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1. Sickle Cell Trait and Kidney Disease in People of African Ancestry With HIV

Author

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

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

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

Published
2022
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2. GSTM1 Copy Number and Kidney Disease in People With HIV

Author

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

Subjects
Nephrology
Published
2022

3. Genetic Variants of APOL1 Are Major Determinants of Kidney Failure in People of African Ancestry With HIV

Author

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

Subjects
kidney, Nephrology, Africa, HIV, diaspora, APOL1, HIVAN
Abstract

Introduction: Variants of the APOL1 gene are associated with chronic kidney disease (CKD) in people of African ancestry, although evidence for their impact in people with HIV are sparse. Methods: We conducted a cross-sectional study investigating the association between APOL1 renal risk alleles and kidney disease in people of African ancestry with HIV in the UK. The primary outcome was end-stage kidney disease (ESKD; estimated glomerular filtration rate [eGFR] of 2, chronic dialysis, or having received a kidney transplant). The secondary outcomes included renal impairment (eGFR 2), albuminuria (albumin-to-creatinine ratio [ACR] >30 mg/mmol), and biopsy-proven HIV-associated nephropathy (HIVAN). Multivariable logistic regression was used to estimate the associations between APOL1 high-risk genotypes (G1/G1, G1/G2, G2/G2) and kidney disease outcomes. Results: A total of 2864 participants (mean age 48.1 [SD 10.3], 57.3% female) were genotyped, of whom, 354 (12.4%) had APOL1 high-risk genotypes, and 99 (3.5%) had ESKD. After adjusting for demographic, HIV, and renal risk factors, individuals with APOL1 high-risk genotypes were at increased odds of ESKD (odds ratio [OR] 10.58, 95% CI 6.22–17.99), renal impairment (OR 5.50, 95% CI 3.81–7.95), albuminuria (OR 3.34, 95% CI 2.00–5.56), and HIVAN (OR 30.16, 95% CI 12.48–72.88). An estimated 49% of ESKD was attributable to APOL1 high-risk genotypes. Conclusion: APOL1 high-risk genotypes were strongly associated with kidney disease in people of African ancestry with HIV and accounted for approximately half of ESKD cases in this cohort.

Published
2022

4. No overall change in the rate of weight gain after switching to an integrase-inhibitor in virologically suppressed adults with HIV

Author

Ana Milinkovic, Sarah Pett, Laura Waters, Richard Gilson, Abigail Severn, Oliver Stirrup, Hinal Lukha, Iain Runcie-Unger, Sophie Candfield, Simon Edwards, David Dunn, and James E. Burns

Subjects
Adult, Male, 0301 basic medicine, Sustained Virologic Response, Pyridones, Immunology, Human immunodeficiency virus (HIV), Integrase inhibitor, HIV Infections, Weight Gain, medicine.disease_cause, Piperazines, Strand transfer, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Raltegravir Potassium, Oxazines, Humans, Immunology and Allergy, Medicine, HIV Integrase Inhibitors, 030212 general & internal medicine, Aged, Retrospective Studies, biology, Drug Substitution, business.industry, Middle Aged, Raltegravir, Virology, Antiretroviral therapy, Integrase, Treatment Outcome, 030104 developmental biology, Infectious Diseases, chemistry, Dolutegravir, HIV-1, biology.protein, Female, medicine.symptom, business, Heterocyclic Compounds, 3-Ring, Weight gain, medicine.drug
Abstract

