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4 results on '"Jonathan, Ainsworth"'

1. Long-term efficacy and safety of a treatment strategy for HIV infection using protease inhibitor monotherapy: 8-year routine clinical care follow-up from a randomised, controlled, open-label pragmatic trial (PIVOT)Research in context

Author

Nicholas I. Paton, Wolfgang Stöhr, Alejandro Arenas-Pinto, Amanda Clarke, Ian Williams, Margaret Johnson, Chloe Orkin, Fabian Chen, Vincent Lee, Alan Winston, Mark Gompels, Julie Fox, Karen Sanders, David T. Dunn, Martin Fisher, Wendy Hadley, David Stacey, Pat Byrne, Nahum De Esteban, Pierre Pellegrino, Lewis Haddow, James Hand, Carl De Souza, Lisa Murthen, Andrew Crawford-Jones, Ruth Wilson, Elizabeth Green, John Masterson, Kamlesh Patel, Rebecca Howe, Scott Mullaney, Louise Jennings, Nicholas Beeching, Rebecca Tamaklo, Alistair Teague, Isabelle Jendrulek, Juan Manuel Tiraboschi, Ed Wilkins, Yvonne Clowes, Andrew Thompson, Gary Brook, Manoj Trivedi, Kazeem Aderogba, Martin Jones, Andrew DeBurgh-Thomas, Liz Jones, Iain Reeves, Sifiso Mguni, David Chadwick, Pauline Spence, Nellie Nkhoma, Zoe Warwick, Suzanne Price, Sally Read, Elbushra Herieka, James Walker, Ruth Woodward, John Day, Laura Hilton, Veerakathy Harinda, Helen Blackman, Phillip Hay, Wendy Mejewska, Olanike Okolo, Edmund Ong, Karen Martin, Lee Munro, David Dockrell, Lynne Smart, Jonathan Ainsworth, Anele Waters, Stephen Kegg, Sara McNamara, Steve Taylor, Gerry Gilleran, Brian Gazzard, Jane Rowlands, Sris Allan, Rumun Sandhu, Nigel O'Farrell, Sheena Quaid, Fabiola Martin, Caroline Bennett, Moses Kapembwa, Jane Minton, James Calderwood, Frank Post, Lucy Campbell, Emily Wandolo, Adrian Palfreeman, Linda Mashonganyika, Thambiah Balachandran, Memory Kakowa, Rebecca O'Connell, Cheryl Tanawa, Sinna Jebakumar, Lesley Hagger, Say Quah, Sinead McKernan, Charles Lacey, Sarah Douglas, Sarah Russell-Sharpe, Christine Brewer, Clifford Leen, Sheila Morris, Sharmin Obeyesekera, Shirley Williams, Nelson David, Mark Roberts, Julie Wollaston, Nicholas Paton, Karen Scott, David Dunn, Emma Beaumont, Sue Fleck, Mark Hall, Susie Hennings, Ischa Kummeling, Sara Martins, Ellen Owen-Powell, Fionna van Hooff, Livia Vivas, Ellen White, Brian Angus, Andrew Freedman, Ben Cromerty, Danielle Mercey, Sarah Fidler, Estee Torok, Abdel Babiker, Tim Peto, David Lalloo, Andrew Phillips, and Robert James

Subjects
HIV, Randomised, Protease inhibitor monotherapy, Simplification, Darunavir, Medicine (General), R5-920
Abstract

Summary: Background: Treatment-simplification strategies are important tools for patient-centred management. We evaluated long-term outcomes from a PI monotherapy switch strategy. Methods: Eligible participants attending 43 UK treatment centres had a viral load (VL) below 50 copies/ml for at least 24 weeks on combination ART. Participants were randomised to maintain ongoing triple therapy (OT) or switch to a strategy of physician-selected PI monotherapy (PI-mono) with prompt return to combination therapy if VL rebounded. The primary outcome, previously reported, was loss of future drug options after 3 years, defined as new intermediate/high level resistance to at least one drug to which the participant's virus was considered sensitive at trial entry. Here we report resistance and disease outcomes after further extended follow-up in routine care. The study was registered as ISRCTN04857074. Findings: We randomised 587 participants to OT (291) or PI-mono (296) between Nov 4, 2008, and July 28, 2010 and followed them for a median of more than 8 years (100 months) until 2018. At the end of this follow-up time, one or more future drug options had been lost in 7 participants in the OT group and 6 in the PI-mono group; estimated cumulative risk by 8 years of 2.7% and 2.1% respectively (difference −0.6%, 95% CI −3.2% to 2.0%). Only one PI-mono participant developed resistance to the protease inhibitor they were taking (atazanavir). Serious clinical events (death, serious AIDS, and serious non-AIDS) were infrequent; reported in a total of 12 (4.1%) participants in the OT group and 23 (7.8%) in the PI-mono group (P = 0.08) over the entire follow-up period. Interpretation: A strategy of PI monotherapy, with regular VL monitoring and prompt reintroduction of combination treatment following rebound, preserved future treatment options. Findings confirm the high genetic barrier to resistance of the PI drug class that makes them well suited for creative, patient-centred, treatment-simplification approaches. The possibility of a small excess risk of serious clinical events with the PI monotherapy strategy cannot be excluded. Funding: The National Institute for Health Research Health Technology Assessment programme.

