Twelve-month effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide in people with HIV: Real-world insights from BICSTaR cohorts.

BACKGROUND: Real-world evidence is an essential component of evidence-based medicine. The aim of the BICSTaR (BICtegravir Single Tablet Regimen) study is to assess effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in antiretroviral treatment-naïve (TN) and treatment-experienced (TE) people with HIV. METHODS: BICSTaR is a prospective, observational cohort study. Participants (≥18 years) are being followed for 24 months. A pooled analysis is presented at 12 months, with the primary endpoint of effectiveness (HIV-1 RNA <50 copies/mL) and secondary endpoints of safety and tolerability (as per protocol). An exploration of patient-reported outcome measures using standardized questionnaires is included. RESULTS: Between June 2018 and May 2021, 1552 people with HIV were enrolled across 12 countries. The analysed population comprised 1509 individuals (279 TN, 1230 TE); most were white (76%), male (84%) and had one or more comorbid conditions (68%). Median age was 47 years. After 12 months of B/F/TAF treatment, HIV-1 RNA was <50 copies/mL in 94% (221/236) of TN participants and 97% (977/1008) of TE participants. Median CD4 cell count increased by 214 cells/µL (p < 0.001) in TN participants and 13 cells/µL (p = 0.014) in TE participants; median CD4/CD8 ratios increased by 0.30 and 0.03, respectively (both p < 0.001). Persistence was high at 12 months (TN, 97%; TE, 95%). No resistance to B/F/TAF emerged. Study drug-related adverse events occurred in 13% of participants through 12 months, leading to B/F/TAF discontinuation in 6%. CONCLUSIONS: The findings of this study provide robust real-world evidence to support the broad use of B/F/TAF in both TN and TE people with HIV.

Securing wider EU commitment to the elimination of hepatitis C virus.

In 2016, the Hepatitis B and C Public Policy Association (HepBCPPA), gathered all the main stakeholders in the field of hepatitis C virus (HCV) to launch the now landmark HCV Elimination Manifesto, calling for the elimination of HCV in the EU by 2030. Since then, many European countries have made progress towards HCV elimination. Multiple programmes-from the municipality level to the EU level-were launched, resulting in an overall decrease in viremic HCV infections and liver-related mortality. However, as of 2021, most countries are not on track to reach the 2030 HCV elimination targets set by the WHO. Moreover, the COVID-19 pandemic has resulted in a decrease in HCV diagnoses and fewer direct-acting antiviral treatment initiations in 2020. Diagnostic and therapeutic tools to easily diagnose and treat chronic HCV infection are now well established. Treating all patients with chronic HCV infection is more cost-saving than treating and caring for patients with liver-related complications, decompensated cirrhosis or hepatocellular carcinoma. It is more important than ever to reinforce and scale-up action towards HCV elimination. Yet, efforts urgently need the dedicated commitment of policymakers at all governmental and policy levels. Therefore, the third EU Policy Summit, held in March 2021, featured EU parliamentarians and other key decision makers to promote dialogue and take strides towards securing wider EU commitment to advance and achieve HCV elimination by 2030. We have summarized the key action points and reported the 'Call-to-Action' statement supported by all the major relevant European associations in the field.

Impact of vaccination and variants of concern on long COVID clinical phenotypes.

BACKGROUND: Defining patterns of symptoms in long COVID is necessary to advance therapies for this heterogeneous condition. Here we aimed to describe clusters of symptoms in individuals with long COVID and explore the impact of the emergence of variants of concern (VOCs) and vaccination on these clusters. METHODS: In a prospective, multi centre cohort study, individuals with symptoms persisting > 4 weeks from acute COVID-19 were divided into two groups based on timing of acute infection; pre-Alpha VOC, denoted wild type (WT) group and post-Alpha VOC (incorporating alpha and delta dominant periods) denoted VOC group. We used multiple correspondence analysis (MCA) and hierarchical clustering in the WT and VOC groups to identify symptom clusters. We then used logistic regression to explore factors associated with individual symptoms. RESULTS: A total of 417 individuals were included in the analysis, 268 in WT and 149 in VOC groups respectively. In both groups MCA identified three similar clusters; a musculoskeletal (MSK) cluster characterised by joint pain and myalgia, a cardiorespiratory cluster and a less symptomatic cluster. Differences in characteristic symptoms were only seen in the cardiorespiratory cluster where a decrease in the frequency of palpitations (10% vs 34% p = 0.008) and an increase in cough (63% vs 17% p < 0.001) in the VOC compared to WT groups was observed. Analysis of the frequency of individual symptoms showed significantly lower frequency of both chest pain (25% vs 39% p = 0.004) and palpitations (12% vs 32% p < 0.001) in the VOC group compared to the WT group. In adjusted analysis being in the VOC group was significantly associated with a lower odds of both chest pain and palpitations, but vaccination was not associated with these symptoms. CONCLUSION: This study suggests changes in long COVID phenotype in individuals infected later in the pandemic, with less palpitations and chest pain reported. Adjusted analyses suggest that these effects are mediated through introduction of variants rather than an effect from vaccination.

