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12 results on '"Moira Spyer"'

1. Impact of sub-optimal HIV viral control on activated T cells

Author

Francesca I.F. Arrigoni, Moira Spyer, Patricia Hunter, Dagmar Alber, Cissy Kityo, James Hakim, Allen Matubu, Patrick Olal, Nicholas I. Paton, A. Sarah Walker, and Nigel Klein

Subjects
Infectious Diseases, Immunology, Immunology and Allergy
Published
2023

2. Cohort profile: Virus Watch: Understanding community incidence, symptom profiles, and transmission of COVID-19 in relation to population movement and behaviour

Author

Thomas Byrne, Jana Kovar, Sarah Beale, Isobel Braithwaite, Ellen Fragaszy, Wing Lam Erica Fong, Cyril Geismar, Susan Hoskins, Annalan M D Navaratnam, Vincent Nguyen, Parth Patel, Madhumita Shrotri, Alexei Yavlinsky, Pia Hardelid, Linda Wijlaars, Eleni Nastouli, Moira Spyer, Anna Aryee, Ingemar Cox, Vasileios Lampos, Rachel A McKendry, Tao Cheng, Anne M Johnson, Susan Michie, Jo Gibbs, Richard Gilson, Alison Rodger, Ibrahim Abubakar, Andrew Hayward, and Robert W Aldridge

Abstract

Key FeaturesVirus Watch is a national community cohort study of COVID-19 in households in England and Wales, established in June 2020. The study aims to provide evidence on which public health approaches are most effective in reducing transmission, and investigate community incidence, symptoms, and transmission of COVID-19 in relation to population movement and behaviours.28,527 households and 58,628 participants of age (0-98 years, mean age 48), were recruited between June 2020 - July 2022Data collected include demographics, details on occupation, co-morbidities, medications, and infection-prevention behaviours. Households are followed up weekly with illness surveys capturing symptoms and their severity, activities in the week prior to symptom onset and any COVID-19 test results. Monthly surveys capture household finance, employment, mental health, access to healthcare, vaccination uptake, activities and contacts. Data have been linked to Hospital Episode Statistics (HES), inpatient and critical care episodes, outpatient visits, emergency care contacts, mortality, virology testing and vaccination data held by NHS Digital.Nested within Virus Watch are a serology & PCR cohort study (n=12,877) and a vaccine evaluation study (n=19,555).Study data are deposited in the Office of National Statistics (ONS) Secure Research Service (SRS). Survey data are available under restricted access upon request to ONS SRS.

Published
2023

3. In Depth Viral Diversity Analysis in Atypical Neurological and Neonatal Chikungunya Infections in Rio de Janeiro, Brazil

Author

Maria Celeste Torres, Fatima Di Maio, David Brown, Moira Spyer, Eleni Nastouli, Patrícia Brasil, and Ana Maria Bispo de Filippis

Subjects
Infectious Diseases, chikungunya virus, atypical manifestations, placenta, blood–brain barrier, intrahost diversity, Aedes, Nucleotides, Virology, Codon, Terminator, Infant, Newborn, Animals, Chikungunya Fever, Humans, Chikungunya virus, Communicable Diseases, Brazil
Abstract

Chikungunya virus (CHIKV) is an arthropod-borne virus (arbovirus) transmitted by Aedes mosquitoes. The human infection usually manifests as a febrile and incapacitating arthritogenic illness, self-limiting and non-lethal. However, since 2013, CHIKV spreading through the tropics and to the Americas was accompanied by an increasing number of cases of atypical disease presentation, namely severe neuropathies and neonatal infection due to intrapartum vertical transmission. The pathophysiological mechanisms underlying these conditions have not been fully elucidated. However, arbovirus intrahost genetic diversity is thought to be linked to viral pathogenesis. To determine whether particular viral variants could be somehow associated, we analyzed the intrahost genetic diversity of CHIKV in three infected patients with neurological manifestations and three mothers infected during the intrapartum period, as well as their babies following vertical transmission. No statistically supported differences were observed for the genetic variability (nucleotide substitutions/gene length) along the genome between the groups. However, the newborn and cerebrospinal fluid samples (corresponding to virus passed through the placenta and/or the blood–brain barrier (BBB)) presented a different composition of their intrahost mutant ensembles compared to maternal or patient serum samples, even when concurrent. This finding could be consistent with the unidirectional virus transmission through these barriers, and the effect of selective bottlenecks during the transmission event. In addition, a higher proportion of defective variants (insertions/deletions and stop codons) was detected in the CSF and maternal samples and those were mainly distributed within the viral non-structural genes. Since defective viral genomes in RNA viruses are known to contribute to the outcome of acute viral infections and influence disease severity, their role in these atypical cases should be further investigated. Finally, with the in silico approach adopted, we detected no relevant non-conservative mutational pattern that could provide any hint of the pathophysiological mechanisms underlying these atypical cases. The present analysis represents a unique contribution to our understanding of the transmission events in these cases and generates hypotheses regarding underlying mechanisms, that can be explored further.

Published
2022

4. Nucleocapsid and spike antibody responses following virologically confirmed SARS-CoV-2 infection: an observational analysis in the Virus Watch community cohort

Author

Annalan M D Navaratnam, Madhumita Shrotri, Vincent Nguyen, Isobel Braithwaite, Sarah Beale, Thomas E Byrne, Wing Lam Erica Fong, Ellen Fragaszy, Cyril Geismar, Susan Hoskins, Jana Kovar, Parth Patel, Alexei Yavlinsky, Anna Aryee, Alison Rodger, Andrew C Hayward, Robert W Aldridge, Susan Michie, Pia Hardelid, Linda Wijlaars, Eleni Nastouli, Moira Spyer, Ben Killingley, Ingemar Cox, Vasileios Lampos, Rachel A McKendry, Tao Cheng, Yunzhe Liu, Jo Gibbs, Richard Gilson, and Anne M Johnson

Subjects
Microbiology (medical), Adult, Adolescent, SARS-CoV-2, COVID-19, General Medicine, Antibodies, Viral, Cohort Studies, Infectious Diseases, Seroepidemiologic Studies, Antibody Formation, Humans, Female, Prospective Studies, Nucleocapsid
Abstract

Seroprevalence studies can provide a measure of SARS-CoV-2 cumulative incidence, but a better understanding of spike and nucleocapsid (anti-N) antibody dynamics following infection is needed to assess the longevity of detectability.Adults aged ≥18 years, from households enrolled in the Virus Watch prospective community cohort study in England and Wales, provided monthly capillary blood samples, which were tested for spike antibody and anti-N. Participants self-reported vaccination dates and past medical history. Previous polymerase chain reaction (PCR) swabs were obtained through Second Generation Surveillance System linkage data. The primary outcome variables were seropositivity and total anti-N and spike antibody levels after PCR-confirmed infection.A total of 13,802 eligible individuals provided 58,770 capillary blood samples. A total of 537 of these had a previous positive PCR-confirmed SARS-CoV-2 infection within 0-269 days of antibody sample date, among them 432 (80.45%) having a positive anti-N result. Median anti-N levels peaked between days 90 and 119 after PCR results and then began to decline. There is evidence of anti-N waning from 120 days onwards, with earlier waning for females and younger age categories.Our findings suggest that anti-N has around 80% sensitivity for identifying previous COVID-19 infection, and the duration of detectability is affected by sex and age.

