BACKGROUND:Some female sex workers (FSW) are initiated into sex work underage (<18 years) and/or through coercion, potentially increasing vulnerability. We estimated the contribution of these factors to HIV transmission in Tijuana, Mexico. METHODS:Using data from three bio-behavioural studies among adult FSWs in Tijuana (2003-2015), regression analysis assessed associations between underage or coerced entry into sex work and increased sexual or injecting risk behaviours. A dynamic HIV transmission model projected the proportion of new HIV infections prevented among FSWs over 2025-2034 from removing any additional risk behaviours associated with underage or coerced entry into sex work. RESULTS:Across studies (881 FSW), 10.1-39.0% of FSW reported initiating sex work underage, which was associated with client volume (adjusted rate ratio: 1.33; 95%CI:1.15-1.54), recent injecting drug use (IDU last 6 months) (adjusted odds ratio [aOR]: 1.74; 95%CI:1.08-2.79) and decreased odds of always using condoms (aOR: 0.75; 95%CI:0.53-1.06). Additionally, 19.0-20.7% reported coerced entry into sex work, which was marginally associated with recent IDU (aOR: 1.50; 95%CI:0.97-2.31).Removing the additional risks associated with underage or coerced entry into sex work from 2025 could prevent 33.0% (95%CrI:23.8-40.8%) of HIV infections amongst FSWs that started underage, 18.5% (95%CrI:11.3-28.3%) among FSW that were coerced, and 10.3% (95%CrI:6.8-14.5%) among all FSWs. If underage and coerced entry into sex work could also be stopped, then 22.3% (95%CrI:18.4-26.9) of HIV infections could be prevented among all FSWs. CONCLUSIONS:Underage and coerced entry into sex work could be important drivers of HIV transmission among FSWs in Tijuana.

BACKGROUND:Hepatitis C virus (HCV) disproportionately affects incarcerated individuals, and effective interventions are needed to improve HCV care within prisons to achieve global elimination targets. This review aimed to identify and synthesise evidence on interventions to improve HCV testing, linkage to care, and direct-acting antiviral (DAA) treatment initiation among people in prison and post-release. METHODS:We systematically searched MEDLINE (PubMed), Scopus, Web of Science, Cochrane CENTRAL, and PsycINFO for studies assessing non-pharmaceutical interventions with a comparator or control group. Outcomes were HCV antibody testing, HCV RNA testing, linkage to HCV care, and treatment initiation. Randomised controlled trials (RCTs) and controlled non-randomised studies were included; data were extracted and risk of bias assessed in duplicate using standard tools (RoB 2 and ROBINS-I). This analysis was restricted to studies of interventions evaluated in prison settings or among people recently released from prison. Searches had no date restriction and were updated November 2024. This review is registered in PROSPERO (CRD42020178035). FINDINGS:Of 20,643 unique records, 22 studies were included (19 non-randomised; three RCTs). Simplified testing modalities had the most evidence of impact on testing and treatment outcomes: dried blood spot (DBS) testing improved antibody testing uptake in three studies (two RCTs and one non-randomised study; OR 2.90, 95 % CI 1.43-5.86) and point-of-care RNA testing improved treatment initiation in three non-randomised studies (OR 9.60, 95 % CI 3.38-27.32). Simplified opt-out screening strategies also increased antibody testing uptake in three studies (OR 20.41, 95 % CI 1.88-221.19). Other interventions simplifying testing (e.g., reflex RNA testing, broadened testing criteria) were effective in individual studies, but pooled analyses for broadened testing criteria were not statistically significant due to high heterogeneity. Single studies also showed improvements in treatment initiation using DBS testing, nurse-led care, and no-cost coverage of HCV medications. INTERPRETATION:Several interventions, particularly those to enhance testing, may be successful in increasing HCV testing and treatment in prisons. However, the heterogeneity of interventions, methodological limitations of included studies, and limited number of studies underscore the need for further robust research, particularly RCTs, to optimise care in this setting.

