Size estimation of key populations and 'bridge populations' based on the network scale-up method in Ukraine.

INTRODUCTION: Correct estimation of the size of key and bridge populations is crucial for an efficient HIV/AIDS response in resource-limited settings, enabling efficient program planning and resource allocation. The hidden nature of these groups poses challenges to traditional methods, leading to the adoption of innovative approaches like the network scale-up method (NSUM). In this article we present the results of a NSUM study conducted in 2020 in Ukraine, focusing on four key populations and three bridge populations, highlighting challenges and contributions to development of the method. METHODS: From July to September 2020, we conducted a nationally representative survey in Ukraine via computer-assisted telephone interviews, and applied the known population method and summation method to estimate social networks sizes. Results were weighted based on individual sampling probability and adjusted for social respect and visibility factors to address potential limitations. RESULTS: Our study achieved a 20% response rate with 10,000 completed interviews. The social network size, using the known population method, was 213 people, and 125 using the summation method. Adjusting for the social respect and visibility, estimated key populations sizes were 295,857 [248,714-343,001] people who inject drugs, 152,267 [109,960-194,573] men who have sex with men, 78,385 [57,146-99,619] sex workers, and 9,963 [7,352-12,571] transgender people, detailed by age and gender. Bridge populations were estimated at 62,162 [50,445-73,879] sexual partners of people who inject drugs, 284,348 [233,113-335,583] clients of sex workers, and 13,697 [7,370-20,026] female partners of men who have sex with men. CONCLUSIONS: NSUM proves reliable for estimating key populations size with appropriate corrections. It shows promise for further use in Ukraine, considering limited geographic coverage of the integrated bio-behavioral studies to use multiplier-based methods. However, the validity concerns persist for estimating bridge populations size, emphasizing the need for further method refinement and addressing implementation issues, particularly those related to data collection.

Causes and risk factors of death among people who inject drugs in Indonesia, Ukraine and Vietnam: findings from HPTN 074 randomized trial.

INTRODUCTION: The HIV Prevention Trials Network (HPTN) 074 study demonstrated a positive effect of an integrated systems navigation and psychosocial counseling intervention on HIV treatment initiation, viral suppression, medication assisted treatment (MAT) enrollment, and risk of death among people who inject drugs (PWID). In this sub-study, we analyzed the incidence, causes, and predictors of death among HIV-infected and uninfected participants. METHODS: The HPTN 074 randomized clinical trial was conducted in Indonesia, Ukraine, and Vietnam. HIV-infected PWID with unsuppressed viral load (indexes) were recruited together with at least one of their HIV-negative injection partners. Indexes were randomized in a 1:3 ratio to the intervention or standard of care. RESULTS: The trial enrolled 502 index and 806 partner participants. Overall, 13% (66/502) of indexes and 3% (19/806) of partners died during follow-up (crude mortality rates 10.4 [95% CI 8.1-13.3] and 2.1 [1.3-3.3], respectively). These mortality rates were for indexes nearly 30 times and for partners 6 times higher than expected in a population of the same country, age, and gender (standardized mortality ratios 30.7 [23.7-39.0] and 5.8 [3.5-9.1], respectively). HIV-related causes, including a recent CD4 < 200 cells/µL, accounted for 50% of deaths among indexes. Among partners, medical conditions were the most common cause of death (47%). In the multivariable Cox model, the mortality among indexes was associated with sex (male versus female aHR = 4.2 [1.5-17.9]), CD4 count (≥ 200 versus < 200 cells/µL aHR = 0.3 [0.2-0.5]), depression (moderate-to-severe versus no/mild aHR = 2.6 [1.2-5.0]) and study arm (intervention versus control aHR = 0.4 [0.2-0.9]). Among partners, the study arm of the index remained the only significant predictor (intervention versus control aHR = 0.2 [0.0-0.9]) while controlling for the effect of MAT (never versus ever receiving MAT aHR = 2.4 [0.9-7.4]). CONCLUSIONS: The results confirm that both HIV-infected and uninfected PWID remain at a starkly elevated risk of death compared to general population. Mortality related to HIV and other causes can be significantly reduced by scaling-up ART and MAT. Access to these life-saving treatments can be effectively improved by flexible integrated interventions, such as the one developed and tested in HPTN 074.

Multiple Infection and Human Immunodeficiency Virus Superinfection Among Persons who Inject Drugs in Indonesia and Ukraine.

