Antiretroviral therapy increases thymic output in children with HIV


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Abstract

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.

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