322 results on '"C, Sabin"'
Search Results
2. Skull ecomorphological variation of narwhals (Monodon monoceros, Linnaeus 1758) and belugas (Delphinapterus leucas, Pallas 1776) reveals phenotype of their hybrids.
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Deborah Vicari, Eline D Lorenzen, Mikkel Skovrind, Paul Szpak, Marie Louis, Morten T Olsen, Richard P Brown, Olivier Lambert, Giovanni Bianucci, Richard C Sabin, and Carlo Meloro
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Medicine ,Science - Abstract
Narwhals and belugas are toothed whales belonging to the Monodontidae. Belugas have a circumpolar Arctic and sub-Artic distribution while narwhals are restricted to the Atlantic Arctic. Their geographical ranges overlap during winter migrations in the Baffin Bay area (Canada/West Greenland) and successful interbreeding may occur. Here, we employed geometric morphometrics on museum specimens to explore the cranium and mandible morphology of a known hybrid (NHMD MCE 1356) and the cranium morphology of a putative hybrid (NHMD 1963.44.1.4) relative to skull morphological variation in the parental species. Specifically, we used 3D models of skulls from 69 belugas, 86 narwhals, and the two known/putative hybrids and 2D left hemi-mandibles from 20 belugas, 64 narwhals and the known hybrid. Skull shape analyses allowed clear discrimination between species. Narwhals are characterised by a relatively short rostrum and wide neurocranium while belugas show a more elongated and narrower cranium. Sexual size dimorphism was detected in narwhals, with males larger than females, but no sexual shape dimorphism was detected in either species (excluding presence/absence of tusks in narwhals). Morphological skull variation was also dependent on different allometric slopes between species and sexes in narwhals. Our analyses showed that the cranium of the known hybrid was phenotypically close to belugas but its 2D hemi-mandible had a narwhal shape and size morphology. Both cranium and mandible were strongly correlated, with the pattern of covariation being similar to belugas. The putative hybrid was a pure male narwhal with extruded teeth. Comparison of genomic DNA supported this result, and stable carbon and nitrogen isotope values suggested that the putative hybrid had a more benthic foraging strategy compared to narwhals. This work demonstrates that although the known hybrid could be discriminated from narwhals and belugas, detection of its affinities with these parental species was dependent on the part of the skull analysed.
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- 2022
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3. Stable Isotope Analysis of Specimens of Opportunity Reveals Ocean-Scale Site Fidelity in an Elusive Whale Species
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Kerri J. Smith, Clive N. Trueman, Christine A. M. France, Jed P. Sparks, Andrew C. Brownlow, Michael Dähne, Nicholas J. Davison, Guðmundur Guðmundsson, Kamal Khidas, Andrew C. Kitchener, Bram W. Langeveld, Véronique Lesage, Hanneke J. M. Meijer, John J. Ososky, Richard C. Sabin, Zena L. Timmons, Gísli A. Víkingsson, Frederick W. Wenzel, and Markus J. Peterson
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bone ,muscle ,skin ,Sowerby's beaked whale ,Mesoplodon bidens ,δ13 C and δ15 N ,General. Including nature conservation, geographical distribution ,QH1-199.5 - Abstract
Elusive wildlife are challenging to study, manage, or conserve, as the difficulty of obtaining specimens or conducting direct observations leads to major data deficiencies. Specimens of opportunity, such as salvaged carcasses or museum specimens, are a valuable source of fundamental biological and ecological information on data-deficient, elusive species, increasing knowledge of biodiversity, habitat and range, and population structure. Stable isotope analysis is a powerful indirect tool that can be used to infer foraging behavior and habitat use retrospectively from archived specimens. Beaked whales are a speciose group of cetaceans that are challenging to study in situ, and although Sowerby's beaked whale (Mesoplodon bidens) was discovered >200 years ago, little is known about its biology. We measured δ13C and δ15N stable isotope composition in bone, muscle, and skin tissue from 102 Sowerby's beaked whale specimens of opportunity collected throughout the North Atlantic Ocean to infer movement ecology and spatial population structure. Median δ13C and δ15N values in Sowerby's beaked whale bone, muscle, and skin tissues significantly differed between whales sampled from the east and west North Atlantic Ocean. Quadratic discriminant analysis that simultaneously considered δ13C and δ15N values correctly assigned >85% of the specimens to their collection region for all tissue types. These findings demonstrate Sowerby's beaked whale exhibits both short- and long-term site fidelity to the region from which the specimens were collected, suggest that this species is composed of two or more populations or exhibits a metapopulation structure, and have implications for conservation and management policy. Stable isotope analysis of specimens of opportunity proved a highly successful means of generating new spatial ecology data for this elusive species and is a method that can be effectively applied to other elusive species.
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- 2021
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4. Protocol of a two arm randomised, multi-centre, 12-month controlled trial: evaluating the impact of a Cognitive Behavioural Therapy (CBT)-based intervention Supporting UPtake and Adherence to antiretrovirals (SUPA) in adults with HIV
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R. Horne, E. Glendinning, K. King, T. Chalder, C. Sabin, A. S. Walker, L. J. Campbell, I. Mosweu, J. Anderson, S. Collins, R. Jopling, P. McCrone, H. Leake Date, S. Michie, M. Nelson, N. Perry, J. A. Smith, W. Sseruma, V. Cooper, and On behalf of the SUPA Group
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Adherence ,Engagement ,Antiretroviral therapy ,HIV ,Randomised controlled trial ,Beliefs about medicines ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Delay to start antiretroviral therapy (ART) and nonadherence compromise the health and wellbeing of people living with HIV (PLWH), raise the cost of care and increase risk of transmission to sexual partners. To date, interventions to improve adherence to ART have had limited success, perhaps because they have failed to systematically elicit and address both perceptual and practical barriers to adherence. The primary aim of this study is to determine the efficacy of the Supporting UPtake and Adherence (SUPA) intervention. Methods This study comprises 2 phases. Phase 1 is an observational cohort study, in which PLWH who are ART naïve and recommended to take ART by their clinician complete a questionnaire assessing their beliefs about ART over 12 months. Phase 2 is a randomised controlled trial (RCT) nested within the observational cohort study to investigate the effectiveness of the SUPA intervention on adherence to ART. PLWH at risk of nonadherence (based on their beliefs about ART) will be recruited and randomised 1:1 to the intervention (SUPA intervention + usual care) and control (usual care) arms. The SUPA intervention involves 4 tailored treatment support sessions delivered by a Research Nurse utilising a collaborative Cognitive Behavioural Therapy (CBT) and Motivational Interviewing (MI) approach. Sessions are tailored to individual needs and preferences based on the individual patient’s perceptions and practical barriers to ART. An animation series and intervention manual have been developed to communicate a rationale for the personal necessity for ART and illustrate concerns and potential solutions. The primary outcome is adherence to ART measured using Medication Event Monitoring System (MEMS). Three hundred seventy-two patients will be sufficient to detect a 15% difference in adherence with 80% power and an alpha of 0.05. Costs will be compared between intervention and control groups. Costs will be combined with the primary outcome in cost-effectiveness analyses. Quality adjusted life-years (QALYs) will also be estimated over the follow-up period and used in the analyses. Discussion The findings will enable patients, healthcare providers and policy makers to make informed decisions about the value of the SUPA intervention. Trial registration The trial was retrospectively registered 21/02/2014, ISRCTN35514212.
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- 2019
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5. Combining simulation modeling and stable isotope analyses to reconstruct the last known movements of one of Nature’s giants
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Clive N. Trueman, Andrew L. Jackson, Katharyn S. Chadwick, Ellen J. Coombs, Laura J. Feyrer, Sarah Magozzi, Richard C. Sabin, and Natalie Cooper
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Carbon stable isotopes ,Movement models ,Movement ,Models ,Sclerochronology ,Blue whale ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
The spatial ecology of rare, migratory oceanic animals is difficult to study directly. Where incremental tissues are available, their chemical composition can provide valuable indirect observations of movement and diet. Interpreting the chemical record in incremental tissues can be highly uncertain, however, as multiple mechanisms interact to produce the observed data. Simulation modeling is one approach for considering alternative hypotheses in ecology and can be used to consider the relative likelihood of obtaining an observed record under different combinations of ecological and environmental processes. Here we show how a simulation modeling approach can help to infer movement behaviour based on stable carbon isotope profiles measured in incremental baleen tissues of a blue whale (Balaenoptera musculus). The life history of this particular specimen, which stranded in 1891 in the UK, was selected as a case study due to its cultural significance as part of a permanent display at the Natural History Museum, London. We specifically tested whether measured variations in stable isotope compositions across the analysed baleen plate were more consistent with residency or latitudinal migrations. The measured isotopic record was most closely reproduced with a period of residency in sub-tropical waters for at least a full year followed by three repeated annual migrations between sub-tropical and high latitude regions. The latitudinal migration cycle was interrupted in the year prior to stranding, potentially implying pregnancy and weaning, but isotopic data alone cannot test this hypothesis. Simulation methods can help reveal movement information coded in the biochemical compositions of incremental tissues such as those archived in historic collections, and provides context and inferences that are useful for retrospective studies of animal movement, especially where other sources of individual movement data are sparse or challenging to validate.
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- 2019
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6. Quality of life assessment in people living with and without HIV: UPBEAT study
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E. Alvarez, A.M. Barry, A.G. Cotter, C. Sabin, S. Simelane, A. Macken, J.J. Brady, E. Kavanagh, G. McCarthy, J. Compston, and P.W.G. Mallon
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Microbiology ,QR1-502 ,Public aspects of medicine ,RA1-1270 - Published
- 2016
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7. No need for secondary Pneumocystis jirovecii pneumonia prophylaxis in adult people living with HIV from Europe on ART with suppressed viraemia and a CD4 cell count greater than 100 cells/µL
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Atkinson, A. Miro, J.M. Mocroft, A. Reiss, P. Kirk, O. Morlat, P. Ghosn, J. Stephan, C. Mussini, C. Antoniadou, A. Doerholt, K. Girardi, E. De Wit, S. Kraus, D. Zwahlen, M. Furrer, H. De Wit, S. Antoniadou, A. Castagna, A. Doerholt, K. Fätkenheuer, G. Raben, D. Teira, R. Zangerle, R. Judd, A. Zangerle, R. Touloumi, G. Warszawski, J. Meyer, L. Dabis, F. Krause, M.M. Leport, C. Wittkop, L. Wit, F. Prins, M. Bucher, H. Gibb, D. Fätkenheuer, G. Del Amo, J. Obel, N. Thorne, C. Pérez-Hoyos, S. Hamouda, O. Bartmeyer, B. Chkhartishvili, N. Noguera-Julian, A. Antinori, A. d’Arminio Monforte, A. Brockmeyer, N. Prieto, L. Conejo, P.R. Soriano-Arandes, A. Battegay, M. Kouyos, R. Casabona, J. Goetghebuer, T. Sönnerborg, A. Torti, C. Sabin, C. Teira, R. Garrido, M. Haerry, D. Costagliola, D. d’Arminio-Monforte, A. del Amo, J. Raben, D. Chêne, G. Judd, A. Conejo, P.R. Barger, D. Schwimmer, C. Termote, M. Wittkop, L. Frederiksen, C.M. Raben, D. Brandt, R.S. Berenguer, J. Bohlius, J. Bouteloup, V. Bucher, H. Cozzi-Lepri, A. Dabis, F. d’Arminio Monforte, A. Davies, M.-A. del Amo, J. Dorrucci, M. Dunn, D. Egger, M. Guiguet, M. Grabar, S. Judd, A. Lambotte, O. Leroy, V. Lodi, S. Matheron, S. Meyer, L. Monge, S. Nakagawa, F. Paredes, R. Phillips, A. Puoti, M. Rohner, E. Schomaker, M. Smit, C. Sterne, J. Thiebaut, R. Thorne, C. Wqetu, C. van der Valk, M. Wittkop, L. the Opportunistic Infections Working Group of the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) study in EuroCOORD
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Introduction: Since the beginning of the HIV epidemic in resource-rich countries, Pneumocystis jirovecii pneumonia (PjP) is one of the most frequent opportunistic AIDS-defining infections. The Collaboration of Observational HIV Epidemiological Research Europe (COHERE) has shown that primary Pneumocystis jirovecii Pneumonia (PjP) prophylaxis can be safely withdrawn in patients with CD4 counts of 100 to 200 cells/µL if plasma HIV-RNA is suppressed on combination antiretroviral therapy. Whether this holds true for secondary prophylaxis is not known, and this has proved difficult to determine due to the much lower population at risk. Methods: We estimated the incidence of secondary PjP by including patient data collected from 1998 to 2015 from the COHERE cohort collaboration according to time-updated CD4 counts, HIV-RNA and use of PjP prophylaxis in persons >16 years of age. We fitted a Poisson generalized additive model in which the smoothed effect of CD4 was modelled by a restricted cubic spline, and HIV-RNA was stratified as low (10,000copies/mL). Results: There were 373 recurrences of PjP during 74,295 person-years (py) in 10,476 patients. The PjP incidence in the different plasma HIV-RNA strata differed significantly and was lowest in the low stratum. For patients off prophylaxis with CD4 counts between 100 and 200 cells/µL and HIV-RNA below 400 copies/mL, the incidence of recurrent PjP was 3.9 (95% CI: 2.0 to 5.8) per 1000 py, not significantly different from patients on prophylaxis in the same stratum (1.9, 95% CI: 0.1 to 3.7). Conclusions: HIV viraemia importantly affects the risk of recurrent PjP. In virologically suppressed patients on ART with CD4 counts of 100 to 200/µL, the incidence of PjP off prophylaxis is below 10/1000 py. Secondary PjP prophylaxis may be safely withheld in such patients. While European guidelines recommend discontinuing secondary PjP prophylaxis only if CD4 counts rise above 200 cells/mL, the latest US Guidelines consider secondary prophylaxis discontinuation even in patients with a CD4 count above 100 cells/µL and suppressed viral load. Our results strengthen and support this US recommendation. © 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.