BACKGROUND:Current US guidelines recommend annual HCV screening among men who have sex with men (MSM) with HIV and MSM on pre-exposure prophylaxis against HIV (PrEP), but these recommendations were based largely on expert opinion using interferon-era assumptions. METHODS:We calibrated a dynamic economic model of HCV transmission among MSM to US data to determine the cost-effectiveness of HCV testing among MSM with HIV and/or using PrEP; and among MSM not using PrEP, compared to status quo HCV testing. Program costs and quality-adjusted life years (QALYs) were calculated to determine the mean incremental cost-effectiveness ratio (ICER) of each testing combination compared to its next least costly permutation. We defined the optimal strategy as that having the highest health benefits but with an ICER below a willingness-to-pay threshold of $100,000/QALY gained. RESULTS:Six testing strategies dominated the other combinations. Implementing recommended annual screening among MSM with HIV was cost-saving compared to current testing rates. However, the optimal strategy was testing MSM with HIV every 6 months, MSM using PrEP every 12 months, and MSM not using PrEP when tested for HIV (ICER $67,092/QALY gained). The optimal strategy did not change under sensitivity analyses. CONCLUSIONS:The optimal frequency of HCV testing to achieve maximum health benefit in a cost-effective manner for MSM in the US is higher in two subgroups, MSM with HIV, and MSM not using PrEP, than current US guidelines recommend. HCV testing is currently performed less frequently than optimal. Expanding testing is needed to improve HCV outcomes among MSM in the US.

INTRODUCTION:UK is one of a few countries that are likely to meet WHO HCV elimination targets of reducing incidence to <2 per 100 person years in People Who Inject Drugs (PWID), but the economic case may be important for investment elsewhere and in future in UK. We illustrate the impact of real-world scaled-up HCV treatment to assess under what drug treatment costs could the investment be cost-saving. METHODS:We utilised a mathematical and economic model, calibrated to public health surveillance data and HCV testing and treatment scale-up from 4 regions in UK, that projects trends in HCV prevalence and incidence among PWID from 2016 to 2030, and deaths and incremental cost-effectiveness ratio (ICER) from 2016 until 2065, compared to counterfactual of no community and prison testing and treatment scale-up. We vary HCV drug price from £1000 to £10,000 per person treated and estimate the % of runs that are cost-saving for each price. RESULTS:Scaling up HCV treatment in PWID is estimated to avert on average 35-60% of HCV infections over 2016-2030 in the four regions compared to a counterfactual of no treatment scale-up. Over 50 years the intervention would prevent 13 to 34% of deaths assuming current HCV treatment rates continue. The ICER is cost-saving from <£1000 to £5000 across the four regions with the average (weighted by estimated number of PWID in each region) of these threshold costs at approximately £3000 per course. The majority of costs from HCV (∼ 78% before treatment scale-up) and contribution to reducing burden is due to severe liver disease (cirrhosis and decompensated cirrhosis). CONCLUSION:Scaling up HCV testing and treatment to meet WHO elimination targets is highly cost-effective and could be cost-saving at realistic discounted drug costs. The economic case for HCV elimination can be made for countries that are not yet on track.

