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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. Effect of second booster vaccinations and prior infection against SARS-CoV-2 in the UK SIREN healthcare worker cohortResearch in context

Author

Peter D. Kirwan, Victoria J. Hall, Sarah Foulkes, Ashley D. Otter, Katie Munro, Dominic Sparkes, Anna Howells, Naomi Platt, Jonathan Broad, David Crossman, Chris Norman, Diane Corrigan, Christopher H. Jackson, Michelle Cole, Colin S. Brown, Ana Atti, Jasmin Islam, Anne M. Presanis, Andre Charlett, Daniela De Angelis, Susan Hopkins, Tracy Lewis, Steve Bain, Rebeccah Thomas, John Geen, Carla Pothecary, Sean Cutler, John Northfield, Cathy Price, Johanne Tomlinson, Sarah Knight, Emily Macnaughton, Ekaterina Watson, Rajeka Lazarus, Aaran Sinclair, Joanne Galliford, Bridgett Masunda, Tabitha Mahungu, Alison Rodger, Esther Hanison, Simon Warren, Swati Jain, Mariyam Mirfenderesky, Natasha Mahabir, Rowan Pritchard-Jones, Diane Wycherley, Claire Gabriel, Elijah Matovu, Philippa Bakker, Simantee Guha, S. Gormley, James Pethick, Georgina Butt, Stacey Pepper, Luke Bedford, Paul Ridley, Jane Democratis, Manjula Meda, Anu Chawla, Fran Westwell, Nagesh Kalakonda, Sheena Khanduri, Allison Doel, Sumita Pai, Christian Hacon, Davis Nwaka, Veronica Mendez Moro, A. Moody, Cressida Auckland, Stephanie Prince, Thushan de Silva, Helen Shulver, A. Shah, C. Jones, Banerjee Subhro-Osuji, Angela Houston, Tim Planche, Martin Booth, Christopher Duff, Jonnie Aeron-Thomas, Ray Chaudhuri, David Hilton, Hannah Jory, Zehra'a Al-Khafaji, Philippa Kemsley, Ruth Longfellow, David Boss, Simon Brake, Louise Coke, Ngozi Elumogo, Scott Latham, Chinari Subudhi, Ina Hoad, Claire Thomas, Nihil Chitalia, Tracy Edmunds, Helen Ashby, John Elliott, Beverley Wilkinson, Abby Rand, Catherine Thompson, K. Agwuh, Anna Grice, Kelly Moran, Vijayendra Waykar, Yvonne Lester, Lauren Sach, Kathryn Court, Nikki White, Clair Favager, Kyra Holliday, Jayne Harwood, Brendan Payne, Karen Burns, Lynda Fothergill, Alejandro Arenas-Pinto, Abigail Severn, Kerryanne Brown, Katherine Gray, Jane Dare, Qi Zheng, Kathryn Hollinshead, Robert Shorten, Alun Roebuck, Christopher Holmes, Martin Wiselka, Barzo Faris, Liane Marsh, Clare McAdam, Lisa Ditchfield, Zaman Qazzafi, G. Boyd, N. Wong, Sarah Brand, Jack Squires, John Ashcroft, Ismaelette Del Rosario, Joanne Howard, Emma Ward, Gemma Harrison, Joely Morgan, Claire Corless, Ruth Penn, Nick Wong, Manny Bagary, Nadezda Starkova, Mandy Beekes, Mandy Carnahan, Shivani Khan, Shekoo Mackay, Keneisha Lewis, Graham Pickard, Joy Dawson, Lauren Finlayson, Euan Cameron, Anne Todd, Sebastien Fagegaltier, Sally Mavin, Alexandra Cochrane, Andrew Gibson, Sam Donaldson, Kate Templeton, Martin Malcolm, Beth Smith, Devesh Dhasmana, Susan Fowler, Antonia Ho, Michael Murphy, Claire Beith, Manish Patel, Elizabeth Boyd, Val Irvine, Alison Grant, Rebecca Temple-Purcell, Clodagh Loughrey, Elinor Hanna, Frances Johnston, Angel Boulos, Fiona Thompson, Yuri Protaschik, Susan Regan, Tracy Donaghy, Maurice O'Kane, Omolola Akinbami, Paola Barbero, Tim Brooks, Meera Chand, Ferdinando Insalata, Palak Joshi, Anne-Marie O'Connell, Mary Ramsay, Ayoub Saei, Maria Zambon, Ezra Linley, Simon Tonge, Enemona Adaji, Omoyeni Adebiyi, Nick Andrews, Joanna Conneely, Paul Conneely, Angela Dunne, Simone Dyer, Hannah Emmett, Nipunadi Hettiarachchi, Nishanthan Kapirial, Jameel Khawam, Edward Monk, Sophie Russell, Andrew Taylor-Kerr, Jean Timeyin, Silvia D'Arcangelo, Cathy Rowe, Amanda Semper, Eileen Gallagher, Robert Kyffin, Lisa Cromey, Desmond Areghan, Jennifer Bishop, Melanie Dembinsky, Laura Dobbie, Josie Evans, David Goldberg, Lynne Haahr, Annelysse Jorgenson, Ayodeji Matuluko, Laura Naismith, Desy Nuryunarsih, Alexander Olaoye, Caitlin Plank, Lesley Price, Nicole Sergenson, Sally Stewart, Andrew Telfer, Jennifer Weir, Ellen De Lacy, Yvette Ellis, Susannah Froude, Guy Stevens, Linda Tyson, Susanna Dunachie, Paul Klenerman, Chris Duncan, Rebecca Payne, Lance Turtle, Alex Richter, Thushan De Silva, Eleanor Barnes, Daniel Wootton, Oliver Galgut, Jonathan Heeney, Helen Baxendale, Javier Castillo-Olivares, Rupert Beale, Edward Carr, Wendy Barclay, Maya Moshe, Massimo Palmarini, Brian Willett, John Kenneth Baillie, Jennie Evans, and Erika Aquino

Subjects
SARS-CoV-2, Vaccine effectiveness, Asymptomatic, Symptomatic, Healthcare worker, Cohort study, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: The protection of fourth dose mRNA vaccination against SARS-CoV-2 is relevant to current global policy decisions regarding ongoing booster roll-out. We aimed to estimate the effect of fourth dose vaccination, prior infection, and duration of PCR positivity in a highly-vaccinated and largely prior-COVID-19 infected cohort of UK healthcare workers. Methods: Participants underwent fortnightly PCR and regular antibody testing for SARS-CoV-2 and completed symptoms questionnaires. A multi-state model was used to estimate vaccine effectiveness (VE) against infection from a fourth dose compared to a waned third dose, with protection from prior infection and duration of PCR positivity jointly estimated. Findings: 1298 infections were detected among 9560 individuals under active follow-up between September 2022 and March 2023. Compared to a waned third dose, fourth dose VE was 13.1% (95% CI 0.9 to 23.8) overall; 24.0% (95% CI 8.5 to 36.8) in the first 2 months post-vaccination, reducing to 10.3% (95% CI −11.4 to 27.8) and 1.7% (95% CI −17.0 to 17.4) at 2–4 and 4–6 months, respectively. Relative to an infection >2 years ago and controlling for vaccination, 63.6% (95% CI 46.9 to 75.0) and 29.1% (95% CI 3.8 to 43.1) greater protection against infection was estimated for an infection within the past 0–6, and 6–12 months, respectively. A fourth dose was associated with greater protection against asymptomatic infection than symptomatic infection, whilst prior infection independently provided more protection against symptomatic infection, particularly if the infection had occurred within the previous 6 months. Duration of PCR positivity was significantly lower for asymptomatic compared to symptomatic infection. Interpretation: Despite rapid waning of protection, vaccine boosters remain an important tool in responding to the dynamic COVID-19 landscape; boosting population immunity in advance of periods of anticipated pressure, such as surging infection rates or emerging variants of concern. Funding: UK Health Security Agency, Medical Research Council, NIHR HPRU Oxford, Bristol, and others.

Published
2024
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3. 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)

Author

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

Published
2024
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4. Effect of second booster vaccinations and prior infection against SARS-CoV-2 in the UK SIREN healthcare worker cohort

Author

Lewis, Tracy, Bain, Steve, Thomas, Rebeccah, Geen, John, Pothecary, Carla, Cutler, Sean, Northfield, John, Price, Cathy, Tomlinson, Johanne, Knight, Sarah, Macnaughton, Emily, Watson, Ekaterina, Lazarus, Rajeka, Sinclair, Aaran, Galliford, Joanne, Masunda, Bridgett, Mahungu, Tabitha, Rodger, Alison, Hanison, Esther, Warren, Simon, Jain, Swati, Mirfenderesky, Mariyam, Mahabir, Natasha, Pritchard-Jones, Rowan, Wycherley, Diane, Gabriel, Claire, Matovu, Elijah, Bakker, Philippa, Guha, Simantee, Gormley, S., Pethick, James, Butt, Georgina, Pepper, Stacey, Bedford, Luke, Ridley, Paul, Democratis, Jane, Meda, Manjula, Chawla, Anu, Westwell, Fran, Kalakonda, Nagesh, Khanduri, Sheena, Doel, Allison, Pai, Sumita, Hacon, Christian, Nwaka, Davis, Moro, Veronica Mendez, Moody, A., Auckland, Cressida, Prince, Stephanie, de Silva, Thushan, Shulver, Helen, Shah, A., Jones, C., Subhro-Osuji, Banerjee, Houston, Angela, Planche, Tim, Booth, Martin, Duff, Christopher, Aeron-Thomas, Jonnie, Chaudhuri, Ray, Hilton, David, Jory, Hannah, Al-Khafaji, Zehra'a, Kemsley, Philippa, Longfellow, Ruth, Boss, David, Brake, Simon, Coke, Louise, Elumogo, Ngozi, Latham, Scott, Subudhi, Chinari, Hoad, Ina, Thomas, Claire, Chitalia, Nihil, Edmunds, Tracy, Ashby, Helen, Elliott, John, Wilkinson, Beverley, Rand, Abby, Thompson, Catherine, Agwuh, K., Grice, Anna, Moran, Kelly, Waykar, Vijayendra, Lester, Yvonne, Sach, Lauren, Court, Kathryn, White, Nikki, Favager, Clair, Holliday, Kyra, Harwood, Jayne, Payne, Brendan, Burns, Karen, Fothergill, Lynda, Arenas-Pinto, Alejandro, Severn, Abigail, Brown, Kerryanne, Gray, Katherine, Dare, Jane, Zheng, Qi, Hollinshead, Kathryn, Shorten, Robert, Roebuck, Alun, Holmes, Christopher, Wiselka, Martin, Faris, Barzo, Marsh, Liane, McAdam, Clare, Ditchfield, Lisa, Qazzafi, Zaman, Boyd, G., Wong, N., Brand, Sarah, Squires, Jack, Ashcroft, John, Rosario, Ismaelette Del, Howard, Joanne, Ward, Emma, Harrison, Gemma, Morgan, Joely, Corless, Claire, Penn, Ruth, Wong, Nick, Bagary, Manny, Starkova, Nadezda, Beekes, Mandy, Carnahan, Mandy, Khan, Shivani, Mackay, Shekoo, Lewis, Keneisha, Pickard, Graham, Dawson, Joy, Finlayson, Lauren, Cameron, Euan, Todd, Anne, Fagegaltier, Sebastien, Mavin, Sally, Cochrane, Alexandra, Gibson, Andrew, Donaldson, Sam, Templeton, Kate, Malcolm, Martin, Smith, Beth, Dhasmana, Devesh, Fowler, Susan, Ho, Antonia, Murphy, Michael, Beith, Claire, Patel, Manish, Boyd, Elizabeth, Irvine, Val, Grant, Alison, Temple-Purcell, Rebecca, Loughrey, Clodagh, Hanna, Elinor, Johnston, Frances, Boulos, Angel, Thompson, Fiona, Protaschik, Yuri, Regan, Susan, Donaghy, Tracy, O'Kane, Maurice, Akinbami, Omolola, Barbero, Paola, Brooks, Tim, Chand, Meera, Insalata, Ferdinando, Joshi, Palak, O'Connell, Anne-Marie, Ramsay, Mary, Saei, Ayoub, Zambon, Maria, Linley, Ezra, Tonge, Simon, Adaji, Enemona, Adebiyi, Omoyeni, Andrews, Nick, Conneely, Joanna, Conneely, Paul, Dunne, Angela, Dyer, Simone, Emmett, Hannah, Hettiarachchi, Nipunadi, Kapirial, Nishanthan, Khawam, Jameel, Monk, Edward, Russell, Sophie, Taylor-Kerr, Andrew, Timeyin, Jean, D'Arcangelo, Silvia, Rowe, Cathy, Semper, Amanda, Gallagher, Eileen, Kyffin, Robert, Cromey, Lisa, Areghan, Desmond, Bishop, Jennifer, Dembinsky, Melanie, Dobbie, Laura, Evans, Josie, Goldberg, David, Haahr, Lynne, Jorgenson, Annelysse, Matuluko, Ayodeji, Naismith, Laura, Nuryunarsih, Desy, Olaoye, Alexander, Plank, Caitlin, Price, Lesley, Sergenson, Nicole, Stewart, Sally, Telfer, Andrew, Weir, Jennifer, De Lacy, Ellen, Ellis, Yvette, Froude, Susannah, Stevens, Guy, Tyson, Linda, Dunachie, Susanna, Klenerman, Paul, Duncan, Chris, Payne, Rebecca, Turtle, Lance, Richter, Alex, De Silva, Thushan, Barnes, Eleanor, Wootton, Daniel, Galgut, Oliver, Heeney, Jonathan, Baxendale, Helen, Castillo-Olivares, Javier, Beale, Rupert, Carr, Edward, Barclay, Wendy, Moshe, Maya, Palmarini, Massimo, Willett, Brian, Baillie, John Kenneth, Evans, Jennie, Aquino, Erika, Kirwan, Peter D., Hall, Victoria J., Foulkes, Sarah, Otter, Ashley D., Munro, Katie, Sparkes, Dominic, Howells, Anna, Platt, Naomi, Broad, Jonathan, Crossman, David, Norman, Chris, Corrigan, Diane, Jackson, Christopher H., Cole, Michelle, Brown, Colin S., Atti, Ana, Islam, Jasmin, Presanis, Anne M., Charlett, Andre, De Angelis, Daniela, and Hopkins, Susan

Published
2024
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5. Bone turnover change after randomized switch from tenofovir disoproxil to tenofovir alafenamide fumarate in men with HIV

Author

Moore, Amelia E.B., Burns, James E., Sally, Deirdre, Milinkovic, Ana, Krokos, Georgios, John, Joemon, Rookyard, Christopher, Borca, Alessandro, Pool, Erica R.M., Tostevin, Anna, Harman, Alyss, Dulnoan, Dwight S., Gilson, Richard, Arenas-Pinto, Alejandro, Cook, Gary J.R., Saunders, John, Dunn, David, Blake, Glen M., and Pett, Sarah L.

