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Abstract Background Including structural determinants (e.g. criminalisation, stigma, inequitable gender norms) in dynamic HIV transmission models is important to help quantify their population-level impacts and guide implementation of effective interventions that reduce the burden of HIV and inequalities thereof. However, evidence-based modelling of structural determinants is challenging partly due to a limited understanding of their causal pathways and few empirical estimates of their effects on HIV acquisition and transmission. Methods We conducted a scoping review of dynamic HIV transmission modelling studies that evaluated the impacts of structural determinants, published up to August 28, 2023, using Ovid Embase and Medline online databases. We appraised studies on how models represented exposure to structural determinants and causal pathways. Building on this, we developed a new methodological framework and recommendations to support the incorporation of structural determinants in transmission dynamics models and their analyses. We discuss the data and analyses that could strengthen the evidence used to inform these models. Results We identified 17 HIV modelling studies that represented structural determinants and/or interventions, including incarceration of people who inject drugs (number of studies [n] = 5), violence against women (n = 3), HIV stigma (n = 1), and housing instability (n = 1), among others (n = 7). Most studies (n = 10) modelled exposures dynamically. Almost half (8/17 studies) represented multiple exposure histories (e.g. current, recent, non-recent exposure). Structural determinants were often assumed to influence HIV indirectly by influencing mediators such as contact patterns, condom use, and antiretroviral therapy use. However, causal pathways’ assumptions were sometimes simple, with few mediators explicitly represented in the model, and largely based on cross-sectional associations. Although most studies calibrated models using HIV epidemiological data, less than half (7/17) also fitted or cross-validated to data on the prevalence, frequency, or effects of exposure to structural determinants. Conclusions Mathematical models can play a crucial role in elucidating the population-level impacts of structural determinants and interventions on HIV. We recommend the next generation of models reflect exposure to structural determinants dynamically and mechanistically, and reproduce the key causal pathways, based on longitudinal evidence of links between structural determinants, mediators, and HIV. This would improve the validity and usefulness of predictions of the impacts of structural determinants and interventions.

Ukraine faced significant fluctuations in COVID-19 morbidity and mortality, alongside an escalating HIV epidemic. This mixed-methods study, conducted between February and August 2022, employed a sequential explanatory design combining a quantitative analysis of national data and qualitative interviews to investigate the pandemic's effects on HIV services in Ukraine. The observed trends confirmed that the pandemic significantly disrupted facility-based HIV testing due to logistical challenges, an increased burden on healthcare workers, and supply shortages. Meanwhile, community-based testing showed resilience, largely attributed to programmatic adjustments rather than the pandemic itself. The initiation of antiretroviral therapy declined, especially during initial lockdowns, reflecting diminished treatment capacities. Despite these challenges, telemedicine and home medication delivery innovations supported antiretroviral therapy adherence. Furthermore, improvements in viral load testing and suppression rates showed healthcare resilience. The study highlights the critical need for adaptable, sustainable healthcare strategies in crises, emphasized during the war with Russia.

Abstract 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.

Abstract Introduction Daily oral HIV pre‐exposure prophylaxis (PrEP) with tenofovir/emtricitabine (TDF/FTC) is recommended for people who inject drugs (PWID) but coverage is low. The real‐life effectiveness of PrEP among PWID is unknown as previous studies were conducted in controlled settings and mainly relied on self‐report. Analysis of PrEP metabolites—tenofovir diphosphate (TFVdp) and emtricitabine triphosphate (FTCtp)—offers an objective measure of adherence. Methods To analyse longitudinal patterns of PrEP adherence among PWID in Ukraine, we used data from a community‐based implementation trial conducted in Kyiv between July 2020 and March 2021 to test the efficacy of SMS reminders to improve adherence. Among 199 enrolled participants, 156 (78.4%) were retained through 6 months. Based on TFVdp/FTCtp levels assessed at 3 and 6 months, we identified groups with various adherence patterns (adherent at ≥2 doses/week, improved, worsened, non‐adherent). Correlates of adherence were analysed using multinomial logistic regression. Results Most participants (53.8%, n = 84/156) had no detectable metabolites at both assessments; 7.1% (n = 11/156) were consistently taking ≥2 doses/week; 1.3% (n = 2/156) were consistently taking ≥4 doses/week; 13.5% (n = 21/156) exhibited improved and 21.8% (n = 34/156) had worsened adherence at 6 compared to 3 months. “White coat compliance” (increased dosing prior to assessment) was common. Consistent adherence was associated with SMS reminders, younger age, employment, lower income, longer injection drug use duration, recent high‐risk injecting (receptive syringe sharing, using pre‐filled syringe, back‐ or front‐loading, container sharing), absence of overdose in the past 6 months, perceived HIV risk through sexual intercourse and higher PrEP self‐efficacy. Alcohol consumption was associated with inconsistent PrEP use. Groups with improved and worsened adherence did not differ. Conclusions Daily oral PrEP may not achieve the desired effectiveness among PWID as a standalone intervention, calling for testing of alternative PrEP formulations and innovative integrated risk reduction strategies, especially in the context of HIV epidemics associated with injection drug use in eastern Europe and central Asia and the public health crisis in Ukraine caused by the war with Russia. SMS reminders may be effective among PWID who prioritize PrEP. Our findings offer practical guidance in identifying PWID who are likely to benefit from PrEP and those who need additional support.