Published
2022

5. Once-daily dolutegravir-based antiretroviral therapy in infants and children living with HIV from age 4 weeks: results from the below 14 kg cohort in the randomised ODYSSEY trial

Author

Pauline Amuge, Abbas Lugemwa, Ben Wynne, Hilda A Mujuru, Avy Violari, Cissy M Kityo, Moherndran Archary, Ebrahim Variava, Ellen White, Rebecca M Turner, Clare Shakeshaft, Shabinah Ali, Kusum J Nathoo, Lorna Atwine, Afaaf Liberty, Dickson Bbuye, Elizabeth Kaudha, Rosie Mngqibisa, Modehei Mosala, Vivian Mumbiro, Annet Nanduudu, Rogers Ankunda, Lindiwe Maseko, Adeodata R Kekitiinwa, Carlo Giaquinto, Pablo Rojo, Diana M Gibb, Anna Turkova, Deborah Ford, Amina Farhana Mehar (nee Abdulla), Pattamukkil Abraham, Elaine Abrams, Judith Acero, Gerald Muzorah Agaba, Grace Ahimbisibwe, Barbara Ainebyoona, Winnie Akobye, Yasmeen Akhalwaya, Nazim Akoojee, Shabinah S. Ali, Catherine Andrea, Maria Angeles Muñoz Fernandez, Diana Antonia Rutebarika, Suvaporn Anugulruengkitt, Tsitsi Apollo, Ronelle Arendze, Juliet Ategeka, Eunice Atim, Abdel Babiker, Sarah Babirye, Enock Babu, Edward Bagirigomwa, Angella Baita, David Balamusani, Patsy Baliram, David Baliruno, Colin Ball, Henry Balwa, Alasdair Bamford, Srini Bandi, Dominique Barker, Linda Barlow-Mosha, Shazia Begum, Osee Behuhuma, Sarah Bernays, Rogers Besigye, Maria Bester, Joyline Bhiri, Davide Bilardi, Kristien Bird, Pauline Bollen, Chiara Borg, Anne-Marie Borges Da Silva, Jackie Brown, Elena Bruno, Torsak Bunupuradah, David Burger, Nomzamo Buthelezi, Mutsa Bwakura-Dangarembizi, Africanus Byaruhanga, Joanna Calvert, Petronelle Casey, Haseena Cassim, Sphiwee Cebekhulu, Sanuphong Chailert, Suwalai Chalermpantmetagul, Wanna Chamjamrat, Man Chan, Precious Chandiwana, Thannapat Chankun, Sararut Chanthaburanun, Nuttawut Chanto, Ennie Chidziva, Minenhle Chikowore, Joy Chimanzi, Dujrudee Chinwong, Stuart Chitongo, Moses Chitsamatanga, Joshua Choga, Duangrat Chutima, Polly Clayden, Alexandra Coelho, Angela Colbers, Alexandra Compagnucci, Ana Constança Mendes, Magda Conway, Mark F. Cotton, Jane Crawley, Tim R. Cressey, Jacky Crisp, Ana Cristina Matos, Sumaya Dadan, Jacqui Daglish, Siva Danaviah, Tseleng Daniel, Anita De Rossi, Sukanda Denjanta, Els Dobbels, Maria Dowie, Prosper Dube, Benedictor Dube, Nimisha Dudakia, Alice Elwana, Cristina Epalza, David Eram, Juan Erasmus, Peter Erim, Luis Escosa Garcia, Zaakirah Essack, Carolina Estepa, Monica Etima, Alexandre Fernandes, Maite Fernandez, Felicity Fitzgerald, Jacquie Flynn, Claudia Fortuny Guasch, Caroline Foster, George Fourie, Yolandie Fourie, Sophie Foxall, Derusha Frank, Kate Gandhi, India Garcia, Kathleen Gartner, Joshua Gasa, Gugu Gasa, Diana M. Gibb, Coral Gomez Rico, Daniel Gomez-Pena, Secrecy Gondo, Anna Goodman, Maria Gorreti Nakalema, Winnie Gozhora, Pisut Greetanukroh, Biobanco Gregorio Maranon, Tiziana Grossele, Shamiso Gwande, Tapiwa Gwaze, Tsitsi Gwenzi, James Hakim, Emmanuel Hakiza, Abdul Hamid Kaka, Ashley Harley, Mornay Isaacs, Richard Isabirye, Wilber Ishemunyoro, Tom Jacobs, Lungile Jafta, Nasir Jamil, Anita Janse Janse van Rensburg, Vinesh Jeaven, Maria José Mellado Peña, Gonzague Jourdain, Katabalwa Juliet, Thidarat Jumpimai, Raungwit Junkaew, Thidarat Jupimai, Winfred Kaahwa, Mildred Kabasonga, Olivia Kaboggoza, Rose Jacqueline Kadhuba, Ampika Kaewbundit, Kanyanee Kaewmamueng, Bosco Kafufu, Brenda Kakayi, Phakamas Kamboua, Suparat Kanjanavanit, Gladys Kasangaki, Naruporn Kasipong, Miriam Kasozi, Hajira Kataike, Chrispus Katemba, Nkata Kekane, Adeodata R. Kekitiinwa, Edridah Keminyeto, Woottichai Khamduang, Warunee Khamjakkaew, Jiraporn Khamkon, Sasipass Khannak, Orapin Khatngam, Tassawan Khayanchoomnoom, Busi Khumalo, Mirriam Khunene, Suwimon Khusuwan, Phionah Kibalama, Robinah Kibenge, Anthony Kirabira, Cissy M. Kityo, Lameck Kiyimba, Nigel Klein, Soraya Klinprung, Robin Kobbe, Olivia Kobusingye, Josephine Kobusungye, Areerat Kongponoi, Christoph Königs, Olivier Koole, Christelle Kouakam, Nitinart Krueduangkam, Namthip Kruenual, Nuananong Kunjaroenrut, Raymonds Kyambadde, Priscilla Kyobutungi, Flavia Kyomuhendo, Erinah Kyomukama, Reshma Lakha, Cleopatra Langa, Laddawan Laomanit, Emily Lebotsa, Prattana Leenasirimakul, Lawrence Lekku, Sarah Lensen, Valériane Leroy, Jin Li, Juthamas Limplertjareanwanich, Emma Little, Ezra Lutalo, Jose Luis Jimenez, Hermione Lyall, Candice MacDonald, Gladness Machache, Penelope Madlala, Tryphina Madonsela, Nomfundo Maduna, Joel Maena, Apicha Mahanontharit, Collin Makanga, Candice Makola, Shafic Makumbi, Lucille Malgraaf, Angelous Mamiane, Felicia Mantkowski, Wendy Mapfumo, Laura Marques, Agnes Mary Mugagga, Tshepiso Masienyane, Ruth Mathiba, Farai Matimba, Sajeeda Mawlana, Emmanuel Mayanja, Fatima Mayat, Ritah Mbabazi, Nokuthula Mbadaliga, Faith Mbasani, Kathleen McClaughlin, Helen McIlleron, Watchara Meethaisong, Patricia Mendez Garcia, Annet Miwanda, Carlota Miranda, Siphiwe Mkhize, Kgosimang Mmolawa, Fatima Mohamed, Tumelo Moloantoa, Maletsatsi Monametsi, Samuel Montero, Cecilia L. Moore, Rejoice Mosia, Columbus Moyo, Mumsy Mthethwa, Shepherd Mudzingwa, Tawona Mudzviti, Hilda Mujuru, Emmanuel Mujyambere, Trust Mukanganiki, Cynthia Mukisa Williams, Mark Mulder, Disan Mulima, Alice Mulindwa, Zivai Mupambireyi, Alba Murciano Cabeza, Herbert Murungi, Dorothy Murungu, Sandra Musarurwa, Victor Musiime, Alex V. Musiime, Maria Musisi, Philippa Musoke, Barbara Musoke Nakirya, Godfrey Musoro, Sharif Musumba, Sobia Mustafa, Shirley Mutsai, Phyllis Mwesigwa Rubondo, Mariam Naabalamba, Immaculate Nagawa, Allemah Naidoo, Shamim Nakabuye, Sarah Nakabuye, Sarah Nakalanzi, Justine Nalubwama, Annet Nalugo, Stella Nalusiba, Clementine Namajja, Sylvia Namanda, Paula Namayanja, Esther Nambi, Rachael Kikabi Namuddu, Stella Namukwaya, Florence Namuli, Josephine Namusanje, Rosemary Namwanje, Anusha Nanan-kanjee, Charity Nankunda, Joanita Nankya Baddokwaya, Maria Nannungi, Winnie Nansamba, Kesdao Nanthapisal, Juliet Nanyonjo, Sathaporn Na-Rajsima, Claire Nasaazi, Helena Nascimento, Eleni Nastouli, Wipaporn Natalie Songtaweesin, Kusum Nathoo, Ian Natuhurira, Rashidah Nazzinda, Thabisa Ncgaba, Milly Ndigendawani, Makhosonke Ndlovu, Georgina Nentsa, Chaiwat Ngampiyaskul, Ntombenhle Ngcobo, Nicole Ngo Giang Huong, Pia Ngwaru, Ruth Nhema, Emily Ninsiima, Gloria Ninsiima, Misheck Nkalo Phiri, Antoni Noguera Julian, Monica Nolan, Thornthun Noppakaorattanamanee, Muzamil Nsibuka Kisekka, Eniola Nsirim, Rashina Nundlal, Rosita Nunes, Lungile Nyantsa, Mandisa Nyati, Sean O'Riordan, Paul Ocitti Labeja, Denis Odoch, Rachel Oguntimehin, Martin Ojok, Geoffrey Onen, Wilma Orange, Pradthana Ounchanum, Benson Ouma, Andreia Padrao, Deborah Pako, Anna Parker, Malgorzata Pasko-Szcech, Reena Patel, Rukchanok Peongjakta, Turian Petpranee, Tasmin Phillips, Jackie Philps, Laura Picault, Sonja Pieterse, Helena Pinheiro, Supawadee Pongprapass, Anton Pozniak, Andrew Prendergast, Luis Prieto Tato, Patcharee Puangmalai, Thanyawee Puthanakit, Modiehi Rakgokong, Helena Ramos, Nastassja Ramsagar, Cornelius Rau, Yoann Riault, Pablo Rojo Conejo, Basiimwa Roy Clark, Eddie Rubanga, Baker Rubinga, Chutima Ruklao, Pattira Runarassamee, Chalermpong Saenjum, Chayakorn Saewtrakool, Yacine Saidi, Talia Sainz Costa, Chutima Saisaengjan, Rebecca Sakwa, Tatiana Sarfati, Noshalaza Sbisi, Dihedile Scheppers, Stephan Schultze-Strasser, Ulf Schulze-Sturm, Karen Scott, Janet Seeley, Robert Serunjogi, Leora Sewnarain, Subashinie Sidhoo, Mercy Shibemba, Delane Shingadia, Sheleika Singh, Wasna Sirirungsi, Sibongile Sithebe, Theresa Smit, Kurt Smith, Marlize Smuts, Moira Spyer, Worathip Sripaoraya, Ussanee Srirompotong, Warunee Srisuk, Mark Ssenyonga, Patamawadee Sudsaard, Praornsuda Sukrakanchana, Pathanee Tearsansern, Carla Teixeira, Kanchana Than-in-at, Thitiwat Thapwai, Yupawan Thaweesombat, Jutarat Thewsoongnoen, Rodolphe Thiébaut, Margaret Thomason, Laura Thrasyvoulou, Khanungnit Thungkham, Judith Tikabibamu, Gloria Tinago, Ketmookda Trairat, Gareth Tudor-Williams, Mercy Tukamushaba, Deogratiuos Tukwasibwe, Julius Tumusiime, Joana Tuna, Rebecca Turner, Arttasid Udomvised, Aasia Vadee, Hesti Van Huyssteen, Nadine Van Looy, Yvonne Vaughan-Gordon, Giulio Vecchia, Richard Vowden, Hylke Waalewijn, Rebecca Wampamba, Steve Welch, Ian Weller, Sibusisiwe Weza, Ian White, Kaja Widuch, Helen Wilkes, Sookpanee Wimonklang, Pacharaporn Yingyong, Zaam Zinda Nakawungu, and Peter Zuidewind