Published
2024
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2. Sickle Cell Trait and Kidney Disease in People of African Ancestry With HIV

Author

Rachel K.Y. Hung, Elizabeth Binns-Roemer, John W. Booth, Rachel Hilton, Julie Fox, Fiona Burns, Mark Harber, Andrew Ustianowski, Lisa Hamzah, James E. Burns, Amanda Clarke, David A. Price, Stephen Kegg, Denis Onyango, Beatriz Santana-Suarez, Lucy Campbell, Kate Bramham, Claire C. Sharpe, Caroline A. Sabin, Cheryl A. Winkler, Frank A. Post, John Booth, Anele Waters, James Hand, Chris Clarke, Sarah Murphy, Maurice Murphy, Marion Campbell, Celia Richardson, Alyson Knott, Gemma Weir, Rebecca Cleig, Helena Soviarova, Lisa Barbour, Tanya Adams, Vicky Kennard, Vittorio Trevitt, Rachael Jones, Jeremy Levy, Alexandra Schoolmeester, Serah Duro, May Rabuya, Deborah Jordan, Teresa Solano, Hiromi Uzu, Karen Williams, Julianne Lwanga, Linda Ekaette Reid-Amoruso, Hannah Gamlen, Robert J. Stocker, Fiona Ryan, Karina Mahiouz, Tess Cheetham, Claire Williams, Achyuta Nori, Caroline Thomas, Sivaraj Venkateshwaran, Jessica Doctor, Andrea Berlanga, Frank Post, Leigh McQueen, Priya Bhagwandin, Bee Barbini, Emily Wandolo, Tim Appleby, Lois Driver, Sophy Parr, Hongbo Deng, Julie Barber, Andrew Crowe, Chris Taylor, Mary Poulton, Vida Boateng, Marie-Pierre Klein, Caitlin O’Brien, Samuel Ohene-Adomako, Christian Buckingham, Daniel Trotman, Killian Quinn, Kate Flanagan, Verity Sullivan, Holly Middleditch, Itty Samuel, Elizabeth Hamlyn, Candice McDonald, Ana Canoso, Emeka Agbasi, Maria Liskova, Sarah Barber, Amanda Samarawickrama, Zoe Ottaway, Claire Norcross, Amelia Oliveira, Jane Minton, Gary Lamont, Ruby Cross, Gaushiya Saiyad, Shadia Ahmed, Rebecca Ashworth, Nicola Window, J. Murira, Khine Phyu, Gabriella Lindergard, Jonathan Shaw, Sarah Holland, Claire Fox, Jan Flaherty, Margaret-Anne Bevan, Valerie George, David Chadwick, Marie Branch, Pauline Lambert, Adele Craggs, Sarah Pett, Hinal Lukha, Nina Vora, Marzia Fiorino, Maria Muller Nunez, Deirdre Sally, Erica Pool, Rebecca Matthews, David Ashley Price, Tara Stothard, Bijal Patel, Ian McVittie, Ciara Kennedy, Uli Shwab, Brendan Payne, Sarah Duncan, Jill Dixon, Mathias Schmid, Adam Evans, Christopher Duncan, Ewan Hunter, Yusri Taha, Natasha Astill, Cheryl Winkler, Victor David, Jonathan Ainsworth, Rachel Vincent, Chloe Saad, Sarah Skinner, Hocine Azzoug, Judith Russell, Tarik Moussaoui, Emily Mabonga, Donna Ward, J. Francoise, W. Larbi, Sue Mitchell, A. Manning, V. Russell, Nnenna Ngwu, Jonathan Edwards, Nargis Hemat, Tom Fernandez, Filippo Ferro, Jorge Ferreira, Alice Nightingale, Tasha Oakes-Monger, Darwin Matila, Pedro Nogueira, Victoria Mutagwanya, Catherine Cosgrove, Catherine Emily Isitt, Helen Webb, Joyce Popoola, Kate Korley, Mark Mencias, Patricia Ribeiro, Rajeshwar Ramkhelawn, Sandra Oliva Lara, Sara Sajijad, Alan Winston, Amber Shaw, Claire Petersen, Kyle Ring, Melanie Rosenvinge, Thembi Moyo, Faith Odong, Katherine Gantert, Tina Ibe, Caroline Sabin, and Teresa Hill

