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Journal articleEvangeli M, Gnan G, Musiime V, et al., 2026, , Glob Public Health, Vol: 21
Sharing one's HIV status with others (onward HIV disclosure) for youth with perinatally acquired HIV (PAH) is often difficult but may assist with challenges associated with living with HIV. We describe the development of an intervention to help HIV-sharing decision-making for UK and Ugandan youth with PAH. The methods included : (1) semi-structured interviews with 50 participants (20 with PAH patients aged 18-25 years, 20 friends, family or partners and 10 professionals), (2) a survey of 57 UK participants with PAH patients aged ≥17, (3) the development of an intervention conceptual model, (4) intervention development, including obtaining intervention feedback from 13 youth with PAH. The survey showed that group (23/57; 40%) and mixed individual and group formats (21/57; 37%), mixed gender groups (52/57; 91%) and peer worker involvement (54/57; 95%) were preferred. The interviews highlighted the importance of overcoming feelings of shame and accepting one's status before sharing, having support to feel confident to share, personal values playing a part in sharing decisions and friends and partners explaining that they had not been educated about HIV until someone had shared their status with them. We describe the finalised intervention, and strengths and limitations of the intervention development process are outlined.Trial registration: ISRCTN Registry, ISRCTN31852047, Registered on 21 January 2019.
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Journal articleHenderson M, Dutey-Magni P, Herrera C, et al., 2026, , HIV Med
BACKGROUND: Data on changes in biomarkers of brain health, and their associations with cognitive function in adults commencing either dual- or triple-antiretroviral therapy (ART) are sparse. METHODS: Plasma biomarkers (neurofilament light [NfL], glial fibrillary acidic protein [GFAP], sCD14, CXCL10, neopterin and IL-6) were measured at baseline and after 96 weeks on ART in individuals randomized to darunavir/ritonavir and either tenofovir-DF/emtricitabine (triple-ART, n = 119) or raltegravir (dual-ART, n = 119) in NEAT-001/ANRS143. Regression models examined associations of baseline and week-96 biomarker concentrations with HIV clinical parameters, composite cognitive test scores (Standardized neuropsychological test [NPZ], 7-domains) and treatment arm. RESULTS: In 238 individuals, median age was 38 (interquartile range [IQR] 31, 46) years, 87% male and 83% of white ethnicity. Baseline median log10 HIV RNA 4.73 (IQR 4.23, 5.11) copies/mL and CD4 350 (IQR 285, 412) cells/mm3. At baseline, higher biomarker concentrations were associated with lower CD4 (NfL, GFAP, CXCL10; p < 0.03), higher log10 HIV RNA (sCD14, neopterin, CXCL10; p < 0.02) and longer known duration of HIV (sCD14; p = 0.044). At week-96, 94% had plasma HIV <50 copies/mL, and a decline in biomarker concentrations was observed: GFAP -14.4%, sCD14 -6.8%, neopterin -47.4%, CXCL10 -58.8%, IL-6 -29.5% (all p < 0.001) and NfL -4.4% (p = 0.075). NPZ improved by 0.21 mean points. Change in GFAP, CXCL10, sCD14, neopterin and NfL was negatively associated with change in CD4 (all p ≤ 0.002) but not change in NPZ (p > 0.05). A greater decline in neopterin concentration was observed with dual- (-50.2%) versus triple-ART (-44.3%; p = 0.022). CONCLUSIONS: Plasma biomarkers of brain health improved following ART initiation, associated predominantly wi
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Journal articleFenn J, 2026,
Elevated body mass index is associated with delayed protective airway mucosal immune responses in mild SARS-CoV-2 infection
, EBioMedicine, ISSN: 2352-3964BackgroundSARS-CoV-2 viral load in the upper respiratory tract (URT) typically peaks and declines within days of infection, even in individuals without prior infection or vaccination. Although this implicates the URT innate immune response in effectively restricting viral replication, the nature of the protective responses and how they are affected by demographic factors is poorly defined.MethodsWe recruited 54 seronegative household contacts of recently diagnosed COVID-19 cases and prospectively collected URT samples during and after exposure. Among the 39 individuals who became infected, we quantified airway mucosal cytokine and chemokine responses and virus-specific nasal IgA using Meso Scale Discovery assays, and assessed associations with demographic factors, viral load, and symptoms.FindingsParticipants with higher BMI had higher URT viral loads and more marked symptoms. This was significantly associated with delayed induction of protective inflammatory mediators in the airway mucosa but not in blood. Induction of virus-specific nasal IgA at 1-week post-infection also correlated with lower viral load.InterpretationElevated BMI retards initial airway mucosal innate immune responses to infection, which may partially explain the pronounced adverse impact of higher BMI on clinical and virological outcomes in COVID-19. FundingThis work is supported by the NIHR Health Protection Research Unit in Respiratory Infections, 51³Ô¹ÏÍø in partnership with the UK Health Security Agency (Grant number: NIHR200927; AL) and the Medical Research Council (Grant number: MR/X004058/1). Infrastructure support for this research was provided by the NIHR 51³Ô¹ÏÍø Biomedical Research Centre (BRC).