Published
2024
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6. How surgical Trainee Research Collaboratives achieve success: a mixed methods study to develop trainee engagement strategies

Author

Graeme Maclennan, Nick Heywood, Clare Clement, Natalie S Blencowe, Jane Blazeby, Dmitri Nepogodiev, Laura Magill, Alejandro Arenas-Pinto, Tom Pinkney, J Athene Lane, James Glasbey, Victoria Hardy, Karen Coulman, Jonathan Alistair Cook, Claire Snowdon, Richard Bulbulia, and Zoe Hilton

Subjects
Medicine
Abstract

Objectives This study aimed to understand the role of surgical Trainee Research Collaboratives (TRCs) in conducting randomised controlled trials and identify strategies to enhance trainee engagement in trials.Design This is a mixed methods study. We used observation of TRC meetings, semi-structured interviews and an online survey to explore trainees’ motivations for engagement in trials and TRCs, including barriers and facilitators. Interviews were analysed thematically, alongside observation field notes. Survey responses were analysed using descriptive statistics. Strategies to enhance TRCs were developed at a workshop by 13 trial methodologists, surgical trainees, consultants and research nurses.Setting This study was conducted within a secondary care setting in the UK.Participants The survey was sent to registered UK surgical trainees. TRC members and linked stakeholders across surgical specialties and UK regions were purposefully sampled for interviews.Results We observed 5 TRC meetings, conducted 32 semi-structured interviews and analysed 73 survey responses. TRCs can mobilise trainees thus gaining wider access to patients. Trainees engaged with TRCs to improve patient care, surgical evidence and to help progress their careers. Trainees valued the TRC infrastructure, research expertise and mentoring. Challenges for trainees included clinical and other priorities, limited time and confidence, and recognition, especially by authorship. Key TRC strategies were consultant support, initial simple rapid studies, transparency of involvement and recognition for trainees (including authorship policies) and working with Clinical Trials Units and research nurses. A 6 min digital story on YouTube disseminated these strategies.Conclusion Trainee surgeons are mostly motivated to engage with trials and TRCs. Trainee engagement in TRCs can be enhanced through building relationships with key stakeholders, maximising multi-disciplinary working and offering training and career development opportunities.

Published
2023
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7. Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial

Author

Tierney, John, Vogel, Susan E., McNay, Laura A., Cahill, Kelly, Crew, Page, Sardana, Ratna, Segal Raim, Sharo, Shaw-Saliba, Katy, Atri, Negin, Miller, Mark, Vallee, David, Chung, Lucy, Delph, Yvette, Adam, Stacey J., Read, Sarah, Draghia-Akli, Ruxandra, Harrigan, Rachel, Carlsen, Amy, Carter, Anita, DuChene, Alain, Eckroth, Kate, Frase, Alex, Harrison, Merrie, Meger, Sue, Quan, Kien, Quan, Siu Fun, Reilly, Cavan, Thompson, Greg, Walski, Jamie, Moskowitz, Alan J., Bagiella, Emilia, Moquete, Ellen, O'Sullivan, Karen, Marks, Mary E., Accardi, Evan, Kinzel, Emily, Bedoya, Gabriela, Gupta, Lopa, Overbey, Jessica R., Padillia, Maria L., Santos, Milerva, Gillinov, Marc A., Miller, Marissa A., Taddei-Peters, Wendy C., Fenton, Kathleen, Smith, Peter K., Vekstein, Andrew M., Ko, Emily R., Al-Hegelan, Mashael S., McGowan, Lauren M., Motta, Mary, Howell, Shauna, Bent, Francine, Kalager, Rachel, Chan, Emmanuel, Aloor, Heather L., Griffin, S. Michelle, Covington, Anna, McLendon-Arvik, Beth, Bussadori, Barbara, Miller-Bell, Mary, Sampey, Cathy, Gaver, Vincent, Hollister, Beth A., Giangiacomo, Dana M., Pauley, Alena, Patel, Aashay, Classon, Chris, Frazier, Madison, Osborne, Robyn, Conlon, Debbi H., Joshi, Marybeth, Gottlieb, Robert L., Mack, Michael, Berhe, Mezgebe, Haley, Clinton, Dishner, Emma, Bettacchi, Christopher, Golden, Kevin, Duhaime, Erin, Ryan, Madison, Tallmadge, Catherine, Estrada, Lorie, Jones, Felecia, Villa, Samantha, Wang, Samantha, Robert, Raven, Coleman, Tanquinisha, Clariday, Laura, Baker, Rebecca, Hurutado-Rodriguez, Mariana, Iram, Nazia, Fresnedo, Michelle, Davis, Allyson, Leonard, Kiara, Ramierez, Noelia, Thammavong, Jon, Duque, Krizia, Turner, Emma, Fisher, Tammy, Robinson, Dianna, Ransom, Desirae, Maldonado, Nicholas, Lusk, Erica, Killian, Aaron, Palacios, Adriana, Solis, Edilia, Jerrow, Janet, Watts, Matthew, Whitacre, Heather, Cothran, Elizabeth, Bender, William, Miller, Jeffrey, Nugent, Katherine, Farrington, Woodrow, Baio, Kim T., McBride, Mary K., Fielding, Michele, Mathewson, Sonya, Porte, Kristina, Haley, Elizabeth, Rogers, Susan, Tyler, Derrick, Perin, Emerson, Costello, Briana, Postalian, Alexander, Sohail, Rizwan, Hinsu, Punit, Watson, Carolyn, Kappenman, Casey, Chen, James, Walker, Kim, Fink, Melyssa, Phillip, Gabrielle, Mahon, Kim, Sturgis, Lydia, Maher, Patrick, Rogers, Linda, Ng, Nicole, Marshall, Jason, Bassily-Marcus, Adel, Cohen, Ivy, Ramoo, Shamini, Malhotra, Aryan, Kessler, Jonathan, Goetz, Rebekah, Badhwar, Vinay, Hayanga, Jeremiah, Giblin Sutton, Lisa, Williams, Roger, Berry Bartolo, Elizabeth, Walker, Dmitry, Bunner, Robin, Glaze, Chad, Aucremanne, Tanja, Bishop, James, Kelley, Macey, Peterson, Autumn, Sauerborn, Erica, Reckart, Robin, Miller, Brittany, Mittel, Aaron, Darmanian, Anita, Rosen, Amanda, Madahar, Purnema, Schicchi, John, Gosek, Katarzyna, Dzierba, Amy, Wahab, Romina, Eng, Connie, Al-Saadi, Mukhtar, Zahiruddin, Faisal, Syed, Mohi, George, Michael, Patel, Varsha, Onwunyi, Chisom, Barroso da Costa, Rosa, North, Crystal, Ringwood, Nancy, Fitzgerald, Laura, Muzikansky, Ariela, Morse, Richard, Brower, Roy G., Reineck, Lora A., Bienstock, Karen, Hou, Peter, Steingrub, Jay S., Tidswell, Mark A., Kozikowski, Lori-Ann, Kardos, Cynthia, De Souza, Leslie, Talmor, Daniel, Shapiro, Nathan, Hibbert, Kathryn, Brait, Kelsey, Kone, Mamary, Hendey, Gregory, Kangelaris, Kirsten N., Ashktorab, Kimia, Gropper, Rachel, Agrawal, Anika, Timothy, Kelly, Zhou, Hanjing, Hughes, Alyssa, Garcia, Rebekah, Torres, Adrian, Hernandez-Almaraz, Maria Elena, Vojnik, Rosemary, Perez, Cynthia, McDowell, Jordan, Chang, Steven Y., Vargas, Julia, Moss, Marc, McKeehan, Jeffrey, Higgins, Carrie, Johnson, Emily, Slaughter, Suzanne, Wyles, David, Hiller, Terra, Oakes, Judy, Garcia, Ana, Gravitz, Stephanie, Lyle, Carolynn, Swanson, Diandra, Gong, Michelle Ng., Richardson, Lynnne D., Chen, Jen-Ting, Moskowitz, Ari, Mohamed, Amira, Lopez, Brenda, Amosu, Omowunmi, Tzehaie, Hiwet, Boujid, Sabah, Bixby, Billie, Lopez, Anitza A., Durley, JaVon, Gilson, Boris, Hite, R. Duncan, Wang, Henry, Wiedemann, Hebert P., Mehkri, Omar, Ashok, Kiran, King, Alexander, Brennan, Connery, Exline, Matthew C., Englert, Joshua A., Karow, Sarah, Schwartz, Elizabeth, So, Preston, So, Madison, Krol, Olivia F., Briceno Parra, Genesis I., Mills, Emmanuel Nii Lantei, Oh, Minn, Pena, Jose, Martínez, Jesús Alejandro, Jackman, Susan E., Bayoumi, Emad, Pascual, Ethan, Caudill, Antonina, Chen, Po-En, Richardson, Tabia, Clapham, Gregg J., Herrera, Lisa, Ojukwu, Cristabelle, Fine, Devin, Gomez, Millie J., Choi-Kuaea, Yunhee, Weissberg, Gwendolyn, Isip, Katherine, Mattison, Brittany, Tran, Dana, Emilov Dukov, Jennifer, Chung, Paul, Kang, Bo Ran, Escobar, Lauren, Tran, Trung, Baig, Saba, Wallick, Julie A., Duven, Alexandria M., Fletcher, Dakota D., Gundel, Stephanie, Fuentes, Megan, Newton, Maranda, Peterson, Emily, Jiang, Kelsey, Files, D. Clark, Miller, Chadwick, Lematty, Caitlin, Rasberry, April, Warden, Ashley, Bledsoe, Joseph, Knowlton, Kirk, Knox, Daniel B., Klippel, Carolyn, Armbruster, Brent P., Applegate, Darrin, Imel, Karah, Fergus, Melissa, Rahmati, Kasra, Jensen, Hannah, Aston, Valerie T., Jeppson, Joshua, Marshall, J. Hunter, Lumpkin, Jenna, Smith, Cassie, Burke, Tyler, Gray, Andrew, Paine, Robert, Callahan, Sean, Yamane, Misty, Waddoups, Lindsey, Rice, Todd W., Johnson, Jakea, Gray, Christopher, Hays, Margaret, Roth, Megan, Musick, Sarah, Miller, Karen, Semler, Matthew W., Popielski, Laura, Kambo, Amy, Viens, Kimberly, Turner, Melissa, Vjecha, Michael J., Denyer, Rachel, Khosla, Rahul, Rajendran, Bindu, Gonzales, Melissa, Moriarty, Theresa, Biswas, Kousick, Harrington, Cristin, Garcia, Amanda, Bremer, Tammy, Burke, Tara, Koker, Brittany, Pittman, David, Vasudeva, Shikha S., Anholm, James D., Specht, Lennard, Rodriguez, Aimee, Ngo, Han, Duong, Lien, Previte, Matthew, Raben, Dorthe, Nielsen, Charlotte B., Friis Larsen, Jakob, Peters, Lars, Matthews, Gail, Kelleher, Anthony, Polizzotto, Mark, Carey, Catherine, Chang, Christina, Dharan, Nila, Hough, Sally, Virachit, Sophie, Davidson, Sarah, Bice, Daniel J., Ognenovska, Katherine, Cabrera, Gesalit, Flynn, Ruth, Abdelghany, Mazin, Baseler, Beth, Teitelbaum, Marc, Holley, H. Preston, Jankelevich, Shirley, Adams, Amy, Becker, Nancy, Doleny, Suzanne, Hissey, Debbie, Simpson, Shelly, Kim, Mi Ha, Beeler, Joy, Harmon, Liam, Vanderpuye, Sharon, Yeon, Lindsey, Frye, Leanna, Rudzinski, Erin, Buehn, Molly, Eccard-Koons, Vanessa, Frary, Sadie, MacDonalad, Leah, Cash, Jennifer, Hoopengardner, Lisa, Linton, Jessica, Nelson, Michaela, Spinelli-Nadzam, Mary, Proffitt, Calvin, Lee, Christopher, Engel, Theresa, Fontaine, Laura, Osborne, CK, Hohn, Matt, Galcik, Michael, Thompson, DeeDee, Sandrus, Jen, Manchard, Jon, Giri, Jiwan, Kopka, Stacy, Chang, Weizhong, Sherman, Brad T., Rupert, Adam W., Highbarger, Helene, Baseler, Michael, Lallemand, Perrine, Rehman, Tauseef, Imamichi, Tom, Laverdure, Sylvain, Paudel, Sharada, Cook, Kyndal, Haupt, Kendra, Hazen, Allison, Badralmaa, Yunden, Highbarger, Jeroen, McCormack, Ashley, Gerry, Norman P., Smith, Kenneth, Patel, Bhakti, Domeraski, Nadia, Hoover, Marie L., DuChateau, Nadine, Flosi, Adam, Nelson, Rich, Stojanovic, Jelena, Wenner, Christine, Brown, Samuel M, Barkauskas, Christina E, Grund, Birgit, Sharma, Shweta, Phillips, Andrew N, Leither, Lindsay, Peltan, Ithan D, Lanspa, Michael, Gilstrap, Daniel L, Mourad, Ahmad, Lane, Kathleen, Beitler, Jeremy R, Serra, Alexis L, Garcia, Ivan, Almasri, Eyad, Fayed, Mohamed, Hubel, Kinsley, Harris, Estelle S, Middleton, Elizabeth A, Barrios, Macy A G, Mathews, Kusum S, Goel, Neha N, Acquah, Samuel, Mosier, Jarrod, Hypes, Cameron, Salvagio Campbell, Elizabeth, Khan, Akram, Hough, Catherine L, Wilson, Jennifer G, Levitt, Joseph E, Duggal, Abhijit, Dugar, Siddharth, Goodwin, Andrew J, Terry, Charles, Chen, Peter, Torbati, Sam, Iyer, Nithya, Sandkovsky, Uriel S, Johnson, Nicholas J, Robinson, Bryce R H, Matthay, Michael A, Aggarwal, Neil R, Douglas, Ivor S, Casey, Jonathan D, Hache-Marliere, Manuel, Georges Youssef, J, Nkemdirim, William, Leshnower, Brad, Awan, Omar, Pannu, Sonal, O'Mahony, Darragh Shane, Manian, Prasad, Awori Hayanga, J W, Wortmann, Glenn W, Tomazini, Bruno M, Miller, Robert F, Jensen, Jens-Ulrik, Murray, Daniel D, Bickell, Nina A, Zatakia, Jigna, Burris, Sarah, Higgs, Elizabeth S, Natarajan, Ven, Dewar, Robin L, Schechner, Adam, Kang, Nayon, Arenas-Pinto, Alejandro, Hudson, Fleur, Ginde, Adit A, Self, Wesley H, Rogers, Angela J, Oldmixon, Cathryn F, Morin, Haley, Sanchez, Adriana, Weintrob, Amy C, Cavalcanti, Alexandre Biasi, Davis-Karim, Anne, Engen, Nicole, Denning, Eileen, Taylor Thompson, B, Gelijns, Annetine C, Kan, Virginia, Davey, Victoria J, Lundgren, Jens D, Babiker, Abdel G, Neaton, James D, and Lane, H Clifford

Published
2023
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8. Derivation of a Protein Risk Score for Cardiovascular Disease Among a Multiracial and Multiethnic HIV+ Cohort

Author

Sandra E. Safo, Lillian Haine, Jason Baker, Cavan Reilly, Daniel Duprez, James D. Neaton, Mamta K. Jain, Alejandro Arenas‐Pinto, Mark Polizzotto, and Therese Staub

Subjects
cardiovascular disease, HIV, Olink, protein biomarkers, proteomics, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background Cardiovascular disease risk prediction models underestimate CVD risk in people living with HIV (PLWH). Our goal is to derive a risk score based on protein biomarkers that could be used to predict CVD in PLWH. Methods and Results In a matched case–control study, we analyzed normalized protein expression data for participants enrolled in 1 of 4 trials conducted by INSIGHT (International Network for Strategic Initiatives in Global HIV Trials). We used dimension reduction, variable selection and resampling methods, and multivariable conditional logistic regression models to determine candidate protein biomarkers and to generate a protein score for predicting CVD in PLWH. We internally validated our findings using bootstrap. A protein score that was derived from 8 proteins (including HGF [hepatocyte growth factor] and interleukin‐6) was found to be associated with an increased risk of CVD after adjustment for CVD and HIV factors (odds ratio: 2.17 [95% CI: 1.58–2.99]). The protein score improved CVD prediction when compared with predicting CVD risk using the individual proteins that comprised the protein score. Individuals with a protein score above the median score were 3.10 (95% CI, 1.83–5.41) times more likely to develop CVD than those with a protein score below the median score. Conclusions A panel of blood biomarkers may help identify PLWH at a high risk for developing CVD. If validated, such a score could be used in conjunction with established factors to identify CVD at‐risk individuals who might benefit from aggressive risk reduction, ultimately shedding light on CVD pathogenesis in PLWH.

