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Journal articleWhitaker M, Elliott J, Gerard-Ursin I, et al., 2026,
Profiling vaccine attitudes and subsequent uptake in 1·1 million people in England: a nationwide cohort study
, The Lancet, ISSN: 0140-6736BackgroundDespite highly effective vaccines against SARS-CoV-2, COVID-19 vaccine hesitancy persisted in some populations in England during the pandemic, with rates and motivations for hesitancy varying by demographic group. Addressing the drivers of vaccine hesitancy through targeted interventions in hesitant groups is a public health priority for better and more rapid control of disease spread. We aimed to characterise the determinants and subtypes of vaccine hesitancy and identify more persistent forms of hesitancy via analysis of vaccine uptake in a large cross-sectional cohort with linked National Health Service (NHS) data.MethodsWe conducted an initial cross-sectional analysis of vaccine hesitancy at baseline, followed by a longitudinal analysis of vaccine uptake in the hesitant cohort. We analysed survey data from the Real-time Assessment of Community Transmission (REACT) studies, which monitored the prevalence of SARS-CoV-2 in England during the COVID-19 pandemic at regular intervals from May 1, 2020, to March 31, 2022, in random samples of the population. Participants self-reported detailed sociodemographic information, vaccination status, and attitudes towards vaccination. Participants were classified as hesitant if they reported that they had refused, planned to refuse, or had not yet decided whether to receive the COVID-19 vaccine. Participants who said they were unvaccinated when NHS records showed that they had been vaccinated were excluded from further analysis. The primary outcome of the cross-sectional analysis was vaccine hesitancy. Longitudinal analysis of vaccine uptake was done in participants in the hesitant cohort who consented to the use of linked NHS vaccination records to track their vaccination history after the survey, with post-survey vaccination as the outcome. Consensus clustering was used to categorise reasons for vaccine hesitancy, and cross-sectional and longitudinal analyses used logistic regression models to identify demographic pr
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Journal articleKhawaja AA, Whitlock G, Fidler S, et al., 2025,
Evaluation of the effect of 48 weeks of BIC/F/TAF and DRV/c/F/TAF on platelet function in the context of rapid ART start
, HIV Research & Clinical Practice, Vol: 26, ISSN: 2578-7470IntroductionThe BIC-T&T study aimed to determine the efficacy of bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF) and darunavir/cobicistat/emtricitabine/tenofovir alafenamide (DRV/c/F/TAF) at suppressing viral load in a two-arm, open-label, multi-centre, randomised trial under a UK test-and-treat setting. This sub-study aimed to evaluate potential off-target cardiovascular impact by examining ex vivo platelet function.MethodsPlatelets were isolated by centrifugation of citrated blood from participants attending Chelsea and Westminster Hospital or St Mary’s Hospital at Week 48 following enrolment. Platelet activation was assessed by real-time flow cytometry to examine integrin activation and granule release and platelet aggregation was evaluated by light transmission aggregometry. Statistical significance was determined by 2-way ANOVA with a Šidák’s multiple comparisons post-test.ResultsAn analysis of 21 participants was performed at Week 48 (96% male and 48% white; mean (range) age was 37 (23–78) years). No difference between arms was observed in ADP-, collagen- or thrombin receptor activator for peptide (TRAP)-6-evoked platelet αIIbβ3 integrin activation, granule release or platelet aggregation in response to any of the agonists tested. Despite differences in the demographics between treatment arms, the presence of an unboosted integrase inhibitor or boosted protease inhibitor in a test-and-treat setting did not impact platelet function.ConclusionsOur study provides no evidence of differences in downstream platelet responses between participants taking BIC/F/TAF compared to DRV/c/F/TAF following 48 wk of treatment. Further data are required to explore whether there are biologically significant off-target effects, including effects on platelets and other components of the cardiovascular system between these two test-and-treat regimens.