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- 2021
8. A new spectroscopic analysis of the massive O + O type binary HD 54662 AB
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C. Sabin-Sanjulian, M. V. McSwain, C. Putkuri, Nidia Morrell, Rodolfo H. Barbá, Alexander W. Fullerton, S. S. Diaz, G. Ferrero, Tabetha S. Boyajian, J. Maíz Apellániz, José Ignacio Arias, Roberto Claudio Gamen, Maíz Apellániz, J. [0000-0003-0825-3443], Simón Díaz, S. [0000-0003-1168-3524], Boyajian, T. S. [0000-0001-9879-9313], Barbá, R. H. [0000-0003-1086-1579], Arias, J. I. [0000-0001-7500-7352], Gamen, R. C. [0000-0002-5227-9627], Morrell, N. I. [0000-0003-2535-3091], Comisión Nacional de Investigación Científica y Tecnológica (CONICYT), National Aeronautics & Space Administration (NASA), National Science Foundation (NSF), Dirección de Investigación y Desarrollo (DIDULS) de la Universidad de La Serena, Unidad de Excelencia Científica María de Maeztu Centro de Astrobiología del Instituto Nacional de Técnica Aeroespacial y CSIC, MDM-2017-0737, and Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT)
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fundamental parameters [stars] ,stars: individual: HD 54662 AB ,Binary number ,Type (model theory) ,spectroscopic [binaries] ,01 natural sciences ,early-type [stars] ,individual: HD 54662 AB [stars] ,purl.org/becyt/ford/1 [https] ,individual [Stars] ,stars: atmospheres ,0103 physical sciences ,HD 54662 AB ,010303 astronomy & astrophysics ,early type [Stars] ,Physics ,atmospheres [stars] ,010308 nuclear & particles physics ,Astronomy and Astrophysics ,purl.org/becyt/ford/1.3 [https] ,stars: early-type ,Astronomía ,Crystallography ,Space and Planetary Science ,stars: fundamental parameters ,binaries: spectroscopic - Abstract
HD 54662 AB is one of the three O + OB binaries known so far with orbital period longer than 1000 d, offering the opportunity to test scenarios of massive star formation and models of single stellar evolution. Here, we present a detailed study of this system based on new high-resolution spectra and data. A disentangling method is used to recover the individual spectra of the primary and secondary components, which are classified as O6.5 V(n)z and O7.5 Vz, respectively. Combining radial velocity measurements and astrometric data, a new absolute orbit with a period of 2113 ± 9 d and an eccentricity of 0.062 ± 0.008 is determined, confirming previous findings. However, absolute masses of 23.8 ± 1.1 M¿ for the primary and 20.3 ± 1.1 M¿ for the secondary are obtained, differing from previous determinations but in reasonable agreement with the spectral types of the stars. Primary and secondary components show remarkably different projected rotational velocities (160 and ¿40 $\rm km\, s^{-1}$, respectively), which is probably related to the formation process of the binary. Contrary to previously interpretations, the star with broader spectral features is the most massive object in the system. Stellar and wind parameters of both stars are derived through quantitative spectroscopic analysis of the disentangled spectra using fastwind models, and they are consistent with the current calibrations for O-type stars. Evolutionary masses and ages are also computed with the bonnsai tool. Ages below 2.5 Ma are obtained, in agreement with the youth expected from their Vz nature., With funding from the Spanish government through the "María de Maeztu Unit of Excellence" accreditation (MDM-2017-0737)
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- 2020
9. Monitoring liver transplant rates in persons diagnosed with hepatitis C:a data linkage study, England 2008 to 2017
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Mary Ramsay, Sema Mandal, Georgina Ireland, Ruth Simmons, Matthew Hickman, and C Sabin
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hepatitis C virus ,Adult ,Male ,medicine.medical_specialty ,Cirrhosis ,Adolescent ,medicine.medical_treatment ,Information Storage and Retrieval ,Hepacivirus ,Kaplan-Meier Estimate ,Liver transplantation ,Rate ratio ,Antiviral Agents ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Interquartile range ,Virology ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Registries ,Aged ,Retrospective Studies ,Aged, 80 and over ,blood-borne infections ,liver transplantation ,business.industry ,Incidence (epidemiology) ,Research ,Incidence ,direct‐acting antivirals ,Public Health, Environmental and Occupational Health ,Hepatitis C ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,Transplant Recipients ,Transplantation ,England ,Hepatocellular carcinoma ,HCV ,030211 gastroenterology & hepatology ,epidemiology ,Female ,business ,laboratory surveillance - Abstract
Introduction Liver transplantation is an important measure of burden from hepatitis C virus (HCV)-associated liver disease. Aims To describe transplant rates and survival in individuals with HCV infection from 2008 to 2017 in England through data linkage. Methods This is a retrospective observational cohort study. Laboratory reports of HCV infection were linked to the Liver Transplant Registry for individuals aged 15 years and over, first diagnosed between 1998 and 2017. We estimated age-sex standardised incidence rates and used Poisson regression to investigate predictors of liver transplantation and test for a change in incidence after introduction of direct-acting antivirals (DAAs) in 2014. Kaplan-Meier survival analysis was used to calculate post-transplant survival rates. Results Of 124,238 individuals diagnosed with HCV infection, 1,480 were registered and 1,217 received a liver transplant. Of individuals registered, 1,395 had post-HCV cirrhosis and 636 had hepatocellular carcinoma (618 also had post-HCV cirrhosis). Median time from HCV diagnosis to transplant was 3.4 years (interquartile range: 1.3–6.8 years). Liver transplant rates were lower 2014–17 compared with 2011–13 (incidence rate ratio: 0.64; 95% confidence interval: 0.55–0.76). Survival rates were 93.4%, 79.9% and 67.9% at 1, 5 and 10 years, respectively. Data linkage showed minimal under-reporting of HCV in the transplant registry. Conclusion In the post-DAA era, liver transplant rates have fallen in individuals with HCV infection, showing early impact of HCV treatment scale-up; but the short time from HCV diagnosis to liver transplant suggests late diagnosis is a problem.
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- 2019
10. Response to Comment on 'An excess of massive stars in the local 30 Doradus starburst'
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Jesús Maíz Apellániz, Nevy Markova, Artemio Herrero, Francisco Najarro, Jacco Th. van Loon, D. J. Lennon, Mark Gieles, Frank Tramper, Sergio Simón-Díaz, V. Kalari, Norberto Castro, Joachim Puls, Hugues Sana, Miriam Garcia, J. M. Bestenlehner, C. Sabin-Sanjulian, Robert G. Izzard, Philipp Podsiadlowski, Vincent Hénault-Brunet, Philip Dufton, O.H. Ramírez-Agudelo, Luca Fossati, Chris Evans, W. D. Taylor, Paul A. Crowther, Colin Norman, Fabian Schneider, G. Gräfener, Norbert Langer, Alexander de Koter, Selma E. de Mink, Jorick S. Vink, and Low Energy Astrophysics (API, FNWI)
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0301 basic medicine ,Physics ,Solar mass ,Multidisciplinary ,Initial mass function ,Extraterrestrial Environment ,Astronomy ,FOS: Physical sciences ,Astrophysics ,01 natural sciences ,Astrophysics - Astrophysics of Galaxies ,Time ,03 medical and health sciences ,Stars ,030104 developmental biology ,Stars, Celestial ,Astrophysics - Solar and Stellar Astrophysics ,Astrophysics of Galaxies (astro-ph.GA) ,0103 physical sciences ,010303 astronomy & astrophysics ,Solar and Stellar Astrophysics (astro-ph.SR) - Abstract
Farr and Mandel reanalyse our data, finding initial-mass-function slopes for high mass stars in 30 Doradus that agree with our results. However, their reanalysis appears to underpredict the observed number of massive stars. Their technique results in more precise slopes than in our work, strengthening our conclusion that there is an excess of massive stars above $30\,\mathrm{M}_\odot$ in 30 Doradus., Comment: Authors' version of a response to a technical comment published in Science; 8 pages, 1 figure
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- 2018
11. Baleen stable isotope data
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Clive N Trueman, Andrew L Jackson, Katharyn S Chadwick, Ellen J Coombs, Sarah Magozzi, Richard C Sabin & Natalie Cooper
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This dataset contains d13C and d15N stable isotope data from northern hemisphere rorqual whale (Balaenoptera) baleen taken from our collections. This includes data from the baleen of the Hintze Hall blue whale. The data has been used in various research papers. Additional data allow the analyses in these papers to be carried out and mostly encompass environmental datasets or the outputs of various simulation models. **Note that if trying to link these data to analyses in GitHub, an update to this site has changed all "." in column headers to "_". These will need to be changed before the code will work. Apologies.**
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- 2018
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12. What can cetacean stranding records tell us? A study of UK and Irish cetacean diversity over the past 100 years
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Ellen J Coombs, Rob Deaville, Richard C. Sabin, Louise Allan, Mick O’Connell, Simon Berrow, Andrew Brownlow, Mariel Ten Doeschate, Rod Penrose, Ruth Williams, Paul Jepson and Natalie Cooper
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Data from the paper: **What can cetacean stranding records tell us? A study of UK and Irish cetacean diversity over the past 100 years**. Ellen J. Coombs et al. 2019. *Marine Mammal Science*, DOI: [https://doi.org/10.1111/mms.12610](https://doi.org/10.1111/mms.12610). This dataset contains information on cetaceans stranded in the UK and Ireland between 1913 and 2015. It also contains yearly data on various environmental variables believed to influence strandings. The full strandings datasets are available from: * UK (1913 - 1989): NHM Data Portal: [https://doi.org/10.5519/0028204](https://doi.org/10.5519/0028204). * UK (1990 - 2015): CSIP http://data.ukstrandings.org * Irish records (1990 - 2015): Irish Whale and Dolphin group (contact them for access).
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- 2018
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13. When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries: A Prospective Observational Study
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Caniglia, Ellen C. Sabin, Caroline Robins, James M. Logan, Roger Cain, Lauren E. Abgrall, Sophie Mugavero, Michael J. and Hernandez-Diaz, Sonia Meyer, Laurence Seng, Remonie and Drozd, Daniel R. Seage, III, George R. Bonnet, Fabrice and Dabis, Francois Moore, Richard R. Reiss, Peter van Sighem, Ard Mathews, William C. del Amo, Julia Moreno, Santiago and Deeks, Steven G. Muga, Roberto Boswell, Stephen L. Ferrer, Elena Eron, Joseph J. Napravnik, Sonia Jose, Sophie and Phillips, Andrew Olson, Ashley Justice, Amy C. Tate, Janet P. Bucher, Heiner C. Egger, Matthias Touloumi, Giota and Sterne, Jonathan A. Costagliola, Dominique Saag, Michael and Hernan, Miguel A. Ctr AIDS Res Network Integrated
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Objective: To illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART). Design: Prospective studies of HIV-positive individuals in Europe and the USA in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems. Methods: Antiretroviral-naive individuals who initiated ART and became virologically suppressed within 12 months were followed from the date of suppression. We compared 3 CD4 cell count and HIV-RNA monitoring strategies: once every (1) 3 +/- 1 months, (2) 6 +/- 1 months, and (3) 9-12 +/- 1 months. We used inverseprobability weighted models to compare these strategies with respect to clinical, immunologic, and virologic outcomes. Results: In 39,029 eligible individuals, there were 265 deaths and 690 AIDS-defining illnesses or deaths. Compared with the 3-month strategy, the mortality hazard ratios (95% CIs) were 0.86 (0.42 to 1.78) for the 6 months and 0.82 (0.46 to 1.47) for the 9-12 month strategy. The respective 18-month risk ratios (95% CIs) of virologic failure (RNA >200) were 0.74 (0.46 to 1.19) and 2.35 (1.56 to 3.54) and 18-month mean CD4 differences (95% CIs) were -25.3 (-18.6 to 7.9) and -31.7 (-52.0 to -11.3). The estimates for the 2-year risk of AIDS-defining illness or death were similar across strategies. Conclusions: Our findings suggest that monitoring frequency of virologically suppressed individuals can be decreased from every 3 months to every 6, 9, or 12 months with respect to clinical outcomes. Because effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question.
