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Background & AimsPeople who inject drugs (PWID) experience high incarceration rates which are associated with increased hepatitis C virus (HCV) transmission risk. We assess the importance of prison-based interventions for achieving HCV elimination among PWID in New South Wales (NSW), Australia.MethodsA model of incarceration and HCV transmission among PWID was calibrated in a Bayesian framework to epidemiological and incarceration data from NSW, incorporating elevated HCV acquisition risk among recently released PWID. We projected the contribution of differences in transmission risk during/following incarceration to HCV transmission over 2020–2029. We estimated the past and potential future impact of prison-based opioid agonist therapy (OAT; ~33% coverage) and HCV treatment (1500 treatments in 2019 with 32.9%–83.3% among PWID) on HCV transmission. We estimated the time until HCV incidence reduces by 80% (WHO elimination target) compared to 2016 levels with or without prison-based interventions.ResultsOver 2020–2029, incarceration will contribute 23.0% (17.9–30.5) of new HCV infections. If prison-based interventions had not been implemented since 2010, HCV incidence in 2020 would have been 29.7% (95% credibility interval: 22.4–36.1) higher. If current prison and community HCV treatment rates continue, there is an 98.8% probability that elimination targets will be achieved by 2030, with this decreasing to 10.1% without current prison-based interventions.ConclusionsExisting prison-based interventions in NSW are critical components of strategies to reduce HCV incidence among PWID. Prison-based interventions are likely to be pivotal for achieving HCV elimination targets among PWID by 2030.

As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing and/or sequencing capacity, which can also introduce biases1–3. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing4,5. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We developed and deployed improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detected emerging variants of concern up to 14 days earlier in wastewater samples, and identified multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission.

Background Injection drug use (IDU) following treatment for hepatitis C virus (HCV) infection may lead to reinfection, particularly if access to harm reduction services is suboptimal. This study assessed HCV reinfection risk following direct-acting antiviral therapy within Australian prisons that had opioid agonist therapy (OAT) programs but did not have needle and syringe programs (NSPs). Methods The Surveillance and Treatment of Prisoners With Hepatitis C (SToP-C) study enrolled people incarcerated in 4 prisons between 2014 and 2019. Participants treated for HCV were followed every 3–6 months to identify reinfection (confirmed by sequencing). Reinfection incidence and associated factors were evaluated. Results Among 388 participants receiving treatment, 161 had available posttreatment follow-up and were included in analysis (92% male; median age, 33 years; 67% IDU in prison; median follow-up 9 months). Among those with recent (in the past month) IDU (n = 71), 90% had receptive needle/syringe sharing. During 145 person-years (PY) of follow-up, 18 cases of reinfection were identified. Reinfection incidence was 12.5/100 PY (95% confidence interval [CI]: 7.9–19.8) overall, increasing to 28.7/100 PY (95% CI: 16.3–50.6) among those with recent IDU and needle/syringe sharing. In adjusted analysis, recent IDU with needle/syringe sharing was associated with increased reinfection risk (adjusted hazard ratio [aHR], 4.74 [95% CI: 1.33–16.80]; P = .016) and longer HCV testing interval with decreased risk (ie, chance of detection; aHR, 0.41 per each month increase [95% CI: .26–.64]; P Conclusions A high rate of HCV reinfection was observed within prison. Posttreatment surveillance and retreatment are ­essential to limit the impact of reinfection. High-coverage OAT and NSPs should be considered within prisons. Clinical Trials Registration NCT02064049

Background Rising incidence of hepatitis C virus (HCV) among people with HIV (PWH) in San Diego County (SDC) was reported. In 2018, the University of California San Diego (UCSD) launched a micro-elimination initiative among PWH, and in 2020 SDC launched an initiative to reduce HCV incidence by 80% across 2015–2030. We model the impact of observed treatment scale-up on HCV micro-elimination among PWH in SDC. Methods A model of HCV transmission among people who inject drugs (PWID) and men who have sex with men (MSM) was calibrated to SDC. The model was additionally stratified by age, gender, and HIV status. The model was calibrated to HCV viremia prevalence among PWH in 2010, 2018, and 2021 (42.1%, 18.5%, and 8.5%, respectively), and HCV seroprevalence among PWID aged 18–39 years, MSM, and MSM with HIV in 2015. We simulate treatment among PWH, weighted by UCSD Owen Clinic (reaching 26% of HCV-infected PWH) and non-UCSD treatment, calibrated to achieve the observed HCV viremia prevalence. We simulated HCV incidence with observed and further treatment scale-up (+/− risk reductions) among PWH. Results Observed treatment scale-up from 2018 to 2021 will reduce HCV incidence among PWH in SDC from a mean of 429 infections/year in 2015 to 159 infections/year in 2030. County-wide scale-up to the maximum treatment rate achieved at UCSD Owen Clinic (in 2021) will reduce incidence by 69%, missing the 80% incidence reduction target by 2030 unless accompanied by behavioral risk reductions. Conclusions As SDC progresses toward HCV micro-elimination among PWH, a comprehensive treatment and risk reduction approach is necessary to reach 2030 targets.

SummaryThe maturation of genomic surveillance in the past decade has enabled tracking of the emergence and spread of epidemics at an unprecedented level. During the COVID-19 pandemic, for example, genomic data revealed that local epidemics varied considerably in the frequency of SARS-CoV-2 lineage importation and persistence, likely due to a combination of COVID-19 restrictions and changing connectivity. Here, we show that local COVID-19 epidemics are driven by regional transmission, including across international boundaries, but can become increasingly connected to distant locations following the relaxation of public health interventions. By integrating genomic, mobility, and epidemiological data, we find abundant transmission occurring between both adjacent and distant locations, supported by dynamic mobility patterns. We find that changing connectivity significantly influences local COVID-19 incidence. Our findings demonstrate a complex meaning of ‘local’ when investigating connected epidemics and emphasize the importance of collaborative interventions for pandemic prevention and mitigation.

There is an opportunity to determine how best to deploy sexually transmitted infection testing technologies to improve health. Our results suggest that a mixed (hub-and-spoke) approach offered the lowest cost per adverse outcome averted. Supplemental digital content is available in the text., Background Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are common sexually transmitted infections (STIs) associated with adverse outcomes, yet most countries do not test and conduct syndromic management, which lacks sensitivity and specificity. Innovations allow for expanded STI testing; however, cost is a barrier. Methods Using inputs from a pilot program in Botswana, we developed a model among a hypothetical population of 50,000 pregnant women to compare 1-year costs and outcomes associated with 3 antenatal STI testing strategies: (1) point-of-care, (2) centralized laboratory, and (3) a mixed approach (point of care at high-volume sites, and hubs elsewhere), and syndromic management. Results Syndromic management had the lowest delivery cost but was associated with the most infections at delivery, uninfected women treated, CT/NG-related low-birth-weight infants, disability-adjusted life years, and low birth weight hospitalization costs. Point-of-care CT/NG testing would treat and cure the most infections but had the highest delivery cost. Among the testing scenarios, the mixed scenario had the most favorable cost per woman treated and cured ($534/cure). Compared with syndromic management, the mixed approach resulted in a mean incremental cost-effectiveness ratio of $953 per disability-adjusted life years averted, which is cost-effective under World Health Organization's one-time per-capita gross domestic product willingness-to-pay threshold. Conclusions As countries consider new technologies to strengthen health services, there is an opportunity to determine how to best deploy resources. Compared with point-of-care, centralized laboratory, and syndromic management, the mixed approach offered the lowest cost per infection averted and is cost-effective if policy makers' willingness to pay is informed by the World Health Organization's gross domestic product/capita threshold.

