24 results on '"Halford, Rachel"'
Search Results
2. Peer support for people living with hepatitis B virus—A foundation for treatment expansion
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Downs, Louise O., primary, Kabagambe, Kenneth, additional, Williams, Sarah, additional, Waddilove, Elizabeth, additional, Delphin, Marion, additional, Lumley, Sheila F., additional, Ndungutse, Richard, additional, Kimono, Beatrice, additional, Newton, Robert, additional, Ko, Joy, additional, Martyn, Emily, additional, Carter, Jessica, additional, Kemper, Agnieszka, additional, Monteiro, Fernando, additional, O'Regan, Sive, additional, Surey, Julian, additional, Sultan, Binta, additional, Story, Alistair, additional, MacDonald, Douglas, additional, Tu, Thomas, additional, Seeley, Janet, additional, Dusheiko, Geoffrey, additional, Maponga, Tongai, additional, Andersson, Monique I., additional, Spearman, C. Wendy, additional, Tucker, Joseph D., additional, Cohen, Chari, additional, Wang, Su, additional, Adda, Danjuma, additional, Freeland, Catherine, additional, Halford, Rachel, additional, Jack, Kathryn, additional, Ghosh, Indrajit, additional, Elsharkawy, Ahmed M., additional, Matthews, Philippa C., additional, and Flanagan, Stuart, additional
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- 2024
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3. Cost-Effectiveness Analysis of Baseline Testing for Resistance-Associated Polymorphisms to Optimize Treatment Outcome in Genotype 1 Noncirrhotic Treatment-Naïve Patients With Chronic Hepatitis C Virus
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Barnes, Eleanor, Ball, Jonathan, Brainard, Diana, Burgess, Gary, Cooke, Graham S., Dillon, John, Foster, Graham, Gore, Charles, Guha, Neil, Halford, Rachel, Whitby, Kevin, Holmes, Chris, Howe, Anita, Hudson, Emma, Hutchinson, Sharon, Irving, William, Khakoo, Salim, Klenerman, Paul, Martin, Natasha, Massetto, Benedetta, Mbisa, Tamyo, McHutchison, John, McKeating, Jane, McLauchlan, John, Miners, Alec, Murray, Andrea, Shaw, Peter, Simmonds, Peter, Spencer, Chris, Thomson, Emma, Vickerman, Peter, Zitzmann, Nicole, Fawsitt, Christopher G., and Welton, Nicky J.
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- 2020
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4. A Cost-Effectiveness Analysis of Shortened Direct-Acting Antiviral Treatment in Genotype 1 Noncirrhotic Treatment-Naive Patients With Chronic Hepatitis C Virus
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Barnes, Eleanor, Ball, Jonathan, Brainard, Diana, Burgess, Gary, Cooke, Graham, Dillon, John, Foster, Graham, Gore, Charles, Guha, Neil, Halford, Rachel, Whitby, Kevin, Holmes, Chris, Howe, Anita, Hudson, Emma, Hutchinson, Sharon, Irving, William, Khakoo, Salim, Klenerman, Paul, Martin, Natasha, Massetto, Benedetta, Mbisa, Tamyo, McHutchison, John, McKeating, Jane, McLauchlan, John, Miners, Alec, Murray, Andrea, Shaw, Peter, Simmonds, Peter, Spencer, Chris, Thomson, Emma, Vickerman, Peter, Zitzmann, Nicole, Fawsitt, Christopher G., and Welton, Nicky J.
