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1 August 2002

Volume 186, Number 3
The Journal of Infectious Diseases 2002;186:312–320
© 2002 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2002/18603-0003$15.00
DOI: 10.1086/341657

Increased Thymic Output after Initiation of Antiretroviral Therapy in Human Immunodeficiency Virus Type 1–Infected Children in the Paediatric European Network for Treatment of AIDS (PENTA) 5 Trial

Anita De Rossi,1

A. Sarah Walker,2

Nigel Klein,3

Davide De Forni,1

Doug King,4,a and

Diana M. Gibb2 for the

Paediatric European Network for Treatment of AIDSb

1Department of Oncology and Surgical Sciences, AIDS Reference Center, Padova, Italy; 2Medical Research Council Clinical Trials Unit, 3Institute of Child Health, and 4Chelsea and Westminster Hospital, London, United Kingdom

To investigate the thymic contribution to immune reconstitution during antiretroviral therapy (ART), T cell receptor gene rearrangement excision circles (TRECs) were measured in peripheral blood mononuclear cells (PBMC) and CD4 cells from 33 human immunodeficiency virus (HIV) type 1–infected children monitored for 96 weeks after ART initiation. Baseline TREC levels were associated positively with baseline CD4 cell percentage and inversely with age and HIV‐1 RNA load. During therapy, TREC level changes in PBMC and CD4 cells were fairly comparable. TREC level changes were inversely related to baseline CD4 cell percentage and positively associated with CD4 cell percentage increases, the main source being naive CD4 cells. TREC changes were independent of age and baseline HIV‐1 RNA load; however, HIV‐1 suppression was independently associated with smaller TREC changes. Thymic output appears to be the main source of CD4 cell repopulation in children receiving ART. Recovery of thymic function is independent of age and influenced by the status of peripheral CD4 cell depletion and HIV‐1 suppression.

Received 17 January 2002; revised 27 March 2002; electronically published 5 July 2002.

Reprints or correspondence: Dr. Diana M. Gibb, Medical Research Council Clinical Trials Unit, 222 Euston Rd., London NW1 2DA, United Kingdom ().

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  • Presented in part: 9th Conference on Retroviruses and Opportunistic Infections, Seattle, 24–28 February 2002 (abstract 807‐W).

    Ethics committees at all participating centers approved the Paediatric European Network for Treatment of AIDS (PENTA) 5 trial protocol and the taking of samples for further immunological testing. All primary care givers gave written consent for study participation; additional written consent was obtained from children, when appropriate, according to their age and knowledge of human immunodeficiency virus status.

    Financial support: European Commission (contract QLK2‐2000‐00150); Medical Research Council (MRC) (support of MRC Clinical Trials Unit) and Agence Nationale de Recherche sur le SIDA (support of INSERM SC10; these 2 centers jointly coordinate the PENTA studies); Istituto Superiore di Sanità‐Progetto Terapia (grant to Italian collaborating centers and Progetto AIDS grant 30.C.26); Glaxo‐Wellcome and Agouron provided drugs for the trial and contributed funding for this study.

    No member of the writing committee has commercial or other associations that might pose a conflict of interest.

  • Present affiliation: Institute of Child Health, London, United Kingdom.

  • Study group members are listed after the text.

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