BACKGROUND: The HIV Prevention Trials Network (HPTN) 074 study evaluated an integrated human immunodeficiency virus (HIV) treatment and prevention strategy among persons who inject drugs (PWID) in Indonesia, Ukraine, and Vietnam. We previously detected multiple HIV infection in 3 of 7 (43%) of seroconverters with 3-8 HIV strains per person. In this report, we analyzed multiple HIV infection and HIV superinfection (SI) in the HPTN 074 cohort. METHODS: We analyzed samples from 70 participants in Indonesia and Ukraine who had viral load >400 copies/mL at enrollment and the final study visit (median follow-up, 2.5 years). HIV was characterized with Sanger sequencing, next-generation sequencing, and phylogenetic analysis. Additional methods were used to characterize a rare case of triple-variant SI. RESULTS: At enrollment, multiple infection was detected in only 3 of 58 (5.2%) participants with env sequence data. SI was detected in only 1 of 70 participants over 172.3 person-years of follow-up (SI incidence, 0.58/100 person-years [95% confidence interval, .015-3.2]). The SI case involved acquisition of 3 HIV strains with rapid selection of a strain with a single pol region cluster. CONCLUSIONS: These data from a large cohort of PWID suggest that intrahost viral selection and other factors may lead to underestimation of the frequency of multiple HIV infection and SI events.

Challenges of sexually transmitted infections and sexual health among people who inject drugs.

PURPOSE OF REVIEW: This review provides a summary of recently published research on sexually transmitted infections (STI) and related behaviors among people who inject drugs (PWID), covering three major areas: sexual behavior and its role in STI transmission among PWID, multilevel factors associated with STI risk, and strategies addressing sexual health of PWID. This review is timely given the growing priority of combination prevention approaches and integrated care for PWID. RECENT FINDINGS: Modern research improves the understanding that PWID have an increased risk of STI, which varies by gender, setting, type of substance used, and presence of mental disorders. Major socioeconomic and structural factors, specific and nonspecific to PWID, facilitate inequality and sexual risk behavior. Sexual transmission continues to contribute substantially to the spread of bloodborne infections among PWID, accounting for at least 10% of new HIV cases according to epidemiological modeling. Despite the substantial evidence that behavioral interventions can improve sexual health and reduce sex-related risks among PWID, there is a research-practice gap, reflected in the scarcity of implementation studies published recently. SUMMARY: Integration of sexual health into prevention programs for PWID is essential to curb transmission of STI, including HIV, among PWID and their sexual partners.

Patient-Reported Treatment Satisfaction and Quality of Life Among People Living with HIV Following the Introduction of Dolutegravir-Based ART Regimens in Ukraine.

In 2017, the government of Ukraine initiated its ART Optimization Initiative, revising its national antiretroviral therapy (ART) guidelines and embracing Dolutegravir (DTG) as a backbone of first-line ART regimens. A cross-sectional survey of 464 ART patients from 22 large ART clinics was carried out in mid-2019. The survey assessed patient-reported outcomes (PROS) including treatment satisfaction, physical health, mental health, depression, side effects of ART, and adherence. The associations between ART regimen and PROs were assessed using bivariable and multivariable generalized estimating equations (GEE) models. More than half (55.6%) of the patients were satisfied with their current ART regimen. Less than a half (45.3%) considered their physical health as good while only 36.9% rated their mental health as good, 21.3% reported moderate or severe depression, 82.3% reported no side effect in the past 4 weeks, and 44.4% reported not missing ART medication in the past month. In adjusted analysis, patients starting ART with DTG had higher treatment satisfaction compared to people continuing LPV-based regimens (aOR = 0.49, 95% confidence interval: 0.22-0.90). Also in adjusted analyses, unemployment, low income, and history of injection drug use were associated with unfavorable PROs. While the results indicate modestly favorable effects of ART Optimization, there is clearly a need for complementary interventions to improve PROs among disadvantaged ART patients in Ukraine.

The impact of the COVID-19 pandemic on illicit drug supply, drug-related behaviour of people who use drugs and provision of drug related services in Georgia: results of a mixed methods prospective cohort study.