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- 2019
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5. Chronic hepatitis C elimination prison initiative: HCV‐intensive test and treat, a whole prisoner population HCV test‐and‐treat program in England
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Halford, Rachel, primary, Christensen, Lee, additional, Cox, Sean, additional, Sheehan, Julia, additional, Brew, Iain, additional, Gillyon‐Powell, Mark, additional, Threadgold, Georgia, additional, O'Moore, Éamonn, additional, Troke, Philip J. F., additional, and Jones, Andy, additional
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- 2023
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6. Prevalence of Drug Resistance Associated Substitutions in Hepatitis C-Infected Patients Whose WHO-Recommended Direct Acting Agents for Initial Treatment and Retreatment Fails: A Systematic Review and Meta-Analysis
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Inzaule, Seth, primary, Easterbrook, Philippa, additional, Latona, Ashley, additional, Ford, Nathan, additional, Irving, William, additional, Matthews, Philippa C., additional, Vitoria, Marco, additional, Duncombe, Chris, additional, Giron, Amalia, additional, McCluskey, Suzanne, additional, Lesi, Olufunmilayo, additional, Tchamgoue, Serge, additional, Halford, Rachel, additional, Thomson, Emma C., additional, Dusheiko, Geoff, additional, and Jordan, Michael R., additional
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- 2023
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7. Results of a Model of Delivering Hepatitis C Care in a Homeless Metropolitan Population in England
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Guerra-Veloz, María Fernanda, primary, Han, Khin, additional, Oakes, Kathryn, additional, Robertson, David, additional, Mohamed, Almuthana, additional, Cannon, Mary, additional, Barnabas, Ashley, additional, Shah, Sital, additional, Halford, Rachel, additional, Dusheiko, Geoffrey, additional, and Agarwal, Kosh, additional
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- 2022
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8. Harm reduction and viral hepatitis C in European prisons: a cross-sectional survey of 25 countries
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Bielen, Rob, Stumo, Samya R., Halford, Rachel, Werling, Klára, Reic, Tatjana, Stöver, Heino, Robaeys, Geert, and Lazarus, Jeffrey V.
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- 2018
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9. Peer-led hepatitis C services reach poorly served populations at scale: a model for tackling health inequalities
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Reid, Leila, primary, Halford, Rachel, additional, Smith, Stuart, additional, and Cox, Sean, additional
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- 2022
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10. High Intensity Test and Treat (HITT): an overview of the initiative as part of the hepatitis C elimination programme in England
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Emmanouil, Beatrice, primary, Cox, Sean, additional, Halford, Rachel, additional, Threadgold, Georgia, additional, Gillyon-Powell, Mark, additional, and Foster, Graham, additional
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- 2022
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11. Results of a Model of Delivering Hepatitis C Care in a Homeless Metropolitan Population in England.
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Fernanda Guerra-Veloz, María, Han, Khin, Oakes, Kathryn, Robertson, David, Mohamed, Almuthana, Cannon, Mary, Barnabas, Ashley, Shah, Sital, Halford, Rachel, Dusheiko, Geoffrey, and Agarwal, Kosh
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- 2023
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12. Viral genome wide association study identifies novel hepatitis C virus polymorphisms associated with sofosbuvir treatment failure
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Smith, David A., Fernandez-Antunez, Carlota, Magri, Andrea, Bowden, Rory, Chaturvedi, Nimisha, Fellay, Jacques, McLauchlan, John, Foster, Graham R., Irving, William L., Simmonds, Peter, Pedergnana, Vincent, Ramirez, Santseharay, Bukh, Jens, Barnes, Eleanor, Ansari, M. Azim, Ball, Jonathan, Brainard, Diana, Burgess, Gary, Cooke, Graham, Dillon, John, Gore, Charles, Guha, Neil, Halford, Rachel, Herath, Cham, Holmes, Chris, Howe, Anita, Hudson, Emma, Irving, William, Khakoo, Salim, Klenerman, Paul, Koletzki, Diana, Martin, Natasha, Massetto, Benedetta, Mbisa, Tamyo, McHutchison, John, McKeating, Jane, Miners, Alec, Murray, Andrea, Shaw, Peter, Spencer, Chris C. A., Targett-Adams, Paul, Thomson, Emma, Vickerman, Peter, Zitzmann, Nicole, Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford, University of Copenhagen = Københavns Universitet (UCPH), The Wellcome Trust Centre for Human Genetics [Oxford], Ecole Polytechnique Fédérale de Lausanne (EPFL), Université de Lausanne = University of Lausanne (UNIL), Swiss Institute of Bioinformatics [Lausanne] (SIB), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), University of Glasgow, Queen Mary University of London (QMUL), University of Nottingham, UK (UON), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), STOP-HCV Consortium, Ball, J., Brainard, D., Burgess, G., Cooke, G., Dillon, J., Gore, C., Guha, N., Halford, R., Herath, C., Holmes, C., Howe, A., Hudson, E., Irving, W., Khakoo, S., Klenerman, P., Koletzki, D., Martin, N., Massetto, B., Mbisa, T., McHutchison, J., McKeating, J., Miners, A., Murray, A., Shaw, P., Spencer, CCA, Targett-Adams, P., Thomson, E., Vickerman, P., and Zitzmann, N.
