Population uptake and effectiveness of test-and-treat antiretroviral therapy guidelines for preventing the global spread of HIV: an ecological cross-national analysis.

OBJECTIVES: Although the benefits of adopting test-and-treat antiretroviral therapy (ART) guidelines that recommend initiation of ART regardless of CD4 cell counts have been demonstrated at the individual level, there is uncertainty about how this translates to the population level. Here, we explored whether adopting ART guidelines recommending earlier treatment initiation improves population ART access and viral suppression and reduces overall disease transmission. METHODS: Data on ART initiation guidelines and treatment coverage, viral suppression, and HIV incidence from 37 European and Central Asian countries were collected from the European Centre for Disease Prevention and Control and the Global HIV Policy Watch and HIV 90-90-90 Watch databases. We used multivariate linear regression models to quantify the association of ART initiation guidelines with population ART access, viral suppression, and HIV incidence, adjusting for potential confounding factors. RESULTS: Test-and-treat policies were associated with 15.2 percentage points (pp) [95% confidence interval (CI) 0.8-29.6 pp; P = 0.039] greater treatment coverage (proportion of HIV-positive people on ART) compared with countries with ART initiation at CD4 cell counts ≤ 350 cells/µL. The presence of test-and-treat policies was associated with 15.8 pp (95% CI 2.4-29.1 pp; P = 0.023) higher viral suppression rates (people on ART virally suppressed) compared with countries with treatment initiation at CD4 counts ≤ 350 cells/µL. ART initiation at CD4 counts ≤ 500 cells/µL did not significantly improve ART coverage compared to initiation at CD4 counts ≤ 350 cells/µL but achieved similar degrees of viral suppression as test-and-treat. CONCLUSIONS: Test-and-treat was found to be associated with substantial improvements in population-level access to ART and viral suppression, further strengthening evidence that rapid initiation of treatment will help curb the spread of HIV.

Monitoring the HIV continuum of care in key populations across Europe and Central Asia.

OBJECTIVES: The aim of the study was to measure and compare national continuum of HIV care estimates in Europe and Central Asia in three key subpopulations: men who have sex with men (MSM), people who inject drugs (PWID) and migrants. METHODS: Responses to a 2016 European Centre for Disease Prevention and Control (ECDC) survey of 55 European and Central Asian countries were used to describe continuums of HIV care for the subpopulations. Data were analysed using three frameworks: Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets; breakpoint analysis identifying reductions between adjacent continuum stages; quadrant analysis categorizing countries using 90% cut-offs for continuum stages. RESULTS: Overall, 29 of 48 countries reported national data for all HIV continuum stages (numbers living with HIV, diagnosed, receiving treatment and virally suppressed). Six countries reported all stages for MSM, seven for PWID and two for migrants. Thirty-one countries did not report data for MSM (34 for PWID and 41 for migrants). In countries that provided key-population data, overall, 63%, 40% and 41% of MSM, PWID and migrants living with HIV were virally suppressed, respectively (compared with 68%, 65% and 68% nationally, for countries reporting key-population data). Variation was observed between countries, with higher outcomes in subpopulations in Western Europe compared with Eastern Europe and Central Asia. CONCLUSIONS: Few reporting countries can produce the continuum of HIV care for the three key populations. Where data are available, differences exist in outcomes between the general and key populations. While MSM broadly mirror national outcomes (in the West), PWID and migrants experience poorer treatment and viral suppression. Countries must develop continuum measures for key populations to identify and address inequalities.

Monitoring response to hepatitis B and C in EU/EEA: testing policies, availability of data on care cascade and chronic viral hepatitis-related mortality - results from two surveys (2016).