BACKGROUND: This study examines the effects of COVID-19 related restrictions on the supply of illicit drugs, drug-use behaviour among people who use drugs (PWUD) regularly (at least weekly), and drug-related service provision in Tbilisi, Georgia. METHODOLOGY: In this mixed methods study, a cohort of 50 Georgian PWUD recruited through a snow-ball sampling participated in a bi-weekly online survey in April-September, 2020. They also took part in the qualitative telephone interviews at 12- and 24-week follow-up time points. In addition, four key informants (field experts) were interviewed monthly to assess their perceptions of changes in the illicit drug market and drug service delivery. RESULTS: Mean age in the sample was 36 (range 18-60); 39 (78%) were males. Perceived availability of drugs was reduced during the lockdown, and many PWUD switched to alternative substances when preferred drugs were not available. On average, participants used significantly fewer substances over the course of the study, from 3.5 substances in the preceding 14 days to 2.1 (aOR 0.92; 95% CI 0.90-0.94). Consumption of cannabis products declined significantly (aOR 0.89; 95% CI 0.84-0.95), likewise alcohol (aOR 0.94; 95% CI 0.88-1.0), diverted medicinal methadone (aOR 0.85; 95% CI 0.8-0.9) and diverted medicinal buprenorphine (aOR 0.91; 95% CI 0.84-0.99). PWUD cited fewer contacts with drug dealers, the lack of transportation, and the lack of conventional recreational environment as the main reasons for these changes. When access to sterile injection equipment was limited, PWUD exercised risk-containing injection behaviours, such as buying drugs in pre-filled syringes (aOR 0.88; 95% CI 0.80-0.96). Harm reduction and treatment programs managed to adopt flexible strategies to recover services that were affected during the initial stage of the pandemic. CONCLUSIONS: COVID-19-related restrictive measures mediated specific changes in supply models and drug-use behaviours. While adjusting to the new environment, many PWUD would engage in activities that put them under increased risk of overdose and blood-borne infections. Harm reduction and treatment services need to develop and implement protocols for ensuring uninterrupted service delivery during lockdowns, in anticipation of the similar epidemics or other emergency situations.

Factors associated with loss to follow-up among people with tuberculosis in the country of Georgia: a cohort study.

Despite having universal access to tuberculosis (TB) treatment, loss to follow-up (LFU) rates remain high in Georgia, 6% among drug-susceptible TB (DS-TB) patients (2017 cohort) and 19% among drug-resistant TB (DR-TB) patients diagnosed in 2016. A cohort study was conducted to analyze secondary data from the Georgian National Tuberculosis Surveillance Database. Study population included adult (≥18 y.o.) patients with bacteriologically confirmed pulmonary TB who were enrolled in Georgian National TB program during 2015-2017. The outcome of interest was loss to follow-up, defined as treatment interruption for more than 2 consecutive months. Patients were stratified by treatment profile (first-line drugs or second-line drugs) and survival analysis was performed within the stratified groups.  A total of 7860 treatment episodes were identified during 2015-2017 which corresponded to 6696 bacteriologically confirmed pulmonary TB treatment episodes of whom 795 (12%) were LFU. After adjustment, final multivariate analysis showed that male sex (aHR 1.5, 95%CI 1.2-2.0), being diagnosed in Tbilisi (aHR 1.3, 95%CI 1.1-1.6), unemployment at the time of diagnosis (aHR 1.7, 95%Ci 1.2-2.3) and previous history of TB treatment were independent risk factors for  LFU (aHR 2.3, 95%CI 1.9-2.8) among patients on first-line drugs. Among patients on second-line drugs being male (aHR 2.0, 95%CI 1.2-3.2), past TB treatment with second-line drugs (aHR 2.2, 95%CI 1.5-3.2) were significantly associated with LFU. LFU rate was high among patients on first-line drugs and second line drugs (10% and 22% respectively). Patients with past TB treatment history should further research to identify factors that lead to treatment interruption in this group. Other factors associated with LFU (being internally displaced person (IDP), being unemployed, and having imprisonment history) were in some level indication of a poor social-economic status, and strengthening approaches for TB care based on patients' need could be considered in light of this finding.

Factors associated with unfavourable treatment outcomes in people with HIV-associated tuberculosis in Armenia, 2015 to 2019.