Tenofovir Alafenamide Plasma Concentrations Are Reduced in Pregnant Women Living With Human Immunodeficiency Virus (HIV): Data From the PANNA Network.

BACKGROUND: Tenofovir alafenamide (TAF), a prodrug of tenofovir (TFV), is included in the majority of the recommended first-line antiretroviral regimens for patients living with human immunodeficiency virus (HIV), but there are limited data on TAF use in pregnant women. We aimed to examine the plasma pharmacokinetics of TAF and TFV in pregnant women from Europe. METHODS: Pregnant women living with HIV were included from treatment centers across Europe, and intensive pharmacokinetic sampling in the third trimester and postpartum was performed. Pharmacokinetic parameters of TAF and TFV were determined with noncompartmental analysis. The proportion of women with a TAF area under the curve (AUClast) below the target of 53.1 ng∗h/mL was determined. Clinical efficacy and safety outcome parameters were reported. RESULTS: In total, 20 pregnant women living with HIV were included. At the third trimester, geometric mean TAF AUClast and Cmax were decreased by 46% and 52%, respectively, compared with postpartum. TFV AUC0-24h, Cmax, and Ctrough decreased by 33%, 30%, and 34%, respectively. The proportion of women with a TAF AUClast < 53.1 ng∗h/mL was 6% at third trimester and 0% postpartum. One out of 20 women had a viral load > 50 copies/mL at third trimester and no mother-to-child transmission occurred. CONCLUSIONS: TAF plasma concentrations were reduced by about half in women living with HIV during third trimester of pregnancy but remained above the predefined efficacy target in the majority of the pregnant women. TFV concentrations were reduced by approximately 30% during third trimester. Despite the observed exposure decrease, high virologic efficacy was observed in this study.

Factors Associated With Peripartum Virologic Suppression in Eastern Cape Province, South Africa: A Retrospective Cross-Sectional Analysis.

BACKGROUND: This study describes the characteristics of pregnant women on antiretroviral therapy (ART) and the rate of peripartum virologic suppression in a large prevention of mother-to-child transmission cohort who delivered in some selected maternity centers in Eastern Cape Province, South Africa. In addition, the study examines the factors associated with virologic suppression in the cohort. METHODS: This multicenter, retrospective cross-sectional analysis included medical data of 1709 women with human immunodeficiency virus between September 2015 and May 2016 in Eastern Cape Province. The main outcome measure was the rate of peripartum virologic suppression, defined as viral load (VL) <1000 copies/mL and undetectable viremia (VL <20 copies/mL). Correlates of peripartum virologic suppression and undetectable viremia were examined by fitting logistic regression model analysis. RESULTS: Of 1463 women with available VL results, the overall rate of peripartum suppression was 82%, and undetectable viremia was 56.9%. Being aged 24 years or younger (adjusted odds ratio [AOR], 0.68 [95% confidence interval {CI}, .48-.94]), smoking during pregnancy (AOR, 0.50 [95% CI, .28-.90]), and starting ART in the first trimester were associated with lower odds of viral suppression (<1000 copies/mL). Women who had never defaulted ART had an increased odds of having an undetectable VL (AOR, 3.09 [95% CI, 2.12-4.49]) and virologic suppression (AOR, 3.88 [95% CI, 2.62-5.74]) compared to those who defaulted. CONCLUSIONS: More than half of the women achieved undetectable VL, and 4 in 5 women achieved viral suppression at delivery in the region. Early antenatal booking, combined with enhanced adherence support for pregnant women on ART, would be crucial toward achieving the goal of elimination of mother-to-child transmission in the region.