Subjects
Adult, Epidemiology, Pyridones, Anti-HIV Agents, Immunology, HIV Infections, 3-Ring, Piperazines, Heterocyclic Compounds, Virology, Oxazines, Humans, Protease Inhibitors, Child, Preschool, Infant, Newborn, Infant, Bayes Theorem, Viral Load, Newborn, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Infectious Diseases, Child, Preschool, Heterocyclic Compounds, 3-Ring, Treatment Outcome
Abstract

Contains fulltext : 283099.pdf (Publisher’s version ) (Open Access) BACKGROUND: Young children living with HIV have few treatment options. We aimed to assess the efficacy and safety of dolutegravir-based antiretroviral therapy (ART) in children weighing between 3 kg and less than 14 kg. METHODS: ODYSSEY is an open-label, randomised, non-inferiority trial (10% margin) comparing dolutegravir-based ART with standard of care and comprises two cohorts (children weighing ≥14 kg and

Published
2022

6. Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Author

Anna Turkova, Hylke Waalewijn, Man K Chan, Pauline D J Bollen, Mutsa F Bwakura-Dangarembizi, Adeodata R Kekitiinwa, Mark F Cotton, Abbas Lugemwa, Ebrahim Variava, Grace Miriam Ahimbisibwe, Ussanee Srirompotong, Vivian Mumbiro, Pauline Amuge, Peter Zuidewind, Shabinah Ali, Cissy M Kityo, Moherndran Archary, Rashida A Ferrand, Avy Violari, Diana M Gibb, David M Burger, Deborah Ford, Angela Colbers, Amina Farhana Mehar (nee Abdulla), Pattamukkil Abraham, Elaine Abrams, Judith Acero, Gerald Muzorah Agaba, Grace Ahimbisibwe, Barbara Ainebyoona, Winnie Akobye, Yasmeen Akhalwaya, Nazim Akoojee, Shabinah S. Ali, Catherine Andrea, Maria Angeles Muñoz Fernandez, Rogers Ankunda, Diana Antonia Rutebarika, Suvaporn Anugulruengkitt, Tsitsi Apollo, Ronelle Arendze, Juliet Ategeka, Eunice Atim, Lorna Atwine, Abdel Babiker, Sarah Babirye, Enock Babu, Edward Bagirigomwa, Angella Baita, David Balamusani, Patsy Baliram, David Baliruno, Colin Ball, Henry Balwa, Alasdair Bamford, Srini Bandi, Dominique Barker, Linda Barlow-Mosha, Dickson Bbuye, Shazia Begum, Osee Behuhuma, Sarah Bernays, Rogers Besigye, Maria Bester, Joyline Bhiri, Davide Bilardi, Kristien Bird, Pauline Bollen, Chiara Borg, Anne-Marie Borges Da Silva, Jackie Brown, Elena Bruno, Torsak Bunupuradah, David Burger, Nomzamo Buthelezi, Mutsa Bwakura-Dangarembizi, Africanus Byaruhanga, Joanna Calvert, Petronelle Casey, Haseena Cassim, Sphiwee Cebekhulu, Sanuphong Chailert, Suwalai Chalermpantmetagul, Wanna Chamjamrat, Man Chan, Precious Chandiwana, Thannapat Chankun, Sararut Chanthaburanun, Nuttawut Chanto, Ennie Chidziva, Minenhle Chikowore, Joy Chimanzi, Dujrudee Chinwong, Stuart Chitongo, Moses Chitsamatanga, Joshua Choga, Duangrat Chutima, Polly Clayden, Alexandra Coelho, Alexandra Compagnucci, Ana Constança Mendes, Magda Conway, Mark F. Cotton, Jane Crawley, Tim R. Cressey, Jacky Crisp, Ana Cristina Matos, Sumaya Dadan, Jacqui Daglish, Siva Danaviah, Tseleng Daniel, Anita De Rossi, Sukanda Denjanta, Els Dobbels, Maria Dowie, Prosper Dube, Benedictor Dube, Nimisha Dudakia, Alice Elwana, Cristina Epalza, David Eram, Juan Erasmus, Peter Erim, Luis Escosa Garcia, Zaakirah Essack, Carolina Estepa, Monica Etima, Alexandre Fernandes, Maite Fernandez, Felicity Fitzgerald, Jacquie Flynn, Claudia Fortuny Guasch, Caroline Foster, George Fourie, Yolandie Fourie, Sophie Foxall, Derusha Frank, Kate Gandhi, India Garcia, Kathleen Gartner, Joshua Gasa, Gugu Gasa, Carlo Giaquinto, Diana M. Gibb, Coral Gomez Rico, Daniel Gomez-Pena, Secrecy Gondo, Anna Goodman, Maria Gorreti Nakalema, Winnie Gozhora, Pisut Greetanukroh, Biobanco Gregorio Maranon, Tiziana Grossele, Shamiso Gwande, Tapiwa Gwaze, Tsitsi Gwenzi, James Hakim, Emmanuel Hakiza, Abdul Hamid Kaka, Ashley Harley, Mornay Isaacs, Richard Isabirye, Wilber Ishemunyoro, Tom Jacobs, Lungile Jafta, Nasir Jamil, Anita Janse Janse van Rensburg, Vinesh Jeaven, Maria José Mellado Peña, Gonzague Jourdain, Katabalwa Juliet, Thidarat Jumpimai, Raungwit Junkaew, Thidarat Jupimai, Winfred Kaahwa, Mildred Kabasonga, Olivia Kaboggoza, Rose Jacqueline Kadhuba, Ampika Kaewbundit, Kanyanee Kaewmamueng, Bosco Kafufu, Brenda Kakayi, Phakamas Kamboua, Suparat Kanjanavanit, Gladys Kasangaki, Naruporn Kasipong, Miriam Kasozi, Hajira Kataike, Chrispus Katemba, Elizabeth Kaudha, Nkata Kekane, Adeodata R. Kekitiinwa, Edridah Keminyeto, Woottichai Khamduang, Warunee Khamjakkaew, Jiraporn Khamkon, Sasipass Khannak, Orapin Khatngam, Tassawan Khayanchoomnoom, Busi Khumalo, Mirriam Khunene, Suwimon Khusuwan, Phionah Kibalama, Robinah Kibenge, Anthony Kirabira, Cissy M. Kityo, Lameck Kiyimba, Nigel Klein, Soraya Klinprung, Robin