BACKGROUND:This global systematic review assesses the prevalence of injecting drug use (IDU) and key infectious diseases (HIV, hepatitis C virus [HCV], tuberculosis and hepatitis B virus [HBV]) among people who are incarcerated. METHODS:We conducted a systematic search of peer-reviewed (Medline, Embase, PsycINFO), internet, and grey literature databases, from January 2000 through 2nd June 2025 and engaged international experts and relevant agencies liaising with key agencies focused on incarcerated populations (WHO, UNODC, UNAIDS and EUDA). Data on study methods, size of incarcerated populations and demographic characteristics, and prevalence of IDU, HIV, HCV, HBV and tuberculosis among incarcerated populations were extracted. Meta-analyses pooled data where multiple estimates were available for a country; regional and global estimates were calculated, weighted by incarcerated population size. We present overall country, regional and global prevalence estimates for each variable examined, stratified by sex. We then estimated the ratio of IDU, HIV, HCV, HBV and tuberculosis prevalence among incarcerated populations compared to the general population. RESULTS:Of 75,755 screened documents, 2,968 were eligible for data extraction. There are approximately 11,322,000 people aged 15-64 years incarcerated globally with their incarceration rate being 221 per 100,000 (29 per 100,000 among females and 404 per 100,000 among males). Substantial variation in rates across countries and regions were observed with the highest regional rate being in North America. Globally, we estimate that 11·9% of people who are incarcerated have ever injected drugs (1,348,000; 95%CI 1,061,500-1,687,000), 51·4 times higher than the general population. We estimate that 3·7% (95%CI 2·5-5·4) of people who are incarcerated globally are living with HIV (25.1· times higher than the general population); 11·7% (95%CI 7·7-17·1) have current HCV infection (15·6 times higher); 4·4% (95%CI 2·4-7·7) have current HBV infection (2·2 times higher) and 2·5% (95%CI 1·5-3·8) have active tuberculosis (45·3 times higher than the general population). There is substantial variation geographically and among females and males. CONCLUSION:The substantial concentration of people with multiple risks and comorbidities requires improved strategies to screen, evaluate, treat and prevent these adverse consequences, which is crucial for global control efforts. FUNDING:Australian National Health and Medical Research Council.

INTRODUCTION:Evidence quantifying dimensions of stigma and their health impacts among people who inject drugs (PWID) remains limited. We characterized substance use-related stigma dimensions among PWID and estimated their associations with injection-related bacterial infections (IRBIs). METHODS:We conducted a cross-sectional study nested within a prospective cohort of PWID in Montréal (August 2024-November 2025). Substance use-related stigma was measured using the Substance Use Stigma Mechanisms Scale (SU-SMS), capturing three mechanisms (enacted/anticipated/internalized); enacted and anticipated stigma were further stratified by source (family/healthcare workers). Mean scores were computed for each dimension (range 1-5) and dichotomized as low (<4) or high (≥4); any stigma was defined as high if ≥1 mechanism was high. IRBIs in the past three months included skin/soft tissue infections, bone/joint infections, sepsis, or endocarditis. Associations with IRBIs were estimated for each stigma mechanism, and by source, using Poisson regression with robust standard errors. RESULTS:Among 377 PWID, high enacted, anticipated, and internalized stigma were reported by 10%, 10%, and 9%, respectively. High stigma on any mechanism was reported by 20%. By source, high family-related stigma was more prevalent than healthcare-related stigma for both enacted (30% vs 11%) and anticipated stigma (26% vs 12%). Recent IRBIs were reported by 23% of participants. Associations with recent IRBIs were strongest for enacted stigma, with those reporting high (vs low) levels twice as likely to report one (adjusted prevalence ratio [aPR]=2.1; 95%CI: 1.4-3.1); however, associations were modest and inconclusive for anticipated (aPR=1.3; 95%CI: 0.8-2.1) and internalized stigma (aPR=1.2; 95%CI: 0.7-2.2). When stratified by source, enacted stigma remained associated with IRBIs whether from family or healthcare workers, whereas anticipated stigma showed no clear association from either source. DISCUSSION:One in five PWID experienced high substance use-related stigma on at least one of the three mechanisms. Findings underscore the multifaceted, harmful impact of stigma on PWID health and the need to address stigma from both family members and healthcare workers.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) remain public health threats in the WHO European region, where an estimated 29 million people live with chronic infection and viral hepatitis-related deaths now surpass those from HIV/AIDS and tuberculosis combined. Although effective prevention tools and antiviral treatments reduce the risk of complications, overall mortality has not declined. This Series paper reviews models of care (MoC) implemented between 2015 and 2025, drawing on scientific literature and policy documents to assess regional progress. Simplified testing and treatment, childhood and targeted adult HBV vaccination, harm-reduction programmes, and prison-based interventions have advanced elimination efforts. Pragmatic approaches, including point-of-care testing, decentralised services, and integrated models tailored to key populations demonstrate clear benefits. However, major challenges persist: large undiagnosed populations, regional disparities, inadequate healthcare worker knowledge, and inequities affect at-risk groups. Achieving elimination by 2030 will require accelerated case-finding, broader access to simplified treatment, stronger risk-tailored and vaccination strategies, improved data systems, and renewed commitment.

