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Journal articleTaylor GP, Evans W, Rosadas C, 2024,
High HTLV-1 Proviral Load Predates and Predicts HTLV-1-Associated Disease: Literature Review and the London Experience
, Pathogens, Vol: 13, Pages: 553-553<jats:p>Human T cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects lymphocytes and causes severe diseases. HTLV-1 proviral load (PVL), i.e., the number of host cells that carry HTLV-1 proviral DNA integrated into their genome, can be measured in peripheral blood mononuclear cells (PBMCs) using quantitative polymerase chain reaction. In this narrative review, we discuss the usefulness of HTLV-1 PVL quantification and share our experience acquired during more than 30 years of follow-up of people living with HTLV-1 in the UK. Patients with HTLV-1-associated myelopathy have higher PVL than those with asymptomatic infection. This is consistent across studies in different countries. High PVL predates symptom onset for both inflammatory and proliferative diseases. High PVL is essential but not sufficient for the development of HTLV-1-associated diseases. Therefore, PVL quantification can be used to support the care of people living with HTLV-1 by identifying those most at risk of HTLV-1-associated diseases.</jats:p>
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Journal articleElliott J, Bodinier B, Whitaker M, et al., 2024,
Sex inequalities in cardiovascular risk prediction
, Cardiovascular Research, ISSN: 0008-6363Aims:Evaluate sex differences in cardiovascular disease (CVD) risk prediction, including use of i) optimal sex-specific risk predictors and ii) sex-specific risk thresholds.Methods and results:Prospective cohort study using UK Biobank, including 121,724 and 182,632 healthy men and women, respectively, aged 38-73 years at baseline. There were 11,899 (men) and 9,110 (women) incident CVD cases (hospitalization or mortality) with median 12.1 years follow-up. We used recalibrated Pooled Cohort Equations (PCE, 7.5% 10-year risk threshold as per US guidelines), QRISK3 (10% 10-year risk threshold as per UK guidelines) and Cox survival models using sparse sex-specific variable sets (via LASSO stability selection) to predict CVD risk separately in men and women. LASSO stability selection included 12 variables in common between men and women, with three additional variables selected for men and one for women. C-statistics were slightly lower for PCE than QRISK3 and models using stably-selected variables, but were similar between men and women: 0.67 [0.66-0.68], 0.70 [0.69-0.71], and 0.71 [0.70-0.72] in men and 0.69 [0.68-0.70], 0.72 [0.71-0.73], and 0.72 [0.71-0.73] in women for PCE, QRISK3 and models using stably-selected variables, respectively. At current clinically implemented risk thresholds, test sensitivity was markedly lower in women than men for all models: at 7.5% 10-year risk, sensitivity was 65.1% and 68.2% in men and 24.0% and 33.4% in women for PCE and models using stably-selected variables, respectively; at 10% 10-year risk, sensitivity was 53.7% and 52.3% in men and 16.8% and 20.2% in women for QRISK3 and models using stably-selected variables, respectively. Specificity was correspondingly higher in women than men. However, the sensitivity in women at 5% 10-year risk threshold increased to 50.1%, 58.5% and 55.7% for PCE, QRISK3 and models using stably-selected variables, respectively.Conclusions:Use of sparse sex-specific variables improved CVD risk prediction
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Journal articleHall E, Davis K, Ohrnberger J, et al., 2024,
Associations between HIV stigma and health-related quality-of-life among people living with HIV: cross-sectional analysis of data from HPTN 071 (PopART)
, Scientific Reports, Vol: 14, ISSN: 2045-2322People living with HIV (PLHIV) report lower health-related quality-of-life (HRQoL) than HIV-negative people. HIV stigma may contribute to this. We explored the association between HIV stigma and HRQoL among PLHIV. We used cross-sectional data from 3,991 randomly selected PLHIV who were surveyed in 2017-2018 for HPTN 071 (PopART), a cluster randomised trial in Zambia and South Africa. Participants were 18-44 years, had laboratory-confirmed HIV infection, and knew their status. HRQoL was measured using the EuroQol-5-dimensions-5-levels (EQ-5D-5L) questionnaire. Stigma outcomes included: internalised stigma, stigma experienced in the community, and stigma experienced in healthcare settings. Associations were examined using logistic regression. Participants who had experienced community stigma (n=693/3991) had higher odds of reporting problems in at least one HRQoL domain, compared to those who had not (adjusted odds ratio, aOR: 1.51, 95% confidence interval, 95% Cl: 1.16-1.98, p=0.002). Having experienced internalised stigma was also associated with reporting problems in at least one HRQoL domain (n=552/3991, aOR: 1.98, 95% CI: 1.54-2.54, p<0.001). However, having experienced stigma in a healthcare setting was less common (n=158/3991) and not associated with HRQoL (aOR: 1.04, 95% CI: 0.68-1.58, p=0.850). A stronger focus on interventions for internalised stigma and stigma experienced in the community is required.