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- 2016
14. The VLT-FLAMES Tarantula Survey. I. Introduction and observational overview
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S. E. de Mink, J. Th. van Loon, G. Graefener, M. A. Campbell, E. Doran, T. Bagnoli, Alceste Z. Bonanos, A. Herrero, Nevena Markova, J. M. Bestenlehner, Paul A. Crowther, Hugues Sana, Vincent Hénault-Brunet, P. R. Dunstall, J. S. Clark, V. E. Stroud, Nolan R. Walborn, Matteo Cantiello, Miriam Garcia, D. J. Lennon, Ines Brott, W. D. Taylor, Sergio Simón-Díaz, Nate Bastian, Edgardo Costa, K. Friedrich, I. D. Howarth, Chris Evans, Philip Dufton, J. Maíz Apellániz, Robert G. Izzard, C. Sabin-Sanjulian, Stephen J. Smartt, A. de Koter, Francisco Najarro, O. H. Ramirez, Mark Gieles, J. Puls, Jorick S. Vink, Eli Bressert, Norbert Langer, Giovanni Carraro, and Low Energy Astrophysics (API, FNWI)
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Cosmology and Nongalactic Astrophysics (astro-ph.CO) ,010504 meteorology & atmospheric sciences ,Young stellar object ,fundamental parameters [stars] ,FOS: Physical sciences ,Astrophysics ,Astrophysics::Cosmology and Extragalactic Astrophysics ,Stellar classification ,spectroscopic [binaries] ,01 natural sciences ,early-type [stars] ,individual: 30 Doradus [open clusters and associations] ,0103 physical sciences ,Astrophysics::Solar and Stellar Astrophysics ,Large Magellanic Cloud ,010303 astronomy & astrophysics ,Solar and Stellar Astrophysics (astro-ph.SR) ,Astrophysics::Galaxy Astrophysics ,0105 earth and related environmental sciences ,Physics ,Spectral properties ,Astronomy and Astrophysics ,Wolf-Rayet [stars] ,Photometry (astronomy) ,Stars ,Astrophysics - Solar and Stellar Astrophysics ,Space and Planetary Science ,Observational study ,Astrophysics::Earth and Planetary Astrophysics ,Data reduction ,Astrophysics - Cosmology and Nongalactic Astrophysics - Abstract
The VLT-FLAMES Tarantula Survey (VFTS) is an ESO Large Programme that has obtained multi-epoch optical spectroscopy of over 800 massive stars in the 30 Doradus region of the Large Magellanic Cloud (LMC). Here we introduce our scientific motivations and give an overview of the survey targets, including optical and near-infrared photometry and comprehensive details of the data reduction. One of the principal objectives was to detect massive binary systems via variations in their radial velocities, thus shaping the multi-epoch observing strategy. Spectral classifications are given for the massive emission-line stars observed by the survey, including the discovery of a new Wolf-Rayet star (VFTS 682, classified as WN5h), 2' to the northeast of R136. To illustrate the diversity of objects encompassed by the survey, we investigate the spectral properties of sixteen targets identified by Gruendl & Chu from Spitzer photometry as candidate young stellar objects or stars with notable mid-infrared excesses. Detailed spectral classification and quantitative analysis of the O- and B-type stars in the VFTS sample, paying particular attention to the effects of rotational mixing and binarity, will be presented in a series of future articles to address fundamental questions in both stellar and cluster evolution., Accepted by A&A, 52 pages (main body: 19 pages, supplementary tables: 33 pages), v3: two classifications updated to match a parallel paper
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- 2011
15. Ultra-deep sequencing of HIV-1 near full-length and partial proviral genomes from recently infected blood donors at four blood centers in Brazil
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Jaqueline Tomoko Watanabe, Anna Bárbara F. Carneiro-Proietti, Sabri Saeed Sanabani, Paula Loureiro, Ester C Sabin, Maria Esther Lopes, Michael P Busc, and Rodrigo Pessôa
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Veterinary medicine ,Blood donor ,Infectious Diseases ,Poster Presentation ,Human immunodeficiency virus (HIV) ,medicine ,Ultra deep sequencing ,Biology ,medicine.disease_cause ,Genome ,Proviral genome ,Blood bank ,Blood center - Abstract
Here, we aimed to gain a comprehensive picture of HIV-1 diversity in the north-east and south-east part of Brazil. To this end, a high-throughput sequencing was used to characterize the near full length (NFLG) and partial HIV-1 proviral genome in blood donors at four major blood centers in Brazil: Pro-Sangue foundation (Sao Paulo state (SP), n 48), Hemominas foundation (Minas Gerais state (MG), n 41), Hemope foundation (Recife state (PE), n 97) and Hemorio blood bank (Rio de Janeiro (RJ), n 90).
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16. What is the risk of mortality following diagnosis of multidrug-resistant HIV-1?
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D. Grover, A. Copas, H. Green, S. G. Edwards, D. T. Dunn, C. Sabin, A. Phillips, E. Allen, D. Pillay, and on behalf of the UK Collaborative Group on HIV Drug Resistance and UK Collaborative HIV Cohort Study
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MORTALITY ,HIV ,REGRESSION analysis ,IMMUNE response - Abstract
: Objectives To estimate the risk of death and examine the predictors of death and virological/immunological response, following diagnosis of multidrug-resistant (MDR) HIV-1 in a UK multicentre cohort of HIV-infected individuals. : Methods Five hundred and seventy-two patients were identified with MDR HIV-1 between 1997 and 2004. Factors associated with survival and virological/immunological response 24–48 weeks after MDR diagnosis were determined by the Poisson and linear regression, respectively. : Results Patient characteristics: 86% males; median age 39 years; median CD4 and viral load (VL) at MDR diagnosis 230 cells/mm3 and 4.2 log
10 copies/mL; median number of antiretroviral drugs previously exposed to 8. Sixty patients died over a median follow-up of 31 months (IQR: 17–50), giving an estimated mortality rate of 3.7 deaths per 100 person-years (95% CI 2.9–4.7) following MDR diagnosis. In adjusted analysis, higher CD4 count, lower VL, more recent calendar year, lower number of antiretroviral drugs previously exposed to and greater age at MDR diagnosis were associated with an increased chance of survival. There was some evidence of a better virological response at 24–48 weeks after MDR diagnosis in patients who changed regimen compared with patients who did not change regimen. : Conclusions The risk of death following MDR diagnosis may be at least 3-fold the risk observed overall in HIV-infected individuals. Changing antiretroviral therapy following emergence of MDR HIV-1 may be associated with improved short-term virological response. [ABSTRACT FROM AUTHOR]- Published
- 2008
17. CROI 2024 BHIVA working group summary.
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Barber TJ, Clarke A, Fox A, Mackie NE, Sabin C, and Waters LJ
- Abstract
The Conference on Retroviruses and Opportunistic Infections (CROI) is usually the most significant HIV conference of the year in terms of basic and clinical scientific output. CROI 2024 in Denver, USA, felt very much back to 'business as usual' following COVID-19 disruptions that had impacted preceding years, but also felt more global and outward- facing. The British HIV Association supports a working group to attend CROI annually and deliver feedback in the UK. This article summarizes the highlights from that meeting., (© 2024 British HIV Association.)
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- 2024
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18. Results from a retrospective case finding and re-engagement exercise for people previously diagnosed with hepatitis C virus to increase uptake of directly acting antiviral treatment.
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Etoori D, Simmons R, Desai M, Foster GR, Stuart A, Sabin C, Mandal S, and Rosenberg W
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- Humans, Male, Female, Middle Aged, Retrospective Studies, Adult, England epidemiology, Hepatitis C drug therapy, Hepatitis C diagnosis, Aged, Patient Acceptance of Health Care statistics & numerical data, Hepacivirus isolation & purification, Antiviral Agents therapeutic use
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Background: Direct acting antivirals (DAAs) for the Hepatitis C virus (HCV) have shifted the World Health Organisation global strategic focus to the elimination of HCV by 2030. In England, the UK Health Security Agency (UKHSA) led a national 'patient re-engagement exercise', using routine surveillance data, which was delivered through the HCV Operational Delivery Networks (ODNs) with support from National Health Service England (NHSE), to help find and support people with a positive HCV PCR test result to access treatment. We report a quantitative evaluation of outcomes of this exercise., Methods: Individuals with a recorded positive HCV antibody or PCR result between 1996 and 2017 were identified using UKHSA's records of HCV laboratory diagnosis. Linkage with established health-care datasets helped to enhance patient identification and minimise attempts to contact deceased or previously treated individuals. From September to November 2018 each ODN was provided with a local list of diagnosed individuals. ODNs were asked to perform further data quality checks through local systems and then write to each individual's GP to inform them that the individual would be contacted by the ODN to offer confirmatory HCV PCR testing, assessment and treatment unless the GP advised otherwise. Outcomes of interest were receipt of treatment, a negative PCR result, and death. Data were collected in 2022., Results: Of 176,555 individuals with a positive HCV laboratory report, 55,329 individuals were included in the exercise following linkage to healthcare datasets and data reconciliation. Participants in the study had a median age of 51 years (IQR: 43, 59), 36,779 (66.5%) were males, 47,668 (86.2%) were diagnosed before 2016 and 11,148 (20.2%) lived in London. Of the study population, 7,442 (13.4%) had evidence of treatment after the re-engagement exercise commenced, 6,435 (11.6%) were reported as PCR negative (96% had no previous treatment records), 4,195 (7.6%) had prescription data indicating treatment before the exercise commenced or were reported to have been treated previously by their ODN, and 2,990 (5.4%) had died. The status of 32,802 (59.3%) people remains unknown., Conclusions: A substantial number of those included had treatment recorded after the exercise commenced, however, many more remain unengaged. Evaluation of the exercise highlighted areas that could be streamlined to improve future exercises., (© 2024. The Author(s).)
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- 2024
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19. Seroprevalence of immunity to hepatitis A and hepatitis B among gay, bisexual and other men who have sex with men (GBMSM) attending sexual health clinics in London and Leeds, England, 2017-2018.
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Roche R, Simmons R, Allen H, Glancy M, Balan AM, Bolea M, Harris R, Desai M, Mohammed H, Sabin C, Ijaz S, and Mandal S
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- Humans, Male, Seroepidemiologic Studies, Adult, England epidemiology, London epidemiology, Middle Aged, Young Adult, Adolescent, Sexual and Gender Minorities statistics & numerical data, Hepatitis B Antibodies blood, Ambulatory Care Facilities statistics & numerical data, Sexual Health, Immunoglobulin G blood, Hepatitis A epidemiology, Hepatitis A immunology, Hepatitis B epidemiology, Hepatitis B immunology, Homosexuality, Male statistics & numerical data
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Objectives: Although hepatitis A virus (HAV) and hepatitis B virus (HBV) immunisation is recommended in the UK for gay, bisexual and other men who have sex with men (GBMSM), data on immunisation coverage are limited. We aimed to determine the seroprevalence of HAV and HBV immunity among a sample of GBMSM attending sexual health services (SHS) in England., Methods: Residual serum samples from HIV/syphilis testing for adult GBMSM attending eight SHS in London and one in Leeds were tested for markers of HAV immunity (HAV IgG) and HBV immunity (anti-HBs) using an unlinked anonymous approach. We estimated seroprevalence of HAV and HBV immunity overall and stratified by individuals' characteristics, which we obtained from the Genitourinary Medicine Clinic Activity Dataset Sexually Transmitted Infection (STI) Surveillance System. We used logistic regression to calculate crude and adjusted ORs between seropositivity and demographic and clinical characteristics., Results: Seroprevalence of immunity to HAV (74.5% of 2577) and HBV (77.1% of 2551) was high. In adjusted analysis, HAV IgG seroprevalence varied by clinic and WHO region of birth (global p<0.001 for each), increased with older age (ORs of 1.50 (95% CI 1.18 to 1.86), 2.91 (2.17 to 3.90) and 3.40 (2.44 to 4.75) for ages 26-35, 36-45 and >46 vs 18-25 years (global p<0.001), was higher in those with an STI in the past year (1.58 (1.25 to 2.00); p<0.001) and those who were living with HIV (1.82 (1.25 to 2.64); p<0.001). Anti-HBs seroprevalence varied by clinic (global p<0.001), increased with older age (global p<0.001) and was higher in those with an STI in the past year (1.61 (1.27 to 2.05); p<0.001)., Conclusion: Our findings provide a baseline seroprevalence from which to monitor serial levels of immunity to HBV and HAV in GBMSM accessing SHS. Levels of immunity for both viruses are high, noting samples were taken after recent widespread outbreaks and vaccination campaigns. High vaccine coverage in all GBMSM should be maintained to prevent further outbreaks., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)
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- 2024
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20. Trends in mortality in people with HIV from 1999 to 2020: a multi-cohort collaboration.
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Tusch E, Ryom L, Pelchen-Matthews A, Mocroft A, Elbirt D, Oprea C, Günthard HF, Staehelin C, Zangerle R, Suarez I, Vehreschild JJ, Wit F, Menozzi M, d'Arminio Monforte A, Spagnuolo V, Pradier C, Carlander C, Suanzes P, Wasmuth JC, Carr A, Petoumenos K, Borgans F, Bonnet F, De Wit S, El-Sadr W, Neesgaard B, Jaschinski N, Greenberg L, Hosein SR, Gallant J, Vannappagari V, Young L, Sabin C, Lundgren J, Peters L, and Reekie J
- Abstract
Background: Mortality among people with HIV declined with the introduction of combination antiretroviral therapy. We investigated trends over time in all-cause and cause-specific mortality in people with HIV from 1999-2020., Methods: Data were collected from the D:A:D cohort from 1999 through January 2015 and RESPOND from October 2017 through 2020. Age-standardized all-cause and cause-specific mortality rates, classified using Coding Causes of Death in HIV (CoDe), were calculated. Poisson regression models were used to assess mortality trends over time., Results: Among 55716 participants followed for a median of 6 years (IQR 3-11), 5263 participants died (crude mortality rate [MR] 13.7/1000 PYFU; 95%CI 13.4-14.1). Changing patterns of mortality were observed with AIDS as the most common cause of death between 1999- 2009 (n = 952, MR 4.2/1000 PYFU; 95%CI 4.0-4.5) and non-AIDS defining malignancy (NADM) from 2010 -2020 (n = 444, MR 2.8/1000 PYFU; 95%CI 2.5-3.1). In multivariable analysis, all-cause mortality declined over time (adjusted mortality rate ratio [aMRR] 0.97 per year; 95%CI 0.96, 0.98), mostly from 1999 through 2010 (aMRR 0.96 per year; 95%CI 0.95-0.97), and with no decline shown from 2011 through 2020 (aMRR 1·00 per year; 95%CI 0·96-1·05). Mortality due all known causes except NADM also declined over the entire follow-up period., Conclusion: Mortality among people with HIV in the D:A:D and/or RESPOND cohorts decreased between 1999 and 2009 and was stable over the period from 2010 through 2020. The decline in mortality rates was not fully explained by improvements in immunologic-virologic status or other risk factors., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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21. Priorities for HIV and chronic pain research: results from a survey of individuals with lived experience.