OBJECTIVES: The World Health Organization (WHO) developed a European Regional Action Plan (EAP) to fast-track action towards the goal of eliminating viral hepatitis. Robust monitoring is essential to assess national programme performance. The purpose of this study was to assess the availability of selected monitoring data sources in European Union/European Economic Area (EU/EEA) Member States (MS). METHODS: Availability of data sources at EU/EEA level was assessed using two surveys distributed to 31 EU/EEA MS in 2016. The two surveys covered (A) availability of policy documents on testing; testing practices and monitoring; monitoring of diagnosis and treatment initiation, and; (B) availability of data on mortality attributable to chronic viral hepatitis. RESULTS: Just over two-thirds of EU/EEA MS responded to the surveys. 86% (18/21) reported national testing guidance covering HBV, and 81% (17/21) covering HCV; while 33% (7/21) and 38% (8/21) of countries, respectively, monitored the number of tests performed. 71% (15/21) of countries monitored the number of chronic HBV cases diagnosed and 33% (7/21) the number of people treated. Corresponding figures for HCV were 48% (10/21) and 57% (12/21). 27% (6/22) of countries reported availability of data on mortality attributable to chronic viral hepatitis. CONCLUSIONS: The results of this study suggest that sources of information in EU/EEA Member States to monitor the progress towards the EAP milestones and targets related to viral hepatitis diagnosis, cascade of care and attributable mortality are limited. Our analysis should raise awareness among EU/EEA policy makers and stimulate higher prioritisation of efforts to improve the monitoring of national viral hepatitis programmes.

Estimating the scale of chronic hepatitis C virus infection in the EU/EEA: a focus on migrants from anti-HCV endemic countries.

BACKGROUND: Increasing the proportion diagnosed with and on treatment for chronic hepatitis C (CHC) is key to the elimination of hepatitis C in Europe. This study contributes to secondary prevention planning in the European Union/European Economic Area (EU/EEA) by estimating the number of CHC (anti-HCV positive and viraemic) cases among migrants living in the EU/EEA and born in endemic countries, defining the most affected migrant populations, and assessing whether country of birth prevalence is a reliable proxy for migrant prevalence. METHODS: Migrant country of birth and population size extracted from statistical databases and anti-HCV prevalence in countries of birth and in EU/EEA countries derived from a systematic literature search were used to estimate caseload among and most affected migrants. Reliability of country of birth prevalence as a proxy for migrant prevalence was assessed via a systematic literature search. RESULTS: Approximately 11% of the EU/EEA adult population is foreign-born, 79% of whom were born in endemic (anti-HCV prevalence ≥1%) countries. Anti-HCV/CHC prevalence in migrants from endemic countries residing in the EU/EEA is estimated at 2.3%/1.6%, corresponding to ~580,000 CHC infections or 14% of the CHC disease burden in the EU/EEA. The highest number of cases is found among migrants from Romania and Russia (50-60,000 cases each) and migrants from Italy, Morocco, Pakistan, Poland and Ukraine (25-35,000 cases each). Ten studies reporting prevalence in migrants in Europe were identified; in seven of these estimates, prevalence was comparable with the country of birth prevalence and in three estimates it was lower. DISCUSSION: Migrants are disproportionately affected by CHC, account for a considerable number of CHC infections in EU/EEA countries, and are an important population for targeted case finding and treatment. Limited data suggest that country of birth prevalence can be used as a proxy for the prevalence in migrants.

HIV continuum of care in Europe and Central Asia.

OBJECTIVES: The European Centre for Disease Prevention and Control (ECDC) supports countries to monitor progress in their response to the HIV epidemic. In line with these monitoring responsibilities, we assess how, and to what extent, the continuum of care is being measured across countries. METHODS: The ECDC sent out questionnaires to 55 countries in Europe and Central Asia in 2014. Nominated country representatives were questioned on how they defined and measured six elements of the continuum. We present our results using three previously described frameworks [breakpoints; Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets; diagnosis and treatment quadrant]. RESULTS: Forty countries provided data for at least one element of the continuum. Countries reported most frequently on the number of people diagnosed with HIV infection (37; 93%), and on the number in receipt of antiretroviral therapy (ART) (35; 88%). There was little consensus across countries in their approach to defining linkage to, and retention in, care. The most common breakpoint (>19% reduction between two adjacent elements) related to the estimated number of people living with HIV who were diagnosed (18 of 23; 78%). CONCLUSIONS: We present continuum data from multiple countries that provide both a snapshot of care provision and a baseline against which changes over time in care provision across Europe and Central Asia may be measured. To better inform HIV testing and treatment programmes, standard data collection approaches and definitions across the HIV continuum of care are needed. If countries wish to ensure an unbroken HIV continuum of care, people living with HIV need to be diagnosed promptly, and ART needs to be offered to all those diagnosed.