Tijuana, Mexico, has a concentrated HIV epidemic among overlapping key populations (KPs) including people who inject drugs (PWID), female sex workers (FSW), their male clients, and men who have sex with men (MSM). We developed a dynamic HIV transmission model among these KPs to determine the extent to which their unmet prevention and treatment needs is driving HIV transmission. Over 2020-2029 we estimated the proportion of new infections acquired in each KP, and the proportion due to their unprotected risk behaviours. We estimate that 43.7% and 55.3% of new infections are among MSM and PWID, respectively, with FSW and their clients making-up 10% of new infections. Projections suggest 93.8% of new infections over 2020-2029 will be due to unprotected sex between MSM or unsafe injecting drug use. Prioritizing interventions addressing sexual and injecting risks among MSM and PWID are critical to controlling HIV in Tijuana.Tijuana, México, tiene una epidemia de VIH concentrada en poblaciones claves (PC) superpuestas que incluyen personas que se inyectan drogas (PID), trabajadoras sexuales (MTS), sus clientes hombres, y hombres que tienen sexo con hombres (HSH). Desarrollamos un modelo dinámico de transmisión de VIH en estas PC para determinar hasta dónde sus necesidades no atendidas de prevención y tratamiento dirigen la transmisión del VIH. Para 2020–2029 estimamos la proporción de nuevas infecciones adquiridas en cada PC, y la proporción atribuida a sus comportamientos de riesgo sin protección. Estimamos que 43.7% y 55.3% de nuevas infecciones se dan en HSH y PID, respectivamente, con MTS y clientes conformando 10% de nuevas infecciones. Las proyecciones sugieren que 93.8% de nuevas infecciones en 2020–2029 se deberán a sexo sin protección en HSH o uso inseguro de drogas inyectables. Dar prioridad a intervenciones que atienden los riesgos sexual y de inyección en HSH y PID es crítico para controlar el VIH en Tijuana.

The COVID-19 pandemic has impacted supervised consumption site (SCS) operations in Montréal, Canada, potentially including changes in SCS visits, on-site emergency interventions, injection of specific drugs, and distribution of harm reduction materials.We used administrative data from all four Montréal SCS from 1 March 2018 - 28 February 2021 to conduct an interrupted time series study with 13 March 2020 as the intervention point. We employed segmented regression using generalised least squares fit by maximum likelihood. We analysed monthly SCS visits and materials distributed as counts, and emergency interventions and drugs injected as proportions of visits.SCS visits (level change = -1,286; 95% CI [-1,642, -931]) and the proportion of visits requiring emergency intervention (level = -0.27% [-0.47%, -0.06%]) decreased immediately in March 2020, followed by an increasing trend in emergency interventions (slope change = 0.12% [0.10%, 0.14%]) over the ensuing 12 months. Over the same period, the proportion of injections involving opioids increased (slope = 0.05% [0.03%, 0.07%]), driven by increasing pharmaceutical opioid and novel synthetic opioid injections. Novel synthetic opioids were the drugs most often injected prior to overdose. The proportion of injections involving unregulated amphetamines increased immediately (level = 7.83% [2.93%, 12.73%]), then decreased over the next 12 months (slope = -1.86% [-2.51%, -1.21%]). There was an immediate increase in needle/syringe distribution (level = 16,552.81 [2,373, 30,732]), followed by a decreasing trend (slope = -2,398 [-4,218, -578]). There were no changes in pre-existing increasing trends in naloxone or fentanyl test strip distribution.Reduced SCS use and increasing emergency interventions at SCS are cause for serious concern. Findings suggest increased availability of novel synthetic opioids in Montréal, heightening overdose risk.

Network science methods can be useful in design, monitoring, and analysis of randomized trials for control of spread of infections. Their usefulness arises from the role of statistical network models in molecular epidemiology and in study design. Computational models, such as agent-based models that propagate disease on simulated contact networks, can be used to investigate the properties of different study designs and analysis plans. Particularly valuable is the use of these methods to assess how magnitude and detectability of intervention effects depend on both individual-level and network-level characteristics of the enrolled populations. Such investigation also provides an important approach to assessing consequences of study data being incomplete or measured with error. To address these goals, we consider two statistical network models: exponential random graph models and the more flexible congruence class models. We focus first on an historical use of these methods in design and monitoring of a cluster randomized trial in Botswana to evaluate the effect of combination HIV prevention modalities compared to standard of care on HIV incidence. We then present a framework for the design of a study of booster vaccine effects on infection with, and forward transmission of, SARS-CoV-2 variants. Motivation for the study is driven in part by guidance from the United Kingdom to base approval of booster vaccines with “strain changes” that target variants on results of neutralizing antibody tests and information about safety, but without requiring evidence of clinical efficacy. Using designs informed by our agent-based network models, we show it may be feasible to conduct a trial of novel SARS-CoV-2 vaccines in a single large campus to obtain useful information regarding vaccine efficacy against susceptibility and infectiousness. If needed, the sample size could be increased by extending the study to a small number of campuses. Novel network methods may be useful in developing pragmatic SARS-CoV-2 vaccine trials that can leverage existing infrastructure to reduce costs and hasten the development of results.

People who inject drugs (PWID) have likely borne disproportionate health consequences of the COVID-19 pandemic. PWID experienced both interruptions and changes to drug supply and delivery modes of harm reduction, treatment, and other medical services, leading to potentially increased risks for HIV, hepatitis C virus (HCV), and overdose. Given surveillance and research disruptions, proximal, indirect indicators of infectious diseases and overdose should be developed for timely measurement of health effects of the pandemic on PWID.We used group concept mapping and a systems thinking approach to produce an expert stakeholder-generated, multi-level framework for monitoring changes in PWID health outcomes potentially attributable to COVID-19 in the U.S. This socio-ecological measurement framework elucidates proximal and distal contributors to infectious disease and overdose outcomes, many of which can be measured using existing data sources.The framework includes multi-level components including policy considerations, drug supply/distribution systems, the service delivery landscape, network factors, and individual characteristics such as mental and general health status and service utilization. These components are generally mediated by substance use and sexual behavioral factors to cause changes in incidence of HIV, HCV, sexually transmitted infections, wound/skin infections, and overdose.This measurement framework is intended to increase the quality and timeliness of research on the impacts of COVID-19 in the context of the current pandemic and future crises. Next steps include a ranking process to narrow the drivers of change in health risks to a concise set of indicators that adequately represent framework components, can be written as measurable indicators, and are quantifiable using existing data sources, as well as a publicly available web-based platform for summary data contributions.