BACKGROUND:Some evidence suggests the benefits of opioid agonist therapy (OAT) in preventing hepatitis C virus (HCV) acquisition are stronger in men than women. However, existing analyses have used crude OAT exposure measures. We compared HCV incidence and estimated the effects of OAT on HCV acquisition among women and men who inject drugs using granular OAT exposure data. METHODS:Data were from Montréal's Hepatitis Cohort (HEPCO) study, March 2011-March 2024. We estimated overall and gender-stratified HCV incidence rates and performed discrete-time survival analyses, overall and gender-stratified, to estimate the associations between OAT engagement and HCV acquisition. In multivariable analyses, we adjusted for age and incarceration. RESULTS:HCV incidence was similar in women and men, with a rate of 6.93 (95% CI 5.67, 8.46) per 100 p-y in men, and 7.84 (95% CI 5.13, 11.98) per 100 p-y in women. In the men's adjusted model of the association between OAT engagement and HCV acquisition (in OAT versus not in OAT (but eligible)), the aHR was 0.52 (95% CI 0.33, 0.83). Among women, the aHR was 0.89 (95% CI 0.30, 2.70). However, the confidence interval was wide and crossed the null in the women's model. CONCLUSION:We found similar HCV incidence among women and men who inject drugs in Montréal; however, among OAT-eligible men, OAT engagement was strongly associated with a lower risk of HCV acquisition. These findings highlight that gender disparities in HCV, as observed in some settings, are not consistent. Further research is needed to determine factors underlying gender differences.

[This corrects the article DOI: 10.1371/journal.pgph.0004706.].

OBJECTIVE:This study aims to understand the characteristics of people who inject drugs approached by others for injection assistance. METHOD:Peer-referral and outreach were used to recruit rural adults who recently injected drugs in Appalachian Kentucky (n=435). Interviewer-administered questionnaires elicited data on participant characteristics and injection assistance. Descriptive statistics and generalized estimating equations clustered on peer-referral recruitment chain were used for analysis. RESULTS:Nearly one-third (30.1%) reported others had come to them for injection assistance. People approached for assistance were slightly younger (prevalence ratio [PR]: 0.91, 95% confidence interval [CI]: 0.85-0.99) but otherwise, demographically similar to their counterparts. Those approached for assistance were more likely to have tested HCV antibody positive (PR: 1.65, 95%CI: 1.08-2.51), recently (past six months) engaged in distributive syringe sharing (PR: 1.33, 95%CI: 1.05-1.69), used buprenorphine "to get high" (PR: 1.32, 95%CI: 1.01-1.75), witnessed an overdose (PR: 1.71, 95%CI: 1.25-2.32), and used fentanyl test strips (PR: 1.54, 95%CI: 1.14-2.08). They were also more likely to have received safer injection education (PR: 1.43, 95%CI: 1.08-1.84) and less likely to believe that sterile syringes were easy to access (PR: 0.60, 95%CI: 0.40-0.88). Among those who visited the syringe services program (SSP), those approached for injection assistance provided more people with SSP-issued syringes (PR: 1.02, 95%CI: 1.01-1.03) than those not approached. CONCLUSIONS:Injection assistance is common in rural Appalachian Kentucky and those approached for assistance have unmet harm reduction needs. Interventions that improve syringe coverage and strengthen efforts to provide support to peers in this population are needed.