Ten years after Dublin: principal trends in HIV surveillance in the EU/EEA, 2004 to 2013.

In 2004, the 31 countries of the European Union and European Economic Area (EU/EEA) adopted the Dublin Declaration on Partnership to Fight HIV/AIDS in Europe and Central Asia. In 2013, 29,157 persons were diagnosed with HIV in 30 EU/EEA countries (adjusted rate: 6.2/100,000); new diagnoses have increased by 33% since 2004 among men who have sex with men and late diagnosis remains common. Evidence-based prevention measures and efforts towards earlier testing need to be expanded.

New times for migrants' health in Europe.

Patterns of migration can change greatly over time, with the size and composition of migrant populations reflecting both, current and historical patterns of migration flows. The recent economic crisis has caused a decrease on migration flows towards the most affected areas, as well as cut offs in health interventions addressed to migrants. The objective of this paper is to review available data about interventions on migrants' health in Europe, and to describe changes in migrant health policies across Europe after the economic crisis, that can have a negative effect in their health status. Although migrants have the right to health care under legal settlements issued by the EU, there is no a standard European approach to offer health care to migrants, since; policies in each EU Member State are developed according to specific migrant experience, political climate, and attitudes towards migration. Migrants use to face greater health problems and major health care access barriers, compared with their counterparts from the EU. Therefore, migrant health policies should focus in protects this vulnerable group, especially during economic hardship, taking into account economic and socio-demographic risk factors. There is an especial need for research in the cost-effectiveness of investing in the health care of the migrant population, demonstrating the benefit of such, even in the health of the European native population, and the need for constant intervention despite of resource constraints.

Seasonal influenza immunisation in Europe. Overview of recommendations and vaccination coverage for three seasons: pre-pandemic (2008/09), pandemic (2009/10) and post-pandemic (2010/11).

Since 2008, annual surveys of influenza vaccination policies, practices and coverage have been undertaken in 29 European Union (EU)/ European Economic Area (EEA) countries. After 2009, this monitored the impact of European Council recommendation to increase vaccination coverage to 75% among risk groups. This paper summarises the results of three seasonal influenza seasons: 2008/09, 2009/10 and 2010/11. In 2008/09, 27/29 countries completed the survey; in 2009/10 and 2010/11, 28/29 completed it. All or almost all countries recommended vaccination of older people (defined as those aged ≥50, ≥55, ≥59, ≥60 or ≥65 years), and people aged ≥6 months with clinical risk and healthcare workers. A total of 23 countries provided vaccination coverage data for older people, but only 7 and 10 had data for the clinical risk groups and healthcare workers, respectively. The number of countries recommending vaccination for some or all pregnant women increased from 10 in 2008/09 to 22 in 2010/11. Only three countries could report coverage among pregnant women. Seasonal influenza vaccination coverage during and after the pandemic season in older people and clinical groups remained unchanged in countries with higher coverage. However, small decreases were seen in most countries during this period. The results of the surveys indicate that most EU/EEA countries recommend influenza vaccination for the main target groups; however, only a few countries have achieved the target of 75% coverage among risk groups. Coverage among healthcare workers remained low.

A functional genomics screen identifies PCAF and ADA3 as regulators of human granzyme B-mediated apoptosis and Bid cleavage.