Subjects
Africa, APOL1, HIV, kidney, SCT, sickle cell trait, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Introduction: Sickle cell trait (SCT) has been associated with chronic kidney disease (CKD) in African Americans, although evidence for its impact in Africans and people with HIV is currently lacking. We conducted a cross-sectional study investigating the association between SCT and kidney disease in people of African ancestry with HIV in the UK. Methods: The primary outcome was estimated glomerular filtration rate (eGFR) 50 mg/mmol), and albuminuria (albumin-to-creatinine ratio >3 mg/mmol). Multivariable logistic regression was used to estimate the associations between SCT and kidney disease outcomes. Results: A total of 2895 participants (mean age 48.1 [SD 10.3], 57.2% female) were included, of whom 335 (11.6%) had SCT and 352 (12.2%) had eGFR

Published
2022
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3. Associations between baseline characteristics, CD4 cell count response and virological failure on first-line efavirenz + tenofovir + emtricitabine for HIV

Author

Oliver T. Stirrup, Caroline A. Sabin, Andrew N. Phillips, Ian Williams, Duncan Churchill, Anna Tostevin, Teresa Hill, David T. Dunn, David Asboe, Anton Pozniak, Patricia Cane, David Chadwick, Duncan Clark, Simon Collins, Valerie Delpech, Samuel Douthwaite, David Dunn, Esther Fearnhill, Kholoud Porter, Oliver Stirrup, Christophe Fraser, Anna Maria Geretti, Rory Gunson, Antony Hale, Stéphane Hué, Linda Lazarus, Andrew Leigh-Brown, Tamyo Mbisa, Nicola Mackie, Chloe Orkin, Eleni Nastouli, Deenan Pillay, Andrew Phillips, Caroline Sabin, Erasmus Smit, Kate Templeton, Peter Tilston, Erik Volz, Hongyi Zhang, Keith Fairbrother, Justine Dawkins, Siobhan O’Shea, Jane Mullen, Alison Cox, Richard Tandy, Tracy Fawcett, Mark Hopkins, Clare Booth, Lynne Renwick, Matthias L. Schmid, Brendan Payne, Jonathan Hubb, Simon Dustan, Stuart Kirk, Amanda Bradley-Stewart, Sophie Jose, Alicia Thornton, Susie Huntington, Adam Glabay, Shaadi Shidfar, Janet Lynch, James Hand, Carl de Souza, Nicky Perry, Stuart Tilbury, Elaney Youssef, Brian Gazzard, Mark Nelson, Tracey Mabika, Sundhiya Mandalia, Jane Anderson, Sajid Munshi, Frank Post, Ade Adefisan, Chris Taylor, Zachary Gleisner, Fowzia Ibrahim, Lucy Campbell, Kirsty Baillie, Richard Gilson, Nataliya Brima, Jonathan Ainsworth, Achim Schwenk, Sheila Miller, Chris Wood, Margaret Johnson, Mike Youle, Fiona Lampe, Colette Smith, Rob Tsintas, Clinton Chaloner, Samantha Hutchinson, John Walsh, Nicky Mackie, Alan Winston, Jonathan Weber, Farhan Ramzan, Mark Carder, Clifford Leen, Alan Wilson, Sheila Morris, Mark Gompels, Sue Allan, Adrian Palfreeman, Adam Lewszuk, Stephen Kegg, Akin Faleye, Victoria Ogunbiyi, Sue Mitchell, Phillip Hay, Christian Kemble, Fabiola Martin, Sarah Russell-Sharpe, Janet Gravely, Sris Allan, Andrew Harte, Anjum Tariq, Hazel Spencer, Ron Jones, Jillian Pritchard, Shirley Cumming, Claire Atkinson, Dushyant Mital, Veronica Edgell, Juli Allen, Andy Ustianowski, Cynthia Murphy, Ilise Gunder, Roy Trevelion, and Abdel Babiker