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ns2 ,Sofosbuvir ,[SDV]Life Sciences [q-bio] ,viruses ,General Physics and Astronomy ,Genome-wide association study ,resistance-associated substitutions ,Hepacivirus ,Viral Nonstructural Proteins ,Chronic liver disease ,medicine.disease_cause ,chemistry.chemical_compound ,0302 clinical medicine ,Treatment Failure ,0303 health sciences ,Multidisciplinary ,Hepatitis C virus ,virus diseases ,Viral Load ,Antivirals ,3. Good health ,Hepatocellular carcinoma ,030211 gastroenterology & hepatology ,Viral load ,medicine.drug ,Genotype ,ribavirin ,Science ,Genome, Viral ,Antiviral Agents/therapeutic use ,Genome, Viral/genetics ,Hepacivirus/drug effects ,Hepacivirus/genetics ,Hepacivirus/isolation & purification ,Hepatitis C, Chronic/drug therapy ,Hepatitis C, Chronic/virology ,Humans ,Polymorphism, Genetic ,Sofosbuvir/therapeutic use ,Viral Load/drug effects ,Viral Load/genetics ,Viral Nonstructural Proteins/genetics ,Antiviral Agents ,General Biochemistry, Genetics and Molecular Biology ,Article ,Virus ,03 medical and health sciences ,medicine ,Potency ,emergence ,030304 developmental biology ,NS3 ,business.industry ,Ribavirin ,General Chemistry ,biochemical phenomena, metabolism, and nutrition ,Hepatitis C, Chronic ,medicine.disease ,Virology ,infection ,digestive system diseases ,chemistry ,Viral infection ,protein ,business - Abstract
Sofosbuvir is a common therapy in hepatitis C virus infection, which targets the NS5B polymerase. Here, Smith et al. analyze the association between whole genome HCV polymorphisms and sofosbuvir treatment failure and identify three common polymorphisms present in non-targeted NS2 and NS3 proteins associated with reduced treatment response., Persistent hepatitis C virus (HCV) infection is a major cause of chronic liver disease, worldwide. With the development of direct-acting antivirals, treatment of chronically infected patients has become highly effective, although a subset of patients responds less well to therapy. Sofosbuvir is a common component of current de novo or salvage combination therapies, that targets the HCV NS5B polymerase. We use pre-treatment whole-genome sequences of HCV from 507 patients infected with HCV subtype 3a and treated with sofosbuvir containing regimens to detect viral polymorphisms associated with response to treatment. We find three common polymorphisms in non-targeted HCV NS2 and NS3 proteins are associated with reduced treatment response. These polymorphisms are enriched in post-treatment HCV sequences of patients unresponsive to treatment. They are also associated with lower reductions in viral load in the first week of therapy. Using in vitro short-term dose-response assays, these polymorphisms do not cause any reduction in sofosbuvir potency, suggesting an indirect mechanism of action in decreasing sofosbuvir efficacy. The identification of polymorphisms in NS2 and NS3 proteins associated with poor treatment outcomes emphasises the value of systematic genome-wide analyses of viruses in uncovering clinically relevant polymorphisms that impact treatment.