Excessive weight gain has been reported with integrase strand transfer inhibitors (INSTIs). We evaluated weight changes in virologically suppressed adults with HIV who switched from non-INSTI regimens to raltegravir (RAL)-containing or dolutegravir (DTG)-containing antiretroviral therapy.Retrospective single-centre cohort.Adults who switched to RAL or DTG before or between January 2015 and October 2017 were identified. Virologically suppressed, treatment-experienced (≥2 years) individuals, at least 6 months on INSTI, with weight measurements 2 years or less pre and postswitch were included. Our analysis used a random effects model with linear slope pre and post-INSTI with adjustment for age, sex, ethnicity, preswitch-regimen (protease inhibitor vs. nonprotease inhibitor), and RAL vs. DTG use.A total of 378 individuals, 81.2% male, 70.1% white ethnicity, median age of 49 years, median of four weight measurements per participant, and median weight and BMI at switch of 76.6 kg and 25.3 kg/m, respectively, were included. Weight increased by an average of 0.63 kg/year (95% confidence interval 0.17-1.09) preswitch with no overall change in rate of weight gain postswitch [+0.05 kg/year (-0.61-0.71, P = 0.88)]. In our adjusted model, a transition from minimal weight change to weight gain postswitch was isolated to older individuals though this lacked statistical significance [e.g., +1.59 kg/year (-0.26-3.45) if aged 65 years]. Our findings did not differ by sex, ethnicity, preswitch regimen, or RAL vs. DTG. Similar results were seen for BMI and after adjusting for fixed nucleoside/nucleotide reverse transcriptase inhibitor backbone.We found no clear evidence of an overall increase in rate of weight gain following switch to INSTI in virologically suppressed individuals.

Published
2020

5. Sickle Cell Trait and Kidney Disease in People of African Ancestry With HIV

Author

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

Subjects
Nephrology
Abstract

Sickle cell trait (SCT) has been associated with chronic kidney disease (CKD) in African Americans, although evidence for its impact in Africans and people with HIV is currently lacking. We conducted a cross-sectional study investigating the association between SCT and kidney disease in people of African ancestry with HIV in the UK.The primary outcome was estimated glomerular filtration rate (eGFR) 60 ml/min per 1.73 mA total of 2895 participants (mean age 48.1 [SD 10.3], 57.2% female) were included, of whom 335 (11.6%) had SCT and 352 (12.2%) had eGFR 60 ml/min per 1.73 mOur results extend previously reported associations between SCT and kidney disease to people with HIV. In people of African ancestry with HIV, these associations were largely restricted to those with

Published
2021

6. Incoming HIV virion-derived Gag Spacer Peptide 2 (p1) is a target of effective CD8(+) T cell antiviral responses

Author

Hongbing Yang, Anuska Llano, Samandhy Cedeño, Annette von Delft, Angelica Corcuera, Geraldine M. Gillespie, Andrew Knox, Darren B. Leneghan, John Frater, Wolfgang Stöhr, Sarah Fidler, Beatriz Mothe, Johnson Mak, Christian Brander, Nicola Ternette, Lucy Dorrell, Eric Sandström, Janet Darbyshire, Frank Post, Christopher Conlon, Jane Anderson, Mala Maini, Timothy Peto, Peter Sasieni, Veronica Miller, Ian Weller, Abdel Babiker, Sarah Pett, Matthew Pace, Natalia Olejniczak, Helen Brown, Nicola Robinson, Jakub Kopycinski, Tomáš Hanke, Alison Crook, Steven Kaye, Myra McClure, Otto Erlwein, Andrew Lovell, Maryam Khan, Michelle Gabrielle, Rachel Bennett, Aminata Sy, Adam Gregory, Fleur Hudson, Charlotte Russell, Gemma Wood, Hanna Box, Cherry Kingsley, Katie Topping, Andrew Lever, Mark Wills, Axel Fun, Mikaila Bandara, Damian Kelly, Simon Collins, Alex Markham, Mary Rauchenberger, Yinka Sowunmi, Shaadi Shidfar, Dominic Hague, Mark Nelson, Maddalena Cerrone, Nadia Castrillo Martinez, Tristan Barber, Alexandra Schoolmeesters, Christine Weaver, Orla Thunder, Jane Rowlands, Christopher Higgs, Serge Fedele, Margherita Bracchi, Lervina Thomas, Peter Bourke, Nneka Nwokolo, Gaynor Lawrenson, Marzia Fiorino, Hinal Lukha, Sabine Kinloch-de Loes, Margaret Johnson, Alice Nightingale, Nnenna Ngwu, Patrick Byrne, Zoe Cuthbertson, Martin Jones, Tina Fernandez, Amanda Clarke, Martin Fisher, Rebecca Gleig, Vittorio Trevitt, Colin Fitzpatrick, Tanya Adams, Fiounnuala Finnerty, John Thornhill, Heather Lewis, Kristin Kuldanek, Julie Fox, Julianne Lwanga, Hiromi Uzu, Ming Lee, Simon Merle, Patrick O’Rourke, Isabel Jendrulek, Taras Zarko Flynn, Mark Taylor, Juan Manuel Tiraboschi, Tammy Murray, group, Research in Viral Eradication of Reservoirs (RIVER) trial study, Imperial College Healthcare NHS Trust- BRC Funding, and Medical Research Council (MRC)