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Journal articleAlagaratnam J, Stöhr W, Hamlyn E, et al., 2024,
Impact of interrupting antiretroviral therapy started during primary HIV-1 infection on plasma neurofilament light chain protein, a marker of neuronal injury: the SPARTAC trial
, Journal of Virus Eradication, Vol: 10, ISSN: 2055-6640ObjectiveAntiretroviral therapy (ART)-conferred suppression of HIV replication limits neuronal injury and inflammation. ART interruption tests efficacy in HIV cure trials and viral rebound after ART interruption may induce neuronal injury. We investigated the impact of protocol-defined ART interruption, commenced during primary HIV-1 infection (PHI) on a biomarker of neuro-axonal injury (neurofilament light protein (NfL)), and its associations with inflammation (D-dimer and interleukin-6 (IL-6)) and HIV-1 reservoir size (total HIV-1 DNA).DesignRetrospective study measuring plasma NfL in 83 participants enrolled in SPARTAC randomised to receive 48-weeks ART initiated during PHI, followed by ART interruption.MethodsNfL (Simoa immunoassay, Quanterix™) was measured before ART, after 48 weeks on ART, and 12 weeks after stopping ART. Plasma D-dimer and IL-6, and total HIV-1 DNA in peripheral CD4+ T-cells results were available in a subset of participants. Longitudinal NfL changes were assessed using mixed models, and associations with clinical and laboratory parameters using linear regression.ResultsNfL decreased following 48-weeks ART (geometric mean 6.9 to 5.8 pg/mL, p = 0.006) with no further significant change up to 12-weeks post-stopping ART despite viral rebound in the majority of participants (median 1.7 to 3.9 plasma HIV-1 RNA log10 copies/mL). Higher baseline NfL was independently associated with higher plasma HIV-1 RNA (p = 0.020) and older age (p = 0.002). While NfL was positively associated with D-dimer (n = 48; p = 0.002), there was no significant association with IL-6 (n = 48) or total HIV-1 DNA (n = 51).ConclusionsUsing plasma NfL as a surrogate marker, a decrease in neuro-axonal injury was observed in a cohort of participants following ART initiation during PHI, with no evidence of neuro-axonal injury rebound following ART interruption for up to 12 weeks, despite viral rebound in the majority of participants.
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Journal articleMccabe L, Burns JE, Latifoltojar A, et al., 2024,
MAVMET trial: maraviroc and/or metformin for metabolic dysfunction-associated fatty liver disease(MAFLD) in adults with suppressed HIV
, AIDS, ISSN: 0269-9370OBJECTIVE: Metabolic dysfunction-associated fatty liver disease (MAFLD) is over-represented in people living with HIV (PLWH). Maraviroc (MVC) and/or metformin (MET) may reduce MAFLD by influencing inflammatory pathways and fatty acid metabolism. DESIGN: Open-label, 48-week randomised trial with a 2x2 factorial design. SETTING: Multicentre HIV clinics. PARTICIPANTS: Nondiabetic, virologically-suppressed PLWH, aged ≥35 years, with confirmed/suspected MAFLD (≥1 biochemical/anthropometric/radiological/histological features). INTERVENTION: Adjunctive MVC; MET; MVC+MET vs. antiretroviral therapy (ART) alone. PRIMARY OUTCOME: Change in liver fat fraction (LFF) between baseline and week-48 using Magnetic Resonance Proton Density Fat Fraction (MR PDFF). RESULTS: Six sites enrolled 90 participants (93% male; 81% white; median age 52 [interquartile range, IQR 47-57] years) between 19-Mar-2018 and 11-November-2019. 70% had imaging/biopsy plus ≥1 MAFLD criteria. The analysis included 82/90 with week-0 and -48 scans. Median baseline MR PDFF was 8.9 (4.6-17.1); 40%, 38%, 8%, and 14% had grade zero, one, two, and three steatosis respectively. Mean LFF increased slightly between baseline and follow-up scans: 2.22% MVC, 1.26% MET, 0.81% MVC+MET, and 1.39% ART alone. Prolonged intervention exposure (delayed week-48 scans) exhibited greater increases in MR PDFF (estimated difference 4.23% [95% CI 2.97, 5.48], P < 0.001). There were no differences in predicted change for any intervention compared to ART alone: MVC (-0.42% [95% CI -1.53-0.68, P = 0.45]), MET (-0.62 [-1.81-0.56, P = 0.30]), and MVC+MET (-1.04 [-2.74-0.65, P = 0.23]). Steatosis grade remained unchanged in 55% and increased in 24%. CONCLUSIONS: Baseline levels of liver fat were lower than predicted. Contrary to our hypothesis, neither MVC, MET, or the combination significantly reduced MR PDFF compared to ART alone.