Kobbe, Olivia Kobusingye, Josephine Kobusungye, Areerat Kongponoi, Christoph Königs, Olivier Koole, Christelle Kouakam, Nitinart Krueduangkam, Namthip Kruenual, Nuananong Kunjaroenrut, Raymonds Kyambadde, Priscilla Kyobutungi, Flavia Kyomuhendo, Erinah Kyomukama, Reshma Lakha, Cleopatra Langa, Laddawan Laomanit, Emily Lebotsa, Prattana Leenasirimakul, Lawrence Lekku, Sarah Lensen, Valériane Leroy, Jin Li, Afaaf Liberty, Juthamas Limplertjareanwanich, Emma Little, Ezra Lutalo, Jose Luis Jimenez, Hermione Lyall, Candice MacDonald, Gladness Machache, Penelope Madlala, Tryphina Madonsela, Nomfundo Maduna, Joel Maena, Apicha Mahanontharit, Collin Makanga, Candice Makola, Shafic Makumbi, Lucille Malgraaf, Angelous Mamiane, Felicia Mantkowski, Wendy Mapfumo, Laura Marques, Agnes Mary Mugagga, Lindiwe Maseko, Tshepiso Masienyane, Ruth Mathiba, Farai Matimba, Sajeeda Mawlana, Emmanuel Mayanja, Fatima Mayat, Ritah Mbabazi, Nokuthula Mbadaliga, Faith Mbasani, Kathleen McClaughlin, Helen McIlleron, Watchara Meethaisong, Patricia Mendez Garcia, Annet Miwanda, Carlota Miranda, Siphiwe Mkhize, Kgosimang Mmolawa, Rosie Mngqibisa, Fatima Mohamed, Tumelo Moloantoa, Maletsatsi Monametsi, Samuel Montero, Cecilia L. Moore, Rejoice Mosia, Columbus Moyo, Mumsy Mthethwa, Shepherd Mudzingwa, Tawona Mudzviti, Hilda Mujuru, Emmanuel Mujyambere, Trust Mukanganiki, Cynthia Mukisa Williams, Mark Mulder, Disan Mulima, Alice Mulindwa, Zivai Mupambireyi, Alba Murciano Cabeza, Herbert Murungi, Dorothy Murungu, Sandra Musarurwa, Victor Musiime, Alex V. Musiime, Maria Musisi, Philippa Musoke, Barbara Musoke Nakirya, Godfrey Musoro, Sharif Musumba, Sobia Mustafa, Shirley Mutsai, Phyllis Mwesigwa Rubondo, Mariam Naabalamba, Immaculate Nagawa, Allemah Naidoo, Shamim Nakabuye, Sarah Nakabuye, Sarah Nakalanzi, Justine Nalubwama, Annet Nalugo, Stella Nalusiba, Clementine Namajja, Sylvia Namanda, Paula Namayanja, Esther Nambi, Rachael Kikabi Namuddu, Stella Namukwaya, Florence Namuli, Josephine Namusanje, Rosemary Namwanje, Anusha Nanan-kanjee, Annet Nanduudu, Charity Nankunda, Joanita Nankya Baddokwaya, Maria Nannungi, Winnie Nansamba, Kesdao Nanthapisal, Juliet Nanyonjo, Sathaporn Na-Rajsima, Claire Nasaazi, Helena Nascimento, Eleni Nastouli, Wipaporn Natalie Songtaweesin, Kusum Nathoo, Ian Natuhurira, Rashidah Nazzinda, Thabisa Ncgaba, Milly Ndigendawani, Makhosonke Ndlovu, Georgina Nentsa, Chaiwat Ngampiyaskul, Ntombenhle Ngcobo, Nicole Ngo Giang Huong, Pia Ngwaru, Ruth Nhema, Emily Ninsiima, Gloria Ninsiima, Misheck Nkalo Phiri, Antoni Noguera Julian, Monica Nolan, Thornthun Noppakaorattanamanee, Muzamil Nsibuka Kisekka, Eniola Nsirim, Rashina Nundlal, Rosita Nunes, Lungile Nyantsa, Mandisa Nyati, Sean O'Riordan, Paul Ocitti Labeja, Denis Odoch, Rachel Oguntimehin, Martin Ojok, Geoffrey Onen, Wilma Orange, Pradthana Ounchanum, Benson Ouma, Andreia Padrao, Deborah Pako, Anna Parker, Malgorzata Pasko-Szcech, Reena Patel, Rukchanok Peongjakta, Turian Petpranee, Tasmin Phillips, Jackie Philps, Laura Picault, Sonja Pieterse, Helena Pinheiro, Supawadee Pongprapass, Anton Pozniak, Andrew Prendergast, Luis Prieto Tato, Patcharee Puangmalai, Thanyawee Puthanakit, Modiehi Rakgokong, Helena Ramos, Nastassja Ramsagar, Cornelius Rau, Yoann Riault, Pablo Rojo Conejo, Basiimwa Roy Clark, Eddie Rubanga, Baker Rubinga, Chutima Ruklao, Pattira Runarassamee, Chalermpong Saenjum, Chayakorn Saewtrakool, Yacine Saidi, Talia Sainz Costa, Chutima Saisaengjan, Rebecca Sakwa, Tatiana Sarfati, Noshalaza Sbisi, Dihedile Scheppers, Stephan Schultze-Strasser, Ulf Schulze-Sturm, Karen Scott, Janet Seeley, Robert Serunjogi, Leora Sewnarain, Clare Shakeshaft, Subashinie Sidhoo, Mercy Shibemba, Delane Shingadia, Sheleika Singh, Wasna Sirirungsi, Sibongile Sithebe, Theresa Smit, Kurt Smith, Marlize Smuts, Moira Spyer, Worathip Sripaoraya, Warunee Srisuk, Mark Ssenyonga, Patamawadee Sudsaard, Praornsuda Sukrakanchana, Pathanee Tearsansern, Carla Teixeira, Kanchana Than-in-at, Thitiwat Thapwai, Yupawan Thaweesombat, Jutarat Thewsoongnoen, Rodolphe Thiébaut, Margaret Thomason, Laura Thrasyvoulou, Khanungnit Thungkham, Judith Tikabibamu, Gloria Tinago, Ketmookda Trairat, Gareth Tudor-Williams, Mercy Tukamushaba, Deogratiuos Tukwasibwe, Julius Tumusiime, Joana Tuna, Rebecca Turner, Arttasid Udomvised, Aasia Vadee, Hesti Van Huyssteen, Nadine Van Looy, Yvonne Vaughan-Gordon, Giulio Vecchia, Richard Vowden, Rebecca Wampamba, Steve Welch, Ian Weller, Sibusisiwe Weza, Ellen White, Ian White, Kaja Widuch, Helen Wilkes, Sookpanee Wimonklang, Ben Wynne, Pacharaporn Yingyong, and Zaam Zinda Nakawungu

