Association of CD4 + T-lymphocyte counts and new thymic emigrants in HIV-infected children during successful highly active antiretroviral therapy

Akihiko Saitoh, Kumud K. Singh, Sharsti Sandall, Christine A. Powell, Terrence Fenton, Courtney V Fletcher, Karen Hsia, Stephen A. Spector

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: In a cohort of children receiving highly active antiretroviral therapy (HAART) with sustained plasma HIV-1 RNA < 50 copies/mL, children who reached undetectable RNA after week 8 (slow responders, median: week 20) had higher HIV-1 intracellular DNA (HIV-1 DNA) and equal or greater CD4 + T-lymphocyte counts compared with children who reached undetectable plasma HIV-1 RNA by week 8 (rapid responders) throughout HAART. Objective: To determine whether levels of T-cell receptor excision circles (TRECs) could explain the apparent inconsistency between the quantity of HIV-1 DNA and CD4 + T-lymphocyte counts in HIV-1-infected children receiving HAART with sustained virologic suppression. Methods: T-cell receptor excision circles and HIV-1 DNA and plasma HIV-1 RNA were quantified longitudinally by PCR in 31 children (median age, 5.6 years) with sustