Analytical treatment interruption in children living with HIV: position statement from the EPIICAL consortium

Louise Kuhn; Shaun Barnabas; Nicola Cotugno; Holly Peay; Philip Goulder; Mark Cotton; Avy Violari; Savita Pahwa; Kavidha Reddy; Alfredo Tagarro; Kennedy Otwombe; Samantha Fry; Paula Vaz; Maria Grazia Lain; Tacilta Nhampossa; Moherndran Archary; Almoustapha Issiaka Maiga; Thanyawee Puthanakit; Cissy M Kityo; Caroline Foster; Pablo Rojo; Nigel Klein; Eleni Nastouli; Caroline T Tiemessen; Anita de Rossi; Thumbi Ndung'u; Deborah Persaud; Mathias Lichterfeld; Carlo Giaquinto; Paolo Palma; Paolo Rossi; EPIICAL consortium

doi:10.1016/S2352-3018(24)00157-7

Analytical treatment interruption in children living with HIV: position statement from the EPIICAL consortium

Lancet HIV. 2024 Jul 23:S2352-3018(24)00157-7. doi: 10.1016/S2352-3018(24)00157-7. Online ahead of print.

Authors

Louise Kuhn¹, Shaun Barnabas², Nicola Cotugno³, Holly Peay⁴, Philip Goulder⁵, Mark Cotton², Avy Violari⁶, Savita Pahwa⁷, Kavidha Reddy⁸, Alfredo Tagarro⁹, Kennedy Otwombe⁶, Samantha Fry², Paula Vaz¹⁰, Maria Grazia Lain¹⁰, Tacilta Nhampossa¹¹, Moherndran Archary¹², Almoustapha Issiaka Maiga¹³, Thanyawee Puthanakit¹⁴, Cissy M Kityo¹⁵, Caroline Foster¹⁶, Pablo Rojo¹⁷, Nigel Klein¹⁸, Eleni Nastouli¹⁹, Caroline T Tiemessen²⁰, Anita de Rossi²¹, Thumbi Ndung'u²², Deborah Persaud²³, Mathias Lichterfeld²⁴, Carlo Giaquinto²⁵, Paolo Palma³, Paolo Rossi³; EPIICAL consortium

Affiliations

¹ Gertrude H Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University Irving Medical Center, New York, NY, USA. Electronic address: lk24@cumc.columbia.edu.
² Family Centre for Research with Ubuntu, Department of Paediatrics and Child Health, Stellenbosch University, Tygerberg Academic Hospital, Cape Town, South Africa.
³ Research Unit of Clinical Immunology and Vaccinology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; Department of Systems Medicine, Tor Vergata University of Rome, Rome, Italy.
⁴ RTI International, Durham, NC, USA.
⁵ Department of Paediatrics, University of Oxford, Oxford, UK; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa; Africa Health Research Institute, Durban, South Africa; Ragon Institute of MGH, MIT and Harvard, Boston, MA, USA.
⁶ Perinatal HIV Research Unit, Chris Hani Baragwanath Academic Hospital, Faculty of Health Sciences, University of the Witwatersrand, Soweto, South Africa; School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁷ Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, USA.
⁸ Africa Health Research Institute, Durban, South Africa.
⁹ Fundación de Investigación Biomédica, Hospital 12 de Octubre, Instituto de Investigación 12 de Octubre, Madrid, Spain; Department of Pediatrics, Infanta Sofía University Hospital, Fundación para la Investigación Biomédica e Innovación Hospital Universitario Infanta Sofía y Hospital del Henares, Madrid, Spain; Universidad Europea de Madrid, Madrid, Spain.
¹⁰ Fundação Ariel Glaser contra o SIDA Pediátrico, Maputo, Mozambique.
¹¹ Centro de Investigação em Saúde de Manhiç, Maputo, Mozambique.
¹² Africa Health Research Institute, Durban, South Africa; Department of Paediatrics and Department of Infectious Diseases, University of KwaZulu Natal, Durban, South Africa.
¹³ Department of Medical Biology, CHU Gabriel Toure, University of Sciences Techniques and Technologies of Bamako, Bamako, Mali.
¹⁴ Department of Pediatrics and Center of Excellence for Pediatric Infectious Diseases and Vaccines, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
¹⁵ Joint Clinical Research Centre, Kampala, Uganda.
¹⁶ Department of Paediatric Infectious Diseases, Imperial College Healthcare NHS Trust, London, UK.
¹⁷ Universidad Complutense Madrid, Hospital 12 de Octubre, Instituto de Investigación 12 de Octubre, Madrid, Spain.
¹⁸ Africa Health Research Institute, Durban, South Africa; Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, London, UK.
¹⁹ Department of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
²⁰ Centre for HIV and STIs, National Institutes of Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa; Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
²¹ Department of Surgery, Oncology and Gastroenterology, Section of Oncology and Immunology, University of Padua, Padua, Italy.
²² HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa; Africa Health Research Institute, Durban, South Africa; Ragon Institute of MGH, MIT and Harvard, Boston, MA, USA; Division of Infection and Immunity, University College London, London, UK.
²³ Johns Hopkins University School of Medicine; Department of Pediatrics, Division of Infectious Diseases, Baltimore, MD, USA.
²⁴ Ragon Institute of MGH, MIT and Harvard, Boston, MA, USA; Infectious Disease Division, Brigham and Women's Hospital Harvard, Cambridge, MA, USA.
²⁵ Department of Women's and Children's Health, University of Padua, Padua, Italy.

PMID: 39059402
DOI: 10.1016/S2352-3018(24)00157-7

Abstract

Analytical treatment interruption (ATI) is widely acknowledged as an essential component of studies to advance our understanding of HIV cure, but discussion has largely been focused on adults. To address this gap, we reviewed evidence related to the safety and utility of ATI in paediatric populations. Three randomised ATI trials using CD4 T-cell and clinical criteria to guide restart of antiretroviral therapy (ART) have been conducted. These trials found low risks associated with ATI in children, including reassuring findings pertaining to neurocognitive outcomes. Similar to adults treated during acute infection, infants treated early in life have shifts in virological and immunological parameters that increase their likelihood of achieving ART-free viral control. Early ART limits the size and diversity of the viral reservoir and shapes effective innate and HIV-specific humoral and cellular responses. Several cases of durable ART-free viral control in early treated children have been reported. We recommend that, where appropriate for the study question and where adequate monitoring is available, ATI should be integrated into ART-free viral control research in children living with HIV. Paediatric participants have the greatest likelihood of benefiting and potentially the most years to prospectively realise those benefits. Excluding children from ATI trials limits the evidence base and delays access to interventions.

Publication types

Review