Published
2023
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9. Peripheral Neuropathy in Virologically Suppressed People Living with HIV: Evidence from the PIVOT Trial

Author

Anna L. Schuldt, Henry Bern, Melanie Hart, Mark Gompels, Alan Winston, Amanda Clarke, Fabian Chen, Wolfgang Stöhr, Amanda Heslegrave, Nicholas I. Paton, Axel Petzold, and Alejandro Arenas-Pinto

Subjects
peripheral neuropathy, HIV, monotherapy, protease inhibitor, metabolic syndrome, Microbiology, QR1-502
Abstract

The aim of this study is to identify the factors associated with peripheral neuropathy and to explore neurofilament light chain (NfL) as a biomarker for peripheral neuropathy (PN) in effectively virologically suppressed adults living with HIV. All protease inhibitor monotherapy versus ongoing triple therapy in the long-term management of HIV infection (PIVOT) trial participants with data on PN at baseline were included in the study. NfL plasma levels (pNfL) were measured in a sub-set of participants. Multivariable logistic regression was used to examine the associations of PN with potential risk factors (including age, sex, nadir CD4 cell count, history of dideoxynucleoside (d-drugs) exposure, and blood glucose levels) and NfL levels. Of the 585 participants included, 131 (22.4%) reported PN during the study period (median of 44 months). The participants were predominantly male (76.6%), White (68.2%), and virologically suppressed for a median period of 37 months (range of 20–63) before recruitment. The age at baseline was 44.3 years (standard deviation (SD) of 9.2). PN was independently associated with age (adjusted odds ratio (aOR) = 1.35, 95% CI of 1.20–1.52; additional 5 years), history of d-drugs (aOR 1.88, 95% CI of 1.12–3.16), height (aOR 1.19, 95% CI of 1.05–1.35; additional 5 cm), nadir CD4 cell count (aOR 1.10 CI of 1.00–1.20; 50 cells fewer), and metabolic syndrome (aOR 2.31, 95% CI of 1.27 4.20), but not pNfL. The excess risk for PN associated with d-drug use remains after the exposure has stopped for years, suggesting non-reversible toxicity. In people with HIV, metabolic syndrome is independently associated with PN. There was no additional value for pNfL as a screening test for peripheral neuropathy in effectively virologically suppressed adults living with HIV.

Published
2023
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10. No neurocognitive advantage for immediate antiretroviral treatment in adults with greater than 500 CD4+ T-cell counts

Author

Wright, Edwina J, Grund, Birgit, Robertson, Kevin R, Cysique, Lucette, Brew, Bruce J, Collins, Gary L, Poehlman-Roediger, Mollie, Vjecha, Michael J, Penalva de Oliveira, Augusto César, Standridge, Barbara, Carey, Cate, Avihingsanon, Anchalee, Florence, Eric, Lundgren, Jens D, Arenas-Pinto, Alejandro, Mueller, Nicolas J, Winston, Alan, Nsubuga, Moses S, Lal, Luxshimi, and Price, Richard W

Subjects
Infectious Diseases, HIV/AIDS, Clinical Research, Neurosciences, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, AIDS Dementia Complex, Adult, Anti-Retroviral Agents, CD4 Lymphocyte Count, Female, HIV Infections, Humans, Longitudinal Studies, Male, Secondary Prevention, Treatment Outcome, antiretroviral treatment, central nervous system, HAND, HIV, neurocognitive impairment, INSIGHT START Neurology Substudy Group, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Virology
Abstract

ObjectiveTo compare the effect of immediate versus deferred antiretroviral treatment (ART) on neuropsychological test performance in treatment-naive HIV-positive adults with more than 500 CD4 cells/μl.DesignRandomized trial.MethodsThe START parent study randomized participants to commence immediate versus deferred ART until CD4 less than 350 cells/μl. The START Neurology substudy used eight neuropsychological tests, at baseline, months 4, 8, 12 and annually, to compare groups for changes in test performance. Test results were internally standardized to z-scores. The primary outcome was the average of the eight test z-scores (QNPZ-8). Mean changes in QNPZ-8 from baseline were compared by intent-to-treat using longitudinal mixed models. Changes from baseline to specific time points were compared using ANCOVA models.ResultsThe 592 participants had a median age of 34 years; median baseline CD4 count was 629 cells/μl; the mean follow-up was 3.4 years. ART was used for 94 and 32% of accrued person-years in the immediate and deferred groups, respectively. There was no difference between the immediate and deferred ART groups in QNPZ-8 change through follow-up [-0.018 (95% CI -0.062 to 0.027, P = 0.44)], or at any visit. However, QNPZ-8 scores increased in both arms during the first year, by 0.22 and 0.24, respectively (P

Published
2018

11. SARS-CoV-2 inhibition using a mucoadhesive, amphiphilic chitosan that may serve as an anti-viral nasal spray

Author

Krzysztof Pyrć, Aleksandra Milewska, Emilia Barreto Duran, Paweł Botwina, Agnieszka Dabrowska, Malwina Jedrysik, Malgorzata Benedyk, Rui Lopes, Alejandro Arenas-Pinto, Moutaz Badr, Ryan Mellor, Tammy L. Kalber, Delmiro Fernandez-Reyes, Andreas G. Schätzlein, and Ijeoma F. Uchegbu

Subjects
Medicine, Science
Abstract

Abstract There are currently no cures for coronavirus infections, making the prevention of infections the only course open at the present time. The COVID-19 pandemic has been difficult to prevent, as the infection is spread by respiratory droplets and thus effective, scalable and safe preventive interventions are urgently needed. We hypothesise that preventing viral entry into mammalian nasal epithelial cells may be one way to limit the spread of COVID-19. Here we show that N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (GCPQ), a positively charged polymer that has been through an extensive Good Laboratory Practice toxicology screen, is able to reduce the infectivity of SARS-COV-2 in A549ACE2+ and Vero E6 cells with a log removal value of − 3 to − 4 at a concentration of 10–100 μg/ mL (p

Published
2021
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13. Effect of second booster vaccinations and prior infection against SARS-CoV-2 in the UK SIREN healthcare worker cohort

Author

Kirwan, Peter D., primary, Hall, Victoria J., additional, Foulkes, Sarah, additional, Otter, Ashley D., additional, Munro, Katie, additional, Sparkes, Dominic, additional, Howells, Anna, additional, Platt, Naomi, additional, Broad, Jonathan, additional, Crossman, David, additional, Norman, Chris, additional, Corrigan, Diane, additional, Jackson, Christopher H., additional, Cole, Michelle, additional, Brown, Colin S., additional, Atti, Ana, additional, Islam, Jasmin, additional, Presanis, Anne M., additional, Charlett, Andre, additional, De Angelis, Daniela, additional, Hopkins, Susan, additional, Lewis, Tracy, additional, Bain, Steve, additional, Thomas, Rebeccah, additional, Geen, John, additional, Pothecary, Carla, additional, Cutler, Sean, additional, Northfield, John, additional, Price, Cathy, additional, Tomlinson, Johanne, additional, Knight, Sarah, additional, Macnaughton, Emily, additional, Watson, Ekaterina, additional, Lazarus, Rajeka, additional, Sinclair, Aaran, additional, Galliford, Joanne, additional, Masunda, Bridgett, additional, Mahungu, Tabitha, additional, Rodger, Alison, additional, Hanison, Esther, additional, Warren, Simon, additional, Jain, Swati, additional, Mirfenderesky, Mariyam, additional, Mahabir, Natasha, additional, Pritchard-Jones, Rowan, additional, Wycherley, Diane, additional, Gabriel, Claire, additional, Matovu, Elijah, additional, Bakker, Philippa, additional, Guha, Simantee, additional, Gormley, S., additional, Pethick, James, additional, Butt, Georgina, additional, Pepper, Stacey, additional, Bedford, Luke, additional, Ridley, Paul, additional, Democratis, Jane, additional, Meda, Manjula, additional, Chawla, Anu, additional, Westwell, Fran, additional, Kalakonda, Nagesh, additional, Khanduri, Sheena, additional, Doel, Allison, additional, Pai, Sumita, additional, Hacon, Christian, additional, Nwaka, Davis, additional, Moro, Veronica Mendez, additional, Moody, A., additional, Auckland, Cressida, additional, Prince, Stephanie, additional, de Silva, Thushan, additional, Shulver, Helen, additional, Shah, A., additional, Jones, C., additional, Subhro-Osuji, Banerjee, additional, Houston, Angela, additional, Planche, Tim, additional, Booth, Martin, additional, Duff, Christopher, additional, Aeron-Thomas, Jonnie, additional, Chaudhuri, Ray, additional, Hilton, David, additional, Jory, Hannah, additional, Al-Khafaji, Zehra'a, additional, Kemsley, Philippa, additional, Longfellow, Ruth, additional, Boss, David, additional, Brake, Simon, additional, Coke, Louise, additional, Elumogo, Ngozi, additional, Latham, Scott, additional, Subudhi, Chinari, additional, Hoad, Ina, additional, Thomas, Claire, additional, Chitalia, Nihil, additional, Edmunds, Tracy, additional, Ashby, Helen, additional, Elliott, John, additional, Wilkinson, Beverley, additional, Rand, Abby, additional, Thompson, Catherine, additional, Agwuh, K., additional, Grice, Anna, additional, Moran, Kelly, additional, Waykar, Vijayendra, additional, Lester, Yvonne, additional, Sach, Lauren, additional, Court, Kathryn, additional, White, Nikki, additional, Favager, Clair, additional, Holliday, Kyra, additional, Harwood, Jayne, additional, Payne, Brendan, additional, Burns, Karen, additional, Fothergill, Lynda, additional, Arenas-Pinto, Alejandro, additional, Severn, Abigail, additional, Brown, Kerryanne, additional, Gray, Katherine, additional, Dare, Jane, additional, Zheng, Qi, additional, Hollinshead, Kathryn, additional, Shorten, Robert, additional, Roebuck, Alun, additional, Holmes, Christopher, additional, Wiselka, Martin, additional, Faris, Barzo, additional, Marsh, Liane, additional, McAdam, Clare, additional, Ditchfield, Lisa, additional, Qazzafi, Zaman, additional, Boyd, G., additional, Wong, N., additional, Brand, Sarah, additional, Squires, Jack, additional, Ashcroft, John, additional, Rosario, Ismaelette Del, additional, Howard, Joanne, additional, Ward, Emma, additional, Harrison, Gemma, additional, Morgan, Joely, additional, Corless, Claire, additional, Penn, Ruth, additional, Wong, Nick, additional, Bagary, Manny, additional, Starkova, Nadezda, additional, Beekes, Mandy, additional, Carnahan, Mandy, additional, Khan, Shivani, additional, Mackay, Shekoo, additional, Lewis, Keneisha, additional, Pickard, Graham, additional, Dawson, Joy, additional, Finlayson, Lauren, additional, Cameron, Euan, additional, Todd, Anne, additional, Fagegaltier, Sebastien, additional, Mavin, Sally, additional, Cochrane, Alexandra, additional, Gibson, Andrew, additional, Donaldson, Sam, additional, Templeton, Kate, additional, Malcolm, Martin, additional, Smith, Beth, additional, Dhasmana, Devesh, additional, Fowler, Susan, additional, Ho, Antonia, additional, Murphy, Michael, additional, Beith, Claire, additional, Patel, Manish, additional, Boyd, Elizabeth, additional, Irvine, Val, additional, Grant, Alison, additional, Temple-Purcell, Rebecca, additional, Loughrey, Clodagh, additional, Hanna, Elinor, additional, Johnston, Frances, additional, Boulos, Angel, additional, Thompson, Fiona, additional, Protaschik, Yuri, additional, Regan, Susan, additional, Donaghy, Tracy, additional, O'Kane, Maurice, additional, Akinbami, Omolola, additional, Barbero, Paola, additional, Brooks, Tim, additional, Chand, Meera, additional, Insalata, Ferdinando, additional, Joshi, Palak, additional, O'Connell, Anne-Marie, additional, Ramsay, Mary, additional, Saei, Ayoub, additional, Zambon, Maria, additional, Linley, Ezra, additional, Tonge, Simon, additional, Adaji, Enemona, additional, Adebiyi, Omoyeni, additional, Andrews, Nick, additional, Conneely, Joanna, additional, Conneely, Paul, additional, Dunne, Angela, additional, Dyer, Simone, additional, Emmett, Hannah, additional, Hettiarachchi, Nipunadi, additional, Kapirial, Nishanthan, additional, Khawam, Jameel, additional, Monk, Edward, additional, Russell, Sophie, additional, Taylor-Kerr, Andrew, additional, Timeyin, Jean, additional, D'Arcangelo, Silvia, additional, Rowe, Cathy, additional, Semper, Amanda, additional, Gallagher, Eileen, additional, Kyffin, Robert, additional, Cromey, Lisa, additional, Areghan, Desmond, additional, Bishop, Jennifer, additional, Dembinsky, Melanie, additional, Dobbie, Laura, additional, Evans, Josie, additional, Goldberg, David, additional, Haahr, Lynne, additional, Jorgenson, Annelysse, additional, Matuluko, Ayodeji, additional, Naismith, Laura, additional, Nuryunarsih, Desy, additional, Olaoye, Alexander, additional, Plank, Caitlin, additional, Price, Lesley, additional, Sergenson, Nicole, additional, Stewart, Sally, additional, Telfer, Andrew, additional, Weir, Jennifer, additional, De Lacy, Ellen, additional, Ellis, Yvette, additional, Froude, Susannah, additional, Stevens, Guy, additional, Tyson, Linda, additional, Dunachie, Susanna, additional, Klenerman, Paul, additional, Duncan, Chris, additional, Payne, Rebecca, additional, Turtle, Lance, additional, Richter, Alex, additional, De Silva, Thushan, additional, Barnes, Eleanor, additional, Wootton, Daniel, additional, Galgut, Oliver, additional, Heeney, Jonathan, additional, Baxendale, Helen, additional, Castillo-Olivares, Javier, additional, Beale, Rupert, additional, Carr, Edward, additional, Barclay, Wendy, additional, Moshe, Maya, additional, Palmarini, Massimo, additional, Willett, Brian, additional, Baillie, John Kenneth, additional, Evans, Jennie, additional, and Aquino, Erika, additional

Published
2024
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14. Learning and memory function in young people with and without perinatal HIV in England

Author

Alejandro Arenas-Pinto, Ali Judd, Diane Melvin, Marthe Le Prevost, Caroline Foster, Kate Sturgeon, Alan Winston, Lindsay C. Thompson, Diana M. Gibb, Hannah Castro, and on behalf of the Adolescents and Adults Living with Perinatal HIV (AALPHI) Steering Committee

Subjects
Medicine, Science
Abstract

Learning and memory are important for successful education and career progression. We assess these functions in young people (YP) with perinatal HIV (PHIV) (with or without a previous AIDS-defining illness) and a comparable group of HIV-negative YP. 234 PHIV and 68 HIV-negative YP completed 9 tests; 5 National Institutes of Health (NIH) Toolbox tests (2 executive function, 1 speed of information processing, 2 memory); 2 Hopkins Verbal Learning Test Revised (HVLT-R) (learning (L), delayed recall (R)), and 2 verbal application measures. Z-scores for each test were calculated using normative data and averaged by domain where appropriate. The effect of predictors on test scores in the three domains with the lowest z-scores were analysed using linear regression. 139(59%) and 48(71%) PHIV and HIV-negative YP were female, 202(86%) and 52(76%) Black, and median age was 19 [17, 21] and 18 [16, 21] years respectively. 55(24%) PHIV had a previous Center for Disease Control and Prevention (CDC) class C AIDS-defining diagnosis (PHIV/C). For HVLT-R, there was a trend towards PHIV/C YP having the lowest mean z-scores (L -1.5 (95% CI -1.8,-1.2), R -1.7 (-2.0,-1.4)) followed by PHIV without a CDC C diagnosis (L -1.3 (-1.4,-1.1), R -1.4 (-1.5,-1.2)) and then the HIV-negative group (L -1.0 (-1.3,-0.7), R -1.1 (-1.3,-0.8)); all were greater than 1 SD below the reference mean. The same trend was seen for verbal application measures; however, z-scores were within 1 SD below the reference mean. NIH Toolbox tests were similar for all groups. In multivariable analyses PHIV/C and Black ethnicity predicted lower HVLT-R scores. Black ethnicity also predicted lower executive function scores, however each year increase in age predicted higher scores. In conclusion, cognitive performance in verbal learning and recall fell below population normative scores, and was more pronounced in PHIV/C, supporting wider findings that earlier antiretroviral therapy initiation, before the occurrence of AIDS-defining conditions, may protect aspects of cognitive development.