Abstract Introduction Russia's invasion of Ukraine in February 2022 has severely impacted the healthcare system, including the provision of HIV care. The ongoing war is a human‐caused mass trauma, a severe ecological and psychosocial disruption that greatly exceeds the coping capacity of the community. The bioecological model of mass trauma builds on Bronfenbrenner's concept of interaction between nested systems to argue that social context determines the impact of life events on the individual and how an individual responds. This paper uses the bioecological model of mass trauma to explore the impact of Russia's aggression against Ukraine and the ongoing war on HIV‐positive people who use drugs in Ukraine, a particularly vulnerable population that may be negatively affected by disruptions to social networks, healthcare infrastructure and economic conditions caused by mass trauma. Methods Data were collected between September and November 2022. A convenience sample of 18 HIV‐positive people who use drugs were recruited from community organizations that work with people living with HIV, drug treatment programmes, and HIV clinics through direct recruitment and participant referral. A total of nine men and nine women were recruited; the age ranged from 33 to 62 years old (mean = 46.44). Participants completed a single interview that explored how the war had affected their daily lives and access to HIV care and other medical services; their relationships with healthcare providers and social workers; and medication access, supply and adherence. Data were analysed using the Framework Method for thematic analysis. Results The war had a profound impact on the social, emotional and financial support networks of participants. Changes in social networks, coupled with limited job opportunities and rising prices, intensified financial difficulties for participants. Relocating to different regions of Ukraine, staying at somebody else's home, and losing connections with social workers impacted medication adherence and created lengthy treatment gaps. Participants also experienced a decreased supply of antiretroviral therapy, concerns about accessing medication for opioid use disorder, and overwhelming fears associated with the war, which overshadowed their HIV‐related health concerns and negatively impacted medication adherence. Conclusions Our analysis reveals the complex impact of war on social networks and healthcare access. Maintaining support networks and competent healthcare providers will be essential amid the ongoing war.

BackgroundUkraine has the second-largest HIV epidemic in Europe, with most new cases officially attributed to heterosexual transmission. Indirect evidence suggested substantial HIV transmission from people who inject drugs (PWID) to their sexual partners. This study examined the extent of heterosexual HIV transmission between PWID and non-drug-using adolescent girls and young women (AGYW).MethodsA cross-sectional survey recruited AGYW diagnosed with heterosexually-acquired HIV between 2016 and 2019 in nine regions of Ukraine. AGYW were asked to identify and refer their sexual partners ('Partners'), who subsequently underwent HIV testing, and, if positive, HCV testing. Both AGYW and Partners completed an interview assessing HIV risk behaviors prior to AGYW's HIV diagnosis.ResultsIn August-December 2020, we enrolled 321 AGYW and 64 Partners. Among the Partners, 42% either self-reported IDU or were HCV-positive, indicating an IDU-related mode of HIV transmission. PWID Partners were more likely to report sexually transmitted infections (STI) and had lower educational levels. Of the 62 women who recruited at least one Partner, 40% had a PWID Partner. Within this subgroup, there was a higher prevalence of STIs (52% vs. 24%) and intimate partner violence (36% vs. 3%). Condom use was less common (52% vs. 38% reporting never use), and frequent alcohol or substance use before sex was higher (48% vs 30%) among AGYW with PWID Partner, although this difference did not reach statistical significance. Notably, 52% of women were aware of their Partners' IDU.ConclusionAt least 40% of heterosexual transmission among AGYW in Ukraine can be linked to PWID partners. Intensified, targeted HIV prevention efforts are essential for key and bridge populations (PWID and their sexual partners), addressing the biological and structural determinants of transmission between key and bridge populations, such as IDU- and HIV status disclosure, STIs, IPV, and stigma.

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.

Abstract 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

Abstract 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.

Abstract 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).

Abstract 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.

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; p3 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.

