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BackgroundElite controllers (ECs) are therapy-naïve HIV-infected individuals capable of spontaneous control of plasma viraemia for at least a year. Although viraemic non-progressors are more common in vertical HIV-infection than in adults infection, elite control has been rarely characterised in the paediatric population.DesignWe analysed the T-cell immunophenotype and the HIV-specific response by flow cytometry in four paediatric elite controllers (PECs) compared to age-matched non-progressors (PNPs), progressors (PPs) and HIV-exposed uninfected (HEUs) adolescents.ResultsPECs T-cell populations had lower immune activation and exhaustion levels when compared to PP, reflected by a more sustained and preserved effector function. The HIV-specific T-cell responses among PECs were characterised by high-frequency Gag-specific CD4+ T-cell activity, and markedly more polyfunctional Gag-specific CD8+ activity, compared to PNPs and PPs. These findings were consistently observed even in the absence of protective HLA-I molecules such as HLA-B*27/57/81.ConclusionsPaediatric elite control is normally achieved after years of infection, and low immune activation in PNPs precedes the increasing ability of CD8+ T-cell responses to achieve immune control of viraemia over the course of childhood, whereas in adults, high immune activation in acute infection predicts subsequent CD8+ T-cell-mediated immune control of viraemia, and in adult elite controllers low immune activation is therefore the consequence of the rapid CD8+ T-cell-mediated immune control generated after acute infection. This distinct strategy adopted by PECs may help identify pathways that facilitate remission in post-treatment controllers, where protective HLA-I molecules are not the main factor.

Original publication

DOI

10.1097/qad.0000000000003078

Type

Journal article

Journal

AIDS (London, England)

Publication Date

27/09/2021

Addresses

Department of Paediatrics, University of Oxford, Oxford, UK HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal (UKZN), Durban, South Africa. Max von Pettenkofer-Institute, Department of Virology, Ludwig-Maximilians-University, Munich, Germany German Center for Infection Research (DZIF), Munich, Germany Department of Infectious Diseases, Ludwig-Maximilians-University, Munich, Germany Unidad de Enfermedades Infecciosas, Servicio de Pediatría, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain Instituto de Infectologia Emílio Ribas, Sao Paulo, Brazil Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Medicina Preventiva, São Paulo, Brazil IrsiCaixa - AIDS Research Institute, Badalona, Spain Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK UCL Great Ormond Street Institute of Child Health, London, UK Universitat de Vic-Universitat Central de Catalunya, Vic, Spain Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge, USA Basic Science Program, Frederick National Laboratory for Cancer Research in the Laboratory of Integrative Cancer Immunology, Bethesda, USA Nuffield Department of Medicine, University of Oxford, Oxford, UK Oxford NIHR Biomedical Research Centre, Oxford, UK Department of Infectious Diseases, Imperial College, London, UK.