Subjects
Male, Adolescent, Pyridones, Epidemiology, Immunology, Infant, HIV Infections, 3-Ring, Piperazines, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Infectious Diseases, Child, Child, Preschool, Female, Heterocyclic Compounds, 3-Ring, Humans, Oxazines, Rifampin, Uganda, HIV-1, Tuberculosis, Heterocyclic Compounds, Virology, Preschool
Abstract

Contains fulltext : 282959.pdf (Publisher’s version ) (Open Access) BACKGROUND: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. METHODS: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to

Published
2022

7. Deprivation and Exposure to Public Activities during the COVID-19 Pandemic in England and Wales

Author

Sarah Beale, Isobel Braithwaite, Annalan M D Navaratnam, Pia Hardelid, Alison Rodger, Anna Aryee, Thomas Byrne, Wing Lam Erica Fong, Ellen Fragaszy, Cyril Geismar, Jana Kovar, Vincent Nguyen, Parth Patel, Madhumita Shrotri, Robert W Aldridge, Andrew Hayward, Susan Michie, Linda Wijlaars, Eleni Nastouli, Moira Spyer, Ben Killingley, Ingemar Cox, Vasileios Lampos, Rachel A McKendry, Tao Cheng, Yunzhe Liu, Anne M Johnson, Jo Gibbs, and Richard Gilson

Subjects
Activities of daily living, Coronavirus disease 2019 (COVID-19), Inequality, business.industry, media_common.quotation_subject, Public transport, Environmental health, Pandemic, Medicine, Residence, business, Socioeconomic status, Cohort study, media_common
Abstract

BackgroundDifferential exposure to public activities and non-household contacts may contribute to stark deprivation-related inequalities in SARS-CoV-2 infection and outcomes, but has not been directly investigated. We set out to investigate whether participants in Virus Watch – a large community cohort study based in England and Wales – reported different levels of exposure to public activities and non-household contacts during the Autumn-Winter phase of the COVID-19 pandemic according to postcode-level socioeconomic deprivation.MethodsParticipants (n=20120-25228 across surveys) reported their daily activities during three weekly periods in late November 2020, late December 2020, and mid-February 2021. Deprivation was quantified based on participants’ postcode of residence using English or Welsh Indices of Multiple Deprivation quintiles. We used Poisson mixed effect models with robust standard errors to estimate the relationship between deprivation and risk of exposure to public activities during each survey period.ResultsRelative to participants in the least deprived areas, participants in the most deprived areas persistently exhibited elevated risk of exposure to vehicle sharing (aRR range across time points 1.73-8.52), public transport (aRR 3.13-5.73), work or education outside of the household (aRR 1.09-1.21), essential shops (aRR 1.09-1.13) and non-household contacts (aRR 1.15-1.19) across multiple survey periods.ConclusionDifferential exposure to essential public activities in deprived communities is likely to contribute to inequalities in infection risk and outcomes during the COVID-19 pandemic. Public health interventions to reduce exposure during essential activities and financial and practical support to enable low-paid workers to stay at home during periods of intense transmission may reduce COVID-related inequalities.

