroin, amphetamine-type drugs or cocaine within past 12 months; using alcohol daily or weekly; recent drug treatment; and history of incarceration. Buying drugs or their ingredients through "stashes" (i.e., drugs secretly hidden in various places) and the perception of drug price increase were associated with higher odds of reporting NFOD. CONCLUSION: The identified risk factors underscore the importance of evidence-based prevention efforts, such as scaling-up opioid agonist therapy, providing naloxone in the community and upon prison release, targeting those most likely to witness overdose and sharing overdose prevention strategies with them, and continuous monitoring of trends and contributing factors.

Operationalizing the HIV prevention cascade for PWID using the integrated bio-behavioural survey data from Ukraine.

INTRODUCTION: People who inject drugs (PWID) remain at high risk of HIV in many countries. The HIV prevention cascades have been proposed to replicate the success of the treatment cascades and reinvigorate the prevention programmes through improved monitoring, planning and delivery. We adapted the cascade framework to the PWID context in Ukraine, assessed gaps and analysed factors associated with achieving "access" and "effective use" outcomes. METHODS: Self-reported data on the use of prevention services and risk behaviours from the 2017 integrated bio-behavioural survey among PWID in Ukraine were used to construct cascades for needle/syringe and condom programmes (NSP and CP). Socio-demographic and behavioural variables were evaluated as potential correlates of cascade outcomes. RESULTS: The NSP cascade analysis included 7815 HIV-negative PWID. Motivation to use clean syringes was not assessed and assumed at 100%. Access to clean syringes through NSP in the past 12 months was reported by 2789 participants (35.7%). Effective use of syringes (no sharing in the past 30 days) was reported by 7405 participants (94.8%). NSP access was higher among women, individuals older than 44, and mixed drug users; while effective use was reported more frequently by men and opioid users, with no difference by age. The CP cascade analysis included 6606 (85%) of the HIV-negative PWID who had sex in the past three months. Of those, 2282 (34.5%) received condoms, and 1708 (25.9%) reported consistent use with all partners in the past three months. Older PWID and mixed-drug users accessed condoms more frequently; whereas younger subgroups and opioid users used them more consistently. CONCLUSIONS: Overall, the cascade framework was useful to describe the status of HIV prevention among PWID in Ukraine and to identify areas for improvement in the programming and evaluation of HIV prevention. Access to needle/syringe and condom programmes was substantially below the recommended levels. Effective use of clean syringes was reported by a vast majority of PWID, although likely affected by self-report bias; whereas consistent condom use was infrequent. Socio-demographic and behavioural variables showed significant associations in NSP and CP cascade analyses, with little consistency between the access and effective use outcomes.

HIV treatment cascade among people who inject drugs in Ukraine.

The HIV treatment cascade is an effective tool to track progress and gaps in the HIV response among key populations. People who inject drugs (PWID) remain the most affected key population in Ukraine with HIV prevalence of 22% in 2015. We performed secondary analysis of the 2017 Integrated Bio-Behavioral Surveillance (IBBS) survey data to construct the HIV treatment cascade for PWID and identify correlates of each indicator achievement. The biggest gap in the cascade was found in the first "90", HIV status awareness: only 58% [95% CI: 56%-61%] of HIV-positive PWID reported being aware of their HIV-positive status. Almost 70% [67%-72%] of all HIV-infected PWID who were aware of their status reported that they currently received antiretroviral therapy (ART). Almost three quarters (74% [71%-77%]) of all HIV-infected PWID on ART were virally suppressed. Access to harm reduction services in the past 12 months and lifetime receipt of opioid agonist treatment (OAT) had the strongest association with HIV status awareness. Additionally, OAT patients who were aware of HIV-positive status had 1.7 [1.2-2.3] times the odds of receiving ART. Being on ART for the last 6 months or longer increased odds to be virally suppressed; in contrast, missed recent doses of ART significantly decreased the odds of suppression. The HIV treatment cascade analysis for PWID in Ukraine revealed substantial gaps at each step and identified factors contributing to achievement of the outcomes. More intensive harm reduction outreach along with targeted case finding could help to fill the HIV awareness gap among PWID in Ukraine. Scale up of OAT and community-level linkage to care and ART adherence interventions are viable strategies to improve ART coverage and viral suppression among PWID.

Has resourcing of non-governmental harm-reduction organizations in Ukraine improved HIV prevention and treatment outcomes for people who inject drugs? Findings from multiple bio-behavioural surveys.