Exploring and understanding HCV patient journeys- HEPCARE Europe project.

BACKGROUND: Hepatitis C Virus (HCV) is a leading cause for chronic liver diseases worldwide. The European Union and World Health Organization aspire to eliminate HCV by 2030. However, among at-risk populations, including, homeless people, prisoners and People Who Inject Drugs, access to diagnosis and treatment is challenging. Hepcare Europe is an integrated model of care developed to address this by assessing potential reasons for these restrictions and determining measures needed to improve HCV diagnosis, treatment and access to care within different communities. OBJECTIVES: HepCare Europe is an EU-supported project involving collaboration between five institutions in: Ireland, United Kingdom, Spain and Romania. We aim to explore the journey of care experienced by those living with HCV with a focus on previous care disruptions (loss to follow up) and the new HepCare Europe Programme. METHODS: Research teams conducted semi-structured interviews with patients who accessed services through HepCare Europe thus, patients were recruited by purposeful sampling. Patients interviewed had received, or were in the final weeks of receiving, treatment. The interviews were audio recorded, transcribed and translated into English, and sent to the Dublin team for inductive thematic analysis. Researchers from the HepCare Europe research team coded the data separately, then together. RESULTS: Common themes are introduced to present similarities, following individual site themes to highlight the importance of tailored interventions for each country. Key themes are: 1) Hepatitis C patients lost to follow up 2) HepCare improved access to treatment and 3) the need for improved HCV education. Individual themes also emerged for each site. These are: Ireland: New opportunities associated with achieving Sustained Virologic Responses (SVR). Romania: HCV is comparatively less crucial in light of Human Immunodeficiency Viruses (HIV) coinfections. UK: Patients desire support to overcome social barriers and Spain: Improved awareness of HCV, treatment and alcohol use. CONCLUSION: This study identified how the tailored HepCare interventions enabled improved HCV testing and linkage to care outcomes for these patients. Tailored interventions that targeted the needs of patients, increased the acceptability and success of treatment by patients. HepCare demonstrated the need for flexibility in treatment delivery, and provided additional supports to keep patients engaged and educated on new treatment therapies.

Integrating partner notification and contact tracing services across Europe: findings from the Integrate project.

BACKGROUND: Partner notification/contact tracing (PN/CT) is a process whereby people diagnosed with an infectious disease notify their sexual and needle-sharing partners/close contacts and invite them for testing and treatment due to exposure to the disease. PN is a necessary testing and prevention tool supported by the European Centre for Disease Prevention and Control (ECDC) and World Health Organization (WHO). Traditionally, PN efforts have been siloed within disease areas, with separate pathways and systems responsible for specific diseases. The INTEGRATE project sought to improve PN/CT outcomes by sharing knowledge across diseases and countries. METHODS: INTEGRATE used two mapping exercises to assess the PN landscape in Europe and identify areas for integration and cross-learnings for Sexually Transmitted Infections (STIs) and Tuberculosis. Mapping exercises were surveys to 29 consortium partners and in-depth qualitative interviews at four selected pilot sites: Ireland, Greece, Romania and Italy. RESULTS: Areas for the improvement of PN/CT emerged: lack of resources and insufficient staff training, different modes of disease transmission, country-specific laws and regulations, the advent of General Data Protection Regulation (GDPR), differences in healthcare system pathways, historical concerns, and cultural differences. Activities highlighted key areas PN/CT outcomes could be improved, including PN/CT specific trainings for staff, improving knowledge on laws, regulations, guidelines and pathways and creating a country/region specific Standard Operating Procedures (SOPs) for PN/CT, incorporating information on all four disease areas. Findings were analyzed and three key areas were identified and implemented for knowledge transfer namely the creation of an online repository of European country guidelines, the transfer of SOPs and PN training in pilot sites. CONCLUSION: A major finding of the project was challenges associated with incorporating Tuberculosis (TB) contact tracing alongside other infectious diseases. Professionals in the field, emphasized that integrating TB contact tracing with the other disease areas would be challenging and arguably unjustified, due to the different ways of transmission of TB and because well-established historical pathways for TB in public health systems already exist. However, the success of TB services presents an ideal model to draw from when strengthening PN systems for other infectious diseases.

