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The importance of taking ART appropriately in children and adolescents with HIV-1 to reach the highest capacity of immune function later in life

Sandgaard, Katrine Schou; Gkouleli, Triantafylia; Attenborough, Teresa; Adams, Stuart; Gibbons, Deena; Holm, Mette; Eisen, Sarah; ... Klein, Nigel; + view all (2022) The importance of taking ART appropriately in children and adolescents with HIV-1 to reach the highest capacity of immune function later in life. Frontiers Immunology , 13 , Article 860316. 10.3389/fimmu.2022.860316. Green open access

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Abstract

Current antiretroviral therapy (ART) guidelines recommend treating all children with HIV-1 infection. This has changed from the broader use of ART to treat children to improve morbidity and minimise mortality. However, prior to current recommendations, not everyone with HIV-1 received timely treatment. What happens to the paediatric immune system when HIV-1 replication is not appropriately supressed remains unclear. 11 samples from adolescents with HIV-1 on ART and uninfected controls in the UK, aged 12-25 years, were examined; overall, adolescents with CD4+ counts > 500/μl and a viral load < 50 copies/ml were compared with adolescents with CD4+ counts < 500/μl and a viral load > 50 copies/ml at time of sampling. Measurements of thymic output were combined with high throughput next generation sequencing and bioinformatics to systematically organize CD4+ and CD8+ T cell receptor (TCR) repertoires. TCR repertoire diversity, clonal expansions, TCR sequence sharing, and formation of TCR clusters in HIV-1 infected adolescents with successful HIV-1 suppression were compared to adolescents with ineffective HIV-1 suppression. Thymic output and CD4+ T cell numbers were decreased in HIV-1 infected adolescents with poor HIV-1 suppression. A strong homeostatic TCR response, driven by the decreased CD4+ T cell compartment and reduced thymic output was observed in the virally uncontrolled HIV-1-infected adolescents. Formation of abundant robust TCR clusters and structurally related TCRs were found in the adolescents with effective HIV-1 suppression. Numerous CD4+ T cell numbers in the virally controlled adolescents emphasize the importance of high thymic output and formation of robust TCR clusters in the maintenance of HIV-1 suppression. While the profound capacity for immune recovery in children may allow better opportunity to deal with immunological stress, when ART is taken appropriately, this study demonstrates new insights into the unique paediatric immune system and the immunological changes when HIV-1 replication is ongoing.

Type: Article
Title: The importance of taking ART appropriately in children and adolescents with HIV-1 to reach the highest capacity of immune function later in life
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fimmu.2022.860316
Publisher version: https://doi.org/10.3389/fimmu.2022.860316
Language: English
Additional information: © 2022 Sandgaard, Gkouleli, Attenborough, Adams, Gibbons, Holm, Eisen, Baxendale, De Rossi, Pahwa, Chain, Gkazi and Klein. This is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords: HIV-1, T cell receptor clonal expansions, T cell receptor repertoires, antiretroviral therapy (ART), children, high throughout sequencing, immune reconstitution, thymic output
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10153992
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