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- 2021
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13. Role of peer support in a hepatitis C elimination programme
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Jugnarain, Davina Varsha, primary, Halford, Rachel, additional, Smith, Stuart, additional, Hickman, Matthew, additional, Samartsidis, Pantelis, additional, and Foster, Graham R., additional
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- 2021
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14. Strategic treatment optimization for HCV (STOPHCV1): a randomised controlled trial of ultrashort duration therapy for chronic hepatitis C
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Cooke, Graham S., primary, Pett, Sarah, additional, McCabe, Leanne, additional, Jones, Chris, additional, Gilson, Richard, additional, Verma, Sumita, additional, Ryder, Stephen D., additional, Collier, Jane D., additional, Barclay, Stephen T., additional, Ala, Aftab, additional, Bhagani, Sanjay, additional, Nelson, Mark, additional, Ch'Ng, Chinlye, additional, Stone, Ben, additional, Wiselka, Martin, additional, Forton, Daniel, additional, McPherson, Stuart, additional, Halford, Rachel, additional, Nguyen, Dung, additional, Smith, David, additional, Ansari, Azim, additional, Dennis, Emily, additional, Hudson, Fleur, additional, Barnes, Eleanor J., additional, and Walker, Ann Sarah, additional
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- 2021
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15. Time for a treat all approach for hepatitis B
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Halford, Rachel, Adda, Danjuma, Hicks, Jessica, James, Cary, and Smith, Alexandra
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- 2024
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16. Cost-Effectiveness Analysis of Baseline Testing for Resistance-Associated Polymorphisms to Optimize Treatment Outcome in Genotype 1 Noncirrhotic Treatment-Naïve Patients With Chronic Hepatitis C Virus
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Fawsitt, Christopher G., primary, Vickerman, Peter, additional, Cooke, Graham S., additional, Welton, Nicky J., additional, Barnes, Eleanor, additional, Ball, Jonathan, additional, Brainard, Diana, additional, Burgess, Gary, additional, Dillon, John, additional, Foster, Graham, additional, Gore, Charles, additional, Guha, Neil, additional, Halford, Rachel, additional, Whitby, Kevin, additional, Holmes, Chris, additional, Howe, Anita, additional, Hudson, Emma, additional, Hutchinson, Sharon, additional, Irving, William, additional, Khakoo, Salim, additional, Klenerman, Paul, additional, Martin, Natasha, additional, Massetto, Benedetta, additional, Mbisa, Tamyo, additional, McHutchison, John, additional, McKeating, Jane, additional, McLauchlan, John, additional, Miners, Alec, additional, Murray, Andrea, additional, Shaw, Peter, additional, Simmonds, Peter, additional, Spencer, Chris, additional, Thomson, Emma, additional, and Zitzmann, Nicole, additional
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- 2020
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17. Role of peer support in a hepatitis C elimination programme.
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Jugnarain, Davina Varsha, Halford, Rachel, Smith, Stuart, Hickman, Matthew, Samartsidis, Pantelis, and Foster, Graham R.
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CHRONIC hepatitis C , *HEPATITIS C , *ODDS ratio - Abstract
Many people with chronic hepatitis C infection don't engage in treatment. To eliminate hepatitis C and avoid health inequalities therapy must be provided to everyone. In other diseases peers with lived experience of the condition have improved care but, for hepatitis C, studies have not shown unequivocal benefit. We completed a retrospective analysis of the English National Health Service treatment registry comparing treatment networks with and without peers using Bayesian Poisson (for count outcomes) or Bayesian Binomial (for proportion outcomes) mixed effects models with time fixed effects. For each outcome, we estimated relative ratio (RR‐Poisson model) or odds ratio (Odds Ratio (OR)‐Binomial model) between peer and non‐peer networks. We analysed 30,729 patients within 20 operational delivery networks. In networks with peers there was an increase in the number of people initiating therapy (RR 1.12 95%, credible interval 1.02–1.21) and an increase in the proportion completing therapy (OR 2.45 95%, credible interval 1.49–3.84). However, we saw no change in proportions of people using drugs who initiated therapy nor any significant change in virological response (OR 1.14 95% credible interval 0.979–1.36). We repeated the analysis looking at the impact of peers two months after they had been introduced, when they had established networks of contacts, and saw an increase in the proportion of people treated in addiction services. In treating patients with chronic hepatitis C infection the inclusion of peer supporters may increase the number of people who initiate and complete antiviral therapy. [ABSTRACT FROM AUTHOR]