INTRODUCTION: People who inject drugs (PWID) in Ukraine have high prevalences of HIV and hepatitis C (HCV). Since the turn of the century, various organizations have funded non-governmental organizations (NGOs) in Ukraine to provide PWID with needles and syringes, condoms, HIV and HCV testing, and improve linkage to opioid agonist therapy (OAT) and HIV treatment. We investigated whether contact with these NGOs was associated with improved HIV prevention and treatment outcomes among PWID. METHODS: Five rounds of respondent-driven sampled integrated bio-behavioural survey data (2009 [N = 3962], 2011 [N = 9069], 2013 [N = 9502], 2015 [N = 9405], and 2017 [N = 10076]) among PWID in Ukraine (including HIV/HCV testing and questionnaires) were analysed using mixed-effect logistic regression models (mixed-effects: city, year). These regression models assessed associations between being an NGO client and various behavioural, OAT, HIV testing and HIV treatment outcomes, adjusting for demographic characteristics (age, gender, lifetime imprisonment, registration in a drug abuse clinic, education level). We also assessed associations between being an NGO client and being HIV positive or HCV positive, likewise adjusting for demographic characteristics (as above). RESULTS: NGO clients were more likely to have received HIV testing ever (adjusted odds ratio [aOR] 5.37, 95% confidence interval [95% CI]: 4.97 to 5.80) or in the last year (aOR 3.37, 95% CI: 3.20 to 3.54), to have used condoms at last sexual intercourse (aOR 1.37, 95% CI: 1.30 to 1.44) and sterile needles at last injection (aOR 1.37, 95% CI: 1.20 to 1.56), to be currently (aOR 4.19, 95% CI: 3.48 to 5.05) or ever (aOR 2.52, 95% CI: 2.32 to 2.74) on OAT, and to have received syringes (aOR 109.89, 95% CI: 99.26 to 121.66) or condoms (aOR 54.39, 95% CI: 50.17 to 58.96) in the last year. PWID who were HIV positive (aOR 1.40, 95% CI: 1.33 to 1.48) or HCV positive (aOR 1.57, 95% CI: 1.49 to 1.65) were more likely to have contact with NGOs, with HIV positive PWID in contact with NGOs being more likely to be registered at AIDS centres (aOR 2.34, 95% CI: 1.88 to 2.92) and to be on antiretroviral therapy (aOR 1.60, 95% CI: 1.40 to 1.83). CONCLUSIONS: Contact with PWID targeted NGOs in Ukraine is associated with consistently better preventive, HIV testing and HIV treatment outcomes, suggesting a beneficial impact of harm reduction NGO programming.

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.

Social network approaches to locating people recently infected with HIV in Odessa, Ukraine.

INTRODUCTION: This paper examines the extent to which an intervention succeeded in locating people who had recently become infected with HIV in the context of the large-scale Ukrainian epidemic. Locating and intervening with people who recently became infected with HIV (people with recent infection, or PwRI) can reduce forward HIV transmission and help PwRI remain healthy. METHODS: The Transmission Reduction Intervention Project (TRIP) recruited recently-infected and longer-term infected seeds in Odessa, Ukraine, in 2013 to 2016, and asked them to help recruit their extended risk network members. The proportions of network members who were PwRI were compared between TRIP arms (i.e. networks of recently-infected seeds vs. networks of longer-term infected seeds) and to the proportion of participants who were PwRI in an RDS-based Integrated Biobehavioral Surveillance of people who inject drugs in 2013. RESULTS: The networks of PwRI seeds and those of longer-term infected seeds had similar (2%) proportions who were themselves PwRI. This was higher than the 0.25% proportion in IBBS (OR = 7.80; p = 0.016). The odds ratio among the subset of participants who injected drugs was 11.17 (p = 0.003). Cost comparison analyses using simplified ingredients-based methods found that TRIP spent no more than US $4513 per PwRI located whereas IBBS spent $11,924. CONCLUSIONS: Further research is needed to confirm these results and improve TRIP further, but our findings suggest that interventions that trace the networks of people who test HIV-positive are a cost-effective way to locate PwRI and reduce HIV transmission and should therefore be implemented.

Trends in HIV prevalence among people injecting drugs, men having sex with men, and female sex workers in Ukraine.

Once recognized as the most severe in Europe, the HIV epidemic in Ukraine is concentrated among people who inject drugs, men who have sex with men, and female sex workers. Integrated biobehavioral surveys, as a part of the second generation surveillance, are used to monitor HIV infection trends in key populations since 2002. The present paper is focused on the analysis of HIV prevalence trends in four nationally representative rounds of integrated biobehavioral surveys from 2008/9, 2011, 2013, and 2015 in people who inject drugs, men who have sex with men, and female sex workers. Between 2008/9 and 2015, the HIV prevalence has decreased significantly in people who inject drugs (24.2 to 22.0%) and female sex workers (13.6 to 6.3%), while the change in men who have sex with men was not significant (8.5 to 7.8%). There was a significant increase in people who inject drugs and men who have sex with men between 2013 and 2015. In subgroups younger than 25 years, prevalence increased more than twofold in men who have sex with men (1.9 to 4.3%), with no changes in people who inject drugs and female sex workers. The observed decline in prevalence, especially in young subgroups, may result from the effect of extensive prevention efforts on drug injection-related transmission. Recent increase in young men who have sex with men may be a sign of a new wave of the epidemic in this group.