Documentation of Do-Not-Attempt-Cardiopulmonary-Resuscitation orders amid the COVID-19 pandemic.

INTRODUCTION: the COVID-19 pandemic has brought the decision-making process regarding cardiopulmonary resuscitation (CPR) into focus. The aim of this study is to compare rates of Do-Not-Attempt-CPR (DNACPR) documentation in older hospitalised patients before and during the COVID-19 pandemic. METHODS: this was a retrospective repeated cross-sectional study. Data including co-morbidities and resuscitation status was collected on 300 patients with COVID-19 hospitalised from 1 March to 31 May 2020. DNACPR documentation rates in patients aged ≥65 years with a diagnosis of COVID-19 were compared to those without COVID-19 admitted during the same period and were also compared to the documentation rates pre-COVID-19 pandemic (1 March-31 May 2019). RESULTS: of 300 COVID-19-positive patients, 28% had a DNACPR order documented during their admission. Of 131 older (≥65 years) patients with COVID-19, 60.3% had a DNACPR order compared to 25.4% of 130 older patients without COVID-19 (P < 0.0001). During a comparable time period pre-pandemic, 15.4% of 130 older patients had a DNACPR order in place (P < 0.0001). Almost fifty percent of DNACPR orders were recorded within 24 h of a positive swab result for SARS-CoV-2. Of older COVID-19-positive patients, 39.2% were referred to palliative care services and 70.2% survived. CONCLUSION: the COVID-19 pandemic has prompted more widespread and earlier decision-making regarding resuscitation status. Although case fatality rates were higher for older hospitalised patients with COVID-19, many older patients survived the illness. Advance care planning should be prioritised in all patients and should remain as part of good clinical practice despite the pandemic.

Barriers to and facilitators of HIV serostatus disclosure to sexual partners among postpartum women living with HIV in South Africa.

BACKGROUND: Disclosure of HIV serostatus to a sexual partner can facilitate partner's support and testing and better treatment outcomes. Studies examining changes in disclosure rates of serostatus from delivery and postpartum periods are scarce. Our study fills this gap by using a follow-up survey of postpartum women with HIV to examine if disclosure prevalence has improved compared to the proportion recorded at childbirth. We further assessed the reasons for non-disclosure and correlates of serostatus disclosure to sexual partners. METHODS: We conducted a cross-sectional analytical study (exit interview) with a final sample of 485 postpartum women with HIV drawn from the East London Prospective Cohort study database between January and May 2018. Disclosure of HIV status to partner was based on self-reporting. We fitted adjusted and unadjusted logistic regression models and also conducted descriptive statistical analyses. Sampling weights were used to correct for sampling errors. RESULTS: Overall, 81.8% of women in the study cohort had disclosed their status to their partners, representing a 7.4 percentage point increase since child delivery. After adjusting for important covariates, women were more likely to disclose their status if they were married [adjusted odds ratio (AOR): 3.10; 95% confidence interval (CI):1.39-6.91] but were less likely to disclose if they used alcohol [AOR: 0.61; 95% CI:0.37-0.99] or had reported adherence to ART [AOR: 0.59; 95% CI:0.36-0.96]. Fear of rejection, stigma or being judged, new or casual relationships, and having a violent partner were the main reasons for not disclosing HIV status to sexual partners. CONCLUSION: We found a relatively higher rate of HIV status disclosure in the cohort compared to the rate recorded at childbirth, suggesting an improvement over time. Also, complicated relationship dynamics and fear of social exclusion still constitute barriers to HIV status disclosure to sexual partners despite patients' counselling.

Clinically Significant Lower Elvitegravir Exposure During the Third Trimester of Pregnant Patients Living With Human Immunodeficiency Virus: Data From the Pharmacokinetics of ANtiretroviral agents in HIV-infected pregNAnt women (PANNA) Network.

This phase 4 study investigated the influence of pregnancy on the pharmacokinetics of elvitegravir/cobicistat in 14 women with human immunodeficiency virus type 1. The results support the recommendation against elvitegravir/cobicistat use during pregnancy, as the elvitegravir concentration at the end of the dosing interval (Ctrough) was reduced by 77%, with 85% of pregnant women having a Ctrough below the effective concentration (EC90). Clinical Trials Registration. NCT00825929.