The human lymphocyte toxins granzyme B (hGrzB) and perforin cooperatively induce apoptosis of virus-infected or transformed cells: perforin pores enable entry of the serine protease hGrzB into the cytosol, where it processes Bid to selectively activate the intrinsic apoptosis pathway. Truncated Bid (tBid) induces Bax/Bak-dependent mitochondrial outer membrane permeability and the release of cytochrome c and Smac/Diablo. To identify cellular proteins that regulate perforin/hGrzB-mediated Bid cleavage and subsequent apoptosis, we performed a gene-knockdown (KD) screen using a lentiviral pool of short hairpin RNAs embedded within a miR30 backbone (shRNAmiR). We transduced HeLa cells with a lentiviral pool expressing shRNAmiRs that target 1213 genes known to be involved in cell death signaling and selected cells with acquired resistance to perforin/hGrzB-mediated apoptosis. Twenty-two shRNAmiRs were identified in the positive-selection screen including two, PCAF and ADA3, whose gene products are known to reside in the same epigenetic regulatory complexes. Small interfering (si)RNA-mediated gene-KD of PCAF or ADA3 also conferred resistance to perforin/hGrzB-mediated apoptosis providing independent validation of the screen results. Mechanistically, PCAF and ADA3 exerted their pro-apoptotic effect upstream of mitochondrial membrane permeabilization, as indicated by reduced cytochrome c release in PCAF-KD cells exposed to perforin/hGrzB. While overall levels of Bid were unaltered, perforin/hGrzB-mediated cleavage of Bid was reduced in PCAF-KD or ADA3-KD cells. We discovered that PCAF-KD or ADA3-KD resulted in reduced expression of PACS2, a protein implicated in Bid trafficking to mitochondria and importantly, targeted PACS2-KD phenocopied the effect of PCAF-KD or ADA3-KD. We conclude that PCAF and ADA3 regulate Bid processing via PACS2, to modulate the mitochondrial cell death pathway in response to hGrzB.

Nuevos tiempo para la salud de emigrantes en Europa / New times for migrants’ health in Europe

Los patrones de emigración pueden cambiar considerablemente con el paso del tiempo, y el tamaño y composición de la población de emigrantes pueden reflejar los patrones actuales e históricos de los flujos de emigración. La reciente crisis económica ha provocado un decremento en flujos de emigración hacia las zonas más afectadas y reducciones en asistencia sanitaria para emigrantes. El objetivo de este estudio es revisar la información disponible sobre intervención sobre la salud de los emigrantes en Europa y describir los cambios en políticas de salud para los mismos en el continente después de la crisis económica que pueden repercutir de forma negativa en su estado de salud. Aunque los emigrantes tienen el derecho de asistencia sanitaria bajo acuerdos legales emitidos por la UE, no existe una política común en Europa en cuanto a la provisión de asistencia sanitaria para emigrantes, ya que las políticas en cada estado miembro de la UE se han desarrollado según experiencias concretas relacionadas con los emigrantes, el clima político y las actitudes hacia la inmigración. Los emigrantes suelen encontrarse con mayores problemas de salud y barreras considerables en la asistencia sanitaria en comparación a sus co-residentes de la UE. Por tanto las políticas de salud para emigrantes deben enfocarse en proteger a este grupo vulnerable, sobre todo durante tiempos de dificultad económica, teniendo en cuenta los factores de riesgo económicos y socio-demográficos. Existe una necesidad especial de investigación en la rentabilidad de la inversión en atención sanitaria de la población de emigrantes, demostrando los beneficios del mismo, incluyendo la salud de la población nativa europea, y la necesidad de una intervención constante a pesar de las restricciones de los recursos (AU)

Patterns of migration can change greatly over time, with the size and composition of migrant populations reflecting both, current and historical patterns of migration flows. The recent economic crisis has caused a decrease on migration flows towardsthe most affected areas, as well as cut offs in health interventions addressed to migrants. The objective of this paper is to review available data about interventions on migrants’ health in Europe, and to describe changes in migrant health policies across Europe after the economic crisis, that can have a negative effect in their health status. Although migrants have the right to health care under legal settlements issued by the EU, there is no a standard European approach to offer health care to migrants, since; policies in each EU Member State are developed according to specific migrant experience, political climate, and attitudes towards migration. Migrants use to face greater health problems and major health care access barriers, compared with their counterparts from the EU. Therefore, migrant health policies should focus in protects this vulnerable group, especially during economic hardship, taking into account economic and socio-demographic risk factors. There is an especial need for research in the cost-effectiveness of investing in the health care of the migrant population, demonstrating the benefit of such, even in the health of the European native population, and the need for constant intervention despite of resource constraints (AU)