To evaluate factors associated with tuberculosis (TB) treatment outcomes in human Immunodeficiency Virus-Associated (HIV) TB patients in Armenia, we conducted a nation-wide cohort study using routine programmatic data of all HIV-associated TB patients receiving TB treatment with first- or second-line drugs from 2015 to 2019. Data were obtained from the TB and HIV electronic databases. We analysed occurrence of the combined unfavourable outcome (failure, lost to follow-up, death and not evaluated) and death separately, and factors associated with both outcomes using Cox regression. There were 320 HIV-associated TB patients who contributed a total of 351 episodes of TB treatment. An unfavourable TB treatment outcome was registered in 155 (44.2%) episodes, including 85 (24.2%) due to death, 38 (10.8%) lost to follow up, 13 (3.7%) failure and 19 (5.4%) not evaluated. Multivariable analysis showed that receipt of Antiretroviral Treatment (ART) [ART start before TB treatment: adjusted hazard ratio (aHR)=0.3, 95% confidence interval (CI): 0.2-0.5, aHR=, 95% CI:, 95% CI:, 95% CI:TB meningitis (aHR=4.4, 95% CI: 1.6-11.9) increased the risk. The risk of death was affected by the same factors as above in addition to the low BMI (aHR=2.5, 95% CI: 1.3-4.5) and drug resistance (aHR=2.3, 95% CI: 1.0-5.4). In the subsample of episodes receiving ART, history of interruption of ART during TB treatment increased the risk of unfavourable outcome (aHR=2.1 95% CI: 1.2-3.9), while ART start during TB treatment was associated with lower risk of both unfavourable outcome (within first 8 weeks: aHR: 0.5, 95% CI: 0.3-0.9; after 8 weeks: aHR: 0.4, 95% CI: 0.2-1.0) and death (within first 8 weeks: aHR: 0.2, 95% CI: 0.1-0.4; after 8 weeks: aHR: 0.1, 95% CI: 0.01-0.3). The rates of unfavourable TB treatment outcomes, and death in particular, among HIV-associated TB patients in Armenia are high. Our findings emphasize the protective effect of ART and the importance of proper management of cases complicated by drug resistance or meningitis.

Factors associated with unfavourable treatment outcomes among people with rifampicin-resistant tuberculosis in Armenia, 2014-2017.

Rifampicin-Resistant/Multidrug-Resistant Tuberculosis (RR/MDR-TB) is recognized as a major public health concern globally. In Armenia, the proportion of RR/MDR-TB is increasing among all people affected with TB. We conducted a nationwide cohort study involving analysis of programmatic data to investigate the rates of and factors associated with unfavourable treatment outcomes among patients with RR/MDR-TB registered by the national TB programme from 2014 to 2017 in Armenia. We used Cox regression to identify factors associated with the outcome. Among 451 RR/MDR-TB patients, 80% were men and median age was 46 years. Of them, 53 (11.8%) had Extensively Drug-Resistant Tuberculosis (XDR-TB) and 132 (29.3%) had pre-XDR-TB. Almost half (224, 49.7%) of the patients had unfavourable treatment outcome, which included 26.8% Loss To Follow-Up (LTFU), 13.3% failures and 9.5% deaths. In multivariable analysis, people with pre-XDR-TB [adjusted Hazard Ratio [aHR] 3.13, 95% confidence intervals [CI] 2.16-4.55] and XDR-TB (aHR 4.08, 95% CI 2.45-6.79) had a higher risk of unfavourable outcomes. Patients receiving home-based treatment (71/451, 15.7%) and treatment with new drugs (172/451, 38.1%) had significantly lower risk (aHR 0.45, 95% CI 0.28-0.72 and aHR 0.26, 95% CI 0.18-0.39) of unfavourable treatment outcome.  The proportion of MDR-TB patients reaching favourable treatment outcome in Armenia was substantially lower than the recommended level (75%). The most common treatment outcome was LTFU indicating the need for further assessment of underlying determinants. Home-based treatment looks promising and future studies are required to see if expanding it to all RR/MDR-TB patients is feasible and cost-effective.

Depression and anxiety symptoms among people with rifampicin-resistant tuberculosis receiving in-patient care in the National Pulmonology Reference Institute in Romania.