Antibody-Drug Conjugates for Cancer Treatment.

The concept of exploiting the specific binding properties of monoclonal antibodies as a mechanism for selective delivery of cytotoxic agents to tumor cells is an attractive solution to the challenge of increasing the therapeutic index of cell-killing agents for treating cancer. All three parts of an antibody-drug conjugate (ADC)-the antibody, the cytotoxic payload, and the linker chemistry that joins them together-as well as the biologic properties of the cell-surface target antigen are important in designing an effective anticancer agent. The approval of brentuximab vedotin in 2011 for treating relapsed Hodgkin's lymphoma and systemic anaplastic large cell lymphoma, and the approval of ado-trastuzumab emtansine in 2013 for treating HER2-positive metastatic breast cancer, have sparked vigorous research in the field, with >65 ADCs currently in clinical evaluation. This review highlights the ADCs that are approved for marketing, in pivotal clinical trials, or in at least phase II clinical development for treating both hematologic malignancies and solid tumors.

Therapeutic Drug Monitoring of HIV Antiretroviral Drugs in Pregnancy: A Narrative Review.

To date, therapeutic drug monitoring (TDM) has played an important role in the management of pregnant HIV patients on highly active antiretroviral therapy. Historically, in pregnant women living with HIV, the third agent in triple therapy has been either non-nucleoside reverse transcriptase inhibitors or protease inhibitors (PIs). PIs have been the preferred agents because of their robustness from the perspective of viral resistance and the dominant drug class for the management of HIV during pregnancy for the previous decade. As with many drugs used during pregnancy, pharmacokinetic changes decrease exposure to these agents as the pregnancy progresses. This can lead to viral escape at the time of pregnancy and ultimately increase the risk of mother-to-child transmission (MTCT) of HIV. TDM has been well-established for this class of highly active antiretroviral therapy, and appropriate dose adjustment studies have been performed. At present, there is a shift from the traditional treatment paradigm in pregnancy to a new drug class, integrase strand transfer inhibitors (INSTIs). Although INSTIs are affected by pharmacokinetic changes during pregnancy, they do not harbor the same issues with viral escape as seen with PIs at birth and in general eliminate the need for boosting with additional agents like ritonavir (r) and cobicistat (c) [bar elvitegravir (EVG)] that can lead to interactions with treatment of other common infections in HIV, including tuberculosis. Furthermore, INSTIs are the most successful medication for rapidly reducing the viral load (VL) in HIV patients, a useful factor where VL may be unknown, or in late presenters. These merits make INSTIs the best choice in pregnancy, although their use has been hindered in recent years by a report of neural tube defects from a large African study with dolutegravir (DTG). New data from Botswana and Brazil indicate that this risk is less significant than previously reported, necessitating further data to shed light on this critical issue. Current international guidelines including DHHS, EACS, WHO, and BHIVA (for patients with VLs >100,000 copies/mL or late presenters) now recommend INSTIs as first-line agents. The role of TDM in INSTIs shifts to cases of insufficient viral suppression with standard adherence measures, cases of drug-drug interactions, or cases where EVG/c is continued throughout pregnancy, and thus remains an important aspect of HIV care in pregnancy.

Interferon lambda rs368234815 ΔG/ΔG is associated with higher CD4+:CD8+ T-cell ratio in treated HIV-1 infection.