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Journal articlePhiri MM, Schaap A, Hensen B, et al., 2024,
The impact of an innovative community-based peer-led intervention on uptake and coverage of sexual and reproductive health services among adolescents and young people 15-24 years old: results from the Yathu Yathu cluster randomised trial
, BMC PUBLIC HEALTH, Vol: 24 -
Journal articleMaertens GN, Purcell DFJ, Rosadas C, et al., 2024,
Why not eliminate HTLV-1 while eliminating HIV-1?
, LANCET, Vol: 403, Pages: 2288-2289, ISSN: 0140-6736 -
Journal articleRosadas de Oliveira C, Costa M, Senna K, et al., 2024,
Impact and economic analysis of human T-cell lymphotropic virus type 1 (HTLV-1)-targeted antenatal screening, England and Wales, 2021
, Eurosurveillance, Vol: 29, ISSN: 1025-496XBackgroundHuman T-cell lymphotropic virus type 1 (HTLV-1) is a neglected virus that can cause severe disease and be transmitted from mother to child through breastfeeding. Avoidance of breastfeeding prevents 80% of vertical transmission. The United Kingdom (UK) is currently assessing whether HTLV-1-targeted antenatal screening should be implemented.AimWe aimed to assess the impact and cost-effectiveness of a targeted programme to prevent HTLV-1 vertical transmission in England and Wales.MethodsWe estimated the number of pregnant women who have high risk of HTLV-1 infection based on their or their partner’s country of birth. With data from 2021, we used a mathematical model to assess cost-effectiveness of HTLV-1 antenatal screening. We also estimated the annual number of infant infections and the number that could be prevented with screening and intervention.ResultsWe estimate that ca 99,000 pregnant women in England and Wales have high risk of HTLV-1 infection. In the absence of screening, 74 (range: 25–211) HTLV-1 infections in infants would be expected to occur every year in England and Wales. Implementation of targeted screening would prevent 58 (range: 19–164) infant infections annually. The intervention is effective (incremental 0.00333 quality-adjusted life years (QALY)) and cost-saving (GBP −57.56 (EUR −66.85)).ConclusionOur findings support implementation of HTLV-1 targeted antenatal screening to reduce vertical transmission from mothers to infants in the UK.
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Journal articleAMR-X Collaborators, 2024,
System-wide approaches to antimicrobial therapy and antimicrobial resistance in the UK: the AMR-X framework
, The Lancet Microbe, Vol: 5, Pages: e500-e507, ISSN: 2666-5247Antimicrobial resistance (AMR) threatens human, animal, and environmental health. Acknowledging the urgency of addressing AMR, an opportunity exists to extend AMR action-focused research beyond the confines of an isolated biomedical paradigm. An AMR learning system, AMR-X, envisions a national network of health systems creating and applying optimal use of antimicrobials on the basis of their data collected from the delivery of routine clinical care. AMR-X integrates traditional AMR discovery, experimental research, and applied research with continuous analysis of pathogens, antimicrobial uses, and clinical outcomes that are routinely disseminated to practitioners, policy makers, patients, and the public to drive changes in practice and outcomes. AMR-X uses connected data-to-action systems to underpin an evaluation framework embedded in routine care, continuously driving implementation of improvements in patient and population health, targeting investment, and incentivising innovation. All stakeholders co-create AMR-X, protecting the public from AMR by adapting to continuously evolving AMR threats and generating the information needed for precision patient and population care.
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Journal articleTelisinghe L, Floyd S, Macleod D, et al., 2024,
Incidence of self-reported tuberculosis treatment with community-wide universal testing and treatment for HIV and tuberculosis screening in Zambia and South Africa: A planned analysis of the HPTN 071 (PopART) cluster-randomised trial
, PLOS MEDICINE, Vol: 21, ISSN: 1549-1277
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