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Journal articleKarakosta A, Nicholls EJ, Coukan F, et al., 2026, , HIV Med
OBJECTIVES: To explore missed opportunities for PrEP use among people with recently acquired HIV in the United Kingdom. METHODS: Data were derived from CASCADE, an international, longitudinal, mixed-methods study of adults (≥16 years) with recently acquired HIV (≤12 months). Individuals were recruited from nine UK clinics (08/2022-09/2024) to self-complete a questionnaire; a subset participated in semi-structured interviews (SSIs). RESULTS: 46 questionnaires were completed (39 cisgender men and 7 women, including 2 transgender women) and 11 SSIs (1 cisgender woman). Among men, 22 perceived HIV risk before diagnosis; 21 had ≥5 sexual partners and 17 reported group sex in the 3 months before diagnosis. Thirty (29 men and 1 woman) reported sexualized drug use. Twenty men had ever used PrEP; seven of them had not used it in the 6 months prior to diagnosis. No women had ever used PrEP. Most gay, bisexual and other men who have sex with men (GBMSM) were aware of PrEP; however, risk perception, social meanings of PrEP and concerns about side effects hindered utilization. Among five men using event-based dosing (EBD), three described difficulty predicting sexual activity that led to missed or mistimed pre-/post-sex doses - while others were reluctant to take daily PrEP. For women, the biggest barrier was lack of awareness. CONCLUSIONS: PrEP barriers vary by population. For GBMSM, addressing barriers to uptake/adherence (e.g., EBD challenges) are key, highlighting the potential benefit of long-acting injectables. However, awareness of PrEP remains a key challenge for women to achieve equity in prevention.
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Journal articleNguyen Quoc G, Nguyen Le Thao M, Do Thuy An M, et al., 2026, , Wellcome Open Research, Vol: 11, Pages: 157-157
<ns3:p>Background Hepatitis C virus (HCV) is a significant global health concern that disproportionately affects certain populations, such as people who inject drugs (PWID) and men who have sex with men (MSM). Disparity in access to health services can result in them being ‘underserved’. Methods We utilized a community-based participatory research approach to engage underserved communities at risk of HCV in Ho Chi Minh City, Vietnam to explore the obstacles they face in accessing healthcare and to generate community-led solutions. Through the CBPR process, we identified locally relevant research questions and conducted community-based research, including community-led data collection, analysis, and then designed and implemented solutions. Results We engaged 27 members from three underserved groups, including MSM and transgender people, PWID, and communities with limited financial resources. Collectively they identified financial burdens, insufficient information about HCV treatment, and a lack of awareness of the severity of HCV as the primary issues faced by their communities. The groups generated solutions to address the issues, such as short educational videos, HCV awareness sessions, and a stakeholder dissemination meeting. There was significant interest and participation from the community groups to identify and implement locally driven solutions to issues around HCV care. The capacity for engagement varied among the different groups, for example, the MSM group had more agency to conduct research and act upon it, whereas those with limited financial resources had more barriers that limited participation. Discussion Addressing community health issues requires an integration of community-driven initiatives with more traditional academic research. The CBPR approach facilitated a comprehensive assessment, the implementation of context-specific interventions, and engagement with and empowering of communities related to care seeking. The CBPR proces
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Journal articleHazell L, Cooper N, 2026,
Multi-arm multi-stage randomised controlled trial of Inflammatory Signal Inhibitors (MATIS) for patients hospitalised with COVID-19 pneumonia during the UK pandemic
, BMJ Open, ISSN: 2044-6055Objectives: To determine the safety and efficacy of ruxolitinib and fostamatinib compared to standard of care (SOC) in patients requiring hospital admission for the treatment of COVID-19 pneumonia.Design: Adaptive multi-arm, multi-stage, randomised, open label trial (3-arm, 2-stage)Setting: Five hospitals in England between October 2020 and September 2022.Participants: Hospitalised patients (≥18 years) with COVID-19 pneumonia defined by a modified World Health Organisation (WHO) COVID-19 severity grade of 3 or 4. Interventions: Participants were randomly assigned 1:1:1 to receive ruxolitinib (10mg bd for 7 days then 5mg bd for 7 days), fostamatinib (150mg bd for 7 days then 100mg bd for 7 days) or SOC.Main outcome measures: Primary outcome was development of severe COVID-19 pneumonia (modified WHO severity grade ≥5) within 14 days of randomisation. Secondary outcomes included mortality, invasive and non-invasive ventilation, venous thromboembolism, duration of hospital stay, readmissions, inflammatory markers and serious adverse events (SAE). Results: At Stage 1, 181 patients were randomised, with 4 assessed as ineligible post-randomisation. Fostamatinib was stopped early for futility with 16 participants (27.6%, N=58) developing severe COVID-19 pneumonia compared to 15 (25.0%, N=60) in the SOC arm (adjusted odds ratio (aOR) compared to SOC: 1.12; 95% confidence interval (CI): 0.49 to 2.58; p=0.608). Ruxolitinib progressed to Stage 2 but the trial was stopped early due to slow recruitment. At the final analysis, 10 participants (16.1%, N=62) developed severe COVID-19 pneumonia in the ruxolitinib arm compared to 15 (24.6%, N=61) in the SOC arm (aOR: 0.63; 95% CI: 0.25 to 1.57; p=0.161). Four (7.4%) participants in the fostamatinib arm, none in the ruxolitinib arm and three (5.5%) in the SOC arm died within 14 days of randomisation. Infections were the most frequently reported serious adverse event and were numerically higher in the fostamatinib (10, 17.2%) an