Mental health comorbidities are common among tuberculosis patients, with higher prevalence among people with rifampicin-resistant/multidrug-resistant (RR/MDR) tuberculosis.  TB and depression share common risk factors adding to the overall disease burden. There is limited evidence about prevalence of depression and anxiety symptoms among tuberculosis patients in Romania. We assessed the prevalence of depression and anxiety symptoms and their evolution over the course of the treatment in RR/MDR-TB patients receiving in-patient care at the National Institute of Pneumonology (NIP) "Marius Nasta" in Romania during May-September 2020. We conducted a cohort study and used the Hospital Anxiety and Depression Scale (HADS) to assess the prevalence of depression and anxiety (defined as score≥ 8) symptoms at admission (baseline) and the second month of in-patient treatment (follow-up). Difference between baseline and follow-up depression and anxiety symptoms were assessed using McNemar test. Binary logistic regression was used to evaluate the association between sociodemographic and clinical characteristics with the presence of depression and anxiety symptoms at baseline. The cohort included 46 patients, 63% were male, mean age was 46 (±13.3) years. The prevalence of depression and anxiety in our cohort was 46% and 43% at baseline respectively, and 50% and 39%, at the follow-up respectively. About one third (7/25) of patients who had normal HADS depression score at baseline, had an increase above the threshold at the second month of treatment. No statistical difference in prevalence of depression or anxiety was found between the baseline and second month of treatment. Unadjusted analysis showed that odds of depression at baseline was lower in patients with education above 8th grade compared to patients with education below 8th grade (odds ratio=0.2, 95% confidence interval: 0.1,0.8, p=0.026). The study revealed high prevalence of depression and anxiety among RR/MDR-TB patients admitted to the NIP, underlining the necessity of evaluating the mental health of TB patients and linking them to appropriate care.

Improved ascertainment of modes of HIV transmission in Ukraine indicates importance of drug injecting and homosexual risk.

BACKGROUND: It is important to understand how HIV infection is transmitted in the population in order to guide prevention activities and properly allocate limited resources. In Ukraine and other countries where injecting drug use and homosexuality are stigmatized, the information about mode of transmission in case registration systems is often biased. METHODS: We conducted a cross-sectional survey in a random sample of patients registered at HIV clinics in seven regions of Ukraine in 2013-2015. The survey assessed behavioral risk factors and serological markers of viral hepatitis B and C. We analyzed the discrepancies between the registered mode of transmission and the survey data, and evaluated trends over 3 years. RESULTS: Of 2285 participants, 1032 (45.2%) were females. The proportion of new HIV cases likely caused by injecting drug use based on the survey data was 59.7% compared to 33.2% in official reporting, and proportion of cases likely acquired through homosexual transmission was 3.8% compared to 2.8%. We found a significant decrease from 63.2 to 57.5% in the proportion of injecting drug use-related cases and a steep increase from 2.5 to 5.2% in homosexual transmission over 3 years. CONCLUSIONS: The study confirmed the significant degree of misclassification of HIV mode of transmission among registered cases. The role of injecting drug use in HIV transmission is gradually decreasing, but remains high. The proportion of cases related to homosexual transmission is relatively modest, but is rapidly increasing, especially in younger men. Improvements in ascertaining the risk factor information are essential to monitor the epidemic and to guide programmatic response.

Perspectives of clients and providers on factors influencing opioid agonist treatment uptake among HIV-positive people who use drugs in Indonesia, Ukraine, and Vietnam: HPTN 074 study.

BACKGROUND: Opioid agonist treatment (OAT) is an effective method of addiction treatment and HIV prevention. However, globally, people who inject drugs (PWID) have insufficient OAT uptake. To expand OAT access and uptake, policymakers, program developers and healthcare providers should be aware of barriers to and facilitators of OAT uptake among PWID. METHODS: As a part of the HPTN 074 study, which assessed the feasibility of an intervention to facilitate HIV treatment and OAT in PWID living with HIV in Indonesia, Ukraine, and Vietnam, we conducted in-depth interviews with 37 HIV-positive PWID and 25 healthcare providers to explore barriers to and facilitators of OAT uptake. All interviews were audio-recorded, transcribed, translated into English, and coded in NVivo for analysis. We developed matrices to identify emergent themes and patterns. RESULTS: Despite some reported country-specific factors, PWID and healthcare providers at all geographic locations reported similar barriers to OAT initiation, such as complicated procedures to initiate OAT, problematic clinic access, lack of information on OAT, misconceptions about methadone, financial burden, and stigma toward PWID. However, while PWID reported fear of drug interaction (OAT and antiretroviral therapy), providers perceived that PWID prioritized drug use over caring for their health and hence were less motivated to take up ART and OAT. Motivation for a life change and social support were reported to be facilitators. CONCLUSION: These results highlight a need for support for PWID to initiate and retain in drug treatment. To expand OAT in all three countries, it is necessary to facilitate access and ensure low-threshold, financially affordable OAT programs for PWID, accompanied with supporting interventions. PWID attitudes and beliefs about OAT indicate the need for informational campaigns to counter misinformation and stigma associated with addiction and OAT (especially methadone).