Subjects
0301 basic medicine, immunopeptidome, DETERMINANTS, LYMPHOCYTES, 0601 Biochemistry and Cell Biology, Epitope, kinetics, 0302 clinical medicine, Cytotoxic T cell, CD8 T cells, mass spectrometry, Gag, cytotoxic T lymphocytes, HLA, POLYFUNCTIONALITY, INFECTED-CELLS, peptides, Life Sciences & Biomedicine, Antigen presentation, Human leukocyte antigen, PROVIRUSES, Biology, antigen presentation, REPLICATION CAPACITY, General Biochemistry, Genetics and Molecular Biology, Virus, 03 medical and health sciences, Immune system, CONTROLLERS, KINETICS, Science & Technology, RECOGNITION, HIV, Cell Biology, Virology, Histocompatibility, Research in Viral Eradication of Reservoirs (RIVER) trial study group, 030104 developmental biology, 1116 Medical Physiology, RESERVOIR, 030217 neurology & neurosurgery, CD8
Abstract

Persistence of HIV through integration into host DNA in CD4(+) T cells presents a major barrier to virus eradication. Viral integration may be curtailed when CD8(+) T cells are triggered to kill infected CD4(+) T cells through recognition of histocompatibility leukocyte antigen (HLA) class I-bound peptides derived from incoming virions. However, this has been reported only in individuals with "beneficial'' HLA alleles that are associated with superior HIV control. Through interrogation of the pre-integration immunopeptidome, we obtain proof of early presentation of a virion-derived HLA-A*02:01-restricted epitope, FLGKIWPSH (FH9), located in Gag Spacer Peptide 2 (SP2). FH9-specific CD8(+) T cell responses are detectable in individuals with primary HIV infection and eliminate HIV-infected CD4(+) T cells prior to virus production in vitro. Our data show that non-beneficial HLA class I alleles can elicit an effective antiviral response through early presentation of HIV virion-derived epitopes and also demonstrate the importance of SP2 as an immune target.