BACKGROUND:Understanding the factors that hinder or support engagement with Opioid Agonist Therapy (OAT) and Needle and Syringe Provision (NSP) is essential for increasing retention and reducing drug-related harm. This study comprised a multimethod realist evaluation to develop a theory of the factors influencing service provision, focusing on access, engagement, retention, and successful exit (clients outcome met) from services. DESIGN:Phase 1 involved an online survey of UK drug and alcohol service commissioners, focus groups with interest holders, and a qualitative systematic review to build an initial programme theory of optimal service provision. Phase 2 tested and refined this theory through 86 in-depth interviews across three UK sites with commissioners, managers, staff, and people who use services (both regular attendees and those with limited contact). RESULTS:The Realist Evaluation identified five interrelated contexts (Agency and Empowerment; Self-esteem and Respect; Knowledge and Communication; Goals, Needs and Preferences; and Resources and Demands), within which mechanisms can shape optimal service provision. Person-centred approaches, low-threshold access, and timely provider contact foster agency. Confidentiality, non-stigmatising care, and strengths-based support build self-esteem, while skilled staff, training, and peer networks enhance knowledge and communication. Flexible appointments, integrated services, and shared stakeholder responsibility align care with individual goals and needs. Adequate staffing, training, supervision, and sustainable funding enable responsive, resilient services. CONCLUSIONS:These findings show how interacting relational and structural mechanisms generate optimal outcomes, guiding policy and service design. Implementing a multi-agency approach, integrating different mechanisms across the identified contexts, may be necessary to achieve optimal service delivery.

Background The US government paused funding for the US President’s Emergency Plan for AIDS Relief (PEPFAR) in 2025, including disruptions in funding for opioid agonist therapy (OAT) and needle and syringe programmes (NSP). We evaluated the impact of these disruptions on HIV/HCV transmission and drug-related deaths (DRDs) among people who inject drugs (PWID) for 9 countries where PEPFAR funds OAT. Methods We developed a static model of HIV/HCV transmission and DRD, parameterised using country-level data. We estimated the number of PWID that may stop accessing OAT through PEPFAR (2024 data; 37,024) and used a survey of harm reduction providers to estimate decreases in NSP provision (46.4% decrease, range 21.1-71.7% across 7/9 countries). We estimated the additional primary HIV/HCV infections over 1-year of disruptions, potential secondary infections over 5-years, and relative increase in DRDs over 1-year. Results In 2024, PEPFAR funding enabled 0.6-13.5% of PWID to access OAT in 9 countries. Across these countries, an additional 3,672 (95% uncertainty interval: 1438-7059) and 6709 (3020-12,919) primary HIV and HCV infections could occur over 1-year due to disruptions in OAT and NSP, respectively, equating to an ∼8% increase in HIV and HCV infections among PWID. Impact is driven by NSP disruptions (60-87%). Additionally, 5,791 (2301-9906) and 6508 (3155-12,324) secondary HIV and HCV infections could occur over 5-years, respectively, and an 1.4% (0.3-7.5%) increase in DRDs over 1-year. Conclusions Removing PEPFAR’s funding for OAT and NSP could increase HIV/HCV transmission and DRDs among PWID. Measures need to address these funding gaps.

BACKGROUND:People who are incarcerated experience disproportionately high rates of injecting drug use and infectious disease, including HIV, viral hepatitis and tuberculosis. However, comprehensive global data regarding the availability of services that prevent and manage infectious disease, injecting drug use and related harms remain limited and outdated. We provide the first systematic review to comprehensively examine the availability and coverage of infectious disease prevention, treatment, and harm reduction services for incarcerated populations globally. METHODS:We conducted a systematic review of evidence for provision of opioid agonist treatment (OAT), needle syringe programs (NSPs), HIV testing and antiretroviral therapy (ART), hepatitis C virus (HCV) testing and direct-acting antiviral (DAA) treatment, tuberculosis screening and treatment, hepatitis B virus (HBV) testing, treatment, and vaccination in carceral settings. We searched from peer-reviewed and grey literature databases between 2000 and 2025 and used the most recent data available for each indicator. FINDINGS:OAT was documented in 59/207 countries (29 %), and NSPs in ten (5 %). HIV testing was documented in 86 countries (42 %) and ART in 79 countries (38 %). HCV testing was confirmed in 55 (27 %), with DAA treatment in 47 (23 %). HBV testing was identified in 51 countries (25 %), treatment in 36 (17 %), and vaccination in 41 (20 %). Tuberculosis screening was documented in 96 countries (46 %) and treatment in 81 (39 %). Fewer than 2 % (approximately 172,000) of the 11.3 million people incarcerated worldwide live in countries that offer OAT, NSPs, and treatment for HIV, HCV, HBV, and tuberculosis in at least one carceral facility. There is not a single country where incarcerated people have access to all such services in every facility. Programme level evidence was rarely available. INTERPRETATION:The global shortage of services that prevent and treat infectious disease and harms related to injecting drug use in carceral settings is a critical public health issue and, compared with community standards, a breach of human rights. This study underscores the urgent need for international collaboration and policy reform to scale up and stabilise services that address the health needs of incarcerated populations, ultimately improving health outcomes for both incarcerated populations and wider community. FUNDING:Australian National Health and Medical Research Council.