Published
2022

15. Peripheral Neuropathy in Virologically Suppressed People Living with HIV: Evidence from the PIVOT Trial

Author

Schuldt, Anna L., primary, Bern, Henry, additional, Hart, Melanie, additional, Gompels, Mark, additional, Winston, Alan, additional, Clarke, Amanda, additional, Chen, Fabian, additional, Stöhr, Wolfgang, additional, Heslegrave, Amanda, additional, Paton, Nicholas I., additional, Petzold, Axel, additional, and Arenas-Pinto, Alejandro, additional

Published
2023
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16. How surgical Trainee Research Collaboratives achieve success: a mixed methods study to develop trainee engagement strategies

Author

Clement, Clare, primary, Coulman, Karen, additional, Heywood, Nick, additional, Pinkney, Tom, additional, Blazeby, Jane, additional, Blencowe, Natalie S, additional, Cook, Jonathan Alistair, additional, Bulbulia, Richard, additional, Arenas-Pinto, Alejandro, additional, Snowdon, Claire, additional, Hilton, Zoe, additional, Magill, Laura, additional, MacLennan, Graeme, additional, Glasbey, James, additional, Nepogodiev, Dmitri, additional, Hardy, Victoria, additional, and Lane, J Athene, additional

Published
2023
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19. Hepatic steatosis in people older and younger than fifty who are living with HIV and HIV‐negative controls: A cross‐sectional study nested within the POPPY cohort.

Author

Arenas‐Pinto, Alejandro, Bakewell, Nicholas, Milinkovic, Ana, Williams, Ian, Vera, Jaime, Post, Frank A., Anderson, Jane, Beynon, Michelle, O'Brien, Alastair, Doyle, Nicki, Gilson, Richard, Pett, Sarah L., Winston, Alan, and Sabin, Caroline A.

Subjects
*HIV-positive persons, *KRUSKAL-Wallis Test, *ULTRASONIC imaging, *CONFIDENCE intervals, *FATTY liver, *CROSS-sectional method, *FISHER exact test, *RISK assessment, *COMPARATIVE studies, *WAIST-hip ratio, *RESEARCH funding, *CHI-squared test, *DESCRIPTIVE statistics, *LOGISTIC regression analysis, *ODDS ratio, *DISEASE risk factors, *ADULTS, *MIDDLE age
Abstract

Background: Hepatic steatosis is a major cause of chronic liver disease associated with several negative health outcomes. We compared the prevalence of and factors associated with steatosis in people living with and without HIV. Methods: Older (>50 years) and younger (<50 years) people with HIV and older HIV‐negative controls (>50 years) underwent liver transient elastography examination with controlled attenuation parameter (steatosis ≥238 dB/m, moderate/severe steatosis ≥280 dB/m, liver fibrosis ≥7.1 kPa). We compared groups using logistic regression/Chi‐squared/Fisher's exact/Kruskal–Wallis tests. Results: In total, 317 participants (109 older people with HIV; 101 younger people with HIV; 107 HIV‐negative controls) were predominantly white (86%) and male (76%), and 21% were living with obesity (body mass index ≥30 kg/m2). Most (97%) people with HIV had undetectable HIV RNA. The prevalence of fibrosis was 8.4%, 3.0%, and 6.5% in the three groups, respectively (p = 0.26). Fibrosis was predominately (>65%) mild. The prevalence of steatosis was the same in older people with HIV (66.4%) and controls (66.4%) but lower in younger people with HIV (37.4%; p < 0.001). After adjustment, younger people with HIV were less likely to have steatosis (odds ratio [OR] 0.26; 95% confidence interval [CI] 0.14–0.52) than controls, but male sex (OR 2.45; 95% CI 1.20–4.50) and high waist‐to‐hip ratio (OR 3.04; 95% CI 1.74–5.33) were associated with an increased odds of steatosis. We found no association between steatosis and HIV‐related variables. Conclusions: The prevalence of hepatic steatosis and fibrosis was similar between older participants regardless of HIV status. Age, sex, and abdominal obesity, but not HIV‐related variables, were associated with steatosis. Interventions for controlling obesity should be integrated into routine HIV care. [ABSTRACT FROM AUTHOR]

Published
2024
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20. Peripheral Neuropathy in Virologically Suppressed People Living with HIV: Evidence from the PIVOT Trial.

Author

Schuldt, Anna L., Bern, Henry, Hart, Melanie, Gompels, Mark, Winston, Alan, Clarke, Amanda, Chen, Fabian, Stöhr, Wolfgang, Heslegrave, Amanda, Paton, Nicholas I., Petzold, Axel, and Arenas-Pinto, Alejandro

Subjects
PERIPHERAL neuropathy, HIV-positive persons, CD4 lymphocyte count, HIV infections, BLOOD sugar
Abstract

The aim of this study is to identify the factors associated with peripheral neuropathy and to explore neurofilament light chain (NfL) as a biomarker for peripheral neuropathy (PN) in effectively virologically suppressed adults living with HIV. All protease inhibitor monotherapy versus ongoing triple therapy in the long-term management of HIV infection (PIVOT) trial participants with data on PN at baseline were included in the study. NfL plasma levels (pNfL) were measured in a sub-set of participants. Multivariable logistic regression was used to examine the associations of PN with potential risk factors (including age, sex, nadir CD4 cell count, history of dideoxynucleoside (d-drugs) exposure, and blood glucose levels) and NfL levels. Of the 585 participants included, 131 (22.4%) reported PN during the study period (median of 44 months). The participants were predominantly male (76.6%), White (68.2%), and virologically suppressed for a median period of 37 months (range of 20–63) before recruitment. The age at baseline was 44.3 years (standard deviation (SD) of 9.2). PN was independently associated with age (adjusted odds ratio (aOR) = 1.35, 95% CI of 1.20–1.52; additional 5 years), history of d-drugs (aOR 1.88, 95% CI of 1.12–3.16), height (aOR 1.19, 95% CI of 1.05–1.35; additional 5 cm), nadir CD4 cell count (aOR 1.10 CI of 1.00–1.20; 50 cells fewer), and metabolic syndrome (aOR 2.31, 95% CI of 1.27 4.20), but not pNfL. The excess risk for PN associated with d-drug use remains after the exposure has stopped for years, suggesting non-reversible toxicity. In people with HIV, metabolic syndrome is independently associated with PN. There was no additional value for pNfL as a screening test for peripheral neuropathy in effectively virologically suppressed adults living with HIV. [ABSTRACT FROM AUTHOR]

Published
2024
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22. Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial

Author

Brown, Samuel M, primary, Barkauskas, Christina E, additional, Grund, Birgit, additional, Sharma, Shweta, additional, Phillips, Andrew N, additional, Leither, Lindsay, additional, Peltan, Ithan D, additional, Lanspa, Michael, additional, Gilstrap, Daniel L, additional, Mourad, Ahmad, additional, Lane, Kathleen, additional, Beitler, Jeremy R, additional, Serra, Alexis L, additional, Garcia, Ivan, additional, Almasri, Eyad, additional, Fayed, Mohamed, additional, Hubel, Kinsley, additional, Harris, Estelle S, additional, Middleton, Elizabeth A, additional, Barrios, Macy A G, additional, Mathews, Kusum S, additional, Goel, Neha N, additional, Acquah, Samuel, additional, Mosier, Jarrod, additional, Hypes, Cameron, additional, Salvagio Campbell, Elizabeth, additional, Khan, Akram, additional, Hough, Catherine L, additional, Wilson, Jennifer G, additional, Levitt, Joseph E, additional, Duggal, Abhijit, additional, Dugar, Siddharth, additional, Goodwin, Andrew J, additional, Terry, Charles, additional, Chen, Peter, additional, Torbati, Sam, additional, Iyer, Nithya, additional, Sandkovsky, Uriel S, additional, Johnson, Nicholas J, additional, Robinson, Bryce R H, additional, Matthay, Michael A, additional, Aggarwal, Neil R, additional, Douglas, Ivor S, additional, Casey, Jonathan D, additional, Hache-Marliere, Manuel, additional, Georges Youssef, J, additional, Nkemdirim, William, additional, Leshnower, Brad, additional, Awan, Omar, additional, Pannu, Sonal, additional, O'Mahony, Darragh Shane, additional, Manian, Prasad, additional, Awori Hayanga, J W, additional, Wortmann, Glenn W, additional, Tomazini, Bruno M, additional, Miller, Robert F, additional, Jensen, Jens-Ulrik, additional, Murray, Daniel D, additional, Bickell, Nina A, additional, Zatakia, Jigna, additional, Burris, Sarah, additional, Higgs, Elizabeth S, additional, Natarajan, Ven, additional, Dewar, Robin L, additional, Schechner, Adam, additional, Kang, Nayon, additional, Arenas-Pinto, Alejandro, additional, Hudson, Fleur, additional, Ginde, Adit A, additional, Self, Wesley H, additional, Rogers, Angela J, additional, Oldmixon, Cathryn F, additional, Morin, Haley, additional, Sanchez, Adriana, additional, Weintrob, Amy C, additional, Cavalcanti, Alexandre Biasi, additional, Davis-Karim, Anne, additional, Engen, Nicole, additional, Denning, Eileen, additional, Taylor Thompson, B, additional, Gelijns, Annetine C, additional, Kan, Virginia, additional, Davey, Victoria J, additional, Lundgren, Jens D, additional, Babiker, Abdel G, additional, Neaton, James D, additional, Lane, H Clifford, additional, Tierney, John, additional, Vogel, Susan E., additional, McNay, Laura A., additional, Cahill, Kelly, additional, Crew, Page, additional, Sardana, Ratna, additional, Segal Raim, Sharo, additional, Shaw-Saliba, Katy, additional, Atri, Negin, additional, Miller, Mark, additional, Vallee, David, additional, Chung, Lucy, additional, Delph, Yvette, additional, Adam, Stacey J., additional, Read, Sarah, additional, Draghia-Akli, Ruxandra, additional, Harrigan, Rachel, additional, Carlsen, Amy, additional, Carter, Anita, additional, DuChene, Alain, additional, Eckroth, Kate, additional, Frase, Alex, additional, Harrison, Merrie, additional, Meger, Sue, additional, Quan, Kien, additional, Quan, Siu Fun, additional, Reilly, Cavan, additional, Thompson, Greg, additional, Walski, Jamie, additional, Moskowitz, Alan J., additional, Bagiella, Emilia, additional, Moquete, Ellen, additional, O'Sullivan, Karen, additional, Marks, Mary E., additional, Accardi, Evan, additional, Kinzel, Emily, additional, Bedoya, Gabriela, additional, Gupta, Lopa, additional, Overbey, Jessica R., additional, Padillia, Maria L., additional, Santos, Milerva, additional, Gillinov, Marc A., additional, Miller, Marissa A., additional, Taddei-Peters, Wendy C., additional, Fenton, Kathleen, additional, Smith, Peter K., additional, Vekstein, Andrew M., additional, Ko, Emily R., additional, Al-Hegelan, Mashael S., additional, McGowan, Lauren M., additional, Motta, Mary, additional, Howell, Shauna, additional, Bent, Francine, additional, Kalager, Rachel, additional, Chan, Emmanuel, additional, Aloor, Heather L., additional, Griffin, S. Michelle, additional, Covington, Anna, additional, McLendon-Arvik, Beth, additional, Bussadori, Barbara, additional, Miller-Bell, Mary, additional, Sampey, Cathy, additional, Gaver, Vincent, additional, Hollister, Beth A., additional, Giangiacomo, Dana M., additional, Pauley, Alena, additional, Patel, Aashay, additional, Classon, Chris, additional, Frazier, Madison, additional, Osborne, Robyn, additional, Conlon, Debbi H., additional, Joshi, Marybeth, additional, Gottlieb, Robert L., additional, Mack, Michael, additional, Berhe, Mezgebe, additional, Haley, Clinton, additional, Dishner, Emma, additional, Bettacchi, Christopher, additional, Golden, Kevin, additional, Duhaime, Erin, additional, Ryan, Madison, additional, Tallmadge, Catherine, additional, Estrada, Lorie, additional, Jones, Felecia, additional, Villa, Samantha, additional, Wang, Samantha, additional, Robert, Raven, additional, Coleman, Tanquinisha, additional, Clariday, Laura, additional, Baker, Rebecca, additional, Hurutado-Rodriguez, Mariana, additional, Iram, Nazia, additional, Fresnedo, Michelle, additional, Davis, Allyson, additional, Leonard, Kiara, additional, Ramierez, Noelia, additional, Thammavong, Jon, additional, Duque, Krizia, additional, Turner, Emma, additional, Fisher, Tammy, additional, Robinson, Dianna, additional, Ransom, Desirae, additional, Maldonado, Nicholas, additional, Lusk, Erica, additional, Killian, Aaron, additional, Palacios, Adriana, additional, Solis, Edilia, additional, Jerrow, Janet, additional, Watts, Matthew, additional, Whitacre, Heather, additional, Cothran, Elizabeth, additional, Bender, William, additional, Miller, Jeffrey, additional, Nugent, Katherine, additional, Farrington, Woodrow, additional, Baio, Kim T., additional, McBride, Mary K., additional, Fielding, Michele, additional, Mathewson, Sonya, additional, Porte, Kristina, additional, Haley, Elizabeth, additional, Rogers, Susan, additional, Tyler, Derrick, additional, Perin, Emerson, additional, Costello, Briana, additional, Postalian, Alexander, additional, Sohail, Rizwan, additional, Hinsu, Punit, additional, Watson, Carolyn, additional, Kappenman, Casey, additional, Chen, James, additional, Walker, Kim, additional, Fink, Melyssa, additional, Phillip, Gabrielle, additional, Mahon, Kim, additional, Sturgis, Lydia, additional, Maher, Patrick, additional, Rogers, Linda, additional, Ng, Nicole, additional, Marshall, Jason, additional, Bassily-Marcus, Adel, additional, Cohen, Ivy, additional, Ramoo, Shamini, additional, Malhotra, Aryan, additional, Kessler, Jonathan, additional, Goetz, Rebekah, additional, Badhwar, Vinay, additional, Hayanga, Jeremiah, additional, Giblin Sutton, Lisa, additional, Williams, Roger, additional, Berry Bartolo, Elizabeth, additional, Walker, Dmitry, additional, Bunner, Robin, additional, Glaze, Chad, additional, Aucremanne, Tanja, additional, Bishop, James, additional, Kelley, Macey, additional, Peterson, Autumn, additional, Sauerborn, Erica, additional, Reckart, Robin, additional, Miller, Brittany, additional, Mittel, Aaron, additional, Darmanian, Anita, additional, Rosen, Amanda, additional, Madahar, Purnema, additional, Schicchi, John, additional, Gosek, Katarzyna, additional, Dzierba, Amy, additional, Wahab, Romina, additional, Eng, Connie, additional, Al-Saadi, Mukhtar, additional, Zahiruddin, Faisal, additional, Syed, Mohi, additional, George, Michael, additional, Patel, Varsha, additional, Onwunyi, Chisom, additional, Barroso da Costa, Rosa, additional, North, Crystal, additional, Ringwood, Nancy, additional, Fitzgerald, Laura, additional, Muzikansky, Ariela, additional, Morse, Richard, additional, Brower, Roy G., additional, Reineck, Lora A., additional, Bienstock, Karen, additional, Hou, Peter, additional, Steingrub, Jay S., additional, Tidswell, Mark A., additional, Kozikowski, Lori-Ann, additional, Kardos, Cynthia, additional, De Souza, Leslie, additional, Talmor, Daniel, additional, Shapiro, Nathan, additional, Hibbert, Kathryn, additional, Brait, Kelsey, additional, Kone, Mamary, additional, Hendey, Gregory, additional, Kangelaris, Kirsten N., additional, Ashktorab, Kimia, additional, Gropper, Rachel, additional, Agrawal, Anika, additional, Timothy, Kelly, additional, Zhou, Hanjing, additional, Hughes, Alyssa, additional, Garcia, Rebekah, additional, Torres, Adrian, additional, Hernandez-Almaraz, Maria Elena, additional, Vojnik, Rosemary, additional, Perez, Cynthia, additional, McDowell, Jordan, additional, Chang, Steven Y., additional, Vargas, Julia, additional, Moss, Marc, additional, McKeehan, Jeffrey, additional, Higgins, Carrie, additional, Johnson, Emily, additional, Slaughter, Suzanne, additional, Wyles, David, additional, Hiller, Terra, additional, Oakes, Judy, additional, Garcia, Ana, additional, Gravitz, Stephanie, additional, Lyle, Carolynn, additional, Swanson, Diandra, additional, Gong, Michelle Ng., additional, Richardson, Lynnne D., additional, Chen, Jen-Ting, additional, Moskowitz, Ari, additional, Mohamed, Amira, additional, Lopez, Brenda, additional, Amosu, Omowunmi, additional, Tzehaie, Hiwet, additional, Boujid, Sabah, additional, Bixby, Billie, additional, Lopez, Anitza A., additional, Durley, JaVon, additional, Gilson, Boris, additional, Hite, R. Duncan, additional, Wang, Henry, additional, Wiedemann, Hebert P., additional, Mehkri, Omar, additional, Ashok, Kiran, additional, King, Alexander, additional, Brennan, Connery, additional, Exline, Matthew C., additional, Englert, Joshua A., additional, Karow, Sarah, additional, Schwartz, Elizabeth, additional, So, Preston, additional, So, Madison, additional, Krol, Olivia F., additional, Briceno Parra, Genesis I., additional, Mills, Emmanuel Nii Lantei, additional, Oh, Minn, additional, Pena, Jose, additional, Martínez, Jesús Alejandro, additional, Jackman, Susan E., additional, Bayoumi, Emad, additional, Pascual, Ethan, additional, Caudill, Antonina, additional, Chen, Po-En, additional, Richardson, Tabia, additional, Clapham, Gregg J., additional, Herrera, Lisa, additional, Ojukwu, Cristabelle, additional, Fine, Devin, additional, Gomez, Millie J., additional, Choi-Kuaea, Yunhee, additional, Weissberg, Gwendolyn, additional, Isip, Katherine, additional, Mattison, Brittany, additional, Tran, Dana, additional, Emilov Dukov, Jennifer, additional, Chung, Paul, additional, Kang, Bo Ran, additional, Escobar, Lauren, additional, Tran, Trung, additional, Baig, Saba, additional, Wallick, Julie A., additional, Duven, Alexandria M., additional, Fletcher, Dakota D., additional, Gundel, Stephanie, additional, Fuentes, Megan, additional, Newton, Maranda, additional, Peterson, Emily, additional, Jiang, Kelsey, additional, Files, D. Clark, additional, Miller, Chadwick, additional, Lematty, Caitlin, additional, Rasberry, April, additional, Warden, Ashley, additional, Bledsoe, Joseph, additional, Knowlton, Kirk, additional, Knox, Daniel B., additional, Klippel, Carolyn, additional, Armbruster, Brent P., additional, Applegate, Darrin, additional, Imel, Karah, additional, Fergus, Melissa, additional, Rahmati, Kasra, additional, Jensen, Hannah, additional, Aston, Valerie T., additional, Jeppson, Joshua, additional, Marshall, J. Hunter, additional, Lumpkin, Jenna, additional, Smith, Cassie, additional, Burke, Tyler, additional, Gray, Andrew, additional, Paine, Robert, additional, Callahan, Sean, additional, Yamane, Misty, additional, Waddoups, Lindsey, additional, Rice, Todd W., additional, Johnson, Jakea, additional, Gray, Christopher, additional, Hays, Margaret, additional, Roth, Megan, additional, Musick, Sarah, additional, Miller, Karen, additional, Semler, Matthew W., additional, Popielski, Laura, additional, Kambo, Amy, additional, Viens, Kimberly, additional, Turner, Melissa, additional, Vjecha, Michael J., additional, Denyer, Rachel, additional, Khosla, Rahul, additional, Rajendran, Bindu, additional, Gonzales, Melissa, additional, Moriarty, Theresa, additional, Biswas, Kousick, additional, Harrington, Cristin, additional, Garcia, Amanda, additional, Bremer, Tammy, additional, Burke, Tara, additional, Koker, Brittany, additional, Pittman, David, additional, Vasudeva, Shikha S., additional, Anholm, James D., additional, Specht, Lennard, additional, Rodriguez, Aimee, additional, Ngo, Han, additional, Duong, Lien, additional, Previte, Matthew, additional, Raben, Dorthe, additional, Nielsen, Charlotte B., additional, Friis Larsen, Jakob, additional, Peters, Lars, additional, Matthews, Gail, additional, Kelleher, Anthony, additional, Polizzotto, Mark, additional, Carey, Catherine, additional, Chang, Christina, additional, Dharan, Nila, additional, Hough, Sally, additional, Virachit, Sophie, additional, Davidson, Sarah, additional, Bice, Daniel J., additional, Ognenovska, Katherine, additional, Cabrera, Gesalit, additional, Flynn, Ruth, additional, Abdelghany, Mazin, additional, Baseler, Beth, additional, Teitelbaum, Marc, additional, Holley, H. Preston, additional, Jankelevich, Shirley, additional, Adams, Amy, additional, Becker, Nancy, additional, Doleny, Suzanne, additional, Hissey, Debbie, additional, Simpson, Shelly, additional, Kim, Mi Ha, additional, Beeler, Joy, additional, Harmon, Liam, additional, Vanderpuye, Sharon, additional, Yeon, Lindsey, additional, Frye, Leanna, additional, Rudzinski, Erin, additional, Buehn, Molly, additional, Eccard-Koons, Vanessa, additional, Frary, Sadie, additional, MacDonalad, Leah, additional, Cash, Jennifer, additional, Hoopengardner, Lisa, additional, Linton, Jessica, additional, Nelson, Michaela, additional, Spinelli-Nadzam, Mary, additional, Proffitt, Calvin, additional, Lee, Christopher, additional, Engel, Theresa, additional, Fontaine, Laura, additional, Osborne, CK, additional, Hohn, Matt, additional, Galcik, Michael, additional, Thompson, DeeDee, additional, Sandrus, Jen, additional, Manchard, Jon, additional, Giri, Jiwan, additional, Kopka, Stacy, additional, Chang, Weizhong, additional, Sherman, Brad T., additional, Rupert, Adam W., additional, Highbarger, Helene, additional, Baseler, Michael, additional, Lallemand, Perrine, additional, Rehman, Tauseef, additional, Imamichi, Tom, additional, Laverdure, Sylvain, additional, Paudel, Sharada, additional, Cook, Kyndal, additional, Haupt, Kendra, additional, Hazen, Allison, additional, Badralmaa, Yunden, additional, Highbarger, Jeroen, additional, McCormack, Ashley, additional, Gerry, Norman P., additional, Smith, Kenneth, additional, Patel, Bhakti, additional, Domeraski, Nadia, additional, Hoover, Marie L., additional, DuChateau, Nadine, additional, Flosi, Adam, additional, Nelson, Rich, additional, Stojanovic, Jelena, additional, and Wenner, Christine, additional