BACKGROUND: The objectives of this study were to investigate the relationships between polymorphisms at the interferon lambda (IFNL) locus and CD4+:CD8+ ratio normalisation in people living with HIV (PLWH) on effective antiretroviral therapy (ART); and to examine whether these polymorphisms influence the composition of T lymphocyte compartments in long-term treated HIV-1 infection. METHODS: A cross-sectional study in PLWH enrolled into the Mater Immunology study. We performed IFNL genotyping on stored samples and evaluated the association of IFNL single-nucleotide polymorphisms (rs368234815 and rs12979860) with CD4+:CD8+ ratio normalization (> 1) and expanded CD4+ and CD8+ T-cell subsets; CD45RO+CD62L+ (central-memory), CD45RO+ CD62L-(effector-memory) and CD45RO-CD62L+ (naïve), using logistic and linear regression models, respectively. RESULTS: 190 ambulatory PLWH recruited to the main study, 143 were included in the analysis (38 had no stored DNA and 9 no T-lymphocyte subpopulation). Of 143 included, the median age (IQR) was 45(39-48) years, 64% were male and 66% were of Caucasian ethnicity. Heterosexual-contact (36%), injecting drug-use (33%) and men who have sex with men (24%) were the most presented HIV-transmission risk groups. The majority of subjects (90.2%) were on ART with 79% of the cohort having an undetectable HIV-RNA (< 40 copies/ml) and the time since ART initiation was 7.5 (3.7-10.4) year. rs368234815 and rs12979860 displayed similar allelic frequencies, with minor alleles ΔG and T representing 39% and 42%, respectively, of circulating alleles. rs368234815 ΔG/ΔG minor homozygotes were significantly associated with increased odds for attaining a normalised CD4+:CD8+ ratio compared to rs368234815 T/T major homozygotes in PLWH virologically suppressed on effective ART (OR = 3.11; 95% CI [1.01:9.56]). rs368234815 ΔG/ΔG homozygosity was also significantly associated with lower levels of CD4+ effector memory T-cells (regression coefficient: - 7.1%, p = 0.04) and CD8+ naïve T-cell subsets were significantly higher in HIV-1 mono-infected PLWH with rs368234815 ΔG/ΔG (regression coefficient: + 7.2%, p = 0.04). CONCLUSIONS: In virally-suppressed, long-term ART-treated PLWH, rs368234815 ΔG/ΔG homozygotes were more likely to have attained normalisation of their CD4+:CD8+ ratio, displayed lower CD4+ effector memory and higher naive CD8+ T-cells. Further studies are needed to replicate our findings in other, larger and more diverse cohorts and to determine the impact of IFNL genetic-variation on CD4+:CD8+ ratio normalisation and clinical outcomes in PLWH.

Provision of immediate postpartum contraception to women living with HIV in the Eastern Cape, South Africa; a cross-sectional analysis.

BACKGROUND: Universal access to contraception is an important strategy adopted by the South African government to reduce the high rate of unintended pregnancies, especially in women living with HIV. In this article, we describe the choices of contraception and also, examine the influencing factors of the choices of contraception in the immediate postpartum period in parturient women with HIV in the Eastern Cape, South Africa. METHODS: In this prospective cross-sectional study, 1617 parturient women with HIV completed a survey on the choice of contraception received in the immediate postpartum period (within 72 h) across three large maternity services in the Eastern Cape between September 2015 to May 2016. Additional information was extracted from their medical records. Choices of contraception were categorised as; short-acting (injectables), long-acting reversible (intrauterine device and implants) and permanent contraception (tubal ligation). Adjusted and unadjusted logistic regression models were employed to determine the influencing factors of the choices of contraception received by the cohort. RESULTS: Participants were predominantly single (69.1%), unemployed (75.1%), had a grade 7-12 level of education (88.4%) and were HIV positive before their index pregnancy (81.3%). The prevalence of immediate postpartum contraception was high (n = 1507; 93.2%) with Injectables being the preferred choice in the majority of the participants (n = 1218; 75.3%). After controlling for all relevant covariates, single marital status was associated with a higher likelihood of immediate postpartum contraceptive initiation (AOR; 1.82 95% CI 1.10-3.03). Overall, women were more likely to initiate a long-acting reversible and irreversible methods when older than 35 years and having had more than two children. CONCLUSIONS: We found a high prevalence of immediate postpartum contraception with a preference for Injectables in the study setting. Long-term monitoring of this cohort will elucidate on contraceptive discontinuation and risk of unintended pregnancies in the region. Ensuring universal access to contraceptives is an important strategy to reduce the rate of unintended pregnancies at the population level. This strategy was adopted by the South African government with a vision of stemming the tide of unintended pregnancies among women living with HIV. In this study, the choices of contraception adopted by women living with HIV following the delivery of their babies were explored. In addition, the study highlights the factors that predict these choices. Participants were asked the choice of contraception they had received prior to being discharged from the maternity centres where they had delivered their babies. The various types of contraception were then categorised by their duration of action. Three distinct groups emerged; short-acting injectables, long acting reversible contraceptives and permanent methods. Of the 1617 women included in the study, 1117 were single and 1314 knew their HIV status prior to the onset of the index pregnancy. Almost all the women (1507 out of 1617) received one form of contraception before leaving the hospital. Many women (1218 out of 1617) chose injectable contraception (short-acting contraception) over the other types of contraception. Women who were older than 34 years and who had three or more children were more likely to choose a long-acting reversible contraceptive and permanent method over the short-acting contraception or nothing. In conclusion, given the short duration of action of the predominant method adopted by these women, a long-term follow up of the study participants will provide more information on the continued use of contraception and risk for unintended pregnancies.