Published
2021

8. SARS-CoV-2 recruits a haem metabolite to evade antibody immunity

Author

A.G. Wrobel, Peter B. Rosenthal, Svend Kjaer, George Kassiotis, Richard S. Tedder, Judith Heaney, Andrea Nans, Moira Spyer, Eleni Nastouli, Valerie E. Pye, Charlotte-Eve Short, Eleanor Parker, Andy Riddell, Chloe Rees-Spear, Annachiara Rosa, Nicola J. Cook, Graham P. Taylor, Chloe Roustan, Michael Fertleman, Carl Graham, Marit J. van Gils, Alberto Susana, Rogier W. Sanders, Mariana Silva dos Santos, Peter Cherepanov, Rachel Ulferts, Myra O. McClure, Luke Muir, Michael H. Malim, Hefin Rhys, Massimo Pizzato, Laura E. McCoy, James I. MacRae, Evangelos Christodoulou, Jeffrey Seow, Kevin W. Ng, Rupert Beale, Katie J. Doores, Laura Masino, and Carolina Rosadas

Subjects
Biliverdin, biology, Metabolite, viruses, Allosteric regulation, fungi, food and beverages, SciAdv r-articles, Life Sciences, Tetrapyrrole, Microbiology, Virus, Epitope, Cell biology, body regions, Coronavirus, chemistry.chemical_compound, chemistry, Humoral immunity, biology.protein, Antibody, skin and connective tissue diseases, Research Articles, Research Article
Abstract

SARS-CoV-2 spike N-terminal domain harbors a potent epitope that can be modulated by binding of natural linear tetrapyrroles., The coronaviral spike is the dominant viral antigen and the target of neutralizing antibodies. We show that SARS-CoV-2 spike binds biliverdin and bilirubin, the tetrapyrrole products of heme metabolism, with nanomolar affinity. Using cryo–electron microscopy and x-ray crystallography, we mapped the tetrapyrrole interaction pocket to a deep cleft on the spike N-terminal domain (NTD). At physiological concentrations, biliverdin significantly dampened the reactivity of SARS-CoV-2 spike with immune sera and inhibited a subset of neutralizing antibodies. Access to the tetrapyrrole-sensitive epitope is gated by a flexible loop on the distal face of the NTD. Accompanied by profound conformational changes in the NTD, antibody binding requires relocation of the gating loop, which folds into the cleft vacated by the metabolite. Our results indicate that SARS-CoV-2 spike NTD harbors a dominant epitope, access to which can be controlled by an allosteric mechanism that is regulated through recruitment of a metabolite.

Published
2021

9. Hepatitis B serological markers and plasma DNA concentrations

Author

Huw, Price, David, Dunn, Tamale, Zachary, Tobias, Vudriko, Michael, Chirara, Cissy, Kityo, Paula, Munderi, Moira, Spyer, James, Hakim, Charles, Gilks, Pontiano, Kaleebu, Deenan, Pillay, and Richard, Gilson

Subjects
Adult, Male, Zimbabwe, Adolescent, HIV Infections, hepatitis B ‘e’ antigen, Plasma, Young Adult, Hepatitis B, Chronic, Humans, Uganda, hepatitis B viral load, Hepatitis B Antibodies, Aged, Hepatitis B Surface Antigens, Coinfection, virus diseases, HIV, Middle Aged, Viral Load, Clinical Science, digestive system diseases, DNA, Viral, Female, epidemiology, hepatitis B
Abstract

Objectives: To examine hepatitis B (HBV) serological markers and plasma DNA concentrations in a large group of untreated HBV/HIV-coinfected individuals in two sub-Saharan settings. Design: Baseline analysis of a randomized controlled trial. Methods: DART was a large trial of treatment monitoring practices in HIV-infected adults with advanced disease starting antiretroviral therapy at centres in Kampala or Entebbe, Uganda (n = 2317) and Harare, Zimbabwe (n = 999). HBV serological markers [antibody to HBV core antigen, HBV surface antigen (HBsAg), antibody to HBV surface antigen, HBV ‘e’ antigen (HBeAg), and antibody to hepatitis B ‘e’ antigen] and plasma HBV DNA viral load were measured retrospectively on stored baseline samples. Logistic regression was used to examine associations with baseline demographic and clinical factors. Results: The rate of HBsAg positivity was significantly higher in Zimbabwe than Uganda (12.2 vs. 7.7%, adjusted odds ratio = 1.54, P

Published
2017

10. Safety and efficacy of quinacrine in human prion disease (PRION-1 study): a patient-preference trial

Author

Durre Siddique, Suvankar Pal, Peter Rudge, Tom R. Webb, Janet Darbyshire, Martin N. Rossor, Dafydd Thomas, Michele Gorham, S Wroe, Moira Spyer, John Collinge, A. M. Kennedy, Geraldine Keogh, Sarah Walker, and Fleur Hudson

Subjects
Drug, Adult, Male, medicine.medical_specialty, Adolescent, media_common.quotation_subject, Mepacrine, Clinical Neurology, Disease, Kaplan-Meier Estimate, Neuropsychological Tests, Severity of Illness Index, Prion Diseases, Young Adult, Sex Factors, Risk Factors, Internal medicine, Severity of illness, medicine, Fast track — Articles, Humans, Young adult, Adverse effect, media_common, Aged, Aged, 80 and over, business.industry, Age Factors, Middle Aged, Patient preference, Surgery, Quinacrine, Observational study, Female, Neurology (clinical), business, medicine.drug, Follow-Up Studies
Abstract

Summary Background The propagation of prions, the causative agents of Creutzfeldt-Jakob disease and other human prion diseases, requires post-translational conversion of normal cellular prion protein to disease-associated forms. The antimalarial drug quinacrine (mepacrine) prevents this conversion in vitro, and was given to patients with various prion diseases to assess its safety and efficacy in changing the course of these invariably fatal and untreatable diseases. Methods Patients with prion disease were recruited via the UK national referral system and were offered a choice between quinacrine (300 mg daily), no quinacrine, or randomisation to immediate quinacrine or deferred quinacrine in an open-label, patient-preference trial. The primary endpoints were death and serious adverse events possibly or probably related to the study drug. This study is registered, ISRCTN 06722585. Findings 107 patients with prion disease (45 sporadic, two iatrogenic, 18 variant, and 42 inherited) were enrolled, 23 in a pilot study and 84 in the main study. Only two patients chose randomisation; 40 took quinacrine during follow-up (37 who chose it at enrolment). Choice of treatment was associated with disease severity, with those least and most severely affected more likely to choose not to receive quinacrine. 78 (73%) patients died: one randomly assigned to deferred treatment, 26 of 38 who chose immediate quinacrine, and 51 of 68 who chose no quinacrine. Although adjusted mortality was lower in those who chose to take quinacrine than in those who did not, this was due to confounding with disease severity, and there was no difference in mortality between groups after adjustment. Four of 40 patients who took quinacrine had a transient response on neurological rating scales. Only two of 14 reported serious adverse events were judged quinacrine-related. Interpretation Quinacrine at a dose of 300 mg per day was reasonably tolerated but did not significantly affect the clinical course of prion diseases in this observational study. Funding Department of Health (England); UK Medical Research Council.