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Journal articleSteyn N, Chadeau M, Whitaker M, et al., 2025,
Pandemic-risk-related behaviour change in England from June 2020 to March 2022: the cross-sectional REACT-1 study among over 2 million people
, BMJ Public Health, ISSN: 2753-4294 -
Journal articleJones EM, Sourij C, Stradner M, et al., 2025,
IL-10- and IL-13-biased T cell responses to SARS-CoV-2 vaccination in diabetes
, European Journal of Immunology, ISSN: 0014-2980Type 1 and type 2 diabetes are associated with increased severity and mortality from respiratory virus infections. Vaccination in the general population significantly reduces the risk of severe respiratory viral infection and triggers a strong, polyfunctional and lasting T cell response in healthy individuals. However, vaccine effectiveness in people with type 1 diabetes is unclear. Here we studied the magnitude and functional characteristics of vaccine-specific CD4+ and CD8+ T cell responses to vaccination in people with type 1 and type 2 diabetes and compared them to those of people living without diabetes, using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine as a model. We found defects in both CD4+ and CD8+ T cell memory maintenance and the functionality of the vaccine-specific T cells in people with diabetes compared to people without. In those individuals with type 1 and type 2 diabetes that harbored detectable vaccine-specific T cells, they displayed an unfocused, tolerogenic phenotype characterized by increased expression of IL-10 and IL-13 compared to people without diabetes. These results have implications for vaccination strategies for people with diabetes.
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Journal articleRothhaar P, Arand T, Seong HG-T, et al., 2025,
Highly replicating hepatitis C virus variants emerge in immunosuppressed patients causing severe disease.
, Nat Commun, Vol: 16Hepatitis C virus (HCV) exists as a heterogenous quasispecies, but the phenotypic consequences of viral variability are widely unexplored. Here we identify a replication enhancing domain (ReED) in non-structural protein 5A conferring high replication fitness to clinical isolates. Accumulation of mutations in the ReED mediates high genome replication capacity. In a cohort of liver transplant patients, high replicator variants are exclusively found in individuals with severe disease outcome, suggesting that high viral replication fitness is associated with increased viral pathogenesis. Analysis of large sequence cohorts reveals that overall only 10% of viral genomes show genetic signatures of high replicators, which are enriched in recipients of liver transplantations, patients developing hepatocellular carcinoma and in HIV coinfected individuals. Overall, our data suggests that low replication fitness is a hallmark of HCV, contributing to establishment of persistence, whereas high replicators appear to have an advantage under conditions of immune suppression, thereby enforcing pathogenesis.
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Journal articleGuzman V, Di Gravio C, Cooper E, et al., 2025,
"I put a lot of emphasis on work because I want to keep my job": a population-based interview study of long Covid and employment changes in England
, Health Expectations, Vol: 28, ISSN: 1369-6513BackgroundLong Covid is a complex condition characterised by persistent multisystemic symptoms following a Covid-19 infection, which can influence an individual's capability to sustain employment. However, there is limited evidence of how diverse presentations of long Covid can shape employment and what support strategies might be useful for different groups.AimTo address this, we aimed to explore the experiences of employment changes among people living with long Covid in England and to identify the perceived barriers and enablers they face to cope with work.Design and MethodsWe conducted a qualitative analysis of data from the Real-time Assessment of Community Transmission (REACT) Study. Using a framework analysis approach, we analysed 60 semi-structured interviews with people who experienced persistent Covid-19 symptoms for 12 weeks or more.ResultsWe identified three key themes: (1) Persistent Covid-19 symptoms at work; (2) Ripple effects of balancing work, identity and well-being with persistent Covid-19 symptoms; and (3) Employment changes to cope with and manage persistent Covid-19 symptoms. Participants identified multiple employment changes, including reduction of working hours, restructuring of roles and modification of responsibilities, and adapted ways of working. Drivers of employment changes included disruptive and fluctuating symptoms but also broader pandemic circumstances and the opportunities available for accessing organizational support and putting in place appropriate management strategies.ConclusionOur results provide a thorough understanding of the work changes experienced by people living with long Covid and highlight the need for intersectional, adaptable work accommodations to support their sustainable employment and overall well-being.Patient and Public ContributionMembers of the public who are part of a Public Advisory Group (PAG) have provided ongoing input into various aspects of the umbrella cohort study, the Real-time Assessment of Com