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Robinson-Papp J, Lawrence S, Wadley A, Scott W, George MC, Josh J, O'Brien KK, Price C, Uebelacker L, Edelman EJ, Evangeli M, Goodin BR, Harding R, Nkhoma K, Parker R, Sabin C, Slawek D, Tsui JI, and Merlin JS
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The Global Task Force on Chronic Pain in HIV published seven research priorities in the field of HIV-associated chronic pain in 2019: (1) causes; (2) management; (3) treatment individualization and integration with addiction treatment; (4) mental and social health factors; (5) prevalence; (6) treatment cost effectiveness; and (7) prevention. The current study used a web-based survey to determine whether the research topics were aligned with the priorities of adults with lived experiences of HIV and chronic pain. We also collected information about respondents' own pain and treatment experiences. We received 311 survey responses from mostly US-based respondents. Most respondents reported longstanding, moderate to severe, multisite pain, commonly accompanied by symptoms of anxiety and/or depression. The median number of pain treatments tried was 10 (IQR = 8, 13), with medications and exercise being the most common modalities, and opioids being viewed as the most helpful. Over 80% of respondents considered all research topics either "extremely important" or "very important". Research topic #2, which focused on optimizing management of pain in people with HIV, was accorded the greatest importance by respondents. These findings suggest good alignment between the priorities of researchers and US-based people with lived experience of HIV-associated chronic pain.
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- 2024
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22. Evolution of CD4 T-Cell Count With Age in a Cohort of Young People Growing Up With Perinatally Acquired Human Immunodeficiency Virus.
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Castro H, Sabin C, Collins IJ, Okhai H, Schou Sandgaard K, Prime K, Foster C, Le Prevost M, Crichton S, Klein N, and Judd A
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- Adolescent, Child, Female, Humans, Male, Young Adult, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, HIV, Viral Load, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV Infections epidemiology
- Abstract
Background: Recent studies have shown a decrease in CD4 count during adolescence in young people with perinatally acquired human immunodeficiency virus (HIV, PHIV)., Methods: Young people with PHIV in the United Kingdom, followed in the Collaborative HIV Paediatric Study who started antiretroviral therapy (ART) from 2000 onward were included. Changes in CD4 count over time from age 10 to 20 years were analyzed using mixed-effects models, and were compared to published CD4 data for the gerneral population. Potential predictors were examined and included demographics, age at ART start, nadir CD4 z score (age-adjusted) in childhood, and time-updated viral load., Results: Of 1258 young people with PHIV included, 669 (53%) were female, median age at ART initiation was 8.3 years, and the median nadir CD4 z score was -4.0. Mean CD4 count was higher in young people with PHIV who started ART before age 10 years and had a nadir CD4 z score ≥-4; these young people with PHIV had a decline in CD4 count after age 10 that was comparable to that of the general population. Mean CD4 count was lower in young people with PHIV who had started ART before age 10 and had a nadir CD4 z score <-4; for this group, the decline in CD4 count after age 10 was steeper over time., Conclusions: In children, in addition to starting ART at an early age, optimizing ART to maintain a higher CD4 z score during childhood may be important to maximizing immune reconstitution later in life., Competing Interests: Potential conflicts of interest. C. S. reports funding for membership on data and safety and monitoring boards advisory boards and for preparation of educational materials from Gilead Sciences, ViiV Healthcare, and MSD and a role as vice-chair (until the end of 2022) for the British HIV Association. C. F. reports research grants from ViiV Healthcare and Gilead Sciences. H. O. reports consulting fees to author from Gilead Sciences. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2024
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23. Experiences of mpox illness and case management among cis and trans gay, bisexual and other men who have sex with men in England: a qualitative study.
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Witzel TC, Ghobrial A, Palich R, Charles H, Rodger AJ, Sabin C, Sparrowhawk A, Pool ERM, Prochazka M, Vivancos R, Sinka K, Folkard K, Burns FM, and Saunders J
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Background: The 2022-2024 global mpox outbreak, occurring primarily in the sexual networks of gay, bisexual and other men who have sex with men (GBMSM), has not been accompanied by a focus on patient perspectives of illness. We explore the experiences of GBMSM diagnosed with mpox in England to understand needs for social and clinical support., Methods: In-depth interviews (March/July 2023) were conducted with 22 GBMSM diagnosed with mpox in 2022, randomly selected from a national mpox surveillance database, and 4 stakeholders from clinical/community-based organisations. Interviews covered experiences of illness, testing, diagnosis, treatment and contact tracing, and were recorded, transcribed and analysed with a thematic framework., Findings: Media coverage drawing on homophobic stereotypes around sex between men contributed to feelings of stigma and shame. GBMSM living with HIV appeared to cope better with mpox stigma, drawing on their experiences of being diagnosed with HIV for resilience. Younger GBMSM with less experience of stigmatising illness found mpox diagnosis more traumatic and sometimes required support beyond what was provided. Accessing testing could be complicated when healthcare professionals did not recognise mpox symptoms. Men felt information on course of illness, isolation and vaccination after recovery was often inconsistent and contradictory. GBMSM described that care from sexual health and infectious disease units usually better met their emotional and medical needs. This was frequently linked by men to these services having skills in working with the GBMSM community and managing infection risk sensitively. General hospital services and centralised contact tracing could increase feelings and experiences of stigma as some staff were perceived to lack skills in supporting GBMSM and, sometimes, clinical knowledge. Long-term impacts described by men included mental health challenges, urethral/rectal symptoms and life-changing disability., Interpretation: In this study stigma was a central feature of mpox illness among GBMSM and could be exacerbated or lessened depending on the clinical and social support provided. Involving communities affected by outbreaks in co-producing, planning and delivering care (including contact-tracing) may help improve support provided., Funding: TCW, AJR, AS and FMB received support from the National Institute for Health and Care Research (NIHR) under its Programme Grants for Applied Research Programme (Ref: NIHR202038). CS and JS receive support from the National Institute for Health and Care Research Health Protection Research Unit (NIHR HPRU) in Blood Borne and Sexually Transmitted Infections at UCL in partnership with UKHSA; RV receives support from the NIHR HPRU in Emerging and Zoonotic Infections and NIHR HPRU in Gastrointestinal Infections. The views expressed are those of the author(s) and not necessarily those of the NIHR, UK Health Security Agency, World Health Organization or the Department of Health and Social Care., Competing Interests: TCW reports grant funding from the Wellcome Trust, NIHR and the European Union Horizon 2020. TCW and CS report honoraria for preparing educational materials from Gilead Sciences. CS reports honoraria for preparing education and presentation materials from ViiV healthcare., (© 2024 The Author(s).)
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- 2024
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24. Facilitators and barriers to community pharmacy PrEP delivery: a scoping review.
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Harrison C, Family H, Kesten J, Denford S, Scott A, Dawson S, Scott J, Sabin C, Copping J, Harryman L, Cochrane S, and Horwood J
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- Humans, United States, Motivation, Income, Pharmacies, HIV Infections prevention & control, HIV Infections drug therapy, Anti-HIV Agents therapeutic use
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Introduction: Pre-exposure prophylaxis (PrEP) is an effective medication to reduce the risk of acquiring HIV. PrEP is available free of charge in the UK from sexual health clinics. Expanding PrEP delivery to community pharmacies holds promise and aligns with UK government goals to eliminate new cases of HIV by 2030. The aim of this scoping review was to describe the existing evidence about the barriers to and facilitators of community pharmacy oral PrEP delivery, for pharmacists and pharmacy clients, as aligned with the Capacity Opportunity, Motivation Behaviour (COM-B) Model., Methods: Five bibliographic and five review databases were searched from inception to August 2023. Literature of any study design was included if it discussed barriers and facilitators of community pharmacy PrEP delivery. Trial registrations, protocols and news articles were excluded., Results: A total of 649 records were identified, 73 full texts were reviewed and 56 met the inclusion criteria, predominantly from high-income/westernized settings. Most of the included literature was original research (55%), from the United States (77%) conducted during or after the year 2020 (63%). Barriers to PrEP delivery for pharmacists included lack of knowledge, training and skills (capability), not having the necessary facilities (opportunity), concern about the costs of PrEP and believing that PrEP use could lead to risk behaviours and sexually transmitted infections (motivation). Facilitators included staff training (capability), time, the right facilities (opportunity), believing PrEP could be a source of profit and could reduce new HIV acquisitions (motivation). For clients, barriers included a lack of PrEP awareness (capability), pharmacy facilities (opportunity) and not considering pharmacists as healthcare providers (motivation). Facilitators included awareness of PrEP and pharmacist's training to deliver it (capability), the accessibility of pharmacies (opportunity) and having an interest in PrEP (motivation)., Discussion: To effectively enhance oral PrEP delivery in UK community pharmacies, the identified barriers and facilitators should be explored for UK relevance, addressed and leveraged at the pharmacy team, client and care pathway level., Conclusions: By comprehensively considering all aspects of the COM-B framework, community pharmacies could become crucial providers in expanding PrEP accessibility, contributing significantly to HIV prevention efforts., (© 2024 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)
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- 2024
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25. Humoral Immune Responses after an Omicron-Adapted Booster BNT162b2 Vaccination in Patients with Lymphoid Malignancies.
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Heftdal LD, Hansen CB, Hamm SR, Pérez-Alós L, Fogh K, Pries-Heje M, Hasselbalch RB, Møller DL, Gang AO, Ostrowski SR, Frikke-Schmidt R, Sørensen E, Hilsted L, Bundgaard H, Garred P, Iversen K, Sabin C, Nielsen SD, and Grønbæk K
- Subjects
- Humans, BNT162 Vaccine, Immunity, Humoral, Vaccination, Antibodies, Neutralizing, Immunoglobulin G, Antibodies, Viral, COVID-19 Vaccines, Leukemia, Lymphocytic, Chronic, B-Cell
- Abstract
To accommodate waning COVID-19 vaccine immunity to emerging SARS-CoV-2 variants, variant-adapted mRNA vaccines have been introduced. Here, we examine serological responses to the BA.1 and BA.4-5 Omicron variant-adapted BNT162b2 COVID-19 vaccines in people with lymphoid malignancies. We included 233 patients with lymphoid malignancies (chronic lymphocytic B-cell leukemia: 73 (31.3%), lymphoma: 89 (38.2%), multiple myeloma/amyloidosis: 71 (30.5%)), who received an Omicron-adapted mRNA-based COVID-19 vaccine. IgG and neutralizing antibodies specific for the receptor-binding domain (RBD) of SARS-CoV-2 were measured using ELISA-based methods. Differences in antibody concentrations and neutralizing capacity and associations with risk factors were assessed using mixed-effects models. Over the period of vaccination with an Omicron-adapted COVID-19 vaccine, the predicted mean concentration of anti-RBD IgG increased by 0.09 log10 AU/mL/month (95% CI: 0.07; 0.11) in patients with lymphoid malignancies across diagnoses. The predicted mean neutralizing capacity increased by 0.9 percent points/month (95% CI: 0.2; 1.6). We found no associations between the increase in antibody concentration or neutralizing capacity and the variant included in the adapted vaccine. In conclusion, a discrete increase in antibody concentrations and neutralizing capacity was found over the course of Omicron-adapted vaccination in patients with lymphoid malignancies regardless of the adapted vaccine variant, indicating a beneficial effect of Omicron-adapted booster vaccination in this population.
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- 2023
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26. Retrospective cohort study assessing coverage, uptake and associations with hepatitis B vaccination among females who engage in sex work attending sexual health services in England between 2015 and 2019.
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Hibbert M, Simmons R, Ratna N, Mandal S, Sabin C, Desai M, and Mohammed H
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- Humans, Female, Adult, Male, Sex Work, Retrospective Studies, Hepatitis B virus, England epidemiology, Vaccination, World Health Organization, Hepatitis B Vaccines, Hepatitis B epidemiology, Hepatitis B prevention & control
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Objectives: Females who engage in sex work (FSW) are at high risk of hepatitis B virus (HBV) and are eligible for HBV vaccination. The objective of this analysis was to explore coverage, uptake and correlates of HBV vaccination among FSW who attend sexual health services (SHS) in England., Methods: Data on all attendances at SHS in England were obtained from the GUMCAD STI Surveillance System. Attendees were eligible for inclusion if they were female, had not been previously diagnosed with HIV and sex work was recorded between 2015 and 2019. Bivariable and multivariable logistic regression models were used to investigate sociodemographic factors (age, ethnicity, region of birth and region of residence) associated with having received an HBV vaccination on or after an attendance where sex work was reported., Results: There were 13 769 FSW attending SHS in England between 2015 and 2019 (median age 30 years, 71% white ethnicity). HBV vaccination coverage was 37% (n=5050/13 751, 95% CI 35.9%-37.5%). Among those that first reported sex work between 2015 and 2019, HBV vaccination uptake was 30% (n=3249/10 681, 95% CI 29.6%-31.3%). In multivariable analyses, HBV vaccination uptake was associated with younger age (5-year increase: OR=0.87, 95% CI 0.85, 0.89) and being born in South America (37%, adjusted OR (aOR)=1.40, 95% CI 1.18, 1.66) compared with being born in the UK. Being of Asian ethnicity (19%, aOR=0.63, 95% CI 0.45, 0.89) compared with white ethnicity was associated with reduced odds of HBV vaccination. Sixteen FSW were diagnosed with HBV after their first attendance where sex work was recorded., Conclusions: To achieve the WHO goals of elimination of HBV as a public health threat by the year 2030, further research is needed to understand the individual and structural barriers to the offering and uptake of HBV vaccination among FSW, as well as using health promotion methods to improve uptake., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2023
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27. "I have failed to separate my HIV from this pain": the challenge of managing chronic pain among people with HIV.
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Baker V, Nkhoma K, Trevelion R, Roach A, Winston A, Sabin C, Bristowe K, and Harding R
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- Male, Humans, Female, Homosexuality, Male, Pain Management, Quality of Life, Chronic Pain therapy, HIV Infections complications, HIV Infections therapy, HIV Infections diagnosis, Sexual and Gender Minorities
- Abstract
Pain is a highly prevalent and burdensome symptom among people with HIV (PWH). This study aims to identify how the experience of living with HIV and chronic pain influences pain beliefs, health-seeking and pain management. Thirty-nine purposively sampled PWH with chronic pain (sample characteristics = 61% women, 79% Black, Asian and minority ethnic groups, 18% men who have sex with men, 45-54 median age category) participated in focus groups in London. Focus groups were co-facilitated with community members. Transcripts wereanalysed using a thematic approach. Findings revealed that HIV stigma, fractured care pathways, and general practitioners' lack of HIV training are barriers to supported pain management. Unaddressed pain results in poorer mental health and reduced quality of life, which has important clinical implications for HIV treatment adherence. Creating HIV-specific pain resources, activating social networks, and pain self-management techniques are potential solutions. Person-centred assessment and HIV training is needed to help clinicians identify PWH with chronic pain. Clear guidelines need to be developed to identify which health service providers are responsible for chronic pain management in PWH. This study generated a refined version of the Fear Avoidance Model that introduces a dimension of HIV-specific behaviours that impact PWHs seeking chronic pain management.