Qualitative research is increasingly being integrated within the development and evaluation phases of trials of complex health interventions. Qualitative research can complement effectiveness data and provide insights around how context and implementation impact the results of the trial and to what extent interventions fit implementation contexts after evaluation. Several qualitative studies have been conducted at different stages of trials of mental health and psychosocial support interventions for populations affected by adversity such as armed conflict and disasters. However, these qualitative components are usually implemented as disjointed components within the trial. The current protocol aims to provide a shared framework detailing the qualitative components of the CHANGE project trial: a program of work to address alcohol misuse and associated mental health comorbidities among conflict-affected populations in Uganda and Ukraine. In particular, the objectives of the current protocol are (i) to identify the specific qualitative questions and methods that will be undertaken in CHANGE; (ii) characterize the different methodological approaches to analyzing the data; and (iii) explain how each qualitative component within the different work-packages will cumulatively add value to each other over the duration of the CHANGE project. The current protocol will represent a useful template for the integration of serial qualitative research components within complex health interventions in humanitarian settings. Each qualitative components described will undergo formal ethics approval by ethics boards in the United Kingdom, Uganda, and Ukraine. Multiple mechanisms will be in place to ensure rigor and trustworthiness of the research by meeting the criteria of credibility, transferability, dependability, and confirmability.

Summary: Background: People who inject drugs (PWID) are at increased risk for HIV and hepatitis C virus (HCV) infection and also have high levels of homelessness and unstable housing. We assessed whether homelessness or unstable housing is associated with an increased risk of HIV or HCV acquisition among PWID compared with PWID who are not homeless or are stably housed. Methods: In this systematic review and meta-analysis, we updated an existing database of HIV and HCV incidence studies published between Jan 1, 2000, and June 13, 2017. Using the same strategy as for this existing database, we searched MEDLINE, Embase, and PsycINFO for studies, including conference abstracts, published between June 13, 2017, and Sept 14, 2020, that estimated HIV or HCV incidence, or both, among community-recruited PWID. We only included studies reporting original results without restrictions to study design or language. We contacted authors of studies that reported HIV or HCV incidence, or both, but did not report on an association with homelessness or unstable housing, to request crude data and, where possible, adjusted effect estimates. We extracted effect estimates and pooled data using random-effects meta-analyses to quantify the associations between recent (current or within the past year) homelessness or unstable housing compared with not recent homelessness or unstable housing, and risk of HIV or HCV acquisition. We assessed risk of bias using the Newcastle-Ottawa Scale and between-study heterogeneity using the I2 statistic and p value for heterogeneity. Findings: We identified 14 351 references in our database search, of which 392 were subjected to full-text review alongside 277 studies from our existing database. Of these studies, 55 studies met inclusion criteria. We contacted the authors of 227 studies that reported HIV or HCV incidence in PWID but did not report association with the exposure of interest and obtained 48 unpublished estimates from 21 studies. After removal of duplicate data, we included 37 studies with 70 estimates (26 for HIV; 44 for HCV). Studies originated from 16 countries including in North America, Europe, Australia, east Africa, and Asia. Pooling unadjusted estimates, recent homelessness or unstable housing was associated with an increased risk of acquiring HIV (crude relative risk [cRR] 1·55 [95% CI 1·23–1·95; p=0·0002]; I2= 62·7%; n=17) and HCV (1·65 [1·44–1·90; p

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.

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.

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.

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.

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.

Summary: Background: Globally, an estimated 15·6 million people inject drugs. We aimed to investigate global variation in the age profile of people who inject drugs (PWID), identify country-level factors associated with age of PWID, and assess the association between injecting drug use (IDU) in young people and rates of injecting and sexual risk behaviours at the country level. Methods: We derived data from a previously published global systematic review done in April, 2016 (and updated in June, 2017) on the percentage of young PWID, duration of IDU, average age of PWID, average age at IDU initiation, and the percentage of PWID reporting sexual and injecting risk behaviours. We also derived national development indicators from World Bank data. We estimated the percentage of young PWID for each country, using a random-effects meta-analysis (DerSimonian-Laird methodology) and generated pooled regional and global estimates for all indicators of IDU in young people. We used univariable and multivariable generalised linear models to test for associations between the age indicators and country urban population growth, youth unemployment percentage, the percentage of PWID who are female, the percentage of the general population aged 15–24 years, Gini coefficient, opioid substitution therapy coverage (per PWID per year), gross domestic product (GDP) per capita (US$1000), and sexual and injecting risk behaviours. Findings: In the original systematic review, data on age of PWID was reported in 741 studies across 93 countries. Globally, 25·3% (95% uncertainty interval [UI] 19·6–31·8) of PWID were aged 25 years or younger. The highest percentage of young PWID resided in eastern Europe (43·4%, 95% UI 39·4–47·4), and the lowest percentage resided in the Middle East and north Africa (6·9%, 5·1–8·8). At the country level, in multivariable analysis higher GDP was associated with longer median injecting duration (0·11 years per $1000 GDP increase, 95% CI 0·04–0·18; p=0·002), and older median age of PWID (0·13 years per $1000 increase, 0·06–0·20; p