Subjects
antiretroviral therapy, ART, drug resistance, HIV, NNRTI, NRTI, Microbiology, QR1-502, Public aspects of medicine, RA1-1270
Abstract

Objectives: The aim of this study was to investigate associations between baseline characteristics and CD4 cell count response on first-line antiretroviral therapy and risk of virological failure (VF) with or without drug resistance. Methods: We conducted an analysis of UK Collaborative HIV Cohort data linked to the UK HIV Drug Resistance Database. Inclusion criteria were viral sequence showing no resistance prior to initiation of first-line efavirenz + tenofovir disoproxil fumarate + emtricitabine and virological suppression within 6 months. Outcomes of VF (≥200 copies/mL) with or without drug resistance were assessed using a competing risks approach fitted jointly with a model for CD4 cell count recovery. Hazard ratios for each VF outcome were estimated for baseline CD4 cell count and viral load and characteristics of CD4 cell count response using latent variables on a standard normal scale. Results: A total of 3640 people were included with 338 VF events; corresponding viral sequences were available in 134 with ≥1 resistance mutation in 36. VF with resistance was associated with lower baseline CD4 (0.30, 0.09–0.62), lower CD4 recovery (0.04, 0.00–0.17) and higher CD4 variability (4.40, 1.22–12.68). A different pattern of associations was observed for VF without resistance, but the strength of these results was less consistent across sensitivity analyses. Cumulative incidence of VF with resistance was estimated to be >2% at 3 years for baseline CD4 ≥350 cells/μL. Conclusion: Lower baseline CD4 cell count and suboptimal CD4 recovery are associated with VF with drug resistance. People with low CD4 cell count before ART or with suboptimal CD4 recovery on treatment should be a priority for regimens with high genetic barrier to resistance.

Published
2019
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4. During Stably Suppressive Antiretroviral Therapy Integrated HIV-1 DNA Load in Peripheral Blood is Associated with the Frequency of CD8 Cells Expressing HLA-DR/DP/DQ

Author

Alessandra Ruggiero, Ward De Spiegelaere, Alessandro Cozzi-Lepri, Maja Kiselinova, Georgios Pollakis, Apostolos Beloukas, Linos Vandekerckhove, Matthew Strain, Douglas Richman, Andrew Phillips, Anna Maria Geretti, Paola Vitiello, Nicola Mackie, Jonathan Ainsworth, Anele Waters, Frank Post, Simon Edwards, and Julie Fox

Subjects
Suppression, Reservoir, Persistence, Integration, Activation, Medicine, Medicine (General), R5-920
Abstract

Background: Characterising the correlates of HIV persistence improves understanding of disease pathogenesis and guides the design of curative strategies. This study investigated factors associated with integrated HIV-1 DNA load during consistently suppressive first-line antiretroviral therapy (ART). Method: Total, integrated, and 2-long terminal repeats (LTR) circular HIV-1 DNA, residual plasma HIV-1 RNA, T-cell activation markers, and soluble CD14 (sCD14) were measured in peripheral blood of 50 patients that had received 1–14 years of efavirenz-based or nevirapine-based therapy. Results: Integrated HIV-1 DNA load (per 106 peripheral blood mononuclear cells) was median 1.9 log10 copies (interquartile range 1.7–2.2) and showed a mean difference of 0.2 log10 copies per 10 years of suppressive ART (95% confidence interval −0.2, 0.6; p = 0.28). It was positively correlated with total HIV-1 DNA load and frequency of CD8+HLA-DR/DP/DQ+ cells, and was also higher in subjects with higher sCD14 levels, but showed no correlation with levels of 2-LTR circular HIV-1 DNA and residual plasma HIV-1 RNA, or the frequency of CD4+CD38+ and CD8+CD38+ cells. Adjusting for pre-ART viral load, duration of suppressive ART, CD4 cell counts, residual plasma HIV-1 RNA levels, and sCD14 levels, integrated HIV-1 DNA load was mean 0.5 log10 copies higher for each 50% higher frequency of CD8+HLA-DR/DP/DQ+ cells (95% confidence interval 0.2, 0.9; p = 0.01). Conclusions: The observed positive association between integrated HIV-1 DNA load and frequency of CD8+DR/DP/DQ+ cells indicates that a close correlation between HIV persistence and immune activation continues during consistently suppressive therapy. The inducers of the distinct activation profile warrant further investigation.

Published
2015
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