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Journal articleMartin MA, Reynolds SJ, Foley BT, et al., 2025,
HIV drug resistance during antiretroviral therapy scale-up in Uganda, 2012–19: a population-based, longitudinal study
, The Lancet Microbe, Vol: 6, ISSN: 2666-5247BackgroundWith scale-up of antiretroviral therapy (ART) in sub-Saharan Africa, increasing pretreatment HIV drug resistance has been reported; however, the broader effect of ART expansion on population-level resistance patterns remains insufficiently quantified. We aimed to estimate the longitudinal prevalence of drug resistance and resistance-conferring mutations.MethodsThis study used data collected as part of the Rakai Community Cohort Study (RCCS), an open population-based census and cohort study conducted in southern Uganda. At each survey round, residents aged 15–49 years are invited to participate and receive a structured questionnaire that obtains sociodemographic, behavioural, and health information, including self-reported past and current ART use. Voluntary HIV testing is conducted using a rapid test algorithm and a venous blood sample. People with HIV provide samples for viral load quantification and deep sequencing. We analysed RCCS survey, HIV viral load, and deep sequencing (which was used to predict resistance) data from five survey rounds. The key outcomes were the population prevalence of viraemic people with HIV with non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor (NRTI), protease inhibitor, or multiclass resistance among all participants (regardless of HIV serostatus) in the 2015 and 2017 surveys. Prevalence of class-specific resistance and resistance-conferring substitutions were estimated using robust log-Poisson regression.FindingsBetween Aug 10, 2011, and Nov 4, 2020, there were 43 361 participants in the RCCS and 7923 (18·27%) people with HIV. Over five survey rounds, 93 622 participant visits occurred, among which 17 460 (18·65%) were from people with HIV. Over the analysis period, the median age of study participants remained similar (28 years [22–35] in 2012 and 29 years [21–38] in 2019). Sufficient data were available to reliably genoty
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Journal articleDrysdale M, Gillespie IA, Christensen D, et al., 2025,
Characterisation of People Living With Chronic Hepatitis B Virus Infection in England and Stratification by HBsAg Levels: A Cross-Sectional Study
, JOURNAL OF VIRAL HEPATITIS, Vol: 32, ISSN: 1352-0504 -
Journal articleCooke GS, Walker SA, Barnes E, et al., 2025,
HCV response-guided therapy: is shorter always better? - Authors' reply
, LANCET, Vol: 406, Pages: 2540-2540, ISSN: 0140-6736 -
Journal articleRotsaert A, Phiri M, Sigande L, et al., 2025,
Unmet need for contraceptives and unintended pregnancies among adolescent girls and young women aged 15 to 24 in Zambia: insights from the Yathu Yathu trial.
, Reprod Health, Vol: 22BACKGROUND: In Sub-Saharan Africa, unmet need for contraceptives often remains high among adolescent girls and young women (AGYW), leading to unintended pregnancies. Yathu Yathu, a cluster-randomised trial of a community-based intervention conducted in two communities in Lusaka, Zambia (2019-2021), aimed to provide sexual and reproductive health services, including contraceptive services, to adolescents and young people. The trial showed no impact on pregnancy related outcomes. Hence, this analysis examined the characteristics of AGYW aged 15-24 with an unmet need for modern contraceptives and who experienced an unintended pregnancy. We also explored access to and reach of contraceptive services through Yathu Yathu. METHODS: Secondary analysis of Yathu Yathu endline survey data. Using logistic regression, adjusted for cluster, we explored factors associated with unmet need for modern contraceptives and unintended pregnancies among AGYW in the intervention arm and assessed whether these associations differed in the control arm. Using routinely collected service delivery data from the intervention arm, numbers of AGYW accessing hormonal contraceptive services were described by age, community, educational attainment, and marital status. RESULTS: In the intervention arm, 395 AGYW ever had sex. Unmet need for modern contraceptives was 40.6% (101/249) among AGYW who had sex in the last 12 months and wished to prevent or space childbearing. Unmet need was higher among younger and single/never married AGYW; in control zones unmet need was additionally higher among those currently in school or with infrequent discussion about sexual health promotion with their sexual partners. Among AGYW ever having had sex, 42.1% (165/392) reported an unintended pregnancy. This was higher among AGYW aged 20-24 years and currently not in school, and additionally among those in control zones who reported food absence. According to the routinely collected data, 12.3% (859/7005) of AGYW in inte
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