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- 2022
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18. Nobody Left Outside (NLO) Checklist: Improving access to healthcare for vulnerable and underserved groups
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Lazarus, Jeffrey V., primary, Cascio, Mario, additional, Halford, Rachel, additional, Onyango, Denis, additional, Schatz, Eberhard, additional, Smith, Alyna, additional, Spinnewijn, Freek, additional, and Stevenson, Luca, additional
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- 2019
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19. A Cost-Effectiveness Analysis of Shortened Direct-Acting Antiviral Treatment in Genotype 1 Noncirrhotic Treatment-Naive Patients With Chronic Hepatitis C Virus
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Fawsitt, Christopher G., primary, Vickerman, Peter, additional, Cooke, Graham, additional, Welton, Nicky J., additional, Barnes, Eleanor, additional, Ball, Jonathan, additional, Brainard, Diana, additional, Burgess, Gary, additional, Dillon, John, additional, Foster, Graham, additional, Gore, Charles, additional, Guha, Neil, additional, Halford, Rachel, additional, Whitby, Kevin, additional, Holmes, Chris, additional, Howe, Anita, additional, Hudson, Emma, additional, Hutchinson, Sharon, additional, Irving, William, additional, Khakoo, Salim, additional, Klenerman, Paul, additional, Martin, Natasha, additional, Massetto, Benedetta, additional, Mbisa, Tamyo, additional, McHutchison, John, additional, McKeating, Jane, additional, McLauchlan, John, additional, Miners, Alec, additional, Murray, Andrea, additional, Shaw, Peter, additional, Simmonds, Peter, additional, Spencer, Chris, additional, Thomson, Emma, additional, and Zitzmann, Nicole, additional
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- 2019
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20. MAIT cells are activated during human viral infections
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Van Wilgenburg, Bonnie, Scherwitzl, Iris, Hutchinson, Edward C., Leng, Tianqi, Kurioka, Ayako, Kulicke, Corinna, De Lara, Catherine, Cole, Suzanne, Vasanawathana, Sirijitt, Limpitikul, Wannee, Malasit, Prida, Young, Duncan, Denney, Laura, Moore, Michael D., Fabris, Paolo, Giordani, Maria Teresa, Oo, Ye Htun, Laidlaw, Stephen M., Dustin, Lynn B., Ho, Ling Pei, Thompson, Fiona M., Ramamurthy, Narayan, Mongkolsapaya, Juthathip, Willberg, Christian B., Screaton, Gavin R., Klenerman, Paul, Barnes, Eleanor, Ball, Jonathan, Burgess, Gary, Cooke, Graham, Dillon, John, Gore, Charles, Foster, Graham, Guha, Neil, Halford, Rachel, Herath, Cham, Holmes, Chris, Howe, Anita, Hudson, Emma, Irving, William, Khakoo, Salim, Koletzki, Diana, Martin, Natasha, Mbisa, Tamyo, McKeating, Jane, McLauchlan, John, Miners, Alec, Murray, Andrea, Shaw, Peter, Simmonds, Peter, Spencer, Chris, Targett-Adams, Paul, Thomson, Emma, Vickerman, Peter, and Zitzmann, Nicole
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Mucosal-associated invariant T (MAIT) cells are abundant in humans and recognize bacterial ligands. Here, we demonstrate that MAIT cells are also activated during human viral infections in vivo. MAIT cells activation was observed during infection with dengue virus, hepatitis C virus and influenza virus. This activation - driving cytokine release and Granzyme B upregulation - is TCR-independent but dependent on IL-18 in synergy with IL-12, IL-15 and/or interferon-α/β. IL-18 levels and MAIT cell activation correlate with disease severity in acute dengue infection. Furthermore, HCV treatment with interferon-α leads to specific MAIT cell activation in vivo in parallel with an enhanced therapeutic response. Moreover, TCR-independent activation of MAIT cells leads to a reduction of HCV replication in vitro mediated by IFN-γ. Together these data demonstrate MAIT cells are activated following viral infections, and suggest a potential role in both host defence and immunopathology.