Published
2023
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24. Lopinavir plus nucleoside reverse-transcriptase inhibitors, lopinavir plus raltegravir, or lopinavir monotherapy for second-line treatment of HIV (EARNEST): 144-week follow-up results from a randomised controlled trial

Author

Agweng, E, Awio, P, Bakeinyaga, G, Isabirye, C, Kabuga, U, Kasuswa, S, Katuramu, M, Kiweewa, F, Kyomugisha, H, Lutalo, E, Mulima, D, Musana, H, Musitwa, G, Musiime, V, Ndigendawan, M, Namata, H, Nkalubo, J, Labejja, P Ocitti, Okello, P, Olal, P, Pimundu, G, Segonga, P, Ssali, F, Tamale, Z, Tumukunde, D, Namala, W, Byaruhanga, R, Kayiwa, J, Tukamushaba, J, Abunyang, S, Eram, D, Denis, O, Lwalanda, R, Mugarura, L, Namusanje, J, Nankya, I, Ndashimye, E, Nabulime, E, Senfuma, O, Bihabwa, G, Buluma, E, Elbireer, A, Kamya, D, Katwere, M, Kiggundu, R, Komujuni, C, Laker, E, Lubwama, E, Mambule, I, Matovu, J, Nakajubi, A, Nakku, J, Nalumenya, R, Namuyimbwa, L, Semitala, F, Wandera, B, Wanyama, J, Mugerwa, H, Ninsiima, E, Ssenkindu, T, Mwebe, S, Atwine, L, William, H, Katemba, C, Acaku, M, Ssebutinde, P, Kitizo, H, Kukundakwe, J, Naluguza, M, Ssegawa, K, Namayanja, Nsibuka, F, Tuhirirwe, P, Fortunate, M, Acen, J, Achidri, J, Amone, A, Chamai, M, Ditai, J, Kemigisa, M, Kiconco, M, Matama, C, Mbanza, D, Nambaziira, F, Odoi, M Owor, Rweyora, A, Tumwebaze, G, Kalanzi, H, Katabaazi, J, Kiyingi, A, Mbidde, M, Mugenyi, M, Okong, P, Senoga, I, Abwola, M, Baliruno, D, Bwomezi, J, Kasede, A, Mudoola, M, Namisi, R, Ssennono, F, Tuhirwe, S, Amone, G, Abach, J, Aciro, I, Arach, B, Kidega, P, Omongin, J, Ocung, E, Odong, W, Philliam, A, Alima, H, Ahimbisibwe, B, Atuhaire, E, Atukunda, F, Bekusike, G, Bulegyeya, A, Kahatano, D, Kamukama, S, Kyoshabire, J, Nassali, A, Mbonye, A, Naturinda, T M, Ndukukire, Nshabohurira, A, Ntawiha, H, Rogers, A, Tibyasa, M, Kiirya, S, Atwongyeire, D, Nankya, A, Draleku, C, Nakiboneka, D, Odoch, D, Lakidi, L, Ruganda, R, Abiriga, R, Mulindwa, M, Balmoi, F, Kafuma, S, Moriku, E, Reid, A, Chidziva, E, Musoro, G, Warambwa, C, Tinago, G, Mutsai, S, Phiri, M, Mudzingwa, S, Bafana, T, Masore, V, Moyo, C, Nhema, R, Chitongo, S, Heyderman, Robert, Kabanga, Lucky, Kaunda, Symon, Kudzala, Aubrey, Lifa, Linly, Mallewa, Jane, Moore, Mike, Mtali, Chrissie, Musowa, George, Mwimaniwa, Grace, Sikwese, Rosemary, Ziwoya, Milton, Chitete, H Chimbaka B, Kamanga, S, Makwakwa, T Kayinga E, Mbiya, R, Mlenga, M, Mphande, T, Mtika, C, Mushani, G, Ndhlovu, O, Ngonga, M, Nkhana, I, Nyirenda, R, Cheruiyot, P, Kwobah, C, Ekiru, W Lokitala, Mokaya, M, Mudogo, A, Nzioka, A, Tanui, M, Wachira, S, Wools-Kaloustian, K, Alipalli, P, Chikatula, E, Kipaila, J, Kunda, I, Lakhi, S, Malama, J, Mufwambi, W, Mulenga, L, Mwaba, P, Mwamba, E, Namfukwe, M, Kerukadho, E, Ngwatu, B, Birungi, J, Boles, J, Burke, A, Castle, L, Ghuman, S, Kendall, L, Tebbs, S, Whittle, J, Wilkes, H, Young, N, Spyer, M, Kapuya, C, Kyomuhendo, F, Kyakundi, D, Mkandawire, N, Mulambo, S, Senyonjo, S, Angus, B, Arenas-Pinto, A, Palfreeman, A, Post, F, Ishola, D, Arribas, J, Colebunders, R, Floridia, M, Giuliano, M, Mallon, P, Walsh, P, De Rosa, M, Rinaldi, E, Weller, I, Gilks, C, Kangewende, A, Luyirika, E, Miiro, F, Ojoo, S, Phiri, S, Wapakabulo, A, Peto, T, Matenga, J, Cloherty, G, van Wyk, J, Norton, M, Lehrman, S, Lamba, P, Malik, K, Rooney, J, Snowden, W, Villacian, J, Hakim, James G, Thompson, Jennifer, Kityo, Cissy, Hoppe, Anne, Kambugu, Andrew, van Oosterhout, Joep J, Lugemwa, Abbas, Siika, Abraham, Mwebaze, Raymond, Mweemba, Aggrey, Abongomera, George, Thomason, Margaret J, Easterbrook, Philippa, Mugyenyi, Peter, Walker, A Sarah, and Paton, Nicholas I

Published
2018
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25. Studies on clinical and epidemiological factors associated with peripheral neuropathy and severe hyperlactatemia or lactic acidosis in HIV-infected adults exposed to nucleoside analogues reverse transcriptase inhibitors

Author

Rafael Arenas-Pinto, A.

Subjects
616.07
Abstract

Studies on mitochondrial dysfunction in HIV-infected adults exposed to anti-retroviral therapy. A significant proportion of HIV-infected patients who require anti-retroviral therapy are or have been exposed to nucleoside analogue reverse transcriptase inhibitors (NRTIs). It has been consistently suggested that most of the NRTI-attributed adverse drug reactions (ADR) are due to mitochondrial dysfunction. In a sub-analysis of a large randomised clinical trial (Delta) the incidence of peripheral neuropathy (PN) was constant over time in all study arms, which does not support the hypothesis of cumulative toxicity previously proposed for NRTI-induced ADR. Patients taking zidovudine (AZT)/zalcitabine (ddC) combination were more likely to develop PN than patients on AZT monotherapy (RH= 2.30 95%CI= 1.62 - 3.28). The incidence of PN among patients exposed to zidovudine/didanosine (AZT/ddl) combination was not different from that observed in patients on AZT. In a multi-centre case-control study including 110 cases of lactic acidosis (LA) or severe hyperlactataemia (HL) patients with < 200 CD4 cell/pl were more likely to develop HL/LA than patients with higher levels of CD4 cells (OR=3.44 95%CI= 1.64 - 7.22). Female patients were found to be at higher risk for HULA than men (OR= 4.75 95%CI= 1.96 - 11.53). Patients exposed to either d4T, ddl or the combination of these two were four to six times more likely to develop HL/LA than patients taking other NRTIs based combinations. Interestingly, cases of HL/LA were exposed to d4T for shorter periods of time than controls. Almost 10 % of the cases included in the study were asymptomatic at the time of diagnosis. All these symptom-free cases had blood lactate ranging between 5 and 7 mmol/l. Therefore, case definitions for HL or LA based on clinical presentation may underestimate the magnitude of the problem.