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- 2023
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28. Trends in Cancer Incidence in Different Antiretroviral Treatment-Eras amongst People with HIV.
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Greenberg L, Ryom L, Bakowska E, Wit F, Bucher HC, Braun DL, Phillips A, Sabin C, d'Arminio Monforte A, Zangerle R, Smith C, De Wit S, Bonnet F, Pradier C, Mussini C, Muccini C, Vehreschild JJ, Hoy J, Svedhem V, Miró JM, Wasmuth JC, Reiss P, Llibre JM, Chkhartishvili N, Stephan C, Hatleberg CI, Neesgaard B, Peters L, Jaschinski N, Dedes N, Kuzovatova E, Van Der Valk M, Menozzi M, Lehmann C, Petoumenos K, Garges H, Rooney J, Young L, Lundgren JD, Bansi-Matharu L, Mocroft A, and On Behalf Of The Respond And D A D Study Groups
- Abstract
Despite cancer being a leading comorbidity amongst individuals with HIV, there are limited data assessing cancer trends across different antiretroviral therapy (ART)-eras. We calculated age-standardised cancer incidence rates (IRs) from 2006-2021 in two international cohort collaborations (D:A:D and RESPOND). Poisson regression was used to assess temporal trends, adjusted for potential confounders. Amongst 64,937 individuals (31% ART-naïve at baseline) and 490,376 total person-years of follow-up (PYFU), there were 3763 incident cancers (IR 7.7/1000 PYFU [95% CI 7.4, 7.9]): 950 AIDS-defining cancers (ADCs), 2813 non-ADCs, 1677 infection-related cancers, 1372 smoking-related cancers, and 719 BMI-related cancers (groups were not mutually exclusive). Age-standardised IRs for overall cancer remained fairly constant over time (8.22/1000 PYFU [7.52, 8.97] in 2006-2007, 7.54 [6.59, 8.59] in 2020-2021). The incidence of ADCs (3.23 [2.79, 3.72], 0.99 [0.67, 1.42]) and infection-related cancers (4.83 [4.2, 5.41], 2.43 [1.90, 3.05]) decreased over time, whilst the incidence of non-ADCs (4.99 [4.44, 5.58], 6.55 [5.67, 7.53]), smoking-related cancers (2.38 [2.01, 2.79], 3.25 [2.63-3.96]), and BMI-related cancers (1.07 [0.83, 1.37], 1.88 [1.42, 2.44]) increased. Trends were similar after adjusting for demographics, comorbidities, HIV-related factors, and ART use. These results highlight the need for better prevention strategies to reduce the incidence of NADCs, smoking-, and BMI-related cancers.
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- 2023
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29. Early Antiretroviral Therapy Not Associated With Higher Cryptococcal Meningitis Mortality in People With Human Immunodeficiency Virus in High-Income Countries: An International Collaborative Cohort Study.
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Ingle SM, Miro JM, May MT, Cain LE, Schwimmer C, Zangerle R, Sambatakou H, Cazanave C, Reiss P, Brandes V, Bucher HC, Sabin C, Vidal F, Obel N, Mocroft A, Wittkop L, d'Arminio Monforte A, Torti C, Mussini C, Furrer H, Konopnicki D, Teira R, Saag MS, Crane HM, Moore RD, Jacobson JM, Mathews WC, Geng E, Eron JJ, Althoff KN, Kroch A, Lang R, Gill MJ, and Sterne JAC
- Subjects
- Male, Humans, Adult, Female, HIV, Developed Countries, Anti-Retroviral Agents therapeutic use, Cohort Studies, CD4 Lymphocyte Count, Meningitis, Cryptococcal complications, HIV Infections complications, HIV Infections drug therapy
- Abstract
Background: Randomized controlled trials (RCTs) from low- and middle-income settings suggested that early initiation of antiretroviral therapy (ART) leads to higher mortality rates among people with HIV (PWH) who present with cryptococcal meningitis (CM). There is limited information about the impact of ART timing on mortality rates in similar people in high-income settings., Methods: Data on ART-naive PWH with CM diagnosed from 1994 to 2012 from Europe/North America were pooled from the COHERE, NA-ACCORD, and CNICS HIV cohort collaborations. Follow-up was considered to span from the date of CM diagnosis to earliest of the following: death, last follow-up, or 6 months. We used marginal structural models to mimic an RCT comparing the effects of early (within 14 days of CM) and late (14-56 days after CM) ART on all-cause mortality, adjusting for potential confounders., Results: Of 190 participants identified, 33 (17%) died within 6 months. At CM diagnosis, their median age (interquartile range) was 38 (33-44) years; the median CD4+ T-cell count, 19/μL (10-56/μL); and median HIV viral load, 5.3 (4.9-5.6) log10 copies/mL. Most participants (n = 157 [83%]) were male, and 145 (76%) started ART. Mimicking an RCT, with 190 people in each group, there were 13 deaths among participants with an early ART regimen and 20 deaths among those with a late ART regimen. The crude and adjusted hazard ratios comparing late with early ART were 1.28 (95% confidence interval, .64-2.56) and 1.40 (.66-2.95), respectively., Conclusions: We found little evidence that early ART was associated with higher mortality rates among PWH presenting with CM in high-income settings, although confidence intervals were wide., Competing Interests: Potential conflicts of interest. J. M. M. has received consulting honoraria and/or research grants from AbbVie, Angelini, Contrafect, Cubist, Genentech, Gilead Sciences, Jansen, Medtronic, MSD, Novartis, Pfizer, and ViiV Healthcare, outside the submitted work, as well as consulting fees from Lysovant. L. E. C. has stock or stock options and is an employee of AbbVie. C. Sabin reports payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing, or educational events from Gilead Sciences and ViiV Healthcare (payments to the author for preparation of educational materials); participation on a data and safety monitoring board (DSMB) or advisory board for Gilead Sciences and ViiV Healthcare (paid to the author); and service as vice chair of the British HIV Association. H. S. reports consulting fees from ViiV and MSD and payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing or educational events from MSD, ViiV, and Gilead. P. R., through his institution, has received independent scientific grant support from Gilead Sciences, Janssen Pharmaceuticals, Merck, and ViiV Healthcare and has served on scientific advisory boards for Gilead Sciences, ViiV Healthcare, and Merck, honoraria for which were all paid to his institution (all support outside the submitted work). V. B. reports support for attending meetings and/or travel from Gilead and Janssen and has stock or stock options in DWS Biotech LC Fond (private self-investment; no payments to author or institution received from any third party). F. V. received research or teaching grants from Gilead Sciences, ViiV Healthcare, and MSD, unrelated to the submitted work. N. O. reports grants or contracts from Simonsens Fond (paid to the institution). A. M. reports travel support, lecture fees, honorarium and consultancy fees from ViiV, Gilead, Eiland, and Bonnin, all outside the submitted work. L. W. reports grants or contracts from ANRS MIE. R. T. reports a research grant from Gilead Science; payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing, or educational events from Gilead Science (payment for lectures), Janssen (payment for lectures), and ViiV Healthcare (payment for lectures); support for travel from Gilead Science and Janssen; and participation on an advisory board for Gilead Science. A. D. M. reports consulting fees from ViiV, Gilead, and Janssen (paid to the author); payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing or educational events from Gilead and ViiV (paid to the author); and participation on a DSMB or advisory board for Janssen, Gilead, and ViiV (payment to the author). C. M. reports research grant from Gilead; payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing, or educational events from ViiV and Gilead; and participation on a DSMB or advisory board for Corimuno, Gilead, ViiV, Janssen, and MSD. H. F.’s institution received educational grants from AbbVie, ViiV, Gilead, MSD, Sandoz, and Pfizer, all outside the submitted work. M. S. S. reports research grants from Gilead Sciences and ViiV Healthcare (paid to the institution); payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing; or educational events from IAS-USA (not-for-profit organization); serving on the DSMB for the I-Spy COVID trial; and serving as board chair for IAS-USA. H. M. C. reports grants or contracts from the National Institutes of Health (NIH), the Agency for Healthcare Research and Quality, and ViiV (paid to institution); consulting fees from ViiV (pending); and participation on the Office of AIDS Research Scientific Advisory Board. J. J. E. reports grants or contracts from ViiV Healthcare, Gilead Sciences, and Janssen; consulting fees from Merck, ViiV Healthcare, Gilead Science, and Janssen; and leadership or fiduciary roles in other boards, societies, committees, or advocacy groups for the IAS-USA antiretroviral therapy guidelines committee. K. N. A. reports grants or contracts from the NIH (paid to institution), royalties or licenses from Coursera, consulting fees from the NIH (for the All of US Study), and payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing, or educational events for DC HIV Cohort (author served on the DC HIV Cohort’s external advisory board). M. J. G. reports consulting fees from Merck, Gilead, and ViiV (with occasional honoraria for ad hoc membership on human immunodeficiency virus advisory boards). H. C. B., in the 36 months before the submission of the current manuscript, has received grants, support for traveling, consultancy fees, and honoraria from Gilead, BMS, ViiV Healthcare, Roche, and Pfizer, unrelated to the current work. He served as the president of the Association Contre le HIV et Autres Infections Transmissibles until June 2022; in this function he received support for the Swiss HIV Cohort Study from ViiV Healthcare, Gilead, BMS, and MSD. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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30. Humoral and cellular immune responses eleven months after the third dose of BNT162b2 an mRNA-based COVID-19 vaccine in people with HIV - a prospective observational cohort study.
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Heftdal LD, Pérez-Alós L, Hasselbalch RB, Hansen CB, Hamm SR, Møller DL, Pries-Heje M, Fogh K, Gerstoft J, Grønbæk K, Ostrowski SR, Frikke-Schmidt R, Sørensen E, Hilsted L, Bundgaard H, Garred P, Iversen K, Sabin C, and Nielsen SD
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- Humans, BNT162 Vaccine, COVID-19 Vaccines, Prospective Studies, SARS-CoV-2, Immunoglobulin G, Interferon-gamma, Antibodies, Viral, RNA, Messenger, COVID-19 prevention & control, HIV Infections
- Abstract
Background: We investigated long-term durability of humoral and cellular immune responses to third dose of BNT162b2 in people with HIV (PWH) and controls., Methods: In 378 PWH with undetectable viral replication and 224 matched controls vaccinated with three doses of BNT162b2, we measured IgG-antibodies against the receptor binding domain of SARS-CoV-2 spike protein three months before third dose of BNT162b2, and four and eleven months after. In 178 PWH and 135 controls, the cellular response was assessed by interferon-γ (IFN-γ) release in whole blood four months after third dose. Differences in antibody or IFN-γ concentrations were assessed by uni- and multivariable linear regressions., Findings: Before the third dose the concentration of SARS-CoV-2 antibodies was lower in PWH than in controls (unadjusted geometric mean ratio (GMR): 0.68 (95% CI: 0.54-0.86, p = 0.002). We observed no differences in antibody concentrations between PWH and controls after four (0.90 (95% CI: 0.75-1.09), p = 0.285) or eleven months (0.89 (95% CI: 0.69-1.14), p = 0.346) after the third dose. We found no difference in IFN-γ concentrations four months after the third dose between PWH and controls (1.06 (95% CI: 0.71-1.60), p = 0.767)., Interpretation: We found no differences in antibody concentrations or cellular response between PWH and controls up to eleven months after third dose of BNT162b2. Our findings indicate that PWH with undetectable viral replication and controls have comparable immune responses to three doses of the BNT162b2 vaccine., Funding: This work was funded by the Novo Nordisk Foundation (NFF205A0063505, NNF20SA0064201), the Carlsberg Foundation (CF20-476 0045), the Svend Andersen Research Foundation (SARF2021), and Bio- and Genome Bank Denmark., Competing Interests: Declaration of interests LDH, LP-A, RBH, CBH, SRH, DLM, KF, JG, KG, SRO, RF-S, ES, LH, PG, and KI declare no conflicts of interests concerning this manuscript. MP-H has received travel grants from the Augustinus Foundation, the William Demant Foundation, the Copenhagen University Research Foundation, and Familien Hede Nielsen’s Foundation. MP-H has further received an independent research grant form Dagmar Marshall’s Foundation. HB has received an unrestricted grant from Kirsten and Freddy Johannsen’s Fund. CS has received honoraria from Gilead, ViiV Healthcare, and MSD, and was vice-chair of the British HIV Association. SDN has received unrestricted grants from the Novo Nordisk Foundation, and Dr. Sofus Carl Emil Friis and Wife Olga Doris Friis Scholarship. SDN has further received honoraria from Gilead and MSD and has served on advisory boards for Gilead, MSD, and GSK., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
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31. CASCADE protocol: exploring current viral and host characteristics, measuring clinical and patient-reported outcomes, and understanding the lived experiences and needs of individuals with recently acquired HIV infection through a multicentre mixed-methods observational study in Europe and Canada.