BACKGROUND:UNAIDS' ending AIDS targets include ensuring that less than 10% of people with HIV, at risk of HIV, or affected by HIV experience HIV stigma and discrimination. We aimed to estimate the effect of HIV stigma and discrimination on the HIV care cascade in eastern, southern, central, and western Africa-regions with the largest HIV burden worldwide. METHODS:We used population-based surveys in countries in eastern, southern, central and western Africa from 2000 onward identified through previous reviews and data catalogues. Surveys eligible for inclusion were screened and selected if they contained at least one measure of HIV stigma and discrimination, and at least one HIV outcome (ie, HIV testing, antiretroviral therapy [ART] use, or viral suppression). The individual-level data from all included surveys were pooled for our analyses. We assessed three community-level HIV stigma exposures (continuous): discriminatory attitudes, perceived stigma, and shame of association with people with HIV. Among people with HIV, we examined individual-level, past-year anticipated, or experienced stigma in health-care settings (binary). Using Poisson regression, we estimated adjusted prevalence ratios (aPRs) for the effect of each stigma measure on past-year HIV testing, ART use, and viral suppression. We used segmented regression with a median breakpoint to model non-linear effects of community-level stigma. FINDINGS:We identified 124 surveys in 38 countries published between 2000 and 2023. Stigma towards people with HIV was high. 51% of participants held discriminatory attitudes, 71% perceived HIV stigma, and 43% reported shame of association. Among people with HIV, 34% had anticipated, and 8% experienced, health-care stigma. Where the prevalence of community-level discriminatory attitudes was equal to or above the median, people were less likely to have tested for HIV (aPR 0·88 per 10% increase, 95% CI 0·87-0·88), and people with HIV had lower ART use (0·96 per 10% increase, 0·94-0·97) and viral suppression (0·96, 0·95-0·98). Similarly, communities with higher (≥median) shame of association levels had lower testing (aPR 0·97 per 10% increase, 95% CI 0·96-0·98) and viral suppression (0·98, 0·96-1·00). People with HIV who anticipated or experienced health-care stigma were 7% (95% CI 4-10) less likely to be on ART and 10% (6-14) less likely to be virally suppressed, possibly reaching 14% (7-21) and 16% (9-23) when adjusted for selection bias. INTERPRETATION:HIV stigma and discrimination have measurable, widespread, negative effects on the full cascade of care: HIV testing, treatment, and viral suppression. These effects are most pronounced in communities with the highest levels of stigma. Stigma reduction strategies should be prioritised to improve health outcomes and reduce health inequities. FUNDING:Canadian Institutes of Health Research, Canada Research Chairs Program, and Wellcome Trust.