HepCare Europe: a service innovation project. HepCheck: enhancing HCV identification and linkage to care for vulnerable populations through intensified outreach screening. A prospective multisite feasibility study.

OBJECTIVES: Hepatitis C is one of the main causes of chronic liver diseases worldwide. One of the major barriers to effecting EU- and WHO-mandated HCV elimination by 2030 is underdiagnosis. Community-based screening strategies have been identified as important components of HCV models of care. HepCheck Europe is a large-scale intensified screening initiative aimed at enhancing identification of HCV infection among vulnerable populations and linkage to care. METHODS: Research teams across four European countries were engaged in the study and rolled out screening to high-risk populations in community addiction, homeless and prison services. Screening was offered to 2822 individuals and included a self-administered questionnaire, HCV antibody and RNA testing, liver fibrosis assessment and referral to specialist services. RESULTS: There was a 74% (n=2079) uptake of screening. The majority (85.8%, n=1783) were male. In total 44.6% (n=927) of the sample reported ever injecting drugs, 38.4% (n=799) reported ever being homeless and 27.9% (n=581) were prisoners. In total 397 (19%) active HCV infections were identified and 136 (7% of total sample and 34% of identified active infections) were new cases. Of those identified with active HCV infection, 80% were linked to care, which included liver fibrosis assessment and referral to specialist services. CONCLUSIONS: HepCheck's screening and linkage to care is a clear strategy for reaching high-risk populations, including those at highest risk of transmission who are not accessing any type of care in the community. Elimination of HCV in the EU will only be achieved by such innovative, patient-centred approaches.

Integrating primary and secondary care to optimize hepatitis C treatment: development and evaluation of a multidisciplinary educational Masterclass series.

BACKGROUND: It is increasingly being recognized that the elimination of HCV requires a multidisciplinary approach and effective cooperation between primary and secondary care. OBJECTIVES: As part of a project (HepCare Europe) to integrate primary and secondary care for patients at risk of or infected with HCV, we developed a multidisciplinary educational Masterclass series for healthcare professionals (HCPs) working in primary care in Dublin and Bucharest. This article aims to describe and evaluate the series and examine how this model might be implemented into practice. METHODS: GPs and other HCPs working in primary care, addiction treatment services and NGOs were invited to eight 1 day symposia (HCV Masterclass series), examining the burden and management of HCV in key populations. Peer-support sessions were also conducted, to give people affected by HCV and community-based organizations working with those directly affected, an update on the latest developments in HCV treatment. RESULTS: One hundred percent of participants 'strongly agreed' or 'agreed' that the Masterclass helped them to appreciate the role of integrated services in 'the management of patients with HCV'. One hundred percent of participants indicated the importance of a 'designated nurse to liaise with hospital services'. An improvement of knowledge regarding HCV management of patients with high-risk behaviour was registered at the end of the course. CONCLUSIONS: Integrated approaches to healthcare and improving the knowledge of HCPs and patients of the latest developments in HCV treatment are very important strategies that can enhance the HCV care pathway and treatment outcomes.

Integrating hepatitis C care for at-risk groups (HepLink): baseline data from a multicentre feasibility study in primary and community care.