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Journal articleHoneyford K, Cooke G, Kinderler A, et al., 2026, , Health Soc Care Deliv Res, Vol: 14, Pages: 1-23
BACKGROUND: Identifying clinical deterioration is a global health priority. Sepsis is a leading cause of deterioration, responsible for around 46,000 deaths annually in the United Kingdom. Early warning scores based on patients' vital signs can be embedded into electronic patient records to digitally alert clinicians to those at risk. Rapid identification and treatment - particularly with targeted intravenous antibiotics - are critical to improving outcomes in sepsis patients. RESEARCH QUESTION: This study aimed to evaluate the effectiveness of digital alerts in improving outcomes for patients with sepsis. Using routine electronic patient record data from four United Kingdom National Health Service acute trusts, we investigated how digital alert systems influence patient outcomes and explored mechanisms and mediators of their effectiveness. OBJECTIVES: Map the types of digital alerts currently in use across United Kingdom hospitals for identifying patients at risk of sepsis (Workstream 1). Evaluate the impact of digital alerts on patient outcomes (Workstream 2). Examine how the implementation process affects alert performance, guided by the consolidated framework for implementation research (Workstream 3). Provide recommendations on alert effectiveness and implementation strategies using systems modelling and mediation analysis (Workstream 4). METHODS: A mixed-methods approach was employed. A national survey assessed the use of digital sepsis alerts in English National Health Survey hospitals (Workstream 1). Qualitative interviews and focus groups explored the implementation process and its influence on alert performance (Workstream 3). A natural experiment with multilevel interrupted time series analysis examined the impact of sepsis screening tools and digital alerts on outcomes, primarily in-hospital mortality (Workstream 2). Routinely collected clinical data were processed following National Institute for Health Research-Health Information Collaborative standard
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Journal articleVandekerckhove L, Fox J, Mora-Peris B, et al., 2026, , Nat Commun, Vol: 17
HIV persistence in reservoirs despite antiretroviral therapy (ART) is a barrier to a permanent cure. We present the affinity-enhanced TCR bispecific IMC-M113V as a potential therapeutic for targeted HIV reservoir elimination. Preclinical studies demonstrate that IMC-M113V redirects T cells towards cells expressing the variable viral peptide, Gag77-85, presented by HLA-A*02:01 at low copy number, without binding to HIV-negative cells. Here, we conduct a first-in-human, open-label single ascending dose study of IMC-M113V (1.6-15 µg) in twelve HLA-A*02:01-positive males living with HIV on suppressive ART (EudraCT number 2021-002008-11). Participants receive one intravenous infusion of IMC-M113V on Day 1 and are monitored through Day 29 to evaluate safety, tolerability (primary endpoints) and pharmacodynamic (PD) activity (secondary endpoint). IMC-M113V is well tolerated and not associated with any serious adverse event. PD activity is dose-dependent and strongest in participants with highly IMC-M113V-sensitive Gag77-85 variant sequences. Thus, we provide a promising foundation to evaluate multiple and higher doses of IMC-M113V as a strategy for achieving ART-free virological control.
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Journal articleGnan G, Vosper J, Foster C, et al., 2026, , AIDS Care, Pages: 1-14
Sharing one's HIV status with others is complex for youth with perinatally acquired HIV (PAH). However, the support from sharing one's HIV status may assist with HIV-related challenges. This study explored barriers and facilitators of HIV status sharing among UK-based youth living with PAH. Drawing on semi-structured interviews with ten youth with PAH, ten members of their social networks and five HIV professionals, this study examined the complex relational nature of disclosure. The data were examined using thematic analysis. While many youths expressed a desire to be open, sharing was shaped by stigma, cultural silence, familial secrecy, fear of rejection and lack of HIV education. Facilitators included emotional readiness, peer support, increased knowledge and positive prior experiences of disclosure. Social network participants often saw themselves as supportive, although professionals tended to focus on potential emotional risks. This study underscores disclosure as a process requiring ongoing support and suggests that empowering youth with education, skills and confidence is key. It identifies the need for better professional guidance and disclosure interventions co-designed with youth to support health and well-being. The findings have implications for stigma reduction, education and psychosocial support, contributing to improving the quality of life for youth with PAH.
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Journal articleWhitaker M, Elliott J, Gerard-Ursin I, et al., 2026, , The Lancet, ISSN: 0140-6736
BackgroundDespite 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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