A Global Meta-analysis of the Prevalence of HIV, Hepatitis C Virus, and Hepatitis B Virus Among People Who Inject Drugs-Do Gender-Based Differences Vary by Country-Level Indicators?

BACKGROUND: Women-specific factors exist that increases vulnerability to drug-related harms from injection drug use, including blood-borne viruses (BBVs), but gender-based differences in BBV prevalence have not been systematically examined. METHODS: We conducted meta-analyses to estimate country, regional, and global prevalence of serologically confirmed human immunodeficiency virus (HIV), hepatitis C virus (HCV; based on detection of anti-HCV antibody), and hepatitis B virus (HBV; based on detection of HBV surface antigen) in people who inject drugs (PWID), by gender. Gender-based differences in the BBV prevalence (calculated as the risk among women relative to the risk among men) were regressed on country-level prevalence and inequality measures (Gender inequality index, Human development index, Gini coefficient, and high, low or middle income of the country). RESULTS: Gender-based differences varied by countries and regions. HIV prevalence was higher among women than men in sub-Saharan Africa (relative risk [RR], 2.8; 95% confidence interval [CI], 1.8-4.4) and South Asia (RR, 1.7; 95% CI, 1.1-2.7); anti-HCV was lower among women in the Middle East and North Africa (RR, 0.6; 95% CI, .5-.7) and East and Southeast Asia (RR, 0.8; 95% CI, .7-.9). Gender-based differences varied with country-levels of the BBV prevalence in the general population, human development, and income distribution. CONCLUSION: HIV was more prevalent in women who inject drugs as compared to their male counterparts in some countries, but there is variation between and within regions. In countries where women are at higher risks, there is a need to develop gender-sensitive harm-reduction services for the particularly marginalized population of women who inject drugs.

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.

Use of Antiretroviral Drug Testing to Assess the Accuracy of Self-reported Data from HIV-Infected People Who Inject Drugs.

We used antiretroviral (ARV) drug testing to evaluate the accuracy of self-reported data for HIV status and antiretroviral treatment (ART) among people who inject drugs enrolled in an HIV prevention trial. ARV drugs were detected in enrollment samples from 72/482 = 14.9% HIV-infected participants (39/52 = 75.0% who reported being on ART; 33/430 = 7.7% who reported not being on ART). Overall, 213/482 = 44.2% participants indicated that they were not aware of their HIV-positive status prior to study entry; of those, 30 had ARV drugs detected at enrollment, including 15 who also had ARV drugs detected at the screening visit. These participants were likely aware of their HIV-positive status at study entry but did not report this to study staff. This study shows that self-reported data on HIV testing history and ART may not be accurate and that ARV drug testing can help identify persons who are aware of their HIV-positive status and are on ART.

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.

Evolution of Monitoring and Evaluation of AIDS Response in Ukraine: Laying the Groundwork for Evidence-Based Health Care.

Once facing the most severe HIV epidemic in Eastern Europe, Ukraine has built an elaborate Monitoring and Evaluation (M&E) system to track the response to AIDS. This system was developed using recommendations and input from multiple international expert organizations and donors and, at the current stage, serves as a best practice model in many areas. The present paper aims to provide a comprehensive overview of the evolution of the M&E system in Ukraine since its inception. Notable achievements and challenges are described and illustrated by epidemiological data and the recommendations for future development are discussed. Unique experiences and advances in M&E in Ukraine may be useful to other countries facing similar epidemiological, structural or methodological issues.

Imported "Evidence-Based" or Locally Grown Interventions: A False Dichotomy and Some Hard Choices in Implementation Science.

When public health programs are expanding to new areas or territories, it is often recommended by policy-makers and donors that existing evidence-based practices (EBPs) are to be adapted and implemented. While rationale behind this approach is understandable, proper adaptation to culturally different settings may be no less intensive than development of a new intervention based on the local context. A narrow understanding of implementation science concept may lead to overlooking valuable indigenous practices, which may be summarized into effective and potentially more sustainable models. This paper examines from practical standpoint the process and common caveats in cross-cultural adaptation of EPBs and argues for closer attention to available local experiences.