Background Female sex workers (FSW) are a key population for HIV prevention and care. Increasing evidence suggests that social and structural barriers are key drivers of HIV transmission. This global systematic review assesses whether experiencing violence is associated with worse HIV outcomes among FSW. Methods and Findings We searched MEDLINE, Embase, and PsycINFO databases for studies published from January 1st, 2010 to February 10th, 2025 assessing the impact of violence on HIV outcomes among FSW, without restriction to language and study design. Some studies had multiple estimates due to reporting on multiple outcomes or exposures of interest. We pooled data from eligible studies using multi-level random-effects meta-analyses to quantify associations between recent (past year) or lifetime exposure to violence (physical, sexual, emotional/psychological and/or financial) and HIV outcomes (prevalent and incident HIV infection, HIV testing, ART use, ART adherence, and viral suppression) among FSW. We preferentially used adjusted estimates over unadjusted estimates if both were available. We included 91 studies with 221 estimates, comprising 179,727 FSWs in 37 countries. We found higher odds of prevalent HIV infection among FSWs with recent (pooled odds ratio (pOR):1.33; 95%CI:1.17–1.51; I2:64%; n=73 estimates) and lifetime (pOR:1.36; 95%CI:1.24–1.49; I2:38%; n=67) experiences of violence. Recently experiencing violence was associated with reduced odds of ART use (pOR:0.78; 95%CI:0.64–0.94; I2:8%; n=17). Lifetime exposure to violence was associated with reduced odds of viral suppression (pOR:0.88; 95%CI:0.79–0.98; I2:20%; n=6). There was no evidence of associations between violence and HIV incidence, HIV testing and ART adherence. Conclusions Experiencing violence may increase HIV transmission risk and worsen HIV treatment outcomes among FSW. HIV interventions for FSWs must address violence as a structural determinant of HIV. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement JD and SAK received funding from the GW4 BioMed MRC Doctoral Training Partnership. KAM and JA received funding from a Bristol Postgraduate Research Scholarship. JD, KAM, SAK, JS, AA and PV received funding from The Joint United Nations Programme on HIV/AIDS (UNAIDS) (grant code 2024/1464836). AT, JS, AA and PV received funding from the Wellcome Trust (grant code 226619/Z/22/Z). UNAIDS supported the conceptualisation of the project and reviewed the final draft before submission, but not the data analysis or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All relevant data are within the manuscript and its Supporting Information files.

The risk of drug overdose and disease acquisition is highly elevated for those recently initiated into injecting drug use. Despite this, there are few harm reduction interventions developed specifically for new initiates. Further, international technical documents have historically provided little guidance on how to appropriately meet the needs of what is an inexperienced and difficult to engage sub-population. However, the recently updated operational guide for Needle and Syringe Programmes for People Who Inject Drugs from the World Health Organization (WHO), stresses that reaching new initiates requires “tailored, inclusive approaches”.In this commentary, we leverage the updated WHO guide to call for renewed focus on new initiates and the development of tailored harm reduction interventions. We describe our recent experiences co-designing interventions for new initiates in Kachin, Myanmar as a case study for how such work may proceed. Finally, we make two key recommendations; 1) that an accepted international definition of new initiates be developed that accounts for risk and opportunity to engage, and 2) that more explicit highlighting and technical guidance on targeting new initiates is made in international documentation.Engaging people who inject drugs as soon as possible after initiation, when vulnerability to blood-borne infections and overdose is greatest, will likely maximise the preventive impact of tailored interventions, thereby providing enduring harm reduction outcomes across injecting careers. The updated WHO guide is the perfect time to re-frame this conversation and re-focus these efforts.

Needle and syringe programmes (NSPs) are effective, affordable solutions for preventing the transmission of blood-borne viruses among people who inject drugs. Yet, global NSP coverage remains extremely low; only 2% of people who inject drugs live in countries with high coverage, and many low-income and middle-income countries do not have NSPs. This Health Policy reports outputs from an international working group who used implementation science approaches to prioritise barriers and co-design solutions to scale up NSPs across three domains: global policy, national policy, and procurement. We present six barriers and 11 strategies that align commodity selection and procurement with the needs and preferences of people who inject drugs, strengthen national commitment and regulatory environments, and improve forecasting and market access for preferred products. We provide sector-specific actions for funders, governments, procurement agencies, implementers, community networks, and researchers. Scaling up NSPs is essential for achieving global infectious disease-elimination goals and improving health outcomes among people who inject drugs.