Published
2007

26. A descriptive analysis of transient elastography results and metabolic co-morbidities in people living with HIV mono-infection in an urban clinic in the UK

Author

Mullender, Claire, primary, Owen, Rhiannon, additional, Kohli, Manik, additional, Maan, Irfaan, additional, Waters, Laura Jane, additional, Pett, Sarah, additional, Arenas-Pinto, Alejandro, additional, Ghosh, Indrajit, additional, Flanagan, Stuart, additional, and Gilson, Richard, additional

Published
2023
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27. High prevalence of hepatic steatosis in adults living with hepatitis B, with and without HIV co-infection, in London, UK

Author

Mullender, Claire, primary, Kemper, Angieszka, additional, Ogunnaike, Stephen, additional, Pett, Sarah, additional, Maan, Irfaan, additional, Kohli, Manik, additional, Peppa, Dimitra, additional, Arenas-Pinto, Alejandro, additional, Flanagan, Stuart, additional, Ghosh, Indrajit, additional, Gilson, Richard, additional, and Matthews, Philippa, additional

Published
2023
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28. 89976 ASSESSING PROTEIN BIOMARKERS ROLE IN CVD RISK PREDICTION IN PERSONS LIVING WITH HIV (PWH)

Author

Sandra Safo, Lillian Haine, Jason Baker, Cavan Reilly, Daniel Duprez, Jim Neaton, Jiuzhou Wang, Mamta K. Jain, Alejandro Arenas Pinto, Therese Staub, and Mark Polizzotto

Subjects
Medicine
Abstract

ABSTRACT IMPACT: Our findings could potentially identify CVD at-risk persons living with HIV who might benefit from aggressive risk-reduction. OBJECTIVES/GOALS: PWH have higher rates of CVD than the general population yet CVD risk prediction models rely on traditional risk factors and fail to capture the heterogeneity of CVD risk in PWH. Here we identify protein biomarkers that are able to discriminate between CVD cases and controls in PWH, and we assess their added benefit beyond traditional risk factors. METHODS/STUDY POPULATION: We analyzed 459 baseline protein expression levels from five OLINK panels in a matched CVD (MI, coronary revascularization, stroke, CVD death) case-control study with 390 PWH from INSIGHT trials (131 cases, 259 controls). We formed 200 datasets via bootstrap. For each bootstrap set, a two-component partial least squares discriminant model (PLSDA) was fit. The importance of each variable in the discrimination of cases and controls in the PLSDA projection was assessed by the variable importance in projection (VIP) score. Proteins with average VIP scores > 1 were used in penalized logistic regression models with elastic net penalty, and proteins were ranked based on the number of times the protein had a nonzero coefficient. Proteins in the top 25th percentile were considered to have high discrimination. RESULTS/ANTICIPATED RESULTS: Participants had mean age 47 years, 13% were females, 4.9% had CVD at baseline and 69% were on ART at baseline. Eight proteins including the hepatocyte growth factor and interleukin-6 were identified as able to distinguish between CVD cases and controls within PWH. A protein score (PS) of the top-ranked proteins was developed using the bootstrap (for weights) and the entire data. The PS was found to be predictive of CVD independent of established CVD and HIV factors (Odds ratio: 2.17 CI: 1.58-2.99). A model with the PS and traditional risk factors had a 5.9% improvement in AUC over the baseline model (AUC=0.731 vs 0.69), which is an increase in model predictive power of 18%. Individuals with a PS above the median score were 3.1 (CI: 1.83- 5.41) times more likely to develop CVD than those with a protein score below the median score. DISCUSSION/SIGNIFICANCE OF FINDINGS: A protein score developed improved discrimination of PWH with CVD and those without, and helped identify PWH with high risk for developing CVD. If validated, this score and/or the individual proteins could be used in addition with established factors to identify CVD at-risk individuals who might benefit from aggressive risk-reduction.

Published
2021
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30. Nucleoside reverse-transcriptase inhibitor cross-resistance and outcomes from second-line antiretroviral therapy in the public health approach: an observational analysis within the randomised, open-label, EARNEST trial

Author

Agweng, E, Awio, P, Bakeinyaga, G, Isabirye, C, Kabuga, U, Kasuswa, S, Katuramu, M, Kityo, C, Kiweewa, F, Kyomugisha, H, Lutalo, E, Mugyenyi, P, Mulima, D, Musana, H, Musitwa, G, Musiime, V, Ndigendawan, M, Namata, H, Nkalubo, J, Labejja, P Ocitti, Okello, P, Olal, P, Pimundu, G, Segonga, P, Ssali, F, Tamale, Z, Tumukunde, D, Namala, W, Byaruhanga, R, Kayiwa, J, Tukamushaba, J, Abunyang, S, Eram, D, Denis, O, Lwalanda, R, Mugarura, L, Namusanje, J, Nankya, I, Ndashimye, E, Nabulime, E, Senfuma, O, Bihabwa, G, Buluma, E, Easterbrook, P, Elbireer, A, Kambugu, A, Kamya, D, Katwere, M, Kiggundu, R, Komujuni, C, Laker, E, Lubwama, E, Mambule, I, Matovu, J, Nakajubi, A, Nakku, J, Nalumenya, R, Namuyimbwa, L, Semitala, F, Wandera, B, Wanyama, J, Mugerwa, H, Lugemwa, A, Ninsiima, E, Ssenkindu, T, Mwebe, S, Atwine, L, William, H, Katemba, C, Acaku, M, Ssebutinde, P, Kitizo, H, Kukundakwe, J, Naluguza, M, Ssegawa, K, Namayanja, Nsibuka, F, Tuhirirwe, P, Fortunate, M, Acen, J, Achidri, J, Amone, A, Chamai, M, Ditai, J, Kemigisa, M, Kiconco, M, Matama, C, Mbanza, D, Nambaziira, F, Odoi, M Owor, Rweyora, A, Tumwebaze, G, Kalanzi, H, Katabaazi, J, Kiyingi, A, Mbidde, M, Mugenyi, M, Mwebaze, R, Okong, P, Senoga, I, Abwola, M, Baliruno, D, Bwomezi, J, Kasede, A, Mudoola, M, Namisi, R, Ssennono, F, Tuhirwe, S, Abongomera, G, Amone, G, Abach, J, Aciro, I, Arach, B, Kidega, P, Omongin, J, Ocung, E, Odong, W, Philliam, A, Alima, H, Ahimbisibwe, B, Atuhaire, E, Atukunda, F, Bekusike, G, Bulegyeya, A, Kahatano, D, Kamukama, S, Kyoshabire, J, Nassali, A, Mbonye, A, Naturinda, T M, Ndukukire, Nshabohurira, A, Ntawiha, H, Rogers, A, Tibyasa, M, Kiirya, S, Atwongyeire, D, Nankya, A, Draleku, C, Nakiboneka, D, Odoch, D, Lakidi, L, Ruganda, R, Abiriga, R, Mulindwa, M, Balmoi, F, Kafuma, S, Moriku, E, Hakim, J, Reid, A, Chidziva, E, Musoro, G, Warambwa, C, Tinago, G, Mutsai, S, Phiri, M, Mudzingwa, S, Bafana, T, Masore, V, Moyo, C, Nhema, R, Chitongo, S, Heyderman, Robert, Kabanga, Lucky, Kaunda, Symon, Kudzala, Aubrey, Lifa, Linly, Mallewa, Jane, Moore, Mike, Mtali, Chrissie, Musowa, George, Mwimaniwa, Grace, Sikwese, Rosemary, van Oosterhout, Joep, Ziwoya, Milton, Chimbaka, H, Chitete, B, Kamanga, S, Makwakwa, T Kayinga E, Mbiya, R, Mlenga, M, Mphande, T, Mtika, C, Mushani, G, Ndhlovu, O, Ngonga, M, Nkhana, I, Nyirenda, R, Cheruiyot, P, Kwobah, C, Ekiru, W Lokitala, Mokaya, M, Mudogo, A, Nzioka, A, Siika, A, Tanui, M, Wachira, S, Wools-Kaloustian, K, Alipalli, P, Chikatula, E, Kipaila, J, Kunda, I, Lakhi, S, Malama, J, Mufwambi, W, Mulenga, L, Mwaba, P, Mwamba, E, Mweemba, A, Namfukwe, M, Kerukadho, E, Ngwatu, B, Birungi, J, Paton, N, Boles, J, Burke, A, Castle, L, Ghuman, S, Kendall, L, Hoppe, A, Tebbs, S, Thomason, M, Thompson, J, Walker, S, Whittle, J, Wilkes, H, Young, N, Spyer, M, Kapuya, C, Kyomuhendo, F, Kyakundi, D, Mkandawire, N, Mulambo, S, Senyonjo, S, Angus, B, Arenas-Pinto, A, Palfreeman, A, Post, F, Ishola, D, Arribas, J, Colebunders, R, Floridia, M, Giuliano, M, Mallon, P, Walsh, P, De Rosa, M, Rinaldi, E, Weller, I, Gilks, C, Kangewende, A, Luyirika, E, Miiro, F, Mwamba, P, Ojoo, S, Phiri, S, van Oosterhout, J, Wapakabulo, A, Peto, T, French, N, Matenga, J, Cloherty, G, van Wyk, J, Norton, M, Lehrman, S, Lamba, P, Malik, K, Rooney, J, Snowden, W, Villacian, J, Paton, Nicholas I, Kityo, Cissy, Thompson, Jennifer, Nankya, Immaculate, Bagenda, Leonard, Hoppe, Anne, Hakim, James, Kambugu, Andrew, van Oosterhout, Joep J, Kiconco, Mary, Bertagnolio, Silvia, Easterbrook, Philippa J, Mugyenyi, Peter, and Walker, A Sarah

Published
2017
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34. Poster Abstracts

Author

Alejandro Arenas-Pinto and Adam McDermott

Subjects
Infectious Diseases, Health Policy, Pharmacology (medical)
Published
2022

35. Neurocognitive Function and Neuroimaging Markers in Virologically Suppressed HIV-positive Patients Randomized to Ritonavir-boosted Protease Inhibitor Monotherapy or Standard Combination ART: A Cross-sectional Substudy From the PIVOT Trial

Author

PIVOT Neurocognitive sub-study Team, Arenas-Pinto, Alejandro, Stöhr, Wolfgang, Jäger, Hans Rolf, Haddow, Lewis, Clarke, Amanda, Johnson, Margaret, Chen, Fabian, Winston, Alan, Godi, Claudia, Thust, Steffi, Trombin, Rita, Cairns, Janet, Solanky, Bhavana S., Golay, Xavier, and Paton, Nicholas I.

Published
2016

39. Alcohol, smoking, recreational drug use and association with virological outcomes among people living with HIV: cross‐sectional and longitudinal analyses

Author

Alison Rodger, Lewis J. Haddow, Margaret Johnson, Fiona C Lampe, Anna Maria Geretti, Lorraine Sherr, Simon Collins, Alejandro Arenas-Pinto, Colette Smith, Monica Lascar, Andrew N. Phillips, Timothy Willem Jones, Jeffrey McDonnell, and Elaney Yousef

Subjects
Male, medicine.medical_specialty, Sexual transmission, Anti-HIV Agents, HIV Infections, Medication Adherence, Unit of alcohol, Men who have sex with men, Sexual and Gender Minorities, Recreational Drug Use, Internal medicine, medicine, Humans, Outpatient clinic, Pharmacology (medical), Homosexuality, Male, business.industry, Health Policy, Smoking, Alcohol dependence, Hazard ratio, Odds ratio, Viral Load, Cross-Sectional Studies, Infectious Diseases, Female, business, Viral load
Abstract

Objectives There is increasing evidence to suggest that people living with HIV (PLWH) have significant morbidity from alcohol, recreational drug use and cigarette smoking. Our aim was to report associations of these factors with antiretroviral therapy (ART) non-adherence, viral non-suppression and subsequent viral rebound in PLWH. Methods The Antiretroviral Sexual Transmission Risk and Attitudes (ASTRA) study recruited PLWH attending eight outpatient clinics in England between February 2011 and December 2012. Data included self-reported excessive drinking (estimated consumption of > 20 units of alcohol/week), alcohol dependency (CAGE score ≥ 2 with current alcohol consumption), recreational drug use (including injection drug use in the past 3 months), and smoking status. Among participants established on ART, cross-sectional associations with ART non-adherence [missing ≥2 consecutive days of ART on ≥2 occasions in the past three months] and viral-non suppression [viral load (VL) > 50 copies/mL] were assessed using logistic regression. In participants from one centre, longitudinal associations with subsequent viral rebound (first VL > 200 copies/mL) in those on ART with VL ≤ 50 copies/mL at baseline were assessed using Cox regression during a 7-year follow-up. Results Among 3258 PLWH, 2248 (69.0%) were men who have sex with men, 373 (11.4%) were heterosexual men, and 637 (19.6%) were women. A CAGE score ≥ 2 was found in 568 (17.6%) participants, 325 (10.1%) drank > 20 units/week, 1011 (31.5%) currently smoked, 1242 (38.1%) used recreational drugs and 74 (2.3%) reported injection drug use. In each case, prevalence was much more common among men than among women. Among 2459 people on ART who started at least 6 months previously, a CAGE score ≥ 2, drinking > 20 units per week, current smoking, injection and non-injection drug use were all associated with ART non-adherence. After adjusting for demographic and socioeconomic factors, CAGE score ≥ 2 [adjusted odds ratio (aOR) = 1.52, 95% confidence interval (CI): 1.09-2.13], current smoking (aOR = 1.58, 95% CI: 1.10-2.17) and injection drug use (aOR = 2.11, 95% CI: 1.00-4.47) were associated with viral non-suppression. During follow-up of a subset of 592 people virally suppressed at recruitment, a CAGE score ≥ 2 [adjusted hazard ratio (aHR) = 1.66, 95% CI: 1.03-2.74], use of 3 or more non-injection drugs (aHR = 1.82, 95% CI: 1.12-3.57) and injection drug use (aHR = 2.73, 95% CI: 1.08-6.89) were associated with viral rebound. Conclusions Screening and treatment for alcohol, cigarette and drug use should be integrated into HIV outpatient clinics, while clinicians should be alert to the potential for poorer virological outcomes.

