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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 articleSconza R, Taylor GP, Ene L, et al., 2026, , AIDS, Vol: 40, Pages: 831-839
OBJECTIVE: To assess the effectiveness of once- and twice-daily ritonavir-boosted darunavir (DRV/r)-containing regimens for treating HIV in pregnancy to inform the 2025 World Health Organization antiretroviral treatment guidelines update. DESIGN: Analysis of pooled data from two observational study networks with sites in Romania, Switzerland, and the United Kingdom. METHODS: Pregnancies resulting in a live birth or stillbirth in women receiving 800/100鈥妋g DRV/r once-daily or 600/100鈥妋g twice-daily during pregnancy were included. The primary outcome was viral suppression (<50鈥奵opies/ml) near delivery (from 28鈥奷ays prior to 7鈥奷ays after delivery). RESULTS: Among 162 women on once-daily DRV/r, 95% were virally suppressed near delivery, with no difference between those on DRV/r from conception (95%, 113/119) and those who started on or switched to DRV/r during pregnancy (95%, 41/43). Among 27 women on twice-daily DRV/r, 78% were virally suppressed near delivery. Most women remained on the same DRV/r regimen until delivery, and there were no vertical transmissions. Darunavir drug concentrations for the limited number of pregnancies with data available fell within the expected ranges. CONCLUSIONS: This analysis provides some reassurance that once-daily DRV/r can be used successfully in pregnancy. However, given the possibility of reduced drug levels in pregnancy with once-daily dosing, viral load monitoring during pregnancy remains essential. Surveillance of pregnancies in women receiving once-daily DRV/r is needed to further support the use of this dosing during pregnancy.
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Journal articleTurner H, Ahmed S, Nguyen HA, et al., 2026,
Economic evaluation of alternative hepatitis C treatment options: a post hoc analysis of the VIETNARMS trial
, EClinicalMedicine, ISSN: 2589-5370BackgroundHepatitis C remains a leading cause of liver disease worldwide, and access to Direct-Acting Antiviral (DAA) treatment remains limited in many settings. Alternative treatment strategies that require fewer tablets and clinical visits could help improve equitable access, and new approaches have recently been found to be non-inferior in producing sustained viral suppression. MethodsWe did a cost-minimization analysis of alternative treatment options for non-cirrhotic patients evaluated in the VIETNARMS trial (ISRCTN61522291), conducted between 19/06/2020 and 10/05/2023 in Vietnam. These were: (i) ‘response guided’ (which adjusts treatment duration based on 1-week viral load); (ii) ‘induction maintenance’ (which reduces the dosing frequency in later weeks of treatment); and (iii) ‘Peg-IFN+DAA’ (4 weeks of DAAs combined with four weekly doses of PEGylated interferon (Peg-IFN). The primary outcome was the cost per cure. A disaggregated societal perspective was adopted, including stratification for the healthcare provider and patient costs. FindingsThe three alternative treatment strategies were projected to have lower costs per cure than standard 12-week DAA treatment in the base-case scenario: US$202 (15%) less for ‘response guided’, US$234 (18%) less for ‘induction maintenance’, and US$163 (12%) less for ‘Peg-IFN+DAA’. However, the potential for cost savings, and which strategy had the lowest cost per cure, depended on the assumed cost of DAA drugs: the strategy with the lowest cost per cure was generally ‘induction maintenance’ when DAA drug costs for a standard treatment course were under US$1,000, but Peg-IFN+DAA when DAA costs exceeded US$1,500. In some scenarios, lower costs per cure were achieved through reduced health system expenditures, despite increased costs to patients.InterpretationAlternative strategies for Hepatitis C treatment could reduce costs for providers an
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Journal articleWeterings DA, Chiou Yee LL, Watber P, et al., 2026, , Blood Neoplasia, ISSN: 2950-3280
Adult T-cell Leukemia/Lymphoma (ATL) is caused by chronic infection with Human T-lymphotropic virus type-1 (HTLV-1). HTLV-1 contains highly immunogenic CD8+ T-cell epitopes which elicit high frequencies of virus-specific CD8+ T-cells in most virus-carriers. Despite the virus being present in the tumour, HTLV-1-specific CD8+ cells are often undetectable in ATL. To characterise HTLV-1-specific CD8+ T-cells during ATL development, we studied a sub-group of people living with asymptomatic HTLV-1 infection at very high risk of developing ATL. These so- called ‘high-risk’ carriers have suspected premalignant lesions: expanded, HTLV-1-infected ‘ATL-like’ clones circulating in their peripheral blood. Compared to viral antigen-burden matched controls, high-risk carriers had significantly fewer Tax-specific IFN-γ+CD8+ cells in peripheral blood. Furthermore, ex vivo CD8+ T-cells from high-risk carriers did not efficiently kill autologous HTLV-1-infected T-cells, including premalignant ATL-like clones. We stained Tax11–19/HLA-A*0201 pentamer+CD8+ T-cells to test whether the low frequencies of functional CD8+ T-cells resulted from the phenotype or absolute frequency of HTLV-1-specific CD8+ T-cells. Again, high-risk carriers had significantly lower frequencies of Tax11–19/HLA-A*0201 pentamer+CD8+ T-cells than controls, but we observed no difference in effector function, memory phenotype or expression of checkpoint control molecules (PD-1, TIGIT, TIM-3, LAG-3, CTLA-4). In contrast, there was no difference in the frequency of CD8+ T-cells specific for other viruses (CMV, EBV, Flu) between high-risk carriers and controls. This is the first report of HTLV-1-specific immune dysregulation in the premalignant stage of ATL. Low frequencies of HTLV-1-specific CD8+ T-cells may contribute to ATL development, and may be a novel therapeutic target for ATL prevention.
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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 articleMac Cann R, Alalwan D, Saini G, et al., 2026, , PLoS Comput Biol, Vol: 22
BACKGROUND: People living with HIV remain at elevated risk for a number of non-communicable diseases, including cardiovascular disease (CVD), driven in part by chronic inflammation. While prior studies have identified inflammatory biomarker patterns linked to CVD in people with HIV, it remains unclear which combinations of biomarkers most effectively predict clinical outcomes. We aimed to develop and evaluate a framework for refining biomarker-based clustering approaches to better capture inflammatory patterns associated with a cardiovascular phenotype (CVP) in people with HIV. METHODS: We developed and evaluated three recursive feature addition (RFA) models to enhance biomarker-driven clustering of people with and without HIV. Using a 24-marker initial panel of biomarkers chosen for their links to clinical CVP in people with HIV, we compared three models for selective inclusion of 31 additional, exploratory biomarkers: (1) a stepwise additive model evaluating biomarkers cumulatively based on biological relevance; (2) a stepwise additive model evaluating biomarkers individually; and (3) a greedy forward-backward selection model. Each model was assessed using principal component analysis (PCA), cluster stability, biological coherence and association with a CVP and 10-year Atherosclerotic Cardiovascular Disease (ASCVD) risk. RESULTS: All three RFA models generated three, biomarker-derived clusters. Post RFA cluster biomarker composition, model stability and clinical associations of these clusters differed across models. The individual additive model (Model 2) produced the most distinct separation of inflammatory profiles, incorporating 11 additional biomarkers, including, GDF-15, IFN-λ2 and Thrombopoietin). In this model, Cluster 3 was characterised by heightened innate and adaptive immune activation, the highest CVP prevalence (11%) and the strongest association with CVP (adjusted odds ratio (aOR) 2.3, 95% CI 1.04-5.09). CONCLUSION: We demonstrate that an RFA
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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, 天美传媒 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 Imperial 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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