BACKGROUND:In England, up to 5% of people living with HIV are undiagnosed and the proportion of late diagnoses remains high. Opt-out testing could help to identify people living with undiagnosed HIV who might not access testing in other settings. We aimed to evaluate the cost-effectiveness of the first phase of UK National Health Service (NHS)-funded opt-out testing for HIV in emergency departments, which scaled up from 2022. METHODS:We adapted a previously developed deterministic model of HIV diagnosis, progression, and transmission to simulate the impact of the first 33 months of the opt-out testing intervention in improving HIV diagnosis, incorporating programme data on CD4 cell count at diagnosis. We conducted a bottom-up costing of the intervention in two sites, from an NHS perspective, and gathered costs of HIV care from the literature. In the base case we assumed 93% of new diagnoses would not have been diagnosed elsewhere during the programme as these individuals had never previously been tested for HIV. Cost-effectiveness is presented as incremental costs per quality-adjusted life-year (QALY) gained over 20 years compared with a £25 000-35 000 per QALY threshold. We explored scenario analyses to address the limitations of the model assumptions. FINDINGS:The mean cost per HIV test was £6·31 (US$7·91). Under base case assumptions, emergency department opt-out testing is projected to avert 187 HIV-related deaths (95% credible interval 182-196) and 28 secondary acquisitions (26-52) over 20 years, costing £18 630 (17 413-23 119) per QALY gained. This result is robust (below £35 000 per QALY) to different assumptions about HIV-related quality of life and HIV care costs, HIV-related mortality, and the rate of diagnosis outside the programme. Under a lower test yield scenario of 0·20 new diagnoses per 1000 tests (compared with 0·29 in the base case), the intervention remains cost-effective at £25 000 per QALY. INTERPRETATION:Emergency department opt-out testing for HIV in England was cost-effective due to averted HIV-related morbidity and mortality resulting from improving diagnosis and linkage to care for people who would otherwise not be tested, many of whom have already reached an advanced stage of HIV progression. Our findings provide evidence to support continuation of the opt-out testing programme as part of the HIV Action Plan for England. FUNDING:National Institute for Health and Care Research and NHS England.

Objectives To assess whether transgender women who have sex with men (TGWSM) sampled in men who have sex with men (MSM) biobehavioural surveys in Ukraine experience different levels of sexual risk, stigma, HIV prevalence and engagement in the HIV care than cisgender MSM (CMSM).Design Analysis of secondary data from three population-level cross-sectional surveys.Setting The analysis was conducted on data from three rounds of integrated biobehavioural surveys of MSM in 27 cities of Ukraine from 2013 to 2018.Participants Data from n=18 621 MSM with n=18 102 CMSM and n=503 TGWSM.Primary and secondary outcome measures The primary outcomes were differences in sexual risk behaviours, HIV testing and treatment uptake, and the secondary outcomes were differences in lifetime experiences of stigma, coercive sex and physical assault (in the 2018 survey only) between CMSM and TGWSM.Results Compared with CMSM, TGWSM were more likely to be clients of non-governmental organisations (adjusted OR, aOR: 1.39, 95% CI 1.15 to 1.67), engage in commercial sex (last month; aOR: 1.28, 95% CI 1.01 to 1.61), have group sex (aOR: 1.31, 95% CI 1.06 to 1.61), more long-term sex partners (last month; adjusted incidence rate ratio: 1.14, 95% CI 1.03 to 1.27), history of imprisonment (aOR: 1.51, 95% CI 1.00 to 2.31) and engage in chemsex (last month, aOR: 1.58, 95% CI 1.12 to 2.23). We found no difference in HIV prevalence (5.17% in TGWSM vs 5.43% in CMSM, p=0.065). In 2018, more TGWSM reported lifetime experience of stigma from family and friends (aOR: 3.58, 95% CI 2.54 to 5.04), general social stigma (aOR: 3.13, 95% CI 2.22 to 4.41), anticipated healthcare stigma (aOR: 3.63, 95% CI 2.53 to 5.16), physical assault (aOR: 2.73, 95% CI 1.85 to 4.03) and coercive sex (aOR: 3.01, 95% CI 1.99 to 4.55) than CMSM.Conclusions TGWSM in Ukraine may be at increased risk of HIV acquisition compared to CMSM due to many factors including elevated levels of stigma and violence. Services specifically tailored for transgender people are needed to help reduce these high-risk behaviours.