Exposure to trauma increases the risk of engaging in detrimental health behaviours such as tobacco and substance use. In response, the United States Substance Abuse and Mental Health Services Administration developed Trauma-Informed Care (TIC), an organisational framework for improving the provision of behavioural health care to account for the role exposure to trauma plays in patients' lives. We adapt TIC to introduce a novel theory of behaviour change, the Trauma-Informed Theory of Individual Health Behavior (TTB). TTB posits that individual capacity to undertake intentional health-promoting behaviour change is dependent on three factors: (1) the forms and severity of trauma they have been and are exposed to, (2) how this trauma physiologically manifests (i.e., the trauma response) and (3) resilience to undertake behaviour change despite this trauma response. We define each of these factors and their relationships to one another. We anticipate that the introduction of TTB will provide a foundation for developing theory-driven research, interventions, and policies that improve behavioural health outcomes in trauma-affected populations.

BACKGROUND: Modelling suggests hepatitis C virus (HCV) elimination is possible among men-who-have-sex-with-men (MSM), with key screening groups including HIV-diagnosed MSM and MSM using pre-exposure prophylaxis (PrEP). METHODS: Mathematical modelling was used to determine the cost-effectiveness of HCV case-finding strategies among MSM from the provider perspective, and to determine which interventions could achieve a 90% reduction in HCV incidence over 2015–2030. At baseline, we assume symptomatic screening in HIV-negative MSM (including PrEP users) and 12-monthly screening among HIV-diagnosed MSM. Improved case-finding strategies included screening alongside HIV-testing in HIV-negative MSM not using PrEP (PrEP non-users); 12/6/3-monthly screening in PrEP users; and 6-monthly screening in HIV-diagnosed MSM, with the cost-effectiveness being compared incrementally. Costs (GBP) and quality adjusted life-years (QALYs) were assessed to estimate the mean incremental cost-effectiveness ratio (ICER) with a time horizon to 2050, compared to a willingness-to-pay threshold of £20,000/QALY. RESULTS: From the baseline, the most incrementally cost-effective strategy is to firstly undertake: (1) 12-monthly HCV screening of PrEP users (gaining 6,715 QALYs with ICER £1,760/QALY), followed by (2) HCV screening among PrEP non-users alongside HIV testing (gaining 7,048 QALYs with ICER £4,972/QALY). Compared to the baseline, this combined strategy would cost £46.9 (95%CrI £25.3-£66.9) million and achieve the HCV elimination target in 100% of model runs. Additional screening incurs ICERs >£20,000/QALY compared to this combined strategy. CONCLUSION: HCV elimination can be achieved cost-effectively among UK MSM. Policymakers should consider scaling-up HCV screening in HIV-negative MSM, especially PrEP users, for achieving this target.

In 2019, Mexico was one of the first countries in Latin America to commit resources to achieve hepatitis C elimination by 2030. One year after this commitment, the global COVID-19 pandemic diverted attention to address immediate health needs to combat the spread of the disease. As a result, efforts to implement hepatitis C prevention and management programs were indefinitely postponed. Furthermore, populations at high risk of contracting the hepatitis C virus (HCV) and who bear the greatest burden of HCV national epidemic, including people who inject drugs and people who live with human immunodeficiency virus infection, remain exposed to extreme health disparities, which have potentially been exacerbated during the COVID-19 pandemic. In this article, we discuss the potential impact the COVID-19 pandemic has had on HCV elimination efforts in Mexico and the urgent need to resume them, since without these efforts, HCV elimination goals are likely not be achieved in the country by 2030.En 2019, México fue uno de los primeros países en Latinoamérica en comprometer recursos para eliminar la hepatitis C antes de 2030. Un año después de este compromiso, la pandemia mundial de COVID-19 desvió la atención hacia las necesidades inmediatas de salud para combatir la propagación de esta última. Como resultado, los esfuerzos para implementar programas de prevención y manejo de la hepatitis C se suspendieron indefinidamente. Asimismo, las poblaciones con alto riesgo de contraer el virus de la hepatitis C y que representan el mayor peso de la epidemia nacional, como las personas que se inyectan drogas y las personas que viven con infección por el virus de la inmunodeficia humana, permanecen expuestas a disparidades de salud extremas que potencialmente se han exacerbado durante la pandemia de COVID-19. En este artículo discutimos el impacto potencial que la pandemia de COVID-19 ha tenido sobre los esfuerzos de eliminación de la hepatitis C en México y la necesidad urgente de reanudarlos, ya que sin ellos los objetivos de eliminación no se alcanzarán en el país en 2030.

Author(s): Chaillon, A; Bharat, C; Stone, J; Jones, N; Degenhardt, L; Larney, S; Farrell, M; Vickerman, P; Hickman, M; Martin, NK; Borquez, A | Abstract: BACKGROUND AND AIMS: The individual-level effectiveness of opioid agonist treatment (OAT) in reducing mortality is well established but there is less evidence on population-level benefits. We use modeling informed with linked data from the OAT program in New South Wales (NSW), Australia, to estimate the impact of OAT provision in community and prison on mortality and the impact of eliminating excess mortality during OAT initiation/discontinuation. DESIGN: Dynamic modeling. SETTING AND PARTICIPANTS: A cohort of 49,359 individuals who ever received OAT in NSW from 2001-2018. MEASUREMENTS: Receipt of OAT was represented through five stages: (i) first month on OAT, (ii) short (1-9 months) and (iii) longer (9+ months) duration on OAT, (iv) first month following OAT discontinuation and (v) rest of time following OAT discontinuation. Incarceration was represented as four strata (i) never or not incarcerated in the past year, (ii) currently incarcerated, (iii) released from prison within the past month and (iv) released from prison 1-12 months ago. The model incorporated elevated mortality post-release from prison, and OAT impact on reducing mortality and incarceration. FINDINGS: Among the cohort, mortality was 0.9 per 100 person-years, OAT coverage and retention remained high (g50%, 1.74 years/episode). Over 2001-2020, we estimate OAT provision reduced overdose and other cause mortality among the cohort by 53% [95% credible interval: 49%-56%] and 27% [22%-30%], respectively. We estimate 1.2 deaths averted and 9.7 life-years gained per 100 person-years on OAT. Prison OAT with post-release OAT-linkage accounted for 12% [11%-13%] of all deaths averted by the OAT program, primarily through preventing deaths in the first month post-release. Preventing elevated mortality during OAT initiation and discontinuation could have averted up to 1.4% [1%-2%] and 3% [2%-5%] of deaths, respectively. CONCLUSION: The community and prison opioid agonist treatment program in New South Wales, Australia appears to have substantially reduced population-level overdose and all-cause mortality in the past 20 years, partially due to high retention.