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Ruiz-Burga E, Tariq S, Touloumi G, Gill J, Nicholls EJ, Sabin C, Mussini C, Meyer L, Volny Anne A, Carlander C, Grabar S, Jarrin I, Van der Valk M, Wittkop L, Spire B, Pantazis N, Burns FM, and Porter K
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- Humans, Canada, Europe, Patient Reported Outcome Measures, Observational Studies as Topic, Multicenter Studies as Topic, HIV Infections epidemiology, Acquired Immunodeficiency Syndrome prevention & control, Pre-Exposure Prophylaxis methods
- Abstract
Introduction: Despite the availability of pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART), 21 793 people were newly diagnosed with HIV in Europe in 2019. The Concerted action on seroconversion to AIDS and death in Europe study aims to understand current drivers of the HIV epidemic; factors associated with access to, and uptake of prevention methods and ART initiation; and the experiences, needs and outcomes of people with recently acquired HIV., Methods and Analysis: This longitudinal observational study is recruiting participants aged ≥16 years with documented laboratory evidence of HIV seroconversion from clinics in Canada and six European countries. We will analyse data from medical records, self-administered questionnaires, semistructured interviews and participatory photography. We will assess temporal trends in transmitted drug resistance and viral subtype and examine outcomes following early ART initiation. We will investigate patient-reported outcomes, well-being, and experiences of, knowledge of, and attitudes to HIV preventions, including PrEP. We will analyse qualitative data thematically and triangulate quantitative and qualitative findings. As patient public involvement is central to this work, we have convened a community advisory board (CAB) comprising people living with HIV., Ethics and Dissemination: All respective research ethics committees have approval for data to contribute to international collaborations. Written informed consent is required to take part. A dissemination strategy will be developed in collaboration with CAB and the scientific committee. It will include peer-reviewed publications, conference presentations and accessible summaries of findings on the study's website, social media and via community organisations., Competing Interests: Competing interests: The funders did not participate in the study design and will not intervene in its process, analysis or publication of the findings. ST has received speaker honoraria and consultancy fees from Gilead Sciences. CC has received speaker/moderator honoraria and advisory board fees from Gilead Sciences, GSK/ViiV and MSD as well as an unrestricted Gilead Sciences Nordic Fellowship Research Grant. CS has received funding from Gilead Sciences, ViiV Healthcare and Janssen-Cilag for participation in Advisory Boards, speaker panels and for preparation of educational materials. MVdV has received consultancies fees for participation in advisory boards and research grants from Gilead, MSD and ViiV all paid to his institution. FMB has received funding from Gilead Sciences Ltd for preparation and delivery of educational materials. IJ has received teaching fees from ViiV Healthcare and advisory fees from Gilead Sciences. GT has received research grants and advisory board fees from Gilead, all paid to her institution, and MJG has received honoraria for ad hoc participation in national Advisory boards of Gilead Merck and ViiV., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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32. Hepatitis B virus infection in general practice across England: An analysis of the Royal College of General Practitioners Research and Surveillance Centre real-world database.
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Geretti AM, Austin H, Villa G, Smith C, Sabin C, Tsang R, Sherlock J, Ferreira F, Byford R, Meza-Torres B, Whyte M, and de Lusignan S
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- Male, Pregnancy, Female, Humans, Hepatitis B virus, Homosexuality, Male, Risk Factors, Hepatitis B Surface Antigens, Seroepidemiologic Studies, England epidemiology, Prevalence, HIV Infections complications, General Practitioners, Sexual and Gender Minorities, Hepatitis B complications, General Practice
- Abstract
Objectives: We analyzed hepatitis B surface antigen (HBsAg) screening and seropositivity within a network of 419 general practices representative of all regions of England., Methods: Information was extracted using pseudonymized registration data. Predictors of HBsAg seropositivity were explored in models that considered age, gender, ethnicity, time at the current practice, practice location and associated deprivation index, and presence of nationally endorsed screen indicators including pregnancy, men who have sex with men (MSM), history of injecting drug use (IDU), close HBV contact or imprisonment, and diagnosis of blood-borne or sexually transmitted infections., Results: Among 6,975,119 individuals, 192,639 (2.8 %) had a screening record, including 3.6-38.6 % of those with a screen indicator, and 8065 (0.12 %) had a seropositive record. The odds of seropositivity were highest in London, in the most deprived neighborhoods, among minority ethnic groups, and in people with screen indicators. Seroprevalence exceeded 1 % in people from high-prevalence countries, MSM, close HBV contacts, and people with a history of IDU or a recorded diagnosis of HIV, HCV, or syphilis. Overall, 1989/8065 (24.7 %) had a recorded referral to specialist hepatitis care., Conclusions: In England, HBV infection is associated with poverty. There are unrealized opportunities to promote access to diagnosis and care for those affected., Competing Interests: Conflicts of interests AMG previously served as expert scientist for Roche Pharma Research and Early Development, which included research on the development of curative interventions for chronic HBV infection, and received funding in support of HBV biomarker research (through her institution) from Roche pRED and Roche Diagnostics. SdeL has received funding for vaccine-related research (through his institution) from AstraZeneca, GSK, Sanofi, Seqirus and Takeda (the GSK award relates to hepatitis related research); has been a member of influenza and COVID-19 advisory boards for AstraZeneca, Pfizer, Sanofi and Seqirus; and is Director of the Oxford-RCGP RSC as part of his academic post. HA, GV, CoS, CaS, RB, JS, FF, RB, BM-T and MW have no conflict of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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33. Direct Blockade of the Norovirus Histo-Blood Group Antigen Binding Pocket by Nanobodies.
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Kher G, Sabin C, Lun JH, Devant JM, Ruoff K, Koromyslova AD, von Itzstein M, Pancera M, and Hansman GS
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- Binding Sites drug effects, Cross Reactions, Thermodynamics, Crystallography, X-Ray, Protein Domains, Protein Binding, Models, Molecular, Blood Group Antigens chemistry, Blood Group Antigens metabolism, Norovirus drug effects, Norovirus metabolism, Single-Domain Antibodies chemistry, Single-Domain Antibodies pharmacology
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Noroviruses are the leading cause of outbreaks of acute gastroenteritis. These viruses usually interact with histo-blood group antigens (HBGAs), which are considered essential cofactors for norovirus infection. This study structurally characterizes nanobodies developed against the clinically important GII.4 and GII.17 noroviruses with a focus on the identification of novel nanobodies that efficiently block the HBGA binding site. Using X-ray crystallography, we have characterized nine different nanobodies that bound to the top, side, or bottom of the P domain. The eight nanobodies that bound to the top or side of the P domain were mainly genotype specific, while one nanobody that bound to the bottom cross-reacted against several genotypes and showed HBGA blocking potential. The four nanobodies that bound to the top of the P domain also inhibited HBGA binding, and structural analysis revealed that these nanobodies interacted with several GII.4 and GII.17 P domain residues that commonly engaged HBGAs. Moreover, these nanobody complementarity-determining regions (CDRs) extended completely into the cofactor pockets and would likely impede HBGA engagement. The atomic level information for these nanobodies and their corresponding binding sites provide a valuable template for the discovery of additional "designer" nanobodies. These next-generation nanobodies would be designed to target other important genotypes and variants, while maintaining cofactor interference. Finally, our results clearly demonstrate for the first time that nanobodies directly targeting the HBGA binding site can function as potent norovirus inhibitors. IMPORTANCE Human noroviruses are highly contagious and a major problem in closed institutions, such as schools, hospitals, and cruise ships. Reducing norovirus infections is challenging on multiple levels and includes the frequent emergence of antigenic variants, which complicates designing effective, broadly reactive capsid therapeutics. We successfully developed and characterized four norovirus nanobodies that bound at the HBGA pockets. Compared with previously developed norovirus nanobodies that inhibited HBGA through disrupted particle stability, these four novel nanobodies directly inhibited HBGA engagement and interacted with HBGA binding residues. Importantly, these new nanobodies specifically target two genotypes that have caused the majority of outbreaks worldwide and consequently would have an enormous benefit if they could be further developed as norovirus therapeutics. To date, we have structurally characterized 16 different GII nanobody complexes, a number of which block HBGA binding. These structural data could be used to design multivalent nanobody constructs with improved inhibition properties.
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34. Recommendations for defining preventable HIV-related mortality for public health monitoring in the era of Getting to Zero: an expert consensus.
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Croxford SE, Martin V, Lucas SB, Miller RF, Post FA, Anderson J, Apea VJ, Asboe D, Brough G, Chadwick DR, Collins S, Corkin H, Dean G, Delpech VC, Gogia M, Gold D, Kafkalias A, Korkodilos M, Kowalska JD, Lindo J, Lundgren JD, Lynch L, Martinez E, McDougall N, North S, Rockstroh JK, Sabin C, Vidal-Read M, Waters LJ, and Sullivan AK
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- Humans, Consensus, Public Health, Health Personnel, HIV Infections
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Getting to Zero is a commonly cited strategic aim to reduce mortality due to both HIV and avoidable deaths among people with HIV. However, no clear definitions are attached to these aims with regard to what constitutes HIV-related or preventable mortality, and their ambition is limited. This Position Paper presents consensus recommendations to define preventable HIV-related mortality for a pragmatic approach to public health monitoring by use of national HIV surveillance data. These recommendations were informed by a comprehensive literature review and agreed by 42 international experts, including clinicians, public health professionals, researchers, commissioners, and community representatives. By applying the recommendations to 2019 national HIV surveillance data from the UK, we show that 30% of deaths among people with HIV were HIV-related or possibly HIV-related, and at least 63% of these deaths were preventable or potentially preventable. The application of these recommendations by health authorities will ensure consistent monitoring of HIV elimination targets and allow for the identification of inequalities and areas for intervention., Competing Interests: Declaration of interests SEC reports consultancy fees from the Centre of Excellence for Health, Immunity and Infections, Rigshospitalet and University of Copenhagen outside of the submitted work. FAP reports honoraria and research grants to King's College Hospital from Gilead Sciences, ViiV Healthcare, and Merck Sharp & Dohme (MSD); and conference attendance paid by ViiV Healthcare, all outside of the submitted work. CS reports receipt of funding from ViiV Healthcare and Janssen-Cilag for participation in advisory boards and data safety and monitoring boards; and payment from Gilead Sciences and ViiV Healthcare for preparation of educational materials and lectures, all outside of the submitted work. JA reports consultancy and speaker fees from Gilead Sciences, ViiV Healthcare, and MSD; support to attend meetings and travel by Gilead Sciences; royalties from Elsevier for contributions to a clinical medicine textbook; and payment from the Pharmacokinetic and Clinical Observations in People Over Fifty study team to support hospital participation, all outside the submitted work. JA also reports being a board member of the RIO study, Chair of the National AIDS Trust (unpaid), a medical college Trustee for St Bartholomew's Hospital Trust (unpaid), and a past Master of the Worshipful Society of Apothecaries (unpaid), all outside of the submitted work. LJW reports advisory and speaker fees from Gilead Sciences, ViiV Healthcare, MSD, Janssen-Cilag, Theratechnologies, Mylan, and Cipla, outside of the submitted work. JKR reports consulting fees from Abivax, Boehringer Ingelheim, and Galapagos; and honoraria from Gilead Sciences, Janssen-Cilag, Merck, Theratechnologies, and ViiV Healthcare, all outside of the submitted work. JKR also reports participation on a data safety monitoring board for Abivax and Galapagos, outside of the submitted work, and was the past President of EACS (unpaid). EM reports grants and consultancy fees from MSD, Gilead Sciences, Janssen-Cilag, Theratechnologies, and ViiV Healthcare; honoraria from Gilead Sciences, Janssen-Cilag, MSD, and ViiV Healthcare; support for attending meetings from Gilead Sciences and MSD; and participation on a data safety, monitoring, and advisory board for Gilead Sciences, Janssen-Cilag, MSD, Theratechnologies, and ViiV Healthcare, all outside of the submitted work. VJA reports honoraria and speaker fees from ViiV Healthcare, Gilead Sciences, Janssen-Cilag, and MSD and support for attending meetings from ViiV Healthcare, outside of the submitted work. VJA is the Medical Director of NAZ (some elements paid) and is the Chair of the British Association for Sexual Health and HIV National Audit Group (unpaid), outside of the submitted work. VJA also declares grants from the National Institute of Health and Care Research and Barts Charity. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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35. The Impact of a Universal Mental Health Intervention on Youth with Elevated Negative Affectivity: Building Resilience for Healthy Kids.
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Sabin C, Bowen AE, Heberlein E, Pyle E, Lund L, Studts CR, Shomaker LB, Simon SL, and Kaar JL
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Objective: In response to the rise in mental health needs among youth, a school-based resilience intervention was implemented for sixth graders at an urban middle school. The goal of this analysis is to examine improvements in key mental health parameters among students who endorsed negative affectivity at baseline., Method: A total of 285 11-12-year-olds (72% white, 18% Hispanic, 55% female) participated in a single-arm, non-randomized 6-week 1:1 school-based coaching intervention, Healthy Kids. Youth completed validated surveys at baseline and 6-week follow-up assessing depression/anxiety symptoms, bullying, self-efficacy, academic pressure, grit, and resilience. Participants were determined to have elevated negative affectivity if they reported mild-to-severe symptoms for both depression and anxiety symptoms. General linear models examined differences between groups for each mental health parameter, as well as change in outcomes from baseline to follow-up., Results: A third of participants (38%) at baseline endorsed negative affectivity. Youth who endorsed negative affectivity were more often female (71% vs 29%; p < 0.001) and identified as victims of cyberbullying (25% vs 8%; p < 0.001). Youth with baseline negative affectivity scored lower for self-efficacy (total 70.5 vs 86.8; p < 0.0001). Baseline negative affectivity was a significant moderator for change in mental health parameters. Post-intervention, those who endorsed baseline negative affectivity, medium effect sizes were observed for self-efficacy ( g = 0.6; 95%CI 0.3, 0.9; p < 0.001) and anxiety symptoms ( g = - 0.70; 95%CI - 1.0, - 0.4; p < 0.001). Among all youth, there were significant medium intervention effects in resilience ( g = 0.5; 95%CI 0.3, 0.7; p < 0.001) and self-efficacy ( g = 0.7; 95%CI 0.4, 0.9; p < 0.001)., Conclusions: A universal resiliency program may improve self-efficacy and symptoms of anxiety among youth experiencing negative affectivity, while improving resilience and self-efficacy among all youth. Our findings suggest a universal school-based coaching program benefits all youth, while also specifically targeting the needs of youth with negative affectivity who are most at risk for mental health concerns., Competing Interests: Competing InterestsThe authors declare no competing interests., (© California Association of School Psychologists 2021.)