Published
2021

40. The cost‐effectiveness of prophylaxis strategies for individuals with advanced HIV starting treatment in Africa

Author

Walker, Simon M., Cox, Edward, Revill, Paul, Musiime, Victor, Bwakura?Dangarembizi, Mutsa, Mallewa, Jane, Cheruiyot, Priscilla, Maitland, Kathryn, Ford, Nathan, Gibb, Diana M., Walker, A Sarah, Soares, Marta, Mugyenyi, P, Kityo, C, Musiime, V, Wavamunno, P, Nambi, E, Ocitti, P, Ndigendawani, M, Kabahenda, S, Kemigisa, M, Acen, J, Olebo, D, Mpamize, G, Amone, A, Okweny, D, Mbonye, A, Nambaziira, F, Rweyora, A, Kangah, M, Kabaswahili, V, Abach, J, Abongomera, G, Omongin, J, Aciro, I, Philliam, A, Arach, B, Ocung, E, Amone, G, Miles, P, Adong, C, Tumsuiime, C, Kidega, P, Otto, B, Apio, F, Baleeta, K, Mukuye, A, Abwola, M, Ssennono, F, Baliruno, D, Tuhirwe, S, Namisi, R, Kigongo, F, Kikyonkyo, D, Mushahara, F, Tusiime, J, Musiime, A, Nankya, A, Atwongyeire, D, Sirikye, S, Mula, S, Noowe, N, Lugemwa, A, Kasozi, M, Mwebe, S, Atwine, L, Senkindu, T, Natuhurira, T, Katemba, C, Ninsiima, E, Acaku, M, Kyomuhangi, J, Ankunda, R, Tukwasibwe, D, Ayesiga, L, Hakim, J, Nathoo, K, Bwakura?Dangarembizi, M, Reid, A, Chidziva, E, Mhute, T, Tinago, Gc, Bhiri, J, Mudzingwa, S, Phiri, M, Steamer, J, Nhema, R, Warambwa, C, Musoro, G, Mutsai, S, Nemasango, B, Moyo, C, Chitongo, S, Rashirai, K, Vhembo, S, Mlambo, B, Nkomani, S, Ndemera, B, Willard, M, Berejena, C, Musodza, Y, Matiza, P, Mudenge, B, Guti, V, Etyang, A, Agutu, C, Berkley, J, Maitland, K, Njuguna, P, Mwaringa, S, Etyang, T, Awuondo, K, Wale, S, Shangala, J, Kithunga, J, Mwarumba, S, Maitha, S Said, Mutai, R, Lewa, M Lozi, Mwambingu, G, Mwanzu, A, Kalama, C, Latham, H, Shikuku, J, Fondo, A, Njogu, A, Khadenge, C, Mwakisha, B, Siika, A, Wools?Kaloustian, K, Nyandiko, W, Cheruiyot, P, Sudoi, A, Wachira, S, Meli, B, Karoney, M, Nzioka, A, Tanui, M, Mokaya, M, Ekiru, W, Mboya, C, Mwimali, D, Mengich, C, Choge, J, Injera, W, Njenga, K, Cherutich, S, Orido, M Anyango, Lwande, G Omondi, Rutto, P, Mudogo, A, Kutto, I, Shali, A, Jaika, L, Jerotich, H, Pierre, M, Mallewa, J, Kaunda, S, Van Oosterhout, J, O'Hare, B, Heydermann, R, Gonzalez, C, Dzabala, N, Kelly, C, Denis, B, Selemani, G, Mipando, L Nyondo, Chirwa, E, Banda, P, Mvula, L, Msuku, H, Ziwoya, M, Manda, Y, Nicholas, S, Masesa, C, Mwalukomo, T, Makhaza, L, Sheha, I, Bwanali, J, Limbuni, M, Gibb, D, Thomason, M, Walker, As, Pett, S, Szubert, A, Griffiths, A, Wilkes, H, Rajapakse, C, Spyer, M, Prendergast, A, Klein, N, Rauchenberger, M, Van Looy, N, Little, E, Fairbrother, K, Cowan, F, Seeley, J, Bernays, S, Kawuma, R, Mupambireyi, Z, Kyomuhendo, F, Nakalanzi, S, Peshu, J, Ndaa, S, Chabuka, J, Mkandawire, N, Matandika, L, Kapuya, C, Weller, I, Malianga, E, Mwansambo, C, Miiro, F, Elyanu, P, Bukusi, E, Katabira, E, Mugurungi, O, Peto, T, Musoke, P, Matenga, J, Phiri, S, Lyall, H, Johnston, V, Fitzgerald, F, Post, F, Ssali, F, Arenas?Pinto, A, Turkova, A, and Bamford, A

Subjects
Cost benefit analysis, Practice guidelines (Medicine) -- Evaluation, HIV infection -- Diagnosis -- Care and treatment, Cost benefit analysis, Health
Abstract

: Introduction: Many HIV‐positive individuals in Africa have advanced disease when initiating antiretroviral therapy (ART) so have high risks of opportunistic infections and death. The REALITY trial found that an enhanced‐prophylaxis package including fluconazole reduced mortality by 27% in individuals starting ART with CD4 Methods: The REALITY trial enrolled from June 2013 to April 2015. A decision‐analytic model was developed to estimate the cost‐effectiveness of six management strategies in individuals initiating ART in the REALITY trial countries. Strategies included standard‐prophylaxis, enhanced‐prophylaxis, standard‐prophylaxis with fluconazole; and three CrAg testing strategies, the first stratifying individuals to enhanced‐prophylaxis (CrAg‐positive) or standard‐prophylaxis (CrAg‐negative), the second to enhanced‐prophylaxis (CrAg‐positive) or enhanced‐prophylaxis without fluconazole (CrAg‐negative) and the third to standard‐prophylaxis with fluconazole (CrAg‐positive) or without fluconazole (CrAg‐negative). The model estimated costs, life‐years and quality‐adjusted life‐years (QALY) over 48 weeks using three competing mortality risks: cryptococcal meningitis; tuberculosis, serious bacterial infection or other known cause; and unknown cause. Results: Enhanced‐prophylaxis was cost‐effective at cost‐effectiveness thresholds of US$300 and US$500 per QALY with an incremental cost‐effectiveness ratio (ICER) of US$157 per QALY in the CD4 Conclusions: The REALITY enhanced‐prophylaxis package in individuals with advanced HIV starting ART reduces morbidity and mortality, is practical to administer and is cost‐effective. Efforts should continue to ensure that components are accessed at lowest available prices., Introduction In low‐ and middle‐income settings, more than a third of HIV‐positive individuals starting antiretroviral therapy (ART) present with advanced disease (CD4 ≤ 200 cells/mm[sup.3]); over half of these have [...]

Published
2020
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41. Trypanosoma cruziscreening in people living with HIV in the UK

Author

Ahmed, Nadia, Herbert, Sophie, Arenas-Pinto, Alejandro, Rickman, Hannah, Benn, Paul, Edwards, Simon G, Chiodini, Peter L, and Grant, Alison D

Abstract

People living with HIV (PLWH) are at higher risk of reactivation of Chagas disease, a neglected tropical disease, caused by Trypanosoma cruzi. There are no data from UK HIV clinics on the prevalence of T. cruzi. We implemented T. cruziscreening at our clinic as part of routine care for PLWH with epidemiological risk factors. Among 86 patients screened, none had positive serology: one seropositive patient was identified due to increased clinician awareness. Implementing T. cruziscreening as part of routine clinical care was feasible, though labour intensive and identified at-risk individuals.

Published
2024
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42. SARS-CoV-2 infection rates of antibody-positive compared with antibody-negative health-care workers in England: a large, multicentre, prospective cohort study (SIREN)

Author

Victoria Jane Hall, Sarah Foulkes, Andre Charlett, Ana Atti, Edward J M Monk, Ruth Simmons, Edgar Wellington, Michelle J Cole, Ayoub Saei, Blanche Oguti, Katie Munro, Sarah Wallace, Peter D Kirwan, Madhumita Shrotri, Amoolya Vusirikala, Sakib Rokadiya, Meaghan Kall, Maria Zambon, Mary Ramsay, Tim Brooks, Colin S Brown, Meera A Chand, Susan Hopkins, N Andrews, A Atti, H Aziz, T Brooks, CS Brown, D Camero, C Carr, MA Chand, A Charlett, H Crawford, M Cole, J Conneely, S D'Arcangelo, J Ellis, S Evans, S Foulkes, N Gillson, R Gopal, L Hall, VJ Hall, P Harrington, S Hopkins, J Hewson, K Hoschler, D Ironmonger, J Islam, M Kall, I Karagiannis, O Kay, J Khawam, E King, P Kirwan, R Kyffin, A Lackenby, M Lattimore, E Linley, J Lopez-Bernal, L Mabey, R McGregor, S Miah, EJM Monk, K Munro, Z Naheed, A Nissr, AM O'Connell, B Oguti, H Okafor, S Organ, J Osbourne, A Otter, M Patel, S Platt, D Pople, K Potts, M Ramsay, J Robotham, S Rokadiya, C Rowe, A Saei, G Sebbage, A Semper, M Shrotri, R Simmons, A Soriano, P Staves, S Taylor, A Taylor, A Tengbe, S Tonge, A Vusirikala, S Wallace, E Wellington, M Zambon, D Corrigan, M Sartaj, L Cromey, S Campbell, K Braithwaite, L Price, L Haahr, S Stewart, ED Lacey, L Partridge, G Stevens, Y Ellis, H Hodgson, C Norman, B Larru, S Mcwilliam, S Winchester, P Cieciwa, A Pai, C Loughrey, A Watt, F Adair, A Hawkins, A Grant, R Temple-Purcell, J Howard, N Slawson, C Subudhi, S Davies, A Bexley, R Penn, N Wong, G Boyd, A Rajgopal, A Arenas-Pinto, R Matthews, A Whileman, R Laugharne, J Ledger, T Barnes, C Jones, D Botes, N Chitalia, S Akhtar, G Harrison, S Horne, N Walker, K Agwuh, V Maxwell, J Graves, S Williams, A O'Kelly, P Ridley, A Cowley, H Johnstone, P Swift, J Democratis, M Meda, C Callens, S Beazer, S Hams, V Irvine, B Chandrasekaran, C Forsyth, J Radmore, C Thomas, K Brown, S Roberts, P Burns, K Gajee, TM Byrne, F Sanderson, S Knight, E Macnaughton, BJL Burton, H Smith, R Chaudhuri, K Hollinshead, RJ Shorten, A Swan, C Favager, J Murira, S Baillon, S Hamer, K Gantert, J Russell, D Brennan, A Dave, A Chawla, F Westell, D Adeboyeku, P Papineni, C Pegg, M Williams, S Ahmad, S Ingram, C Gabriel, K Pagget, G Maloney, J Ashcroft, I Del Rosario, R Crosby-Nwaobi, C Reeks, S Fowler, L Prentice, M Spears, G McKerron, K McLelland-Brooks, J Anderson, S Donaldson, K Templeton, L Coke, N Elumogo, J Elliott, D Padgett, M Mirfenderesky, A Cross, J Price, S Joyce, I Sinanovic, M Howard, T Lewis, P Cowling, D Potoczna, S Brand, L Sheridan, B Wadams, A Lloyd, J Mouland, J Giles, G Pottinger, H Coles, M Joseph, M Lee, S Orr, H Chenoweth, C Auckland, R Lear, T Mahungu, A Rodger, K Penny-Thomas, S Pai, J Zamikula, E Smith, S Stone, E Boldock, D Howcroft, C Thompson, M Aga, P Domingos, S Gormley, C Kerrison, L Marsh, S Tazzyman, L Allsop, S Ambalkar, M Beekes, S Jose, J Tomlinson, A Jones, C Price, J Pepperell, M Schultz, J Day, A Boulos, E Defever, D McCracken, K Gray, A Houston, T Planche, R Pritchard Jones, Diane Wycherley, S Bennett, J Marrs, K Nimako, B Stewart, N Kalakonda, S Khanduri, A Ashby, M Holden, N Mahabir, J Harwood, B Payne, K Court, N Staines, R Longfellow, ME Green, LE Hughes, M Halkes, P Mercer, A Roebuck, E Wilson-Davies, L Gallego, R Lazarus, N Aldridge, L Berry, F Game, T Reynolds, C Holmes, M Wiselka, A Higham, M Booth, C Duff, J Alderton, H Jory, E Virgilio, T Chin, MZ Qazzafi, AM Moody, R Tilley, T Donaghy, K Shipman, R Sierra, N Jones, G Mills, D Harvey, YWJ Huang, J Birch, L Robinson, S Board, A Broadley, C Laven, N Todd, DW Eyre, K Jeffery, S Dunachie, C Duncan, P Klenerman, L Turtle, T De Silva, H Baxendale, JL Heeney, Group, SIREN Study, Dunachie, SJ, Kirwan, Peter [0000-0001-6904-0500], and Apollo - University of Cambridge Repository

Subjects
Adult, Male, medicine.medical_specialty, Health Personnel, 030204 cardiovascular system & hematology, Antibodies, Viral, Lower risk, Asymptomatic, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Pandemic, Health care, Humans, Medicine, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Asymptomatic Infections, Pandemics, SARS-CoV-2, business.industry, Incidence (epidemiology), Public health, COVID-19, Articles, General Medicine, Middle Aged, England, COVID-19 Nucleic Acid Testing, Reinfection, Cohort, Female, medicine.symptom, business, Follow-Up Studies
Abstract

Background Increased understanding of whether individuals who have recovered from COVID-19 are protected from future SARS-CoV-2 infection is an urgent requirement. We aimed to investigate whether antibodies against SARS-CoV-2 were associated with a decreased risk of symptomatic and asymptomatic reinfection. Methods A large, multicentre, prospective cohort study was done, with participants recruited from publicly funded hospitals in all regions of England. All health-care workers, support staff, and administrative staff working at hospitals who could remain engaged in follow-up for 12 months were eligible to join The SARS-CoV-2 Immunity and Reinfection Evaluation study. Participants were excluded if they had no PCR tests after enrolment, enrolled after Dec 31, 2020, or had insufficient PCR and antibody data for cohort assignment. Participants attended regular SARS-CoV-2 PCR and antibody testing (every 2–4 weeks) and completed questionnaires every 2 weeks on symptoms and exposures. At enrolment, participants were assigned to either the positive cohort (antibody positive, or previous positive PCR or antibody test) or negative cohort (antibody negative, no previous positive PCR or antibody test). The primary outcome was a reinfection in the positive cohort or a primary infection in the negative cohort, determined by PCR tests. Potential reinfections were clinically reviewed and classified according to case definitions (confirmed, probable, or possible) and symptom-status, depending on the hierarchy of evidence. Primary infections in the negative cohort were defined as a first positive PCR test and seroconversions were excluded when not associated with a positive PCR test. A proportional hazards frailty model using a Poisson distribution was used to estimate incidence rate ratios (IRR) to compare infection rates in the two cohorts. Findings From June 18, 2020, to Dec 31, 2020, 30 625 participants were enrolled into the study. 51 participants withdrew from the study, 4913 were excluded, and 25 661 participants (with linked data on antibody and PCR testing) were included in the analysis. Data were extracted from all sources on Feb 5, 2021, and include data up to and including Jan 11, 2021. 155 infections were detected in the baseline positive cohort of 8278 participants, collectively contributing 2 047 113 person-days of follow-up. This compares with 1704 new PCR positive infections in the negative cohort of 17 383 participants, contributing 2 971 436 person-days of follow-up. The incidence density was 7·6 reinfections per 100 000 person-days in the positive cohort, compared with 57·3 primary infections per 100 000 person-days in the negative cohort, between June, 2020, and January, 2021. The adjusted IRR was 0·159 for all reinfections (95% CI 0·13–0·19) compared with PCR-confirmed primary infections. The median interval between primary infection and reinfection was more than 200 days. Interpretation A previous history of SARS-CoV-2 infection was associated with an 84% lower risk of infection, with median protective effect observed 7 months following primary infection. This time period is the minimum probable effect because seroconversions were not included. This study shows that previous infection with SARS-CoV-2 induces effective immunity to future infections in most individuals. Funding Department of Health and Social Care of the UK Government, Public Health England, The National Institute for Health Research, with contributions from the Scottish, Welsh and Northern Irish governments.

