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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

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Katrine Schou Sandgaard, Triantafylia Gkouleli, Teresa Attenborough, Stuart Adams, Deena Gibbons, Mette Holm, Sarah Eisen, Helen Baxendale, Anita De Rossi, Savita Pahwa, Benny Chain, Athina Gkazi, Nigel Klein

Original languageEnglish
JournalFrontiers in immunology
Accepted/In press28 Jun 2022

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King's Authors

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/l and a viral load < 50 copies/ ml were
compared with adolescents with CD4+ counts < 500/l 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 HIV1 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

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