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36. BHIVA guidelines on antiretroviral treatment for adults living with HIV-1 2022.
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Waters L, Winston A, Reeves I, Boffito M, Churchill D, Cromarty B, Dunn D, Fink D, Fidler S, Foster C, Fox J, Gupta R, Hilton A, Khoo S, Leen C, Mackie N, Naous N, Ogbonmwan D, Orkin C, Panton L, Post F, Pozniak A, Sabin C, and Walsh J
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- Adult, Humans, Anti-Retroviral Agents therapeutic use, HIV-1, HIV Infections drug therapy, HIV Seropositivity
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- 2022
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37. Skeletal muscle mitochondrial dysfunction in contemporary antiretroviral therapy: a single cell analysis.
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Hunt M, McNiff MM, Vincent AE, Sabin C, Winston A, and Payne BAI
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- Humans, Middle Aged, Adult, Cross-Sectional Studies, Single-Cell Analysis, DNA, Mitochondrial, Mitochondria, Muscle, Skeletal, HIV Infections complications
- Abstract
Objective: To quantify mitochondrial function in skeletal muscle of people treated with contemporary antiretroviral therapy., Design: Cross-sectional observational study., Methods: Quantitative multiplex immunofluorescence was performed to determine mitochondrial mass and respiratory chain complex abundance in individual myofibres from tibialis anterior biopsies. Individual myofibres were captured by laser microdissection and mitochondrial DNA (mtDNA) content and large-scale deletions were measured by real-time PCR., Results: Forty-five antiretroviral therapy (ART)-treated people with HIV (PWH, mean age 58 years, mean duration of ART 125 months) were compared with 15 HIV negative age-matched controls. Mitochondrial complex I (CI) deficiency was observed at higher proportional levels in PWH than negative controls ( P = 0.008). Myofibre mitochondrial mass did not differ by HIV status. No ART class was significantly associated with mitochondrial deficiency, including prior exposure to historical NRTIs (nucleoside analogue reverse transcriptase inhibitors) associated with systemic mitochondrial toxicity. To exclude an effect of untreated HIV, we also studied skeletal muscle from 13 ART-naive PWH (mean age 37). These showed negligible CI defects, as well as comparable myofibre mitochondrial mass to ART-treated PWH. Most CI-deficient myofibres contained mtDNA deletions. No mtDNA depletion was detected., Conclusion: Here, we show that PWH treated with contemporary ART have mitochondrial dysfunction in skeletal muscle, exceeding that expected due to age alone. Surprisingly, this was not mediated by prior exposure to mitochondrially toxic NRTIs, suggesting novel mechanisms of mitochondrial dysfunction in contemporary ART-treated PWH. These findings are relevant for better understanding successful ageing in PWH., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2022
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38. Associations with sub-optimal clinic attendance and reasons for missed appointments among heterosexual women and men living with HIV in London.
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Howarth AR, Apea V, Michie S, Morris S, Sachikonye M, Mercer CH, Evans A, Delpech VC, Sabin C, and Burns FM
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- Ambulatory Care Facilities, Female, Humans, London epidemiology, Male, Social Stigma, HIV Infections drug therapy, HIV Infections epidemiology, HIV Infections prevention & control, Heterosexuality
- Abstract
Poor engagement in HIV care is associated with poorer health outcomes and increased mortality. Our survey examined experiential and circumstantial factors associated with clinic attendance among women (n = 250) and men (n = 106) in London with heterosexually-acquired HIV. While no associations were found for women, among men, sub-optimal attendance was associated with insecure immigration status (25.6% vs. 1.8%), unstable housing (32.6% vs. 10.2%) and reported effect of HIV on daily activities (58.7% vs. 40.0%). Among women and men on ART, it was associated with missing doses of ART (OR = 2.96, 95% CI:1.74-5.02), less belief in the necessity of ART (OR = 0.56, 95% CI:0.35-0.90) and more concern about ART (OR = 3.63, 95% CI:1.45-9.09). Not wanting to think about being HIV positive was the top reason for ever missing clinic appointments. It is important to tackle stigma and the underlying social determinants of health to improve HIV prevention, and the health and well-being of people living with HIV., (© 2022. The Author(s).)
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- 2022
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39. The Prevalence and Patterns of Menopausal Symptoms in Women Living with HIV.
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Okhai H, Sabin C, Haag K, Sherr L, Dhairyawan R, Shephard J, Richard G, Burns F, Post F, Jones R, Gilleece Y, and Tariq S
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- Female, Hot Flashes epidemiology, Humans, Menopause psychology, Prevalence, HIV Infections complications, HIV Infections epidemiology, Sleep Wake Disorders epidemiology
- Abstract
Increasing numbers of women with HIV are experiencing menopause. We use data from a large, representative sample of women with HIV to describe the prevalence and clustering of menopausal symptoms amongst pre-, peri- and post-menopausal women using hierarchical agglomerative cluster analysis. Of the 709 women included, 21.6%, 44.9% and 33.6% were pre-, peri- and post-menopausal, respectively. Joint pain (66.4%) was the most commonly reported symptom, followed by hot flashes (63.0%), exhaustion (61.6%) and sleep problems (61.4%). All symptoms were reported more commonly by peri- and post-menopausal women compared to pre-menopausal women. Psychological symptoms and sleep problems clustered together at all menopausal stages. Somatic and urogenital symptom clusters emerged more distinctly at peri- and post-menopause. We recommend regular and proactive assessment of menopausal symptoms in midlife women with HIV, with an awareness of how particular patterns of symptoms may evolve over the menopausal transition., (© 2022. The Author(s).)
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- 2022
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40. Prevalence of hepatitis B immunity and infection in home self-sampling HIV service users.
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Roche R, Simmons R, Logan L, Ledesma J, Sabin C, Ijaz S, and Mandal S
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- Hepatitis B virus, Homosexuality, Male, Humans, Male, Prevalence, Risk Factors, HIV Infections, Hepatitis B complications, Hepatitis B epidemiology, Hepatitis B prevention & control, Sexual and Gender Minorities
- Abstract
Objectives: Although hepatitis B virus (HBV) vaccination for high-risk groups including gay, bisexual and other men who have sex with men (MSM) is recommended in the UK, data on HBV immunisation coverage are limited. This study aimed to understand the prevalence of HBV infection, susceptibility and immunity due to immunisation among a high-risk population of MSM and heterosexuals who are less likely to attend sexual health services., Methods: Residual HIV-negative serology samples archived from a national HIV self-sampling service in 2016 were tested for HBV markers using an unlinked anonymous approach. Prevalence of HBV infection, evidence of immunisation and susceptibility were calculated and stratified by individuals' characteristics. Multinomial logistic regression was used to estimate relative risk ratios (RRRs) associated with covariates., Results: Of 2172 samples tested, 1497 (68.9%) were from MSM and 657 (30.2%) were from heterosexuals. Susceptibility to HBV infection was 66.1% among MSM and 77.0% among heterosexuals. Only 29.9% of MSM and 17.4% of heterosexuals had serological evidence of immunisation. Current infection was 1.1% in heterosexuals and 0.2% in MSM. Adjusted analysis showed evidence of immunisation was lower among heterosexuals (RRR 0.66, 95% CI 0.50 to 0.86) and those with no previous HIV test (RRR 0.41, 95% CI 0.31 to 0.54), and higher in those of other white or other ethnicity., Conclusions: Among MSM and heterosexual users of a self-sampling HIV service, evidence of immunisation to HBV infection was low and susceptibility to infection was comparatively high, suggesting suboptimal delivery of HBV immunisation in sexual health services., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2022
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41. Comorbidities in women living with HIV: A systematic review.
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Raffe S, Sabin C, and Gilleece Y
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- Adolescent, Comorbidity, Female, Humans, Male, Middle Aged, Prevalence, Risk Factors, Dyslipidemias epidemiology, HIV Infections complications, HIV Infections drug therapy, HIV Infections epidemiology
- Abstract
Objectives: Effective antiretroviral therapy (ART) has improved the life expectancy of women living with HIV (WLWH). This population is now experiencing age-related comorbidities. This systematic review presents the current understanding of the prevalence and impact of comorbidities in WLWH in the modern ART era., Methods: MEDLINE and Embase were searched for studies (1 January 2010 to 1 September 2020) reporting the prevalence of cardiovascular, bone, renal and neurocognitive disease in WLWH aged > 18 years. Studies were included if at least 100 participants (or > 50%) were female and data analysis included prevalence by sex., Results: In all, 3050 articles were identified and screened; 153 full-text articles were assessed for eligibility and 38 were included in the final review. Significant gaps in the literature were identified, notably a lack of data on WLWH aged > 50 years. The data suggest a high burden of cardiovascular, bone, renal and neurocognitive disease in WLWH compared with HIV negative women. Traditional risk factors, such as hypertension, diabetes and dyslipidaemia, were common and often poorly managed. Generalizability of the results was limited, as many studies were conducted in the USA. Comparisons between WLWH and men with HIV were limited by marked differences in demographic and socioeconomic factors., Conclusions: Women living with HIV experience a high burden of comorbid disease. Traditional risk factors are common and often poorly managed. This review also highlights the magnitude of differences between women and men living with HIV beyond the pathophysiological. Future research must unpick the complex drivers of morbidity in WLWH, to improve the holistic management of this population., (© 2022 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)
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- 2022
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42. Ethnic inequalities in mental health and socioeconomic status among older women living with HIV: results from the PRIME Study.
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Solomon D, Tariq S, Alldis J, Burns F, Gilson R, Sabin C, Sherr L, Pettit F, and Dhairyawan R
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- Age Factors, Anxiety etiology, Black People psychology, Cross-Sectional Studies, Depression etiology, Female, HIV Infections complications, HIV Infections epidemiology, Healthcare Disparities statistics & numerical data, Humans, Middle Aged, Poverty statistics & numerical data, Social Support, Surveys and Questionnaires, United Kingdom epidemiology, White People, Black People statistics & numerical data, HIV Infections psychology, Healthcare Disparities ethnology, Mental Health ethnology, Socioeconomic Factors
- Abstract
Objectives: Women living with HIV in the UK are an ethnically diverse group with significant psychosocial challenges. Increasing numbers are reaching older age. We describe psychological and socioeconomic factors among women with HIV in England aged 45-60 and explore associations with ethnicity., Methods: Analysis of cross-sectional data on 724 women recruited to the PRIME Study. Psychological symptoms were measured using the Patient Health Questionnaire 4 and social isolation with a modified Duke-UNC Functional Social Support Scale., Results: Black African (BA) women were more likely than Black Caribbean or White British (WB) women to have a university education (48.3%, 27.0%, 25.7%, respectively, p<0.001), but were not more likely to be employed (68.4%, 61.4%, 65.2%, p=0.56) and were less likely to have enough money to meet their basic needs (56.4%, 63.0%, 82.9%, p<0.001). BA women were less likely to report being diagnosed with depression than WB women (adjusted odds ratio (aOR) 0.40, p<0.001) but more likely to report current psychological distress (aOR 3.34, p<0.05)., Conclusions: We report high levels of poverty, psychological distress and social isolation in this ethnically diverse group of midlife women with HIV, especially among those who were BA. Despite being more likely to experience psychological distress, BA women were less likely to have been diagnosed with depression suggesting a possible inequity in access to mental health services. Holistic HIV care requires awareness of the psychosocial needs of older women living with HIV, which may be more pronounced in racially minoritised communities, and prompt referral for support including psychology, peer support and advice about benefits., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)
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- 2022
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43. Patterns of mental health symptoms among women living with HIV ages 45-60 in England: associations with demographic and clinical factors.
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Haag K, Tariq S, Dhairyawan R, Sabin C, Okhai H, Gilson R, Burns F, and Sherr L
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- Cross-Sectional Studies, Depression epidemiology, Depression psychology, England epidemiology, Female, Humans, Menopause psychology, Middle Aged, Prevalence, HIV Infections complications, HIV Infections drug therapy, HIV Infections epidemiology, Mental Health
- Abstract
Objective: We aimed to describe the prevalence of various mental health symptoms according to menopausal status (pre, peri, post) among women living with HIV ages 45-60 in England, and to identify groups of women with similar general and menopause-related mental health symptoms. We then investigated demographic predictors of group-membership and group differences in HIV-related care outcomes (antiretroviral therapy adherence, HIV clinic attendance, CD4-count, and last HIV viral load)., Methods: An analysis of cross-sectional data from the Positive Transitions through Menopause study, an observational study of the health and well-being impacts of menopause on 869 women with HIV aged 45-60 years. Self-reported data on eight mental health indicators were collected from women in pre-, peri- and post-menopausal state using validated measures. Groups (termed "classes") of women with similar mental health symptoms were derived via latent class analysis. Class membership was linked to demographic factors using nominal logistic regression, and to clinical outcomes using Wald tests., Results: We identified five classes: 1) few mental health symptoms (n = 501, 57.8%); 2) high current anxiety/depression (n = 120, 13.8%); 3) history of depression, with elevated current substance use (n = 40, 4.6%); 4) history of depression with current psychological menopause symptoms (n = 81, 9.3%); and 5) high previous and concurrent mental health problems (n = 125, 14.4%). University attendance, ethnicity, and longer time since HIV diagnosis predicted class membership. Antiretroviral therapy adherence was lower in classes 3 (11%), 4 (19%) and 5 (24%) compared to class 1 (4%; all P<0.001). Members of class 5 were more likely to have missed ≥1 HIV clinic appointment in the past year than those in class 1 (34% vs 17%, P = 0.005)., Conclusions: Women with a history of depression, current anxiety/depression, and current menopause-related mental health symptoms were more likely to have poorer clinical outcomes. Although we cannot comment on causality, our findings highlight the importance of assessing and managing menopausal symptoms and mental health to improve well-being and engagement in HIV care., Competing Interests: Funding/support: The PRIME Study was funded by the National Institute for Health Research (NIHR) in the form of a postdoctoral fellowship to ST (PDF-2014-07-071). This research was funded in whole, or in part, by the Wellcome Trust [204841/Z/16/Z]. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Wellcome Trust, Public Health England or the Department of Health and Social Care. Financial disclosures/conflicts of interest: S.T. has previously received a travel bursary funded by Janssen-Cilag through the British HIV Association, and speaker honoraria and funding for preparation of educational materials from Gilead Sciences. C.S. has received funding for participation in Advisory Boards and for preparation of educational materials from Gilead Sciences and ViiV Healthcare and has received previous funding from Janssen-Cilag. R.D. has received funding for participation in Advisory boards from Gilead Sciences and speaker honoraria from Gilead Sciences, ViiV Healthcare and Janssen-Cilag. F.B. has received speaker and consultancy fees from Gilead Sciences and received past conference support from Viiv Healthcare. L.S. has received support from ViiV, Gilead, Jansen for speaker honoraria and conference support. The mental health of women ages 45-60 living with HIV in England: a latent class analysis of the PRIME Study. International Workshop on HIV and Women 2021, Oral presentation. April 21., (Copyright © 2022 by The North American Menopause Society.)