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- 2016
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21. It is time for World Hepatitis Testing Week.
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Halford R, Hicks J, Islam R, James C, Mendão L, Shiha G, Smith A, and Vélez-Möller P
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Competing Interests: The World Hepatitis Alliance has received grants from Abbott, AbbVie, Gilead, GlaxoSmithKline, the John C Martin Foundation, Kedrion, Roche, and Vir Biotechnology.
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- 2024
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22. Prevalence of Drug Resistance Associated Substitutions in Persons With Chronic Hepatitis C Infection and Virological Failure Following Initial or Re-treatment With Pan-genotypic Direct-Acting Antivirals: A Systematic Review and Meta-analysis.
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Inzaule S, Easterbrook P, Latona A, Ford NP, Irving W, Matthews PC, Vitoria M, Duncombe C, Giron A, McCluskey S, Lesi O, Tchamgoue S, Halford R, Adda D, Thomson E, Dusheiko G, and Jordan MR
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Background: The advent of short-course, curative treatment with direct-acting antivirals (DAA) has given promise for the global elimination of hepatitis C virus (HCV) infections by 2030. Virological failure occurs in 2%-12% of persons receiving curative DAA treatment and may be presaged by pre-existing polymorphisms or result from selection of drug resistant variants during therapy., Methods: We conducted a systematic review to assess the prevalence of HCV resistance associated substitutions (RAS) among individuals with chronic hepatitis C infection who had virological failure following initial or re-treatment with pan-genotypic DAA regimens. We included 34 and 22 studies assessing RAS in people with virological failure published between January 2014 and July 2023. Pooled RAS prevalence was estimated using random-effects meta-analysis., Results: The pooled prevalence of RAS in people with virological failure following initial DAA treatment was 78.0% (95% confidence interval [CI]: 62.0-92.0) for sofosbuvir/velpatasvir, 81.0% (95% CI: 67.0-93.0) for sofosbuvir/daclatasvir, and 79.0% (95% CI: 70.0-87.0) for glecaprevir/pibrentasvir, with a high prevalence of resistance to the NS5A inhibitors. Among those with virological failure following re-treatment regimens, RAS were present in 93.0% (95% CI: 83.0-99.0) for sofosbuvir/velpatasvir/voxilepravir and in 100% (95% CI: 92.0-100) for glecaprevir/pibrentasvir, with resistance driven by RAS to NS5A inhibitors., Discussion: At least 1 RAS is present in a high proportion of the few individuals with virological failure following initial or re-treatment with pan-genotypic DAA regimens. There is a need for ongoing surveillance for DAA-associated resistance, to assess risk factors for their development and clinical impact to inform best practice strategies for re-treatment., Competing Interests: Potential conflicts of interest. W. I. reports personal fees from Roche diagnostics, Gilead Sciences, and Source Bioscience Limited outside of the submitted work and stock or stock options in GlaxoSmithKline. P. C. M. reports funding from Francis Crick Institute and University College London Biomedical Research Centre (BRC) and Wellcome Trust during the submitted work, as well as royalties from Oxford University Press and funding from GlaxoSmithKline outside of the submitted work. S. T. reports funding or personal fees ViiV Healthcare and Gilead Sciences outside of the submitted work. D. A. reports funding from Gilead Sciences and Pfizer outside of the submitted work. R. H. serves as the president of World Hepatitis Alliance. All other authors declare no competing interests. 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) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2024
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23. Results of a Model of Delivering Hepatitis C Care in a Homeless Metropolitan Population in England.