Background and aims Syringe-sharing among people who inject drugs, which can occur during incarceration and post-release, has been linked with increased risk of blood-borne infections. We aimed to investigate the cumulative effect of repeated incarceration and the post-release period on receptive syringe-sharing. Design Ongoing community-based cohort, recruited through targeted sampling between 2011 and 2012 with 6-month follow-ups. Setting Tijuana, Mexico. Participants Sample of 185 participants (median age 35 years; 67% female) with no history of incarceration at study entry, followed to 2017. Measurements Cumulative incarceration and post-release period were constructed from incarceration events reported in the past 6 months for each study visit. Receptive syringe-sharing in the past 6 months was assessed as a binary variable. We used logistic regression with generalized estimating equations to examine the association between cumulative incarceration events and the post-release period with receptive syringe-sharing over time. Missing data were handled through multiple imputation. Findings At baseline, 65% of participants engaged in receptive syringe-sharing in the prior 6 months. At follow-up, 150 (81%) participants experienced a total of 358 incarceration events [median = 2, interquartile range (IQR) = 1-3]. The risk of receptive syringe-sharing increased with the number of repeated incarcerations. Compared with never incarcerated, those with one incarceration had 1.28 [95% confidence interval (CI) = 0.97-1.68] higher adjusted odds of syringe-sharing; two to three incarcerations, 1.42 (95% CI = 1.02-1.99) and more than three incarcerations, 2.10 (95% CI = 1.15-3.85). Participants released within the past 6 months had 1.53 (95% CI = 1.14-2.05) higher odds of sharing syringes compared with those never incarcerated. This post-release risk continued up to 1.5 years post-incarceration (adjusted odds ratio = 1.41, 95% CI = 1.04-1.91), but then waned. Conclusions A longitudinal community cohort study among people who inject drugs suggested that the effects of incarceration on increased injecting risk, measured through syringe-sharing, are cumulative and persist during the post-release period.

BACKGROUND: Outcomes following hepatitis C virus (HCV)-viremic heart transplantation into HCV-negative recipients with HCV treatment are good. We assessed cost-effectiveness between cohorts of transplant recipients willing and unwilling to receive HCV-viremic hearts. METHODS: Markov model simulating long-term outcomes among HCV-negative patients on the transplant waitlist. We compared costs (2018 US$) and health outcomes (quality-adjusted life-years, QALYs) between cohorts willing to accept any heart and those only willing to accept HCV-negative hearts. We assumed 4.9% HCV-viremic donor prevalence. Patients receiving HCV-viremic hearts were treated, assuming $39,600/treatment with 95% cure. Incremental cost-effectiveness ratios (ICERs) were compared to a $100,000/QALY gained willingness-to-pay threshold. Sensitivity analyses included stratification by blood type or region, and potential negative consequences of receipt of HCV-viremic hearts. RESULTS: Compared to accepting only HCV-negative hearts, accepting any heart gained 0.14 life-years and 0.11 QALYs, while increasing costs by $9,418/patient. Accepting any heart was cost-effective (ICER $85,602/QALY gained). Results were robust to all transplant regions and blood types, except type AB. Accepting any heart remained cost-effective provided post-transplant mortality and costs among those receiving HCV-viremic hearts was not >7% higher compared to HCV-negative hearts. CONCLUSIONS: Willingness to accept HCV-viremic hearts for transplantation into HCV-negative recipients is cost-effective and improves clinical outcomes.

Background The novel coronavirus, SARS-CoV-2, which was first recognized in December 2019, is responsible for the COVID-19 pandemic that is having a devastating impact on human health, society and the global economy. Methods We summarize lessons learned from the HIV epidemic that offer insights about how the response to COVID-19 can be improved, especially in the United States which has incurred one quarter of world's infections to date. Results Lessons learned include: the need to develop and deploy valid tests for point-of-care diagnosis and surveillance; the importance of considering HIV and COVID-19 in the context of syndemics; the potential role of structural interventions that address drivers of disparities; how existing research infrastructure can be leveraged to accelerate development of therapeutics and vaccines; and how modeling that is tailored to regional epidemics can inform policy. Conclusions The window of opportunity to prevent a widespread COVID-19 epidemic in the United States has already closed, but it is not too late to implement a mitigation strategy that can save thousands of lives. Decisive leadership that develops policies grounded in scientific evidence is key to charting a path forward. The question is whether the United States is prepared to learn from its past successes and mistakes with the HIV epidemic to develop a nation-wide plan that puts politics aside and prioritizes saving lives.

© 2021 Elsevier Ltd. All rights reserved., Liver diseases have become a major health threat across Europe, and the face of European hepatology is changing due to the cure of viral hepatitis C and the control of chronic viral hepatitis B, the increasingly widespread unhealthy use of alcohol, the epidemic of obesity, and undiagnosed or untreated liver disease in migrant populations. Consequently, Europe is facing a looming syndemic, in which socioeconomic and health inequities combine to adversely affect liver disease prevalence, outcomes, and opportunities to receive care. In addition, the COVID-19 pandemic has magnified pre-existing challenges to uniform implementation of policies and equity of access to care in Europe, arising from national borders and the cultural and historical heterogeneity of European societies. In following up on work from the Lancet Commission on liver disease in the UK and epidemiological studies led by the European Association for the Study of the Liver (EASL), our multidisciplinary Commission, comprising a wide range of public health, medical, and nursing specialty groups, along with patient representatives, set out to provide a snapshot of the European landscape on liver diseases and to propose a framework for the principal actions required to improve liver health in Europe. We believe that a joint European process of thinking, and construction of uniform policies and action, implementation, and evaluation can serve as a powerful mechanism to improve liver care in Europe and set the way for similar changes globally., The SHARE data collection has been funded by the European Commission through FP5 (QLK6-CT-2001-00360), FP6 (SHARE-I3: RII-CT-2006-062193; COMPARE: CIT5-CT-2005-028857; SHARELIFE: CIT4-CT-2006-028812), FP7 (SHARE-PREP: GA N°211909; SHARE-LEAP: GA N°227822; SHARE M4: GA N°261982; DASISH: GA N°283646), and Horizon 2020 (SHARE-DEV3: GA N°676536; SHARE-COHESION: GA N°870628; SERISS: GA N°654221; SSHOC: GA N°823782) and by DG Employment, Social Affairs & Inclusion. Additional funding from the German Ministry of Education and Research, the Max Planck Society for the Advancement of Science, the US National Institute on Aging (U01_AG09740-13S2; P01_AG005842; P01_AG08291; P30_AG12815; R21_AG025169; Y1-AG-4553-01; IAG_BSR06-11; OGHA_04-064; HHSN271201300071C), and from various national funding sources is gratefully acknowledged. PC acknowledges support by the French National Agency for HIV, hepatitis and emerging infectious diseases research (ANRS / EMERGING INFECTIOUS DISEASES).

Author(s): Chaillon, Antoine; Thurairajah, Prem Harichander; Hsiang, John Chen; Martin, Natasha K | Abstract: Background and aimThe vast majority of hepatitis C virus (HCV) infection in Singapore is among those with a history of injecting drug use (IDU), yet harm reduction is not available and what is required to achieve the World Health Organization (WHO) HCV elimination targets (80% incidence reduction and 65% mortality reduction by 2030) is unknown. We model the intervention scale-up required to achieve WHO targets in Singapore.MethodsA dynamic model of HCV transmission and progression among those with a history of IDU was calibrated to Singapore, a setting with declining IDU and no harm reduction (~11n000 people with IDU history in 2017 and 45% HCV seropositive). We projected HCV treatment scale-up from 2019 required to achieve WHO targets with varying prioritization scenarios, with/without opiate substitution therapy scale-up (to 40% among people who inject drugs [PWID]).ResultsWe estimated 3855 (95% confidence interval: 2635-5446) chronically HCV-infected individuals with a history of IDU and 148 (87-284) incident HCV cases in Singapore in 2019. Reaching the HCV incidence target requires 272 (187-384) treatments in 2019, totaling 2444 (1683-3452) across 2019-2030. By prioritizing PWID or PWID and cirrhotics, 60% or 30% fewer treatments are required, respectively, whereas the target cannot be achieved with cirrhosis prioritization. Opiate substitution therapy scale-up reduces treatments required by 21-24%. Achieving both WHO targets requires treating 631 (359-1047) in 2019, totaling 3816 (2664-5423) across 2019-2030.ConclusionsHepatitis C virus elimination is achievable in Singapore but even with declining IDU requires immediate treatment scale-up among PWID. Harm reduction provision reduces treatments required and provides additional benefits.