BackgroundPersons who inject drugs (PWID) have high HIV incidence and prevalence, and may have limited access to antiretroviral therapy (ART) in some settings. We evaluated HIV drug resistance in PWID in a randomized clinical trial (HPTN 074). The study intervention included ART at any CD4 cell count with enhanced support for ART and substance use treatment.MethodsHPTN 074 enrolled HIV-infected PWID (index participants) with viral loads ≥1,000 copies/mL and their HIV-uninfected injection-network partners in Indonesia, Ukraine, and Vietnam; the study limited enrollment of people who reported being on ART. HIV drug resistance testing and antiretroviral (ARV) drug testing were performed using samples collected from index participants at study enrollment.ResultsFifty-four (12.0%) of 449 participants had HIV drug resistance; 29 (53.7%) of the 54 participants had multi-class resistance. Prevalence of resistance varied by study site and was associated with self-report of prior or current ART, detection of ARV drugs, and a history of incarceration. Resistance was detected in 10 (5.6%) of 177 newly diagnosed participants. Participants with resistance at enrollment were less likely to be virally suppressed after 52 weeks of follow-up, independent of study arm.ConclusionsIn HPTN 074, many of the enrolled index participants had HIV drug resistance and more than half of those had multi-class resistance. Some newly-diagnosed participants had resistance, suggesting that they may have been infected with drug-resistant HIV strains. Behavioral and geographic factors were associated with baseline resistance. Baseline resistance was associated with reduced viral suppression during study follow-up. These findings indicate the need for enhanced HIV care in this high-risk population to achieve sustained viral suppression on ART.

Summary: Background: Sharing of equipment used for injecting drug use (IDU) is a substantial cause of disease burden and a contributor to blood-borne virus transmission. We did a global multistage systematic review to identify the prevalence of IDU among people aged 15–64 years; sociodemographic characteristics of and risk factors for people who inject drugs (PWID); and the prevalence of HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) among PWID. Methods: Consistent with the GATHER and PRISMA guidelines and without language restrictions, we systematically searched peer-reviewed databases (MEDLINE, Embase, and PsycINFO; articles published since 2008, latest searches in June, 2017), searched the grey literature (websites and databases, searches between April and August, 2016), and disseminated data requests to international experts and agencies (requests sent in October, 2016). We searched for data on IDU prevalence, characteristics of PWID, including gender, age, and sociodemographic and risk characteristics, and the prevalence of HIV, HCV, and HBV among PWID. Eligible data on prevalence of IDU, HIV antibody, HBsAg, and HCV antibody among PWID were selected and, where multiple estimates were available, pooled for each country via random effects meta-analysis. So too were eligible data on percentage of PWID who were female; younger than 25 years; recently homeless; ever arrested; ever incarcerated; who had recently engaged in sex work, sexual risk, or injecting risk; and whose main drugs injected were opioids or stimulants. We generated regional and global estimates in line with previous global reviews. Findings: We reviewed 55 671 papers and reports, and extracted data from 1147 eligible records. Evidence of IDU was recorded in 179 of 206 countries or territories, which cover 99% of the population aged 15–64 years, an increase of 31 countries (mostly in sub-Saharan Africa and the Pacific Islands) since a review in 2008. IDU prevalence estimates were identified in 83 countries. We estimate that there are 15·6 million (95% uncertainty interval [UI] 10·2–23·7 million) PWID aged 15–64 years globally, with 3·2 million (1·6–5·1 million) women and 12·5 million (7·5–18·4 million) men. Gender composition varied by location: women were estimated to comprise 30·0% (95% UI 28·5–31·5) of PWID in North America and 33·4% (31·0–35·6) in Australasia, compared with 3·1% (2·1–4·1) in south Asia. Globally, we estimate that 17·8% (10·8–24·8) of PWID are living with HIV, 52·3% (42·4–62·1) are HCV-antibody positive, and 9·1% (5·1–13·2) are HBV surface antigen positive; there is substantial geographic variation in these levels. Globally, we estimate 82·9% (76·6–88·9) of PWID mainly inject opioids and 33·0% (24·3–42·0) mainly inject stimulants. We estimate that 27·9% (20·9–36·8) of PWID globally are younger than 25 years, 21·7% (15·8–27·9) had recently (within the past year) experienced homelessness or unstable housing, and 57·9% (50·5–65·2) had a history of incarceration. Interpretation: We identified evidence of IDU in more countries than in 2008, with the new countries largely consisting of low-income and middle-income countries in Africa. Across all countries, a substantial number of PWID are living with HIV and HCV and are exposed to multiple adverse risk environments that increase health harms. Funding: Australian National Drug and Alcohol Research Centre, Australian National Health and Medical Research Council, Open Society Foundation, World Health Organization, the Global Fund, and UNAIDS.