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Guerra-Veloz MF, Han K, Oakes K, Robertson D, Mohamed A, Cannon M, Barnabas A, Shah S, Halford R, Dusheiko G, and Agarwal K
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- Humans, Hepacivirus, Analgesics, Opioid therapeutic use, Delivery of Health Care, RNA therapeutic use, Antiviral Agents therapeutic use, Hepatitis C diagnosis, Hepatitis C drug therapy, Hepatitis C epidemiology, Hepatitis C, Chronic diagnosis, Hepatitis C, Chronic drug therapy, Hepatitis C, Chronic epidemiology
- Abstract
Introduction: Given the hepatitis C virus (HCV) burden and despite curative treatments, more efforts focused on scaling-up testing and treatment in homeless populations are needed. This project aimed to implement education and flexible on-site HCV testing, treatment, and follow-up for a homeless population in south London and to evaluate engagement, therapy initiation, and cure rates., Methods: A mobile unit (van) for on-site HCV education, screening, treatment, and follow-up was placed on the street in a well-known homeless population areas from January 2018 to September 2021. Homeless was defined as living in temporary housing (hostel/hotel-based) or living on the street (street-based). Sociodemographic status, risk factors, comorbidities, concomitant medication, and data related with HCV treatment were recorded. Univariable and multivariable modeling were performed for treatment initiation and sustained virological response (SVR)., Results: Nine hundred forty homeless people were identified and 99.3% participated. 56.2% were street-based, 243 (26%) tested positive for HCV antibody, and 162 (17.4%) were viremic. Those with detectable HCV RNA had significantly more frequent psychiatric disorders, active substance use disorders, were on opioid agonist treatment, had advanced fibrosis, and had lower rates of previous treatment in comparison with undetectable HCV RNA. Overall treatment initiation was 70.4% and SVR was 72.8%. In the multivariable analysis, being screened in temporary housing (odds ratio [OR] 3.166; P = 0.002) and having opioid agonist treatment (OR 3.137; P = 0.004) were positively associated with treatment initiation. HCV treatment adherence (OR 26.552; P < 0.001) was the only factor associated with achieving SVR., Discussion: Promoting education and having flexible and reflex mobile on-site testing and treatment for HCV in the homeless population improve engagement with the health care system, meaning higher rates of treatment initiation and SVR. However, street-based homeless population not linked with harm reduction services are less likely to initiate HCV treatment, highlighting an urgent need for a broad health inclusion system., (Copyright © 2022 by The American College of Gastroenterology.)
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- 2023
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24. Variable short duration treatment versus standard treatment, with and without adjunctive ribavirin, for chronic hepatitis C: the STOP-HCV-1 non-inferiority, factorial RCT
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Cooke GS, Pett S, McCabe L, Jones C, Gilson R, Verma S, Ryder SD, Collier JD, Barclay ST, Ala A, Bhagani S, Nelson M, Ch’Ng CL, Stone B, Wiselka M, Forton D, McPherson S, Halford R, Nguyen D, Smith D, Ansari MA, Ainscough H, Dennis E, Hudson F, Barnes EJ, and Walker AS
- Abstract
Background: High cure rates with licensed durations of therapy for chronic hepatitis C virus suggest that many patients are overtreated. New strategies in individuals who find it challenging to adhere to standard treatment courses could significantly contribute to the elimination agenda., Objectives: To compare cure rates using variable ultrashort first-line treatment stratified by baseline viral load followed by retreatment, with a fixed 8-week first-line treatment with retreatment with or without adjunctive ribavirin., Design: An open-label, multicentre, factorial randomised controlled trial., Randomisation: Randomisation was computer generated, with patients allocated in a 1 : 1 ratio using a factorial design to each of biomarker-stratified variable ultrashort strategy or fixed duration and adjunctive ribavirin (or not), using a minimisation algorithm with a probabilistic element., Setting: NHS., Participants: A total of 202 adults (aged ≥ 18 years) infected with chronic hepatitis C virus genotype 1a/1b or 4 for ≥ 6 months, with a detectable plasma hepatitis C viral load and no significant fibrosis [FibroScan
