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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 Res Clin Pract, Vol: 26INTRODUCTION: The 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. METHODS: Platelets 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. RESULTS: An 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. CONCLUSIONS: Our 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. CLINICAL TRIAL NUMBER: NCT04653194.
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Journal articleRosadas de Oliveira C, Baylon J, Greiller C, et al., 2025,
Incidence of HTLV-1-associated myelopathy in the UK from 1991 to 2024: a longitudinal observational cohort study
, Frontiers in Medicine, ISSN: 2296-858X -
Journal articleAlagaratnam J, Kelly N, Dustan S, et al., 2025,
Proviral HIV DNA sequencing to inform suitability for long-acting injectable cabotegravir/rilpivirine
, AIDS, Vol: 39, Pages: 95-98, ISSN: 0269-9370Increasingly, people attending HIV services are requesting long-acting injectable (LAI) antiretroviral treatment (ART). However, without HIV RNA resistance-associated mutation results, individuals are considered unsuitable for LAI ART. We present our experience of sequencing proviral HIV DNA in 30 individuals to inform suitability for LAI ART, of whom 23 were considered suitable. In conclusion, optimization of diagnostic tools such as proviral HIV DNA sequencing to confirm suitability for LAI ART would be a welcome addition.
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Journal articleCallaby H, Olver J, Emery K, et al., 2025,
Monkeypox virus isolation from longitudinal samples in 11 hospitalised patients.
, Lancet Infect Dis, Vol: 25, Pages: e4-e5 -
Journal articleWang T, Campbell C, Stockdale AJ, et al., 2025,
Distinct virologic trajectories in chronic hepatitis B identify heterogeneity in response to nucleos(t)ide analogue therapy.
, JHEP Rep, Vol: 7BACKGROUND & AIMS: The dynamics of HBV viral load (VL) in patients with chronic hepatitis B (CHB) on nucleos(t)ide analogue (NA) treatment and its relationship with liver disease are poorly understood. We aimed to study longitudinal VL patterns and their associations with CHB clinical outcomes. METHODS: Utilising large scale, routinely collected electronic health records from six centres in England, collated by the National Institute for Health and Care Research Health Informatics Collaborative (NIHR HIC), we applied latent class mixed models to investigate VL trajectory patterns in adults receiving NA treatment. We assessed associations of VL trajectory with alanine transaminase, and with liver fibrosis/cirrhosis. RESULTS: We retrieved data from 1,885 adults on NA treatment (median follow-up 6.2 years, IQR 3.7-9.3 years), with 21,691 VL measurements (median 10 per patient, IQR 5-17). Five VL classes were identified from the derivation cohort (n = 1,367, discrimination: 0.93, entropy: 0.90): class 1 'long term suppression' (n = 827, 60.5%), class 2 'timely virological suppression' (n = 254, 18.6%), class 3 'persistent moderate viraemia' (n = 140, 10.2%), class 4 'persistent high-level viraemia' (n = 44, 3.2%), and class 5 'slow virological suppression' (n = 102, 7.5%). The model demonstrated a discrimination of 0.93 and entropy of 0.88 for the validation cohort (n = 518). Alanine transaminase decreased variably over time in VL-suppressed groups (classes 1, 2, 5; all p <0.001), but did not significantly improve in those with persistent viraemia (classes 3, 4). Patients in class 5 had twofold increased hazards of fibrosis/cirrhosis compared with class 1 (adjusted hazard ratio, 2.00; 95% CI, 1.33-3.02). CONCLUSIONS: Heterogeneity exists in virological response to NA therapy in CHB patients, with over 20% showing potentially suboptimal responses. Slow virological suppression is associated with liver disease progression. IMPACT A
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Journal articleOkhai H, Winston A, Post F, et al., 2024,
Exploring the cascade of mental healthcare among people with HIV experiencing depressive symptoms in the UK and Ireland: The POPPY study
, HIV MEDICINE, ISSN: 1464-2662 -
Journal articleFenn J, Madon K, Conibear E, et al., 2024,
An ultra-early, transient interferon-associated innate immune response associates with protection from SARS-CoV-2 infection despite exposure.
, EBioMedicine, Vol: 111BACKGROUND: A proportion of individuals exposed to respiratory viruses avoid contracting detectable infection. We tested the hypothesis that early innate immune responses associate with resistance to detectable infection in close contacts of COVID-19 cases. METHODS: 48 recently-exposed household contacts of symptomatic COVID-19 cases were recruited in London, UK between May 2020 and March 2021 through a prospective, longitudinal observational study. Blood and nose and throat swabs were collected during the acute period of index case viral shedding and longitudinally thereafter. Magnitude of SARS-CoV-2 exposure was quantified, and serial PCR and serological assays used to determine infection status of contacts. Whole-blood RNA-seq was performed and analysed to identify transcriptomic signatures of early infection and resistance to infection. FINDINGS: 24 highly-exposed household contacts became PCR-positive and seropositive whilst 24 remained persistently PCR-negative and seronegative. A 96-gene transcriptomic signature of early SARS-CoV-2 infection was identified using RNA-seq of longitudinal blood samples from PCR-positive contacts. This signature was dominated by interferon-associated genes and expression correlated positively with viral load. Elevated expression of this 96-gene signature was also observed during exposure in 25% (6/24) of persistently PCR-negative, seronegative contacts. PCR-negative contacts with elevated signature expression had higher-magnitude SARS-CoV-2 exposure compared to those with low signature expression. We validated this signature in SARS-CoV-2-infected individuals in two independent cohorts. In naturally-exposed healthcare workers (HCWs) we found that 7/58 (12%) PCR-negative HCWs exhibited elevated signature expression. Comparing gene-signature expression in SARS-CoV-2 Controlled Human Infection Model (CHIM) volunteers pre- and post-inoculation, we observed that 14 signature genes were transiently upregulated as soon as 6 hr post
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Journal articleSun W, Gao C, Gladkov GT, et al., 2024,
Footprints of innate immune activity during HIV-1 reservoir cell evolution in early-treated infection
, Journal of Experimental Medicine, Vol: 221, ISSN: 0022-1007Antiretroviral treatment (ART) initiation during the early stages of HIV-1 infection is associated with a higher probability of maintaining drug-free viral control during subsequent treatment interruptions, for reasons that remain unclear. Using samples from a randomized-controlled human clinical trial evaluating therapeutic HIV-1 vaccines, we here show that early ART commencement is frequently associated with accelerated and efficient selection of genome-intact HIV-1 proviruses in repressive chromatin locations during the first year after treatment initiation. This selection process was unaffected by vaccine-induced HIV-1-specific T cell responses. Single-cell proteogenomic profiling demonstrated that cells harboring intact HIV-1 displayed a discrete phenotypic signature of immune selection by innate immune responses, characterized by a slight but significant upregulation of HLA-C, HLA-G, the IL-10 receptor, and other markers involved in innate immune regulation. Together, these results suggest an accelerated immune selection of viral reservoir cells during early-treated HIV-1 infection that seems at least partially driven by innate immune responses.
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Journal articleTipoe T, Ogbe A, Lee M, et al., 2024,
Impact of antiretroviral therapy during primary HIV infection on T-cell immunity after treatment interruption
, EUROPEAN JOURNAL OF IMMUNOLOGY, Vol: 54, ISSN: 0014-2980 -
Journal articleCockbain B, Fidler S, Lyall H, 2024,
Preventing perinatal HIV acquisition; current gaps and future perspectives
, CURRENT OPINION IN HIV AND AIDS, Vol: 19, Pages: 293-304, ISSN: 1746-630X
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