BACKGROUND AND AIMS People who inject drugs (PWID) are at high risk of hepatitis C virus (HCV) infection; however, ~50% are undiagnosed in England and linkage-to-care is poor. This study investigated the cost-effectiveness of an intervention (HepCATT) to improve case-finding and referral to HCV treatment compared with standard-of-care pathways in drug treatment centres in England. DESIGN HCV transmission and disease progression model with cost-effectiveness analysis using a health-care perspective. Primary outcome and cost data from the HepCATT study parameterized the intervention, suggesting that HepCATT increased HCV testing in drug treatment centres 2.5-fold and engagement onto the HCV treatment pathway 10-fold. A model was used to estimate the decrease in HCV infections and HCV-related deaths from 2016, with costs and health benefits (quality-adjusted life-years or QALYs) tracked over 50 years. Univariable and probabilistic sensitivity analyses (PSA) were undertaken. SETTING England-specific epidemic with 40% prevalence of chronic HCV among PWID. PARTICIPANTS PWID attending drug treatment centres. INTERVENTION Nurse facilitator in drug treatment centres to improve the HCV care pathway from HCV case-finding to referral and linkage to specialist care. Comparator was the standard-of-care HCV care pathway. MEASUREMENTS Incremental cost-effectiveness ratio (ICER) in terms of cost per QALY gained through improved case-finding. FINDINGS Over 50 years per 1000 PWID, the HepCATT intervention could prevent 75 (95% central interval 37-129) deaths and 1330 (827-2040) or 51% (30-67%) of all new infections. The mean ICER was £7986 per QALY gained, with all PSA simulations being cost-effective at a £20 000 per QALY willingness-to-pay threshold. Univariable sensitivity analyses suggest the intervention would become cost-saving if the cost of HCV treatment reduces to £3900. If scaled up to all PWID in England, the intervention would cost £8.8 million and decrease incidence by 56% (33-70%) by 2030. CONCLUSIONS Increasing hepatitis C virus infection case-finding and treatment referral in drug treatment centres could be a highly cost-effective strategy for decreasing hepatitis C virus incidence among people who inject drugs.

Summary We did a global review to synthesise data on the prevalence, harms, and interventions for stimulant use, focusing specifically on the use of cocaine and amphetamines. Modelling estimated the effect of cocaine and amphetamine use on mortality, suicidality, and blood borne virus incidence. The estimated global prevalence of cocaine use was 0·4% and amphetamine use was 0·7%, with dependence affecting 16% of people who used cocaine and 11% of those who used amphetamine. Stimulant use was associated with elevated mortality, increased incidence of HIV and hepatitis C infection, poor mental health (suicidality, psychosis, depression, and violence), and increased risk of cardiovascular events. No effective pharmacotherapies are available that reduce stimulant use, and the available psychosocial interventions (except for contingency management) had a weak overall effect. Generic approaches can address mental health and blood borne virus infection risk if better tailored to mitigate the harms associated with stimulant use. Substantial and sustained investment is needed to develop more effective interventions to reduce stimulant use.

In 2016, the World Health Organization issued global elimination targets for hepatitis C virus (HCV), including an 80% reduction in HCV transmission by 2030. The vast majority of new HCV infections occur among people who inject drugs (PWID), and as such elimination strategies require particular focus on this population. As governments urgently require guidance on how to achieve elimination among PWID, mathematical modeling can provide critical information on the level and targeting of intervention are required. In this paper we review the epidemic modeling literature on HCV transmission and prevention among PWID, highlight main differences in mathematical formulation, and discuss key insights provided by these models in terms of achieving WHO elimination targets among PWID. Overall, the vast majority of modeling studies utilized a deterministic compartmental susceptible-infected-susceptible structure, with select studies utilizing individual-based network transmission models. In general, these studies found that harm reduction alone is unlikely to achieve elimination targets among PWID. However, modeling indicates elimination is achievable in a wide variety of epidemic settings with harm reduction scale-up combined with modest levels of HCV treatment for PWID. Unfortunately, current levels of testing and treatment are generally insufficient to achieve elimination in most settings, and require further scale-up. Additionally, network-based treatment strategies as well as prison-based treatment and harm reduction provision could provide important additional population benefits. Overall, epidemic modeling has and continues to play a critical role in informing HCV elimination strategies worldwide.

SummaryAs SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here, we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We develop and deploy improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detect emerging variants of concern up to 14 days earlier in wastewater samples, and identify multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission.

Background Recent reports indicated declines in hepatitis C virus (HCV) testing during the first half of 2020 in the United States due to coronavirus disease 2019 (COVID-19), but the longer-term impact on HCV testing and treatment is unclear. Methods We obtained monthly state-level volumes of HCV antibody, RNA and genotype testing, and HCV treatment initiation, stratified by age and gender, spanning January 2019 until December 2020 from 2 large national laboratories. We performed segmented regression analysis for each state from a mixed-effects Poisson regression model with month as the main fixed predictor and state as a random intercept. Results During the pre–COVID-19 period (January 2019–March 2020), monthly HCV antibody and genotype tests decreased slightly whereas RNA tests and treatment initiations remained stable. Between March and April 2020, there were declines in the number of HCV antibody tests (37% reduction, P Conclusions HCV testing and treatment dropped by >30% during April 2020 at the start of the COVID-19 pandemic, but although HCV testing increased again later in 2020, HCV treatment rates did not recover. Efforts should be made to link HCV-positive patients to treatment and revitalize HCV treatment engagement by healthcare providers.

Background and AimsBetween 2014 and 2019, the SToP-C trial observed a halving in HCV incidence in four Australian prisons following scale-up of direct-acting antiviral (DAA) therapy. However, the contribution of HCV treatment to this decline is unclear because the study did not have a control group. We used modeling to consider this question.Approach and ResultsWe parameterized and calibrated a dynamic model of HCV transmission in prisons to data from each SToP-C prison on incarceration dynamics, injecting drug use, HCV prevalence trends among prison entrants, baseline HCV incidence before treatment scale-up, and subsequent HCV treatment scale-up. The model projected the decrease in HCV incidence resulting from increases in HCV treatment and other effects. We assessed whether the model agreed better with observed reductions in HCV incidence overall and by prison if we included HCV treatment scale-up, and its prevention benefits, or did not. The model estimated how much of the observed decrease in HCV incidence was attributable to HCV treatment in prison. The model projected a decrease in HCV incidence of 48.5% (95% uncertainty interval [UI], 41.9-54.1) following treatment scale-up across the four prisons, agreeing with the observed HCV incidence decrease (47.6%; 95% CI, 23.4-64.2) from the SToP-C trial. Without any in-prison HCV treatment, the model indicated that incidence would have decreased by 7.2% (95% UI, −0.3 to 13.6). This suggests that 85.1% (95% UI, 72.6-100.6) of the observed halving in incidence was from HCV treatment scale-up, with the remainder from observed decreases in HCV prevalence among prison entrants (14.9%; 95% UI, −0.6 to 27.4).ConclusionsOur results demonstrate the prevention benefits of scaling up HCV treatment in prison settings. Prison-based DAA scale-up should be an important component of HCV elimination strategies.