® (Echosens, Paris, France) score F0–F1 or biopsy-proven minimal fibrosis], a hepatitis C virus viral load < 10,000,000 IU/ml, no previous exposure to direct-acting antiviral therapy for this infection and not pregnant. Patients co-infected with human immunodeficiency virus were eligible if human immunodeficiency virus viral load had been < 50 copies/ml for > 24 weeks on anti-human immunodeficiency virus drugs., Interventions: Fixed-duration 8-week first-line therapy compared with variable ultrashort first-line therapy, initially for 4–6 weeks (continuous scale) stratified by screening viral load (variable ultrashort strategy 1, mean 32 days of treatment) and then, subsequently, for 4–7 weeks (variable ultrashort strategy 2 mean 39 days of duration), predominantly with ombitasvir, paritaprevir, ritonavir (Viekirax® ; AbbVie, Chicago, IL, USA), and dasabuvir (Exviera® ; AbbVie, Chicago, IL, USA) or ritonavir. All patients in whom first-line treatment was unsuccessful were immediately retreated with 12 weeks’ sofosbuvir, ledipasvir (Harvoni® , Gilead Sciences, Inc., Foster City, CA, USA) and ribavirin., Main Outcome Measure: The primary outcome was overall sustained virological response (persistently undetectable) 12 weeks after the end of therapy (SVR12)., Results: A total of 202 patients were analysed. All patients in whom the primary outcome was evaluable achieved SVR12 overall [100% (197/197), 95% confidence interval 86% to 100%], demonstrating non-inferiority between fixed- and variable-duration strategies (difference 0%, 95% confidence interval –3.8% to 3.7%, prespecified non-inferiority margin 4%). A SVR12 following first-line treatment was achieved in 91% (92/101; 95% confidence interval 86% to 97%) of participants randomised to the fixed-duration strategy and by 48% (47/98; 95% confidence interval 39% to 57%) allocated to the variable-duration strategy. However, the proportion achieving SVR12 was significantly higher among those allocated to variable ultrashort strategy 2 [72% (23/32), 95% confidence interval 56% to 87%] than among those allocated to variable ultrashort strategy 1 [36% (24/66), 95% confidence interval 25% to 48%]. Overall, a SVR12 following first-line treatment was achieved by 72% (70/101) (95% confidence interval 65% to 78%) of patients treated with ribavirin and by 68% (69/98) (95% confidence interval 61% to 76%) of those not treated with ribavirin. A SVR12 with variable ultrashort strategies 1 and 2 was 52% (25/48) (95% confidence interval 38% to 65%) with ribavirin, compared with 44% (22/50) (95% confidence interval 31% to 56) without. However, at treatment failure, the emergence of viral resistance was lower with ribavirin [12% (3/26), 95% confidence interval 2% to 30%] than without [38% (11/29), 95% confidence interval 21% to 58%; p = 0.01]. All 10 individuals who became undetectable at day 3 of treatment achieved first-line SVR12 regardless of treatment duration. Five participants in the variable-duration arm and five in the fixed-duration arm experienced serious adverse events ( p = 0.69), as did five participants receiving ribavirin and five participants receiving no ribavirin., Conclusions: SVR12 rates were significantly higher when ultrashort treatment varied between 4 and 7 weeks, rather than between 4 and 6 weeks. We found no evidence of ribavirin significantly affecting first-line SVR12, with unsuccessful first-line short-course therapy also not compromising subsequent retreatment with sofosbuvir, ledipasvir and ribavirin., Future Work: A priority for future work needs to be the development and evaluation of robust predictive measures to identify those patients who can be cured with ultrashort courses of therapy., Trial Registration: Current Controlled Trials ISRCTN37915093, EudraCT 2015-005004-28 and CTA 19174/0370/001-0001., Funding: This project was funded by the Efficacy and Mechanism Evaluation programme, a MRC and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation ; Vol. 8, No. 17. See the NIHR Journals Library website for further project information., (Copyright © 2021 Cooke et al. This work was produced by Cooke et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This is an Open Access publication distributed under the terms of the Creative Commons Attribution CC BY 4.0 licence, which permits unrestricted use, distribution, reproduction and adaption in any medium and for any purpose provided that it is properly attributed. See: https://creativecommons.org/licenses/by/4.0/. For attribution the title, original author(s), the publication source – NIHR Journals Library, and the DOI of the publication must be cited.)- Published
- 2021
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