Published
2021

45. Using trained dogs and organic semi-conducting sensors to identify asymptomatic and mild SARS-CoV-2 infections: an observational study

Author

Guest, Claire, Dewhirst, Sarah Y, Lindsay, Steve W, Allen, David J, Aziz, Sophie, Baerenbold, Oliver, Bradley, John, Chabildas, Unnati, Chen-Hussey, Vanessa, Clifford, Samuel, Cottis, Luke, Dennehy, Jessica, Foley, Erin, Gezan, Salvador A, Gibson, Tim, Greaves, Courtenay K, Kleinschmidt, Immo, Lambert, Sébastien, Last, Anna, Morant, Steve, Parker, Josephine E A, Pickett, John, Quilty, Billy J, Rooney, Ann, Shah, Manil, Somerville, Mark, Squires, Chelci, Walker, Martin, Logan, James G, Jones, Robert, Assis, Ana, Borthwick, Ewan, Caton, Laura, Edwards, Rachel, Heal, Janette, Hill, David, Jahan, Nazifa, Johnson, Cecelia, Kaye, Angela, Kirkpatrick, Emily, Kisha, Sarah, Ledeatte Williams, Zaena, Moar, Robert, Owonibi, Tolulope, Purcell, Benjamin, Rixson, Christopher, Spencer, Freya, Stefanidis, Anastasios, Stewart, Sophie, Tytheridge, Scott, Wakley, Sian, Wildman, Shanice, Aziz, Catherine, Care, Helen, Curtis, Emily, Dowse, Claire, Makepeace, Alan, Oultram, Sally-Anne, Smith, Jayde, Shenton, Fiona, Hutchins, Harry, Mart, Robert, Cartwright, Jo-anne, Forsey, Miranda, Goodsell, Kerry, Kittridge, Lauren, Nicholson, Anne, Ramos, Angelo, Ritches, Joanne, Setty, Niranjan, Vertue, Mark, Bergstrom, Malin, Chaudhary, Zain, De Wilton, Angus, Gaskell, Kate, Houlihan, Catherine, Jones, Imogen, Margaritis, Marios, Miralhes, Patricia, Owens, Leah, Rampling, Tommy, Rickman, Hannah, Boffito, Marta, Fernandez, Candida, Cotterell, Bryony, Guerdette, Anne-Marie, Tsaknis, George, Turns, Margaret, Walsh, Joanne, Frankland, Lisa, West, Raha, Holland, Maureen, Keenan, Natalie, Wassall, Helen, Young, Megan, Rangeley, Jade, Saalmink, Gwendolyn, Adlakha, Sanjay, Buckley, Philip, Allsop, Lynne, Smith, Susan, Sowter, Donna, Campbell, Alison, Jones, Julie, Laird, Steve, O’Toole, Sarah, Ryan, Courteney, Evans, Jessica, Rand, James, Schumacher, Natasha, Hazelton, Tracey, Dodgson, Andrew, Glasgow, Susannah, Kadiu, Denise, Lopuszansky, Orianne, Oommen, Anu, Prabhu, Joshi, Pursell, Molly, Turner, Jane, Walton, Hollie, Andrews, Robert, Cruickshank, Irena, Thompson, Catherine, Wainwright, Tania, Roebuck, Alun, Lawrence, Tara, Netherton, Kimberley, Hewitt, Claire, Shephardson, Sarah, Crasto, Winston Andrew, Lake, Judith, Musanhu, Rosemary, Walker, Rebecca, Burns, Karen, Higham, Andrew, Le Bas, Julie, Mackenzie, Nicola, Thatcher, Hilary, Beadle, Shannen, Buckley, Sarah, Castle, Gail, Fletcher, Aimee, Holbrook, Sara, Kane, Patricia, Lindley, Kate, Lowry, Tracey, Lupton, Stephanie, Oddy, Sharon, Slater, Lynda, Sylvester, Martin, Agwuh, Kenneth, Maxwell, Veronica, Ryder, Stephen, Topham, Kirsty, Egbuniwe, Obi, Matthews, Rebecca, Arenas-Pinto, Alejandro, Prymas, Paulina, Severn, Abigail, Shaw, Amber, Begum, Safia, Lenton, Daniel, Scriven, James, Leeman, Lucy, Rudge, Karen, Storr, Emma, Alvarez, Ana, Forster, Kate, Hind, Daniel, Cook, Natalie, Peeling, Rosanna, Carey, Peter, Wilson, Anne, and Davis, Jane

Subjects
Volatile Organic Compounds, Dogs, SARS-CoV-2, fungi, Animals, COVID-19, Humans, Mass Screening, General Medicine, Asymptomatic Infections, Sensitivity and Specificity
Abstract

Background A rapid, accurate, non-invasive diagnostic screen is needed to identify people with SARS-CoV-2 infection. We investigated whether organic semi-conducting (OSC) sensors and trained dogs could distinguish between people infected with asymptomatic or mild symptoms, and uninfected individuals, and the impact of screening at ports-of-entry. Methods Odour samples were collected from adults, and SARS-CoV-2 infection status confirmed using RT-PCR. OSC sensors captured the volatile organic compound (VOC) profile of odour samples. Trained dogs were tested in a double-blind trial to determine their ability to detect differences in VOCs between infected and uninfected individuals, with sensitivity and specificity as the primary outcome. Mathematical modelling was used to investigate the impact of bio-detection dogs for screening. Results About, 3921 adults were enrolled in the study and odour samples collected from 1097 SARS-CoV-2 infected and 2031 uninfected individuals. OSC sensors were able to distinguish between SARS-CoV-2 infected individuals and uninfected, with sensitivity from 98% (95% CI 95–100) to 100% and specificity from 99% (95% CI 97–100) to 100%. Six dogs were able to distinguish between samples with sensitivity ranging from 82% (95% CI 76–87) to 94% (95% CI 89–98) and specificity ranging from 76% (95% CI 70–82) to 92% (95% CI 88–96). Mathematical modelling suggests that dog screening plus a confirmatory PCR test could detect up to 89% of SARS-CoV-2 infections, averting up to 2.2 times as much transmission compared to isolation of symptomatic individuals only. Conclusions People infected with SARS-CoV-2, with asymptomatic or mild symptoms, have a distinct odour that can be identified by sensors and trained dogs with a high degree of accuracy. Odour-based diagnostics using sensors and/or dogs may prove a rapid and effective tool for screening large numbers of people. Trial Registration NCT04509713 (clinicaltrials.gov).

Published
2022

47. Pneumoproteins and biomarkers of inflammation and coagulation do not predict rapid lung function decline in people living with HIV.

Author

MacDonald, David M., Samorodnitsky, Sarah, Wendt, Chris H., Baker, Jason V., Collins, Gary, Kruk, Monica, Lock, Eric F., Paredes, Roger, Poongulali, Selvamuthu, Weise, Danielle O., Winston, Alan, Wood, Robin, Kunisaki, Ken M., INSIGHT START Pulmonary Substudy Group, International Coordinating Centres, Aagaard, B., Jansson, P. O., Pearson, M. T., Babiker, A. G., and Arenas-Pinto, A.

Subjects
HIV, LUNGS, HIV-positive persons, CHRONIC obstructive pulmonary disease, BLOOD coagulation
Abstract

Chronic obstructive pulmonary disease (COPD) is among the leading causes of death worldwide and HIV is an independent risk factor for the development of COPD. However, the etiology of this increased risk and means to identify persons with HIV (PWH) at highest risk for COPD have remained elusive. Biomarkers may reveal etiologic pathways and allow better COPD risk stratification. We performed a matched case:control study of PWH in the Strategic Timing of Antiretoviral Treatment (START) pulmonary substudy. Cases had rapid lung function decline (> 40 mL/year FEV1 decline) and controls had stable lung function (+ 20 to − 20 mL/year). The analysis was performed in two distinct groups: (1) those who were virally suppressed for at least 6 months and (2) those with untreated HIV (from the START deferred treatment arm). We used linear mixed effects models to test the relationship between case:control status and blood concentrations of pneumoproteins (surfactant protein-D and club cell secretory protein), and biomarkers of inflammation (IL-6 and hsCRP) and coagulation (d-dimer and fibrinogen); concentrations were measured within ± 6 months of first included spirometry. We included an interaction with treatment group (untreated HIV vs viral suppression) to test if associations varied by treatment group. This analysis included 77 matched case:control pairs in the virally suppressed batch, and 42 matched case:control pairs in the untreated HIV batch (n = 238 total) who were followed for a median of 3 years. Median (IQR) CD4 + count was lowest in the controls with untreated HIV at 674 (580, 838). We found no significant associations between case:control status and pneumoprotein or biomarker concentrations in either virally suppressed or untreated PWH. In this cohort of relatively young, recently diagnosed PWH, concentrations of pneumoproteins and biomarkers of inflammation and coagulation were not associated with subsequent rapid lung function decline. Trial registration: NCT00867048 and NCT01797367. [ABSTRACT FROM AUTHOR]

Published
2023
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48. Long-Term Benefits from Early Antiretroviral Therapy Initiation in HIV Infection.

Author

Lundgren, Jens D., Babiker, Abdel G., Sharma, Shweta, Grund, Birgit, Phillips, Andrew N., Matthews, Gail, Kan, Virginia L., Aagaard, Bitten, Abo, Inka, Alston, Beverly, Arenas-Pinto, Alejandro, Avihingsanon, Anchalee, Badal-Faesen, Sharlaa, Brites, Carlos, Carey, Cate, Casseb, Jorge, Clarke, Amanda, Collins, Simon, Corbelli, Giulio Maria, and Dao, Sounkalo

Subjects
HIV prevention, HIV infections, HIV-positive persons, CONFIDENCE intervals, VIRAL load, ANTIRETROVIRAL agents, HIGHLY active antiretroviral therapy, CD4 lymphocyte count, STATISTICAL sampling, EARLY medical intervention, PROPORTIONAL hazards models, LONGITUDINAL method
Abstract

Background: For people with HIV and CD4+ counts >500 cells/mm³, early initiation of antiretroviral therapy (ART) reduces serious AIDS and serious non-AIDS (SNA) risk compared with deferral of treatment until CD4+counts are <350 cells/mm³. Whether excess risk of AIDS and SNA persists once ART is initiated for those who defer treatment is uncertain. Methods: The Strategic Timing of AntiRetroviral Treatment (START) trial, as previously reported, randomly assigned 4684 ART-naive HIV-positive adults with CD4+counts >500 cells/mm³ to immediate treatment initiation after random assignment (n=2325) or deferred treatment (n= 2359). In 2015, a 57% lower risk of the primary end point (AIDS, SNA, or death) for the immediate group was reported, and the deferred group was offered ART. This article reports the follow-up that continued to December 31, 2021. Cox proportional-hazards models were used to compare hazard ratios for the primary end point from randomization through December 31, 2015, versus January 1, 2016, through December 31, 2021. Results: Through December 31, 2015, approximately 7 months after the cutoff date from the previous report, the median CD4+ count was 648 and 460 cells/mm³ in the immediate and deferred groups, respectively, at treatment initiation. The percentage of follow-up time spent taking ART was 95% and 36% for the immediate and deferred groups, respectively, and the time-averaged CD4+ difference was 199 cells/mm³. After January 1, 2016, the percentage of follow-up time on treatment was 97.2% and 94.1% for the immediate and deferred groups, respectively, and the CD4+ count difference was 155 cells/mm³. After January 1, 2016, a total of 89 immediate and 113 deferred group participants experienced a primary end point (hazard ratio of 0.79 [95% confidence interval, 0.60 to 1.04] versus hazard ratio of 0.47 [95% confidence interval, 0.34 to 0.65; P<0.001]) before 2016 (P=0.02 for hazard ratio difference). Conclusions: Among adults with CD4+ counts >500 cells/mm³, excess risk of AIDS and SNA associated with delaying treatment initiation was diminished after ART initiation, but persistent excess risk remained. (Funded by the National Institute of Allergy and Infectious Diseases and others.) In people with HIV and CD4+ counts >500 cells/mm³, immediate initiation of ART reduced serious AIDS and SNA risk, the primary end point, compared with deferring ART until CD4+counts were <350 cells/mm³. Beginning in 2016 after the deferred group was advised to initiate ART, 89 immediate and 113 deferred group participants experienced a primary end point. Persistent excess risk of the primary end point remained in the deferred compared to the immediate ART group. [ABSTRACT FROM AUTHOR]

Published
2023
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49. The Protease Inhibitor Monotherapy Versus Ongoing Triple Therapy (PIVOT) trial: a randomised controlled trial of a protease inhibitor monotherapy strategy for long-term management of human immunodeficiency virus infection

Author

Nicholas I Paton, Wolfgang Stöhr, Lars Oddershede, Alejandro Arenas-Pinto, Simon Walker, Mark Sculpher, David T Dunn, and on behalf of the PIVOT trial team

Subjects
randomised controlled trial, human immunodeficiency virus, protease inhibitor, monotherapy, antiretroviral therapy, combination therapy, Medical technology, R855-855.5
Abstract

Background: Standard-of-care antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection uses a combination of drugs, until now considered essential to minimise treatment failure and development of drug resistance. Protease inhibitors (PIs) are potent with a high genetic barrier to resistance and have the potential for use as monotherapy after viral load (VL) suppression achieved on combination therapy. However, longer-term resistance and toxicity risks are uncertain. Objective: To compare the effectiveness, toxicity profile and cost-effectiveness of PI monotherapy with those of standard-of-care triple therapy in a pragmatic long-term clinical trial. Design: Open-label, parallel-group, randomised controlled trial. Setting: Forty-three HIV clinical centres in the UK NHS. Participants: HIV-positive adults taking standard combination ART with a suppressed VL for ≥ 6 months. Interventions: Patients were randomised to maintain ongoing triple therapy (OT) or switch to a strategy of physician-selected ritonavir-boosted PI monotherapy (PI-mono), with prompt return to combination therapy in the event of VL rebound. Main outcome measures: The primary outcome was reduction of future drug options, defined as new intermediate-/high-level resistance to one or more drugs to which the patient’s virus was considered to be sensitive at trial entry (non-inferiority comparison, 10% margin). Secondary outcomes included confirmed virological rebound, serious drug- or disease-related complications, total grade 3 or 4 adverse events (AEs), neurocognitive function change, cluster of differentiation 4 (CD4) cell count change, change in health-related quality of life, cardiovascular risk change, health-care costs and health economic analysis. Results: In total, 587 participants were randomised (77% male, 68% white) to OT (n = 291) or PI-mono (n = 296) and followed for a median of 44 months, of whom 2.7% withdrew/were lost to follow-up. One or more episodes of confirmed VL rebound were observed in eight patients (Kaplan–Meier estimate 3.2%) in the OT group and 95 patients (35.0%) in the PI-mono group [absolute risk difference 31.8%, 95% confidence interval (CI) 24.6% to 39.0%; p

Published
2016
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50. Genital Secretion HIV RNA Shedding in HIV-Positive Patients on Ritonavir-Boosted Protease Inhibitor Monotherapy or Standard Combination ART: A Cross-Sectional Sub-Study from the PIVOT Trial

Author

Vincent Lee, Wolfgang Stöhr, David Dunn, Alejandro Arenas-Pinto, Bridget Ferns, Eleni Nastouli, Nicholas J. Beeching, Rebecca Wiggins, Nicholas I. Paton, Laura Else, Zoe Warwick, Amanda Clarke, Charles J.N. Lacey, and Saye Khoo

Subjects
Male, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, Semen, Antiretroviral Therapy, Highly Active, Humans, Medicine, Pharmacology (medical), Sex organ, In patient, Genitalia, Pharmacology, Ritonavir, business.industry, HIV Protease Inhibitors, Middle Aged, Virology, Virus Shedding, Cross-Sectional Studies, Infectious Diseases, Genital tract, Vagina, RNA, Viral, Female, Genital secretion, business, medicine.drug
Abstract

Background Protease inhibitors (PI) have relatively low penetration into the genital tract, raising concerns about the potential for genital HIV RNA shedding in patients taking PI-based regimens, particularly PI monotherapy (PI-mono). Methods We measured HIV RNA and PI drug concentrations in samples of semen, cervicovaginal and rectal mucosa secretions, and plasma in patients after 48–96 weeks on PI-mono or standard triple therapy. Results A total of 85 participants were recruited. Of the 43 participants on PI-mono (70% on darunavir [DRV]/ ritonavir [r]), 3 had detectable virus in semen or vaginal secretions (all below quantification limit), and none in rectal mucosa or plasma. Among those taking triple therapy, five had detectable virus in semen or vaginal secretions (HIV RNA >50 copies/ml in one), none in rectal mucosa and one in plasma. The median (IQR) concentration of DRV and atazanavir in semen (659.7 [339–1,089] and 128.8 [63–368] ng/ml, respectively) and cervico-vaginal samples (2,768 [312–7,879] and 1,836 [359–3,314] ng/ml, respectively) exceeded their protein adjusted median inhibition concentration (MIC50). DRV concentration in rectal secretions showed higher variability compared with concentration in the other sites, with particularly high rectal secretion/blood ratios (median 8.4, IQR 2.6–68.7:1). Conclusions We found no substantive evidence of HIV shedding in patients taking PI-mono, suggesting that PIs provide adequate control of virus in the genital compartment and are unlikely to lead to ongoing sexual transmission.

Published
2020

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