Background People who inject drugs may be at elevated SARS-CoV-2 risk due to their living conditions and/or exposures when seeking or using drugs. No study to date has reported upon risk factors for SARS-CoV-2 infection among people who inject drugs. Methods and findings Between October, 2020 and June, 2021, participants aged ≥18 years from San Diego, California, USA and Tijuana, Baja California, Mexico who injected drugs within the last month underwent interviews and testing for SARS-CoV-2 RNA and antibodies. Binomial regressions identified correlates of SARS-CoV-2 seropositivity. Results Of 386 participants, SARS-CoV-2 seroprevalence was 36.3% (95% CI: 31.5%-41.1%); 92.1% had detectable IgM antibodies. Only 37.5% had previously been tested. Seroprevalence did not differ by country of residence. None tested RNA-positive. Most (89.5%) reported engaging in ≥1 protective behavior [e.g., facemasks (73.5%), social distancing (46.5%), or increasing handwashing/sanitizers (22.8%)]. In a multivariate model controlling for sex, older age, and Hispanic/Latinx/Mexican ethnicity were independently associated with SARS-CoV-2 seropositivity, as was engaging in sex work (AdjRR: 1.63; 95% CI: 1.18–2.27) and having been incarcerated in the past six months (AdjRR: 1.49; 95% CI: 0.97–2.27). Comorbidities and substance using behaviors were not associated with SARS-CoV-2 seropositivity. Conclusions In this community-based study of people who inject drugs in the San Diego-Tijuana border region, over one third were SARS-CoV-2 seropositive, exceeding estimates from the general population in either city. We found no evidence that substance use behaviors were associated with an elevated risk of SARS-CoV-2 infection, but observed that circumstances in the risk environment, notably sex work and incarceration, were independently associated with higher SARS-CoV-2 seroprevalence. Our findings suggest that a binational policy response to COVID-19 mitigation is warranted beyond the closure of the U.S.-Mexico border. Furthermore, decriminalizing sex work and drug use could reduce the burden of COVID-19 among people who inject drugs.

BackgroundSchools are high-risk settings for SARS-CoV-2 transmission, but necessary for children’s educational and social-emotional wellbeing. Previous research suggests that wastewater monitoring can detect SARS-CoV-2 infections in controlled residential settings with high levels of accuracy. However, its effective accuracy, cost, and feasibility in non-residential community settings is unknown.MethodsThe objective of this study was to determine the effectiveness and accuracy of community-based passive wastewater and surface (environmental) surveillance to detect SARS-CoV-2 infection in neighborhood schools compared to weekly diagnostic (PCR) testing. We implemented an environmental surveillance system in nine elementary schools with 1700 regularly present staff and students in southern California. The system was validated from November 2020 – March 2021.FindingsIn 447 data collection days across the nine sites 89 individuals tested positive for COVID-19, and SARS-CoV-2 was detected in 374 surface samples and 133 wastewater samples. Ninety-three percent of identified cases were associated with an environmental sample (95% CI: 88% - 98%); 67% were associated with a positive wastewater sample (95% CI: 57% - 77%), and 40% were associated with a positive surface sample (95% CI: 29% - 52%). The techniques we utilized allowed for near-complete genomic sequencing of wastewater and surface samples.InterpretationPassive environmental surveillance can detect the presence of COVID-19 cases in non-residential community school settings with a high degree of accuracy.FundingCounty of San Diego, Health and Human Services Agency, National Institutes of Health, National Science Foundation, Centers for Disease Control

Incarceration is associated with increased risk of hepatitis C virus (HCV) among people who inject drugs (PWID). Mexico's previous attempt in implementing a public health-oriented drug law reform resulted in minimal impact on incarceration among PWID. However, implementation of reforms alongside Mexico's HCV elimination program has the potential to reshape the HCV epidemic among PWID in the next decade. We use data from a cohort of PWID in Tijuana, Mexico, to inform epidemic modeling to assess the contribution of incarceration and fully implemented drug reform on HCV transmission and elimination among PWID.We developed a dynamic, deterministic model of incarceration, HCV transmission and disease progression among PWID. The model was calibrated to data from Tijuana, Mexico, with 90% HCV seroprevalence among 10,000 PWID. We estimated the 10-year population attributable fraction (PAF) of incarceration to HCV incidence among PWID and simulated, from 2022, the potential impact of the following scenarios: 1) decriminalization (80% reduction in incarceration rates); 2) fully implemented drug law reform (decriminalization and diversion to opiate agonist therapy [OAT]); 3) fully implemented drug law reform with HCV treatment (direct-acting antivirals [DAA]). We also assessed the number DAA needed to reach the 80% incidence reduction target by 2030 under these scenarios.Projections suggest a PAF of incarceration to HCV incidence of 5.4% (95% uncertainty interval [UI]:0.6-11.9%) among PWID in Tijuana between 2022-2032. Fully implemented drug reforms could reduce HCV incidence rate by 10.6% (95%UI:3.1-19.2%) across 10 years and reduce the number of DAA required to achieve Mexico's HCV incidence reduction goal by 14.3% (95%UI:5.3-17.1%).Among PWID in Tijuana, Mexico, incarceration remains an important contributor to HCV transmission. Full implementation of public health-oriented drug law reform could play an important role in reducing HCV incidence and improve the feasibility of reaching the HCV incidence elimination target by 2030.

Summary: Background: A considerable proportion of people who inject drugs are unstably housed. Although unstable housing is associated with HIV and HCV infection among people who inject drugs, its contribution to transmission is unknown. We estimated the global and national proportions of incident HIV and HCV infections among people who inject drugs attributed to housing instability from 2020 to 2029. Methods: In this modelling study, we developed country-level models of unstable housing and HIV and HCV transmission among people who inject drugs in 58 countries globally, calibrated to country-specific data on the prevalences of HIV and HCV and unstable housing. Based on a recently published systematic review, unstably housed people who inject drugs were assumed to have a 39% (95% CI 6–84) increased risk of HIV transmission and a 64% (95% CI 43–89%) increased risk of HCV transmission. We used pooled country-level estimates from systematic reviews on HCV and HIV prevalence in people who inject drugs. Our models estimated the transmission population attributable fraction (tPAF) of unstable housing to HIV and HCV transmission among people who inject drugs, defined as the percentage of infections prevented from 2020 to 2029 if the additional risk due to unstable housing was removed. Findings: Our models were produced for 58 countries with sufficient data (accounting for >66% of the global people who inject drugs population). Globally, we project unstable housing contributes 7·9% (95% credibility interval [CrI] 2·3–15·7) of new HIV infections and 11·2% (7·7–15·5) of new HCV infections among people who inject drugs from 2020 to 2029. Country-level tPAFs were strongly associated with the prevalence of unstable housing. tPAFs were greater in high-income countries (HIV 17·2% [95% CrI 5·1–30·0]; HCV 19·4% [95% CrI 13·8–26·0]) than in low-income or middle-income countries (HIV 6·6% [95% CrI 1·8–13·1]; HCV 8·3% [95% CrI 5·5–11·7]). tPAFs for HIV and HCV were highest in Afghanistan, Czech Republic, India, USA, England, and Wales where unstable housing contributed more than 20% of new HIV and HCV infections. Interpretation: Unstable housing is an important modifiable risk factor for HIV and HCV transmission among people who inject drugs in many countries. The study emphasises the importance of implementing initiatives to mitigate these risks and reduce housing instability. Funding: National Institute for Health Research and National Institute of Allergy and Infectious Diseases and National Institute for Drug Abuse.

