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Antiretroviral therapy increases thymic output in children with HIV

Sandgaard, Katrine S.a; Lewis, Joannaa,b; Adams, Stuartc; Klein, Nigela; Callard, Robina,b

doi: 10.1097/QAD.0000000000000063
Clinical Science

Objective: Disease progression and response to antiretroviral therapy (ART) in HIV-infected children is different to that of adults. Immune reconstitution in adults is mainly from memory T cells, whereas in children it occurs predominantly from the naive T-cell pool. It is unclear however what proportion of reconstituted CD4+ T cells comes from thymic export and homeostatic proliferation in the periphery. Thymic output is often estimated by measuring T-cell receptor excision circles and markers such as CD31 expressed on recent thymic emigrants but these are confounded by peripheral T-cell division and cannot in themselves be used as quantitative estimates of thymic output.

Design: To compare thymic output in HIV-infected children on ART, HIV-infected children not on ART and uninfected children of different ages.

Method: Combined T-cell receptor excision circle (TREC) and proliferation data are used with a recently described mathematical model to give explicit measures of thymic output.

Results: We found that age-adjusted thymic output is reduced in untreated children with HIV, which increases significantly with length of time on ART.

Conclusion: Our results suggest that a highly active thymus in early childhood may contribute to better immune reconstitution if ART is initiated early in life.

aImmunobiology Unit, Institute of Child Health

bCoMPLEX, University College London

cHaematology, Great Ormond Street Hospital, London, UK.

Correspondence to Katrine Schou Sandgaard; Broagervej 8, 8240 Risskov, Denmark. Tel: +45 2971 7498; e-mail:

Received 8 May, 2013

Accepted 3 September, 2013

Ā© 2014 Lippincott Williams & Wilkins, Inc.