Risk network approaches to locating undiagnosed HIV cases in Odessa, Ukraine.

INTRODUCTION: Providing HIV healthcare and Treatment as Prevention both depend on diagnosing HIV cases, preferably soon after initial infection. We hypothesized that tracing risk networks recruits higher proportions of undiagnosed positives than outreach-based testing or respondent-driven sampling (RDS) in Odessa, Ukraine. METHODS: The Transmission Reduction Intervention Project (TRIP) used risk network tracing to recruit sexual and injection networks of recently-infected and longer-term infected (LTs) seeds (2013 to 2016). Integrated Biobehavioural Surveillance (IBBS) (2013) used RDS to recruit people who inject drugs (PWID). Outreach Testing tested PWID for HIV at community outreach sites (2013 to 2016). Proportions of undiagnosed positives among those tested were compared TRIP versus IBBS; TRIP versus Outreach Testing and between TRIP arms. Costs were compared across the projects. RESULTS: TRIP tested 1252 people (21% women) in seeds' risk networks; IBBS tested 400 (18% women); Outreach Testing 13,936 (31% women). TRIP networks included a higher proportion of undiagnosed positives (14.6%) than IBBS (5.0%) or Outreach Testing (2.4%); odds ratio (OR) 3.25 (95% CI 2.07, 5.12) versus IBBS and 7.03 (CI 5.95, 8.31) versus Outreach Testing respectively. Findings remained significant in analyses stratified by sex and when PWID in TRIP networks were compared with Outreach Testing and IBBS. Within TRIP, recently-infected participants' networks contained higher proportions of undiagnosed positives (16.3%) than LTs' networks (12.2%); OR 1.41 (CI 1.01, 1.95). TRIP located undiagnosed positives less expensively than did RDS or Outreach Testing. CONCLUSIONS: TRIP's recruiting techniques, including prioritizing networks of the recently infected, find undiagnosed HIV-positive people efficiently. They should be integrated with standard practice to improve case-finding. Research should test these techniques in other socio-epidemiologic contexts. CLINICAL TRIAL REGISTRY: Registered ClinicalTrials.gov: NCT01827228.

Incarceration history and risk of HIV and hepatitis C virus acquisition among people who inject drugs: a systematic review and meta-analysis.

BACKGROUND: People who inject drugs (PWID) experience a high prevalence of incarceration and might be at high risk of HIV and hepatitis C virus (HCV) infection during or after incarceration. We aimed to assess whether incarceration history elevates HIV or HCV acquisition risk among PWID. METHODS: In this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO databases for studies in any language published from Jan 1, 2000 until June 13, 2017 assessing HIV or HCV incidence among PWID. We included studies that measured HIV or HCV incidence among community-recruited PWID. We included only studies reporting original results and excluded studies that evaluated incident infections by self-report. We contacted authors of cohort studies that met the inclusion or exclusion criteria, but that did not report on the outcomes of interest, to request data. We extracted and pooled data from the included studies using random-effects meta-analyses to quantify the associations between recent (past 3, 6, or 12 months or since last follow-up) or past incarceration and HIV or HCV acquisition (primary infection or reinfection) risk among PWID. We assessed the risk of bias of included studies using the Newcastle-Ottawa Scale. Between-study heterogeneity was evaluated using the I2 statistic and the P-value for heterogeneity. FINDINGS: We included published results from 20 studies and unpublished results from 21 studies. These studies originated from Australasia, western and eastern Europe, North and Latin America, and east and southeast Asia. Recent incarceration was associated with an 81% (relative risk [RR] 1·81, 95% CI 1·40-2·34) increase in HIV acquisition risk, with moderate heterogeneity between studies (I2=63·5%; p=0·001), and a 62% (RR 1·62, 95% CI 1·28-2·05) increase in HCV acquisition risk, also with moderate heterogeneity between studies (I2=57·3%; p=0·002). Past incarceration was associated with a 25% increase in HIV (RR 1·25, 95% CI 0·94-1·65) and a 21% increase in HCV (1·21, 1·02-1·43) acquisition risk. INTERPRETATION: Incarceration is associated with substantial short-term increases in HIV and HCV acquisition risk among PWID and could be a significant driver of HCV and HIV transmission among PWID. These findings support the need for developing novel interventions to minimise the risk of HCV and HIV acquisition, including addressing structural risks associated with drug laws and excessive incarceration of PWID. FUNDING: Engineering and Physical Sciences Research Council, National Institute for Health Research, National Institutes of Health.