Wastewater based surveillance has gained prominence and come to the forefront as a leading indicator of forecasting COVID-19 infection dynamics owing to its cost-effectiveness and its ability to inform early public health interventions. A university campus could especially benefit from wastewater surveillance as they are characterized by largely asymptomatic populations and are potential hotspots for transmission that necessitate frequent diagnostic testing. In this study, we employed a large-scale GIS (Geographic information systems) enabled building-level wastewater monitoring system associated with the on-campus residences of 7614 individuals. Sixty-eight automated wastewater samplers were deployed to monitor 239 campus buildings with a focus on residential buildings. Time-weighted composite samples were collected on a daily basis and analyzed within the same day. Sample processing was streamlined significantly through automation, reducing the turnaround time by 20-fold and exceeding the scale of similar surveillance programs by 10 to 100-fold, thereby overcoming one of the biggest bottlenecks in wastewater surveillance. An automated wastewater notification system was developed to alert residents to a positive wastewater sample associated with their residence and to encourage uptake of campus-provided asymptomatic testing at no charge. This system, integrated with the rest of the “Return to Learn” program at UC San Diego-led to the early diagnosis of nearly 85% of all COVID-19 cases on campus. Covid-19 testing rates increased by 1.9-13X following wastewater notifications. Our study shows the potential for a robust, efficient wastewater surveillance system to greatly reduce infection risk as college campuses and other high-risk environments reopen.IMPORTANCEWastewater based epidemiology can be particularly valuable at University campuses where high-resolution spatial sampling in a well-controlled context could not only provide insight into what affects campus community as well as how those inferences can be extended to a broader city/county context. In the present study, a large-scale wastewater surveillance was successfully implemented on a large university campus enabling early detection of 85% of COVID-19 cases thereby averting potential outbreaks. The highly automated sample processing to reporting system enabled dramatically reduced the turnaround time to 5h (sample to result time) for 96 samples. Furthermore, miniaturization of the sample processing pipeline brought down the processing cost significantly ($13/sample). Taken together, these results show that such a system could greatly ameliorate long-term surveillance on such communities as they look to reopen.

One of the main goals of the 2016 Global Health Sector Strategy on viral hepatitis is the elimination of hepatitis C virus (HCV) as a public health problem by 2030, defined as an 80% reduction in incidence and 65% reduction in mortality relative to 2015. Although monitoring HCV incidence is key to validating HCV elimination, it can be resource-intensive for countries to measure this metric using the gold-standard method, which involves prospective HCV re-testing of people at risk. Additionally, few countries have collected quality data in 2015 to document an 80% decrease by 2030. In this paper, we first review different methods by which HCV incidence can be monitored and discuss their resource implications and applicability to various populations. Second, using mathematical models developed for various global settings, we assess whether trends in HCV chronic or antibody prevalence or scale-up levels for HCV testing, treatment and preventative interventions can be used as reliable alternative indicators to validate the HCV incidence target. Third, we discuss the advantages and disadvantages of an absolute HCV incidence target and suggest a suitable threshold. We then propose three options that countries can use to validate the HCV incidence target, depending on the available surveillance infrastructure.

Summary Background Limited empirical evidence exists for the effectiveness of hepatitis C virus (HCV) treatment-as-prevention. The Surveillance and Treatment of Prisoners with hepatitis C (SToP-C) study aimed to assess the effect of HCV treatment-as-prevention in the prison setting. Methods SToP-C was a prospective study, including a before-and-after analysis, within a cohort of people incarcerated in two maximum-security prisons (male) and two medium-security prisons (one male, one female) in New South Wales, Australia. All prison inmates aged at least 18 years were eligible for enrolment. After HCV testing, participants were monitored for risk behaviours and HCV infection, among three sub-populations: uninfected (HCV antibody-negative); previously infected (HCV antibody-positive, HCV RNA-negative); and infected (HCV antibody and HCV RNA-positive). Uninfected participants were followed up every 3–6 months to detect HCV primary infection and previously infected participants were followed up every 3–6 months to detect re-infection. Participants with HCV infection were assessed for treatment, initially standard-of-care treatment (administered by prison health services) from 2014 to mid-2017, then direct-acting antiviral (DAA) treatment scale-up from mid-2017 onwards (12 weeks of sofosbuvir plus velpatasvir, administered through SToP-C). Participants were followed up until study closure in November, 2019. The primary study outcome was HCV incidence before and after DAA treatment scale-up among participants at risk of HCV primary infection or re-infection. This study is registered with ClinicalTrials.gov, NCT02064049. Findings Between Oct 30, 2014, and Sept 30, 2019, 3691 participants were enrolled in the SToP-C study. 719 (19%) participants had detectable HCV RNA, 2240 (61%) were at risk of primary HCV infection, and 725 (20%) were at risk of re-infection at baseline. DAA treatment was initiated in 349 (70%) of 499 eligible participants during the treatment scale-up period. The HCV incidence analysis comprised 1643 participants at risk of HCV infection or re-infection during longitudinal follow-up (median age 33 years [IQR 27–42]; 1350 [82%] male). 487 (30%) of 1643 participants reported injecting drugs in prison. HCV incidence decreased from 8·31 per 100 person-years in the pre-treatment scale-up period to 4·35 per 100 person-years in the post-treatment scale-up period (incidence rate ratio [IRR] 0·52 [95% CI 0·36–0·78]; p=0·0007). The incidence of primary infection decreased from 6·64 per 100 person-years in the pre-treatment scale-up period to 2·85 per 100 person-years in the post-treatment scale-up period (IRR 0·43 [95% CI 0·25–0·74]; p=0·0019), whereas the incidence of re-infection decreased from 12·36 per 100 person-years to 7·27 per 100 person-years (0·59 [0·35–1·00]; p=0·050). Among participants reporting injecting drugs during their current imprisonment, the incidence of primary infection decreased from 39·08 per 100 person-years in the pre-treatment scale-up period to 14·03 per 100 person-years in the post-treatment scale-up period (IRR 0·36 [95% CI 0·16–0·80]; p=0·0091), and the incidence of re-infection decreased from 15·26 per 100 person-years to 9·34 per 100 person-years (0·61 [0·34–1·09]; p=0·093). The adjusted analysis (adjusted for age, Indigenous Australian ethnicity, duration of stay in prison, previous imprisonment, injecting drug use status, and prison site) indicated a significant reduction in the risk of HCV infection between the pre-DAA treatment scale-up and post-DAA treatment scale-up periods (adjusted hazard ratio 0·50 [95% CI 0·33–0·76]; p=0·0014). Interpretation DAA treatment scale-up was associated with reduced HCV incidence in prison, indicative of a beneficial effect of HCV treatment-as-prevention in this setting. These findings support broad DAA treatment scale-up within incarcerated populations. Funding Australian National Health and Medical Research Council Partnership Project Grant and Gilead Sciences.