Published
2009
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11. The Transcriptional Co-Repressor C-Terminal Binding Protein (CtBP) Associates with Centrosomes During Mitosis

Author

Moira Spyer and Martin J. Allday

Subjects
Transcription, Genetic, Recombinant Fusion Proteins, Mitosis, Cell Cycle Proteins, Protein Serine-Threonine Kinases, Biology, symbols.namesake, chemistry.chemical_compound, Prophase, Tubulin, Proto-Oncogene Proteins, Humans, Immunoprecipitation, Interphase, Molecular Biology, Transcription factor, Cells, Cultured, Cell Nucleus, Centrosome, Nocodazole, Reproducibility of Results, Cell Biology, Cell cycle, Golgi apparatus, Brefeldin A, Phosphoproteins, Molecular biology, DNA-Binding Proteins, Repressor Proteins, Alcohol Oxidoreductases, Protein Transport, chemistry, symbols, Corepressor, Developmental Biology
Abstract

CtBP is a corepressor of transcription that acts by inhibiting coactivators and recruiting to promoter control elements (via interactions with DNA-binding transcription factors) a complex of proteins that modify histones, repress transcription and silence gene expression. There are two highly homologous genes, CtBP1 and CtBP2 that encode CtBP. In addition, a CtBP1-related protein has been described that has 11 fewer amino acids at its N-terminus than CtBP1. This variant of CtBP1--known as CtBP3 or BARS [Brefeldin A (BFA) ribosylated substrate]--plays a critical role in the fragmentation of the Golgi complex at the onset of mitosis. Although there are some reports of CtBP with a cytoplasmic distribution after transfection, it is unclear how in normal cells a nuclear corepressor regulates the behavior of the Golgi complex at the onset of mitosis. Using polyclonal rabbit antibodies that were raised against a human CtBP1-GST fusion-protein, here we show by immunofluorescence laser-scanning confocal microscopy that in mitotic cells a species of CtBP becomes associated with the centrosomes at the onset of prophase and then throughout mitosis. The association can be seen in both cycling mitotic cells and nocodazole-arrested cells. The interaction was confirmed by coimmunoprecipitation and centrosome isolation. Since centrosomes are considered to be the organising centre for Golgi morphogenesis, the interaction demonstrated here may explain how a nuclear corepressor of transcription can exert a regulatory effect on the Golgi complex at a specific stage of the cell cycle.

Published
2006

12. ODYSSEY clinical trial design: a randomised global study to evaluate the efficacy and safety of dolutegravir-based antiretroviral therapy in HIV-positive children, with nested pharmacokinetic sub-studies to evaluate pragmatic WHO-weight-band based dolutegravir dosing

Author

Clare Shakeshaft, Carlo Giaquinto, Tim R. Cressey, Adeodata Kekitiinwa, David M. Burger, Pauline Amuge, Pablo Rojo, Cecilia L. Moore, Osee Behuhuma, Yacine Saϊdi, Linda Barlow-Mosha, James Hakim, Alexandra Compagnucci, Lorna Atwine, Diana M. Gibb, Ebrahim Variava, Hilda Mujuru, Mark F. Cotton, Victor Musiime, Moherndran Archary, Deborah Ford, Cissy Kityo, Thanyawee Puthanakit, Anna Turkova, Avy Violari, Abbas Lugemwa, Medical Research Council Clinical Trials Unit (MRC CTU), University College of London [London] (UCL), University of Zimbabwe (UZ), Baylor College of Medicine Children's Foundation [Kampala, Uganda] (BCMCF), Joint Clinical Research Centre, MUJHU Research Collaboration [Kampala, Uganda] (MUJHURC), Chiang Mai University (CMU), Harvard T.H. Chan School of Public Health, University of Liverpool, Perinatal HIV Research Unit [Johannesburg, South Africa] (PHRU), University of the Witwatersrand [Johannesburg] (WITS), Klerksdorp Tshepong Hospital Complex [Matlosana, South Africa] (KTHC), Family Center for Research with Ubuntu [Cape Town, South Africa] (FCRU), Durban International Clinical Research Site [Durban, South Africa] (DICRS), Essais Thérapeutiques et Maladies Infectieuses, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chulalongkorn University [Bangkok], Africa Health Research Institute [Hlabisa, South Africa] (AHRI), Hlabisa Hospital [Hlabisa, South Africa] (HH), Radboud University Medical Center [Nijmegen], Università degli Studi di Padova = University of Padua (Unipd), Hospital Universitario 12 de Octubre [Madrid], ODYSSEY Trial Team: Shabinah Ali, Abdel Babiker, Chiara Borg, Anne-Marie Borges Da Silva, Joanna Calvert, Deborah Ford, Joshua Gasa, Diana M Gibb, Nasir Jamil, Sarah Lensen, Emma Little, Fatima Mohamed, Samuel Montero, Cecilia L Moore, Rachel Oguntimehin, Anna Parker, Reena Patel, Tasmin Phillips, Tatiana Sarfati, Karen Scott, Clare Shakeshaft, Moira Spyer, Margaret Thomason, Anna Turkova, Rebecca Turner, Nadine Van Looy, Ellen White, Kaya Widuch, Helen Wilkes, Ben Wynne, Carlo Giaquinto, Tiziana Grossele, Daniel Gomez-Pena, Davide Bilardi, Giulio Vecchia, Alexandra Compagnucci, Yacine Saidi, Yoann Riault, Alexandra Coelho, Laura Picault, Christelle Kouakam, Tim R Cressey, Suwalai Chalermpantmetagul, Dujrudee Chinwong, Gonzague Jourdain, Rukchanok Peongjakta, Pra-Ornsuda Sukrakanchana, Wasna Sirirungsi, Janet Seeley, Sarah Bernays, Magda Conway, Nigel Klein, Eleni Nastouli, Anita De Rossi, Maria Angeles Munoz Fernandez, David Burger, Pauline Bollen, Angela Colbers, Hylke Waalewijn, Cissy M Kityo, Victor Musiime, Elizabeth Kaudha, Annet Nanduudu, Emmanuel Mujyambere, Paul Ocitti Labeja, Charity Nankunda, Juliet Ategeka, Peter Erim, Collin Makanga, Esther Nambi, Abbas Lugemwa, Lorna Atwine, Edridah Keminyeto, Deogratiuos Tukwasibwe, Shafic Makumbi, Emily Ninsiima, Mercy Tukamushaba, Rogers Ankunda, Ian Natuhurira, Miriam Kasozi, Baker Rubinga, Adeodata R Kekitiinwa, Pauline Amuge, Dickson Bbuye, Justine Nalubwama, Winnie Akobye, Muzamil Nsibuka Kisekka, Anthony Kirabira, Gloria Ninsiima, Sylvia Namanda, Gerald Agaba, Immaculate Nagawa, Annet Nalugo, Florence Namuli, Rose Kadhuba, Rachael Namuddu, Lameck Kiyimba, Angella Baita, Eunice Atim, Olivia Kobusingye, Clementine Namajja, Africanus Byaruhanga, Rogers Besigye, Herbert Murungi, Geoffrey Onen, Philippa Musoke, Linda Barlow-Mosha, Grace Ahimbisibwe, Rose Namwanje, Monica Etima, Mark Ssenyonga, Robert Serunjogi, Hajira Kataike, Richard Isabirye, David Balamusani, Monica Nolan, Mark F Cotton, Anita Janese van Rensburg, Marlize Smuts, Catherine Andrea, Sumaya Dadan Sonja Pieterse, Vinesh Jaeven, Candice Makola, George Fourie, Kurt Smith, Els Dobbels, Peter Zuidewind, Hesti Van Huyssteen, Mornay Isaacs, Georgina Nentsa, Thabis Ncgaba, Candice MacDonald, Mandisa Mtshagi, Maria Bester, Wilma Orange, Ronelle Arendze, Mark Mulder, George Fourie, Avy Violari, Nastassja Ramsagar, Afaaf Liberty, Ruth Mathiba, Lindiwe Maseko, Nakata Kekane, Busi Khumlo, Mirriam Khunene, Noshalaza Sbisi, Jackie Brown, Ryphina Madonsela, Nokuthula Mbadaliga, Zaakirah Essack, Reshma Lakha, Aasia Vadee, Derusha Frank, Nazim Akoojee, Maletsatsi Monametsi, Gladness Machache, Yolandie Fourie, Anusha Nanan-Kanjee, Juan Erasmus, Angelous Mamiane, Tseleng Daniel, Fatima Mayat, Nomfundo Maduna, Patsy Baliram, Chaiwat Ngampiyasakul, Pisut Greetanukroh, Wanna Chamjamrat, Praechadaporn Khannak, Pornchai Techakunakorn, Thitiwat Thapwai, Patcharee Puangmalai, Ampai Maneekaew, Pradthana Ounchanum, Yupawan Thaweesombat, Areerat Kongponoi, Jutarat Thewsoongnoen, Suparat Kanjanavanit, Pacharaporn Yingyong, Thida Namwong, Rangwit Junkaew, Ussanee Srirompotong, Patamawadee Sudsaard, Siripun Nuanbuddee, Sookpanee Wimonklang, Sathaporn Na-Rajsima, Suchart Thongpaen, Pattira Runarassamee, Watchara Meethaisong, Arttasid Udomvised, Ebrahim Variava, Modiehi Rakgokong, Dihedile Scheppers, Tumelo Moloantoa, Abdul Hamid Kaka, Tshepiso Masienyane, Akshmi Ori, Kgosimang Mmolawa, Pattamukkil Abraham, Moherndran Archary, Rejoice Mosia, Sajeeda Mawlana, Rosie Mngqibisa, Rashina Nundlal, Elishka Singh, Penelope Madlala, Allemah Naidoo, Sphiwee Cebekhulu, Petronelle Casey, Collin Pillay, Subashinie Sidhoo, Minenhle Chikowore, Lungile Nyantsa, Melisha Nunkoo, Terence Nair, Enbavani Pillay, Sheleika Singh, Sheroma Rajkumar, Osee Behuhuma, Olivier Koole, Kristien Bird, Nomzamo Buthelezi, Mumsy Mthethwa, James Hakim, Hilda Mujuru, Kusum Nathoo, Mutsa Bwakura-Dangarembizi, Ennie Chidziva, Shepherd Mudzingwa, Themelihle Bafana, Colin Warambwa, Godfrey Musoro, Gloria Tinago, Shirley Mutsai, Columbus Moyo, Ruth Nhema, Misheck Nkalo Phiri, Stuart Chitongo, Joshua Choga, Joyline Bhiri, Wilber Ishemunyoro, Makhosonke Ndlovu, Thanyawee Puthanakit, Naruporn Kasipong, Sararut Chanthaburanun, Kesdao Nanthapisal, Thidarat Jupimai, Thornthun Noppakaorattanamanee, Torsak Bunupuradah, Wipaporn Natalie Songtaweesin, Chutima Saisaengjan, Stephan Schultze-Straber, Christoph Konigs, Robin Kobbe, Felicia Mantkowski, Steve Welch, Jacqui Daglish, Laura Thrasyvoulou, Delane Singadia, Sophie Foxall, Judith Acero, Gosia Pasko-Szcech, Jacquie Flynn, Gareth Tudor-Williams, Farhana Abdulla, Srini Bandi, Jin Li, Sean O'Riordan, Dominique Barker, Richard Vowden, Colin Ball Eniola Nsirim, Kathleen McClughlin, India Garcia, Pablo Rojo Conejo, Cristina Epalza, Luis Prieto Tato, Maite Fernandez, Luis Escosa Garcia, Maria José Mellado Peña, Talia Sainz Costa, Claudia Fortuny Guasch, Antoni Noguera Julian, Carolina Estepa, Elena Bruno, Alba Murciano Cabeza, Maria Angeles Muñoz Fernandez, Paula Palau, Laura Marques, Carla Teixeira, Alexandre Fernandes, Rosita Nunes, Helena Nascimento, Andreia Padrao, Joana Tuna, Helena Ramos, Ana Constança Mendes, Helena Pinheiro, Ana Cristina Matos, Flavia Kyomuhendo, Sarah Nakalanzi, Cynthia Mukisa Williams, Ntombenhle Ngcobo, Deborah Pako, Jacky Crisp, Benedictor Dube, Precious Chandiwana, Winnie Gozhora, Ian Weller, Elaine Abrams, Tsitsi Apollo, Polly Clayden, Valériane Leroy, Anton Pozniak, Jane Crawley, Rodolphe Thiébaut, Helen McIlleron, Alasdair Bamford, Hermione Lyall, Andrew Prendergast, Felicity Fitzgerald, Anna Goodman, Malbec, Odile, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Radboud University Medical Centre [Nijmegen, The Netherlands], and Universita degli Studi di Padova