OBJECTIVES: To examine HCV prevalence and management among people who inject drugs (PWID) attending primary care and community-based health services at four European sites using baseline data from a multicentre feasibility study of a complex intervention (HepLink). METHODS: Primary care and community-based health services in Dublin, London, Bucharest and Seville were recruited from the professional networks of the HepLink consortium. Patients were eligible to participate if aged ≥18 years, on opioid substitution treatment or at risk of HCV (i.e. injecting drug use, homeless or incarcerated), and attended the service. Data on patient demographics and prior HCV management were collected on participants at baseline. RESULTS: Twenty-nine primary care and community-based health services and 530 patients were recruited. Baseline data were collected on all participants. Participants' mean age ranged from 35 (Bucharest) to 51 years (London), with 71%-89% male. Prior lifetime HCV antibody testing ranged from 65% (Bucharest) to 95% (Dublin) and HCV antibody positivity among those who had been tested ranged from 78% (Dublin) to 95% (Bucharest). Prior lifetime HCV RNA testing among HCV antibody-positive participants ranged from 17% (Bucharest) to 84% (London). Among HCV antibody- or RNA-positive participants, prior lifetime attendance at a hepatology/infectious disease service ranged from 6% (London) to 50% (Dublin) and prior lifetime HCV treatment initiation from 3% (London) to 33% (Seville). CONCLUSIONS: Baseline assessment of the HCV cascade of care among PWID attending primary care and community-based health services at four European sites identified key aspects of the care cascade at each site that need to be improved.

A Case Study Comparing Heterogeneous Lysine- and Site-Specific Cysteine-Conjugated Maytansinoid Antibody-Drug Conjugates (ADCs) Illustrates the Benefits of Lysine Conjugation.

Antibody-drug conjugates are an emerging class of cancer therapeutics constructed from monoclonal antibodies conjugated with small molecule effectors. First-generation molecules of this class often employed heterogeneous conjugation chemistry, but many site-specifically conjugated ADCs have been described recently. Here, we undertake a systematic comparison of ADCs made with the same antibody and the same macrocyclic maytansinoid effector but conjugated either heterogeneously at lysine residues or site-specifically at cysteine residues. Characterization of these ADCs in vitro reveals generally similar properties, including a similar catabolite profile, a key element in making a meaningful comparison of conjugation chemistries. In a mouse model of cervical cancer, the lysine-conjugated ADC affords greater efficacy on a molar payload basis. Rather than making general conclusions about ADCs conjugated by a particular chemistry, we interpret these results as highlighting the complexity of ADCs and the interplay between payload class, linker chemistry, target antigen, and other variables that determine efficacy in a given setting.

'HepCheck Dublin': an intensified hepatitis C screening programme in a homeless population demonstrates the need for alternative models of care.

BACKGROUND: Hepatitis C virus (HCV) is one of the main causes of chronic liver disease worldwide. Prevalence of HCV in homeless populations ranges from 3.9 to 36.2%. The HepCheck study sought to investigate and establish the characterisation of HCV burden among individuals who attended an intensified screening programme for HCV in homeless services in Dublin, Ireland. METHODS: The HepCheck study was conducted as part of a larger European wide initiative called HepCare Europe. The study consisted of three phases; 1) all subjects completed a short survey and were offered a rapid oral HCV test; 2) a convenience sample of HCV positive participants from phase 1 were selected to complete a survey on health and social risk factors and 3) subjects were tracked along the referral pathway to identify whether they were referred to a specialist clinic, attended the specialist clinic, were assessed for cirrhosis by transient elastography (Fibroscan) and were treated for HCV. RESULTS: Five hundred ninety-seven individuals were offered HCV screening, 73% were male and 63% reported having had a previous HCV screening. We screened 538 (90%) of those offered screening, with 37% testing positive. Among those who tested positive, 112 (56%) were 'new positives' and 44% were 'known positives'. Undiagnosed HCV was prevalent in 19% of the study sample. Active past 30-day drug use was common, along with attendance for drug treatment. Unstable accommodation was the most common barrier to attending specialist appointments and accessing treatment. Depression and anxiety, dental problems and respiratory conditions were common reported health problems. Forty-six subjects were referred to specialised services and two subjects completed HCV treatment. CONCLUSIONS: This study demonstrates that the current hospital-based model of care is inadequate in addressing the specific needs of a homeless population and emphasises the need for a community-based treatment approach. Findings are intended to inform HepCare Europe in their development of a community-based model of care in order to engage with homeless individuals with multiple co-morbidities including substance abuse, who are affected by or infected with HCV.

Correction to: Rapid development of HIV elite control in a patient with acute infection.

After publication of the original article [1], we were notified in Table 1 a column should be removed.