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- 2022
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44. A new year, and big changes for HIV Medicine.
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Sabin C
- Subjects
- Humans, HIV Infections drug therapy
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- 2022
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45. COVID-19 mortality among people with diagnosed HIV compared to those without during the first wave of the COVID-19 pandemic in England.
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Brown AE, Croxford SE, Nash S, Khawam J, Kirwan P, Kall M, Bradshaw D, Sabin C, Miller RF, Post FA, Harding R, Collins S, Waters L, Asboe D, Chadwick DR, Delpech V, and Sullivan AK
- Subjects
- Adolescent, Adult, England epidemiology, Female, Humans, Male, Middle Aged, Young Adult, COVID-19 mortality, HIV Infections diagnosis, HIV Infections epidemiology, Pandemics
- Abstract
Objectives: We describe COVID-19 mortality among people with and without HIV during the first wave of the pandemic in England., Methods: National surveillance data on adults (aged ≥ 15 years) with diagnosed HIV resident in England were linked to national COVID-19 mortality surveillance data (2 March 2020-16 June 2020); HIV clinicians verified linked cases and provided information on the circumstances of death. We present COVID-19 mortality rates by HIV status, using negative binomial regression to assess the association between HIV and mortality, adjusting for gender, age and ethnicity., Results: Overall, 99 people with HIV, including 61 of black ethnicity, died of/with COVID-19 (107/100 000) compared with 49 483 people without HIV (109/100 000). Compared to people without HIV, higher COVID-19 mortality rates were observed in people with HIV of black (188 vs. 122/100 000) and Asian (131 vs. 77.0/100 000) ethnicity, and in both younger (15-59 years: 58.3 vs. 10.2/100 000) and older (≥ 60 years: 434 vs. 355/100 000) people. After adjustment for demographic factors, people with HIV had a higher COVID-19 mortality risk than those without (2.18; 95% CI: 1.76-2.70). Most people with HIV who died of/with COVID-19 had suppressed HIV viraemia (91%) and at least one comorbidity reported to be associated with poor COVID-19 outcomes (87%)., Conclusions: In the first wave of the pandemic in England, COVID-19 mortality among people with HIV was low, but was higher than in those without HIV, after controlling for demographic factors. This supports the strategy of prioritizing COVID-19 vaccination for people with HIV and strongly encouraging its uptake, especially in those of black and Asian ethnicity., (2021 Crown copyright. HIV Medicine © 2021 British HIV Association. This article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland.)
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- 2022
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46. Cardiovascular risks associated with protease inhibitors for the treatment of HIV.
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Hatleberg CI, Ryom L, and Sabin C
- Subjects
- Animals, Atazanavir Sulfate administration & dosage, Atazanavir Sulfate adverse effects, Atherosclerosis etiology, Darunavir administration & dosage, Darunavir adverse effects, Dyslipidemias chemically induced, Dyslipidemias complications, HIV Protease Inhibitors administration & dosage, Heart Disease Risk Factors, Humans, Randomized Controlled Trials as Topic, Cardiovascular Diseases etiology, HIV Infections drug therapy, HIV Protease Inhibitors adverse effects
- Abstract
Introduction : Cumulative use of some first-generation protease inhibitors has been associated with higher rates of dyslipidemia and increased risk of cardiovascular disease. The protease inhibitors most commonly in use are atazanavir and darunavir, which have fewer detrimental lipid effects and greater tolerability. This paper aims to review the evidence of a potential association of these contemporary protease inhibitors with the risk of ischemic CVD and atherosclerotic markers. Areas covered : We searched for publications of randomized trials and observational studies on PubMed from 1 January 2000 onwards, using search terms including: protease inhibitors; darunavir; atazanavir; cardiovascular disease; cardiovascular events; dyslipidemia; mortality; carotid intima media thickness; arterial elasticity; arterial stiffness and drug discontinuation. Ongoing studies registered on clinicaltrials.gov as well as conference abstracts from major HIV conferences from 2015-2020 were also searched. Expert opinion : Atazanavir and darunavir are no longer part of first-line HIV treatment, but continue to be recommended as alternative first line, second- and third-line regimens, as part of two drug regimens, and darunavir is used as salvage therapy. Although these drugs will likely remain in use globally for several years to come, baseline CVD risk should be considered when considering their use, especially as the population with HIV ages.
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- 2021
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47. The association between use of chemsex drugs and HIV clinic attendance among gay and bisexual men living with HIV in London.
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Howarth AR, Apea V, Michie S, Morris S, Sachikonye M, Mercer CH, Evans A, Delpech VC, Sabin C, and Burns FM
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- Adult, Cross-Sectional Studies, Homosexuality, Male, Humans, London epidemiology, Male, Risk-Taking, Sexual Behavior, HIV Infections drug therapy, HIV Infections epidemiology, Sexual and Gender Minorities, Substance-Related Disorders epidemiology
- Abstract
Objectives: To investigate the association between chemsex drug use and HIV clinic attendance among gay and bisexual men in London., Methods: A cross-sectional survey of adults (> 18 years) diagnosed with HIV for > 4 months, attending seven London HIV clinics (May 2014 to August 2015). Participants self-completed an anonymous questionnaire linked to clinical data. Sub-optimal clinic attenders had missed one or more HIV clinic appointments in the past year, or had a history of non-attendance for > 1 year., Results: Over half (56%) of the 570 men who identified as gay or bisexual reported taking recreational drugs in the past 5 years and 71.5% of these men had used chemsex drugs in the past year. Among men reporting chemsex drug use (past year), 32.1% had injected any drugs in the past year. Sub-optimal clinic attenders were more likely than regular attenders to report chemsex drug use (past year; 46.9% vs. 33.2%, P = 0.001), injecting any drugs (past year; 17.1% vs. 8.9%, P = 0.011) and recreational drug use (past 5 years; 65.5% vs. 48.8%, P < 0.001). One in five sub-optimal attenders had missed an HIV clinic appointment because of taking recreational drugs (17.4% vs. 1.8%, P < 0.001). In multivariable logistic regression, chemsex drug use was significantly associated with sub-optimal clinic attendance (adjusted odds ratio = 1.71, 95% confidence interval: 1.10-2.65, P = 0.02)., Conclusions: Our findings highlight the importance of systematic assessment of drug use and development of tools to aid routine assessment. We suggest that chemsex drug use should be addressed when developing interventions to improve engagement in HIV care among gay and bisexual men., (© 2021 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)
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- 2021
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48. Consensus statement on the role of health systems in advancing the long-term well-being of people living with HIV.
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Lazarus JV, Safreed-Harmon K, Kamarulzaman A, Anderson J, Leite RB, Behrens G, Bekker LG, Bhagani S, Brown D, Brown G, Buchbinder S, Caceres C, Cahn PE, Carrieri P, Caswell G, Cooke GS, Monforte AD, Dedes N, Del Amo J, Elliott R, El-Sadr WM, Fuster-Ruiz de Apodaca MJ, Guaraldi G, Hallett T, Harding R, Hellard M, Jaffar S, Kall M, Klein M, Lewin SR, Mayer K, Pérez-Molina JA, Moraa D, Naniche D, Nash D, Noori T, Pozniak A, Rajasuriar R, Reiss P, Rizk N, Rockstroh J, Romero D, Sabin C, Serwadda D, and Waters L
- Subjects
- Adult, Comorbidity, Consensus, Delivery of Health Care organization & administration, HIV Infections, Humans, Morbidity, Social Stigma, Surveys and Questionnaires, Delivery of Health Care standards, Quality of Life
- Abstract
Health systems have improved their abilities to identify, diagnose, treat and, increasingly, achieve viral suppression among people living with HIV (PLHIV). Despite these advances, a higher burden of multimorbidity and poorer health-related quality of life are reported by many PLHIV in comparison to people without HIV. Stigma and discrimination further exacerbate these poor outcomes. A global multidisciplinary group of HIV experts developed a consensus statement identifying key issues that health systems must address in order to move beyond the HIV field's longtime emphasis on viral suppression to instead deliver integrated, person-centered healthcare for PLHIV throughout their lives., (© 2021. The Author(s).)
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- 2021
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49. A national audit of the management pathways for new HIV diagnoses.
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Kaide E, Curtis H, Freedman A, Croxford S, Burns F, Sabin C, Chadwick DR, and Sullivan A
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- England, Humans, Retrospective Studies, Anti-HIV Agents therapeutic use, HIV Infections diagnosis, HIV Infections drug therapy, HIV Infections epidemiology
- Abstract
The British HIV Association recommends that new diagnoses be reviewed by an HIV specialist within two weeks. NHS England outcome measures include the proportion of new diagnoses commencing antiretroviral therapy (ART) within 91 days. We aimed to review the extent to which these recommendations were followed, to explore the topics discussed with new diagnoses, and to identify reasons behind delayed ART initiation. UK specialist HIV services were invited to retrospectively review the notes of their last 40 new diagnoses over a 15-month period. One-hundred and thirty-two services provided data for 2281 eligible individuals. Most new diagnoses were reviewed by a specialist within two weeks (67.7%) and were commenced on ART within 91 days (83%), however, there were some concerning delays in those tested at home and in general practice. Partner notification and treatment benefits were discussed with most individuals, unlike the availability of community support and U = U ("undetectable equals untransmittable"). Lengthy delays in ART initiation were mostly due to individuals initially declining ART or missing appointments. Our findings suggest a need for more streamlined pathways into HIV care, review of new diagnoses who have not commenced ART within 8 weeks, and protocol development to ensure discussion of relevant topics.
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- 2021
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50. Risk for Non-AIDS-Defining and AIDS-Defining Cancer of Early Versus Delayed Initiation of Antiretroviral Therapy : A Multinational Prospective Cohort Study.
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Chammartin F, Lodi S, Logan R, Ryom L, Mocroft A, Kirk O, d'Arminio Monforte A, Reiss P, Phillips A, El-Sadr W, Hatleberg CI, Pradier C, Bonnet F, Law M, De Wit S, Sabin C, Lundgren JD, and Bucher HC
- Subjects
- Adult, CD4 Lymphocyte Count, Female, HIV Infections immunology, HIV Infections virology, Humans, Incidence, Male, Middle Aged, Prospective Studies, Risk Factors, Viral Load, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, Neoplasms epidemiology, Time-to-Treatment
- Abstract
Background: Immediate initiation of antiretroviral therapy (ART) regardless of CD4 cell count reduces risk for AIDS and non-AIDS-related events in asymptomatic, HIV-positive persons and is the standard of care. However, most HIV-positive persons initiate ART when their CD4 count decreases below 500 × 10
9 cells/L. Consequences of delayed ART on risk for non-AIDS-defining and AIDS-defining cancer, one of the most common reasons for death in HIV, are unclear., Objective: To estimate the long-term risk difference for cancer with the immediate ART strategy., Design: Multinational prospective cohort study., Setting: The D:A:D (Data collection on Adverse events of anti-HIV Drugs) study, which included HIV-positive persons from Europe, Australia, and the United States., Participants: 8318 HIV-positive persons with at least 1 measurement each of CD4 cell count and viral load while ART-naive (study period, 2006 to 2016)., Measurements: The parametric g-formula was used, with adjustment for baseline and time-dependent confounders (CD4 cell count and viral load), to assess the 10-year risk for non-AIDS-defining and AIDS-defining cancer of immediate versus deferred (at CD4 counts <350 and <500 × 109 cells/L) ART initiation strategies., Results: During 64 021 person-years of follow-up, 231 cases of non-AIDS-defining cancer and 272 of AIDS-defining cancer occurred among HIV-positive persons with a median age of 36 years (interquartile range, 29 to 43 years). With immediate ART, the 10-year risk for non-AIDS-defining cancer was 2.97% (95% CI, 2.37% to 3.50%) and that for AIDS-defining cancer was 2.50% (CI, 2.37% to 3.38%). Compared with immediate ART initiation, the 10-year absolute risk differences when deferring ART to CD4 counts less than 500 × 109 cells/L and less than 350 × 109 cells/L were 0.12 percentage point (CI, -0.01 to 0.26 percentage point) and 0.29 percentage point (CI, -0.03 to 0.73 percentage point), respectively, for non-AIDS-defining cancer and 0.32 percentage point (CI, 0.21 to 0.44 percentage point) and 1.00 percentage point (CI, 0.67 to 1.44 percentage points), respectively, for AIDS-defining cancer., Limitation: Potential residual confounding due to observational study design., Conclusion: In this young cohort, effects of immediate ART on 10-year risk for cancer were small, and further supportive data are needed for non-AIDS-defining cancer., Primary Funding Source: Highly Active Antiretroviral Therapy Oversight Committee.- Published
- 2021
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