BackgroundSuccessful containment strategies for SARS-CoV-2, the causative virus of the COVID-19 pandemic, have involved widespread population testing that identifies infections early and enables rapid contact tracing. In this study, we developed a rapid and inexpensive RT- qPCR testing pipeline for population-level SARS-CoV-2 detection, and used this pipeline to establish a clinical laboratory dedicated to COVID-19 testing at the University of California San Diego (UCSD) with a processing capacity of 6,000 samples per day and next-day result turnaround times.Methods and findingsUsing this pipeline, we screened 6,786 healthcare workers and first responders, and 21,220 students, faculty, and staff from UCSD. Additionally, we screened 6,031 preschool-grade 12 students and staff from public and private schools across San Diego County that remained fully or partially open for in-person teaching during the pandemic. Between April 17, 2020 and February 5, 2021, participants provided 161,582 nasal swabs that were tested for the presence of SARS-CoV-2. Overall, 752 positive tests were obtained, yielding a test positivity rate of 0.47%. While the presence of symptoms was significantly correlated with higher viral load, most of the COVID-19 positive participants who participated in symptom surveys were asymptomatic at the time of testing. The positivity rate among preschool-grade 12 schools that remained open for in-person teaching was similar to the positivity rate at UCSD and lower than that of San Diego County, with the children in private schools being less likely to test positive than the adults at these schools.ConclusionsMost schools across the United States have been closed for in-person learning for much of the 2020-2021 school year, and their safe reopening is a national priority. However, as there are no vaccines against SARS-CoV-2 currently available to the majority of school-aged children, the traditional strategies of mandatory masking, physical distancing, and repeated viral testing of students and staff remain key components of risk mitigation in these settings. The data presented here suggest that the safety measures and repeated testing actions taken by participating healthcare and educational facilities were effective in preventing outbreaks, and that a similar combination of risk-mitigation strategies and repeated testing may be successfully adopted by other healthcare and educational systems.

Background Epidemics of COVID-19 in student populations at universities were a key concern for the 2020–2021 school year. The University of California (UC) System developed a set of recommendations to reduce campus infection rates. SARS-CoV-2 test results are summarized for the ten UC campuses during the Fall 2020 term. Methods UC mitigation efforts included protocols for the arrival of students living on-campus students, non-pharmaceutical interventions, daily symptom monitoring, symptomatic testing, asymptomatic surveillance testing, isolation and quarantine protocols, student ambassador programs for health education, campus health and safety pledges, and lowered density of on-campus student housing. We used data from UC campuses, the UC Health–California Department of Public Health Data Modeling Consortium, and the U.S. Census to estimate the proportion of each campus’ student populations that tested positive for SARS-CoV-2 and compared it to the fraction individuals aged 20–29 years who tested positive in their respective counties. Results SARS-CoV-2 cases in campus populations were generally low in September and October 2020, but increased in November and especially December, and were highest in early to mid-January 2021, mirroring case trajectories in their respective counties. Many students were infected during the Thanksgiving and winter holiday recesses and were detected as cases upon returning to campus. The proportion of students who tested positive for SARS-CoV-2 during Fall 2020 ranged from 1.2% to 5.2% for students living on campus and was similar to students living off campus. For most UC campuses the proportion of students testing positive was lower than that for the 20–29-year-old population in which campuses were located. Conclusions The layered mitigation approach used on UC campuses, informed by public health science and augmented perhaps by a more compliant population, likely minimized campus transmission and outbreaks and limited transmission to surrounding communities. University policies that include these mitigation efforts in Fall 2020 along with SARS-CoV-2 vaccination, may alleviate some local concerns about college students returning to communities and facilitate resumption of normal campus operations and in-person instruction.

Twenty-five percent of HIV/hepatitis C virus (HCV) coinfected patients were not referred for HCV treatment despite unrestricted access in California to direct-acting antivirals (DAA) in 2018. Having unstable housing and ongoing drug use directly affected HCV treatment nonreferral. However, psychiatric history and alcohol use impacted HCV treatment nonreferral through the mediation of not being engaged in HIV care. Achieving HCV elimination requires DAA treatment outside conventional health settings, including substance rehabilitation centers, mental health crisis houses, and homeless shelters.

To inform proposed changes in hepatitis C virus (HCV) screening guidelines in the United States, we assessed the cost-effectiveness of HCV antenatal rescreening for women without evidence of HCV during a prior pregnancy, using a previously published model. Universal HCV rescreening among pregnant women was cost-effective (incremental cost-effectiveness ratio, $6000 per quality-adjusted life-year) and should be recommended nationally.

Introduction. Needle and syringe programs (NSP) reduce syringe sharing and HIV transmission among people who inject drugs (PWID). However, their effectiveness relies on sufficient individual and population level coverage. In Tijuana, Mexico, the Global Fund (GF) supported NSP during 10/2011-12/2013, but withdrew funds at the end of 2013 following Mexico’s re-classification as an upper-middle income country. Objective. We tested the hypothesis of higher NSP access and lower receptive syringe sharing among PWID in Tijuana during the GF support period compared to pre-GF initiation and post-GF withdrawal. Method. We used data from an ongoing cohort study of PWID in Tijuana (03/2011-10/2015) to implement a segmented regression analysis investigating changes in the self-reported probability of NSP access, reported difficulty in finding sterile syringes and receptive syringe sharing before GF initiation and after GF discontinuation. Results. We found a large significant increase in the probability of NSP access (+.07) and decrease in receptive syringe sharing (-.23) right after GF initiation, which continued over the GF period. Subsequently, we found a significant decline in NSP access (-.05) and an increase in receptive syringe sharing (+.02) right after post-GF withdrawal, which continued thereafter. Discussion and conclusion. We demonstrated significant temporal changes in NSP access and receptive syringe sharing among PWID in Tijuana after GF initiation and withdrawal consistent with our hypothesis. Coordinated efforts with local authorities are needed to sustain major coverage NSP in settings receiving GF or external aid to guarantee continuity of harm reduction services and prevent reinside in risk behaviors associated with HIV transmission.

The World Health Organisation has established a goal of eliminating the hepatitis C virus (HCV) as a public health threat by 2030. Considerable effort is being directed towards research to support and enhance HCV treatment uptake among people who inject drugs, but there is a distinct lack of attention given to gender in this work. We argue that a gender lens is needed to make visible the limitations of current HCV elimination research, and support the development of innovative, inclusive approaches to HCV treatment. Partnerships between researchers and people who inject drugs are essential in this work, particularly in the development and evaluation of programs by and for women who inject drugs. Failure to acknowledge the gendered dimensions of HCV elimination risks entrenching gender disparities in access to treatment and cure.