Subjects
0301 basic medicine, Male, Pediatrics, [SDV]Life Sciences [q-bio], HIV Infections, Basket trial, Dolutegravir, Efficacy, HIV, Paediatric, Pharmacokinetic, Randomized control trial, Safety, Adolescent, Body Weight, Child, Child, Preschool, Cohort Studies, Drug Dosage Calculations, Europe, Female, HIV Integrase Inhibitors, HIV-1, Heterocyclic Compounds, 3-Ring, Humans, Oxazines, Piperazines, Pyridones, RNA, Viral, South Africa, Thailand, Treatment Outcome, Uganda, Viral Load, World Health Organization, Zimbabwe, law.invention, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, Heterocyclic Compounds, law, Clinical endpoint, Medicine, Viral, 030212 general & internal medicine, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, Viral load, Cohort study, Research Article, medicine.medical_specialty, 030106 microbiology, 3-Ring, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, lcsh:RC109-216, Dosing, Preschool, Pregnancy, business.industry, Clinical study design, medicine.disease, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], chemistry, RNA, business
Abstract

Background Dolutegravir (DTG)-based antiretroviral therapy (ART) is highly effective and well-tolerated in adults and is rapidly being adopted globally. We describe the design of the ODYSSEY trial which evaluates the efficacy and safety of DTG-based ART compared with standard-of-care in children and adolescents. The ODYSSEY trial includes nested pharmacokinetic (PK) sub-studies which evaluated pragmatic World Health Organization (WHO) weight-band-based DTG dosing and opened recruitment to children Methods ODYSSEY (Once-daily DTG based ART in Young people vS. Standard thErapY) is an open-label, randomised, non-inferiority, basket trial comparing the efficacy and safety of DTG + 2 nucleos(t) ides (NRTIs) versus standard-of-care (SOC) in HIV-infected children Results Between September 2016 and June 2018, 707 children weighing ≥14 kg were enrolled; including 311 ART-naïve children and 396 children starting second-line. 47% of children were enrolled in Uganda, 21% Zimbabwe, 20% South Africa, 9% Thailand, 4% Europe. 362 (51%) participants were male; median age [range] at enrolment was 12.2 years [2.9–18.0]. 82 (12%) children weighed 14 to Conclusions By employing a basket design, to include ART-naïve and -experienced children, and nested PK sub-studies, the ODYSSEY trial efficiently evaluates multiple scientific questions regarding dosing and effectiveness of DTG-based ART in children. Trial registration NCT, NCT02259127, registered 7th October 2014; EUDRACT, 2014–002632-14, registered 18th June 2014 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-002632-14/ES); ISRCTN, ISRCTN91737921, registered 4th October 2014.

Published
2021

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