Published
2021

7. Pandemic peak SARS-CoV-2 infection and seroconversion rates in London frontline health-care workers

Author

Catherine F Houlihan, Nina Vora, Thomas Byrne, Dan Lewer, Gavin Kelly, Judith Heaney, Sonia Gandhi, Moira J Spyer, Rupert Beale, Peter Cherepanov, David Moore, Richard Gilson, Steve Gamblin, George Kassiotis, Laura E McCoy, Charles Swanton, Andrew Hayward, Eleni Nastouli, Jim Aitken, Zoe Allen, Rachel Ambler, Karen Ambrose, Emma Ashton, Alida Avola, Samutheswari Balakrishnan, Caitlin Barns-Jenkins, Genevieve Barr, Sam Barrell, Souradeep Basu, Clare Beesley, Nisha Bhardwaj, Shahnaz Bibi, Ganka Bineva-Todd, Dhruva Biswas, Michael J Blackman, Dominique Bonnet, Faye Bowker, Malgorzata Broncel, Claire Brooks, Michael D Buck, Andrew Buckton, Timothy Budd, Alana Burrell, Louise Busby, Claudio Bussi, Simon Butterworth, Fiona Byrne, Richard Byrne, Simon Caidan, Joanna Campbell, Johnathan Canton, Ana Cardoso, Nick Carter, Luiz Carvalho, Raffaella Carzaniga, Natalie Chandler, Qu Chen, Laura Churchward, Graham Clark, Bobbi Clayton, Clementina Cobolli Gigli, Zena Collins, Sally Cottrell, Margaret Crawford, Laura Cubitt, Tom Cullup, Heledd Davies, Patrick Davis, Dara Davison, Annalisa D'Avola, Vicky Dearing, Solene Debaisieux, Monica Diaz-Romero, Alison Dibbs, Jessica Diring, Paul C Driscoll, Christopher Earl, Amelia Edwards, Chris Ekin, Dimitrios Evangelopoulos, Rupert Faraway, Antony Fearns, Aaron Ferron, Efthymios Fidanis, Dan Fitz, James Fleming, Bruno Frederico, Alessandra Gaiba, Anthony Gait, Liam Gaul, Helen M Golding, Jacki Goldman, Robert Goldstone, Belen Gomez Dominguez, Hui Gong, Paul R Grant, Maria Greco, Mariana Grobler, Anabel Guedan, Maximiliano G Gutierrez, Fiona Hackett, Ross Hall, Steinar Halldorsson, Suzanne Harris, Sugera Hashim, Lyn Healy, Susanne Herbst, Graeme Hewitt, Theresa Higgins, Steve Hindmarsh, Rajnika Hirani, Joshua Hope, Elizabeth Horton, Beth Hoskins, Michael Howell, Louise Howitt, Jacqueline Hoyle, Mint R Htun, Michael Hubank, Hector Huerga Encabo, Deborah Hughes, Jane Hughes, Almaz Huseynova, Ming-Shih Hwang, Rachael Instrell, Deborah Jackson, Mariam Jamal-Hanjani, Lucy Jenkins, Ming Jiang, Mark Johnson, Leigh Jones, Nnennaya Kanu, Louise Kiely, Anastacio King Spert Teixeira, Stuart Kirk, Svend Kjaer, Ellen Knuepfer, Nikita Komarov, Paul Kotzampaltiris, Konstantinos Kousis, Tammy Krylova, Ania Kucharska, Robyn Labrum, Catherine Lambe, Michelle Lappin, Stacey-Ann Lee, Andrew Levett, Lisa Levett, Marcel Levi, Hon-Wing Liu, Sam Loughlin, Wei-Ting Lu, James I MacRae, Akshay Madoo, Julie A Marczak, Mimmi Martensson, Thomas Martinez, Bishara Marzook, John Matthews, Joachim M Matz, Samuel McCall, Fiona