Integrated biobehavioral surveillance among people who inject drugs in Ukraine, 2007-2020.

BACKGROUND: Repeated integrated biobehavioral surveys (IBBS) have been implemented among people who inject drugs (PWID) in Ukraine to monitor the trends in key epidemiologic and programmatic indicators. METHODS: The study analyzed seven PWID IBBS rounds from 2007 to 2020 in seven Ukrainian cities. Participants were recruited using respondent-driven sampling, tested for HIV and anti-HCV antibodies, and completed a structured questionnaire. Composite weights (based on individual sampling probability and population size) were applied to generate point estimates and confidence intervals for HIV and HCV prevalence, injection risk behaviors, prevention service coverage, and HIV treatment cascade. Multi-level regression assessed temporal trends in these indicators in 2007-2020. RESULTS: The samples consisted of 1587 participants in 2007, 1905 in 2008/9, 3066 in 2011, 2846 in 2013, 2699 in 2015, 2798 in 2017, and 3651 in the 2020 rounds. HIV prevalence decreased from 27% to 19% overall, and among PWID younger than 25 from 10.5% to 5.5%. Anti-HCV prevalence increased from 50% to 73% overall but decreased from 58% to 27% in the younger subgroup. Past-30-days injection risk behaviors consistently decreased, reaching a minimum of 38% for any risk in 2020. HIV treatment cascade indicators and coverage with opioid agonist treatment substantially improved in the last three rounds. Harm reduction services coverage fluctuated, declining from 52% to 33% in the last three rounds. CONCLUSIONS: This analysis demonstrates the potential of repeated IBBS for monitoring the HIV epidemic and program coverage. We confirmed a sustained decline in overall HIV and HCV transmission, likely driven by reduced risky injection practices among PWID. The impact of harm reduction services requires further study. HIV status awareness and treatment coverage among PWID markedly increased, reaching the national average, possibly indicating the success of case-finding and linkage-to-care interventions. The upcoming IBBS round in Ukraine will also assess the impact of the war on service provision, risk behavior, and HIV transmission among PWID.

Low daily oral PrEP adherence and low validity of self-report in a randomized trial among PWID in Ukraine.

BACKGROUND: The efficacy of daily oral pre-exposure prophylaxis (PrEP) in preventing HIV transmission among people who inject drugs (PWID) was demonstrated over a decade ago. However, only a few studies among PWID have since measured PrEP adherence using laboratory markers. METHODS: In this trial, we randomized recently injecting PWID in Kyiv, Ukraine, to receive daily oral TDF/FTC with or without SMS reminders. Enrollment and PrEP initiation took place at an HIV clinic. Subsequent visits at months 1, 3, and 6 were conducted at a community harm reduction center and included a structured interview, adherence counseling, PrEP dispensing, and dried blood spot collection. PrEP adherence was assessed using standard self-reported measures and TDF/FTC biomarkers. RESULTS: A total of 199 PWID (99 SMS, 100 No-SMS) were enrolled, of whom 24 % were women, with a median age of 37. At month 6, 79.4 % (158/199) of participants were retained, with 84 % (133/158) reporting opioid injection and 20 % (31/158) reporting stimulant injection in the past 30 days. 77 % (122/158) reported taking >95 % of PrEP doses in the past month, and 87 % reported taking the last dose within 2 days. Tenofovir diphosphate was detected in 17 % (28/158) of participants, and emtricitabine triphosphate was detected in 25 % (40/158). Only 3 % (5/158) had metabolite levels indicative of consistent PrEP uptake at 4+ doses per week. There was no association between the SMS intervention and TDF/FTC metabolite detection. CONCLUSION: Adherence to daily oral PrEP among actively injecting PWID, without daily supervision or incentives, was extremely low, despite supportive counseling and SMS reminders. We also observed a high rate of discordance between self-report and classification by a validated biomarker of adherence. Given the scarcity of evidence and emerging data suggesting low oral PrEP adherence among PWID, additional implementation studies with TDF/FTC biomarkers are needed to study whether a sufficient level of adherence to daily PrEP is attainable among PWID, especially as long-acting injectable PrEP offers a promising alternative.