McKay, Edel C McNamara, Carlos M Minutti, Gita Mistry, Miriam Molina-Arcas, Beatriz Montaner, Kylie Montgomery, Catherine Moore, Anastasia Moraiti, Lucia Moreira-Teixeira, Joyita Mukherjee, Cristina Naceur-Lombardelli, Aileen Nelson, Jerome Nicod, Luke Nightingale, Stephanie Nofal, Paul Nurse, Savita Nutan, Caroline Oedekoven, Anne O'Garra, Jean D O'Leary, Jessica Olsen, Olga O'Neill, Paula Ordonez Suarez, Nicola O'Reilly, Neil Osborne, Amar Pabari, Aleksandra Pajak, Venizelos Papayannopoulos, Namita Patel, Yogen Patel, Oana Paun, Nigel Peat, Laura Peces-Barba Castano, Ana Perez Caballero, Jimena Perez-Lloret, Magali S Perrault, Abigail Perrin, Roy Poh, Enzo Z Poirier, James M Polke, Marc Pollitt, Lucia Prieto-Godino, Alize Proust, Rajvee Shah Punatar, Clinda Puvirajasinghe, Christophe Queval, Vijaya Ramachandran, Abhinay Ramaprasad, Peter Ratcliffe, Laura Reed, Caetano Reis e Sousa, Kayleigh Richardson, Sophie Ridewood, Rowenna Roberts, Angela Rodgers, Pablo Romero Clavijo, Annachiara Rosa, Alice Rossi, Chloe Roustan, Andrew Rowan, Erik Sahai, Aaron Sait, Katarzyna Sala, Theo Sanderson, Pierre Santucci, Fatima Sardar, Adam Sateriale, Jill A Saunders, Chelsea Sawyer, Anja Schlott, Edina Schweighoffer, Sandra Segura-Bayona, Joe Shaw, Gee Yen Shin, Mariana Silva Dos Santos, Margaux Silvestre, Matthew Singer, Daniel M Snell, Ok-Ryul Song, Louisa Steel, Amy Strange, Adrienne E Sullivan, Michele SY Tan, Zoe H Tautz-Davis, Effie Taylor, Gunes Taylor, Harriet B Taylor, Alison Taylor-Beadling, Fernanda Teixeira Subtil, Berta Terré Torras, Patrick Toolan-Kerr, Francesca Torelli, Tea Toteva, Moritz Treeck, Hadija Trojer, Ming-Han C Tsai, James MA Turner, Melanie Turner, Jernej Ule, Rachel Ulferts, Sharon P Vanloo, Selvaraju Veeriah, Subramanian Venkatesan, Karen Vousden, Andreas Wack, Claire Walder, Philip A Walker, Yiran Wang, Sophia Ward, Catharina Wenman, Luke Wiliams, Matthew J Williams, Wai Keong Wong, Joshua Wright, Mary Wu, Lauren Wynne, Zheng Xiang, Melvyn Yap, Julian A Zagalak, Davide Zecchin, Rachel Zillwood, Rebecca Matthews, Abigail Severn, Sajida Adam, Louise Enfield, Angela McBride, Kathleen Gärtner, Sarah Edwards, Fabiana Lorencatto, Susan Michie, Ed Manley, Maryam Shahmanesh, Hinal Lukha, Paulina Prymas, Hazel McBain, Robert Shortman, Leigh Wood, Claudia Davies, Bethany Williams, Kevin W Ng, Georgina H Cornish, Nikhil Faulkner, Andrew Riddell, Philip Hobson, Ana Agua-Doce, Kerol Bartolovic, Emma Russell, Lotte Carr, Emilie Sanchez, Daniel Frampton, Matthew Byott, Stavroula M Paraskevopoulou, Elise Crayton, Carly Meyer, Triantafylia Gkouleli, Andrea Stoltenberg, Veronica Ranieri, Tom Byrne, Fiona Roberts, and Emine Hatipoglu

Subjects
Adult, 2019-20 coronavirus outbreak, Infectious Disease Transmission, Patient-to-Professional, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Health Personnel, Pneumonia, Viral, Viral transmission, Antibodies, Viral, Risk Assessment, Article, Betacoronavirus, Environmental health, Occupational Exposure, Pandemic, Health care, London, Medicine, Humans, Prospective Studies, Seroconversion, Pandemics, Cross Infection, business.industry, SARS-CoV-2, COVID-19, General Medicine, Occupational exposure, business, Coronavirus Infections
Published
2020

8. Antiretroviral therapy alone versus antiretroviral therapy with a kick and kill approach, on measures of the HIV reservoir in participants with recent HIV infection (the RIVER trial): a phase 2, randomised trial

Author

Sarah Fidler, Wolfgang Stöhr, Matt Pace, Lucy Dorrell, Andrew Lever, Sarah Pett, Sabine Kinloch-de Loes, Julie Fox, Amanda Clarke, Mark Nelson, John Thornhill, Maryam Khan, Axel Fun, Mikaila Bandara, Damian Kelly, Jakub Kopycinski, Tomáš Hanke, Hongbing Yang, Rachel Bennett, Margaret Johnson, Bonnie Howell, Richard Barnard, Guoxin Wu, Steve Kaye, Mark Wills, Abdel Babiker, John Frater, Eric Sandström, Janet Darbyshire, Frank Post, Christopher Conlon, Jane Anderson, Mala Maini, Timothy Peto, Peter Sasieni, Veronica Miller, Ian Weller, Matthew Pace, Natalia Olejniczak, Helen Brown, Nicola Robinson, Alison Crook, Steven Kaye, Myra McClure, Otto Erlwein, Andrew Lovell, Michelle Gabrielle, Aminata Sy, Adam Gregory, Fleur Hudson, Charlotte Russell, Gemma Wood, Hanna Box, Cherry Kingsley, Katie Topping, Simon Collins, Alex Markham, Mary Rauchenberger, Yinka Sowunmi, Shaadi Shidfar, Dominic Hague, Maddalena Cerrone, Nadia Castrillo Martinez, Tristan Barber, Alexandra Schoolmeesters, Christine Weaver, Orla Thunder, Jane Rowlands, Christopher Higgs, Serge Fedele, Margherita Bracchi, Lervina Thomas, Peter Bourke, Nneka Nwokolo, Gaynor Lawrenson, Marzia Fiorino, Hinal Lukha, Alice Nightingale, Nnenna Ngwu, Patrick Byrne, Zoe Cuthbertson, Martin Jones, Tina Fernandez, Martin Fisher, Rebecca Gleig, Vittorio Trevitt, Colin Fitzpatrick, Tanya Adams, Fiounnuala Finnerty, Heather Lewis, Kristin Kuldanek, Julianne Lwanga, Hiromi Uzu, Ming Lee, Simon Merle, Patrick O'Rourke, Isabel Jendrulek, Taras ZarkoFlynn, Mark Taylor, Juan Manuel Tiraboschi, and Tammy Murray

Subjects
Adult, Male, medicine.medical_specialty, Disease reservoir, Transcription, Genetic, HIV Infections, 030204 cardiovascular system & hematology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, Clinical endpoint, Humans, 030212 general & internal medicine, Adverse effect, Disease Reservoirs, AIDS Vaccines, Vorinostat, Intention-to-treat analysis, business.industry, General Medicine, Histone Deacetylase Inhibitors, Clinical trial, Regimen, Treatment Outcome, Anti-Retroviral Agents, DNA, Viral, business, Viral load
Abstract

Background: Antiretroviral therapy (ART) cannot cure HIV infection because of a persistent reservoir of latently infected cells. Approaches that force HIV transcription from these cells, making them susceptible to killing—termed kick and kill regimens—have been explored as a strategy towards an HIV cure. RIVER is the first randomised trial to determine the effect of ART-only versus ART plus kick and kill on markers of the HIV reservoir. Methods: This phase 2, open-label, multicentre, randomised, controlled trial was undertaken at six clinical sites in the UK. Patients aged 18–60 years who were confirmed as HIV-positive within a maximum of the past 6 months and started ART within 1 month from confirmed diagnosis were randomly assigned by a computer generated randomisation list to receive ART-only (control) or ART plus the histone deacetylase inhibitor vorinostat (the kick) and replication-deficient viral vector T-cell inducing vaccines encoding conserved HIV sequences ChAdV63. HIVconsv-prime and MVA.HIVconsv-boost (the kill; ART + V + V; intervention). The primary endpoint was total HIV DNA isolated from peripheral blood CD4+ T-cells at weeks 16 and 18 after randomisation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02336074. Findings: Between June 14, 2015 and Jul 11, 2017, 60 men with HIV were randomly assigned to receive either an ART-only (n=30) or an ART + V + V (n=30) regimen; all 60 participants completed the study, with no loss-to-follow-up. Mean total HIV DNA at weeks 16 and 18 after randomisation was 3·02 log10 copies HIV DNA per 106 CD4+ T-cells in the ART-only group versus 3·06 log10 copies HIV DNA per 106 CD4+ T-cells in ART + V + V group, with no statistically significant difference between the two groups (mean difference of 0·04 log10 copies HIV DNA per 106 CD4+ T-cells [95% CI −0·03 to 0·11; p=0·26]). There were no intervention-related serious adverse events. Interpretation: This kick and kill approach conferred no significant benefit compared with ART alone on measures of the HIV reservoir. Although this does not disprove the efficacy kick and kill strategy, for future trials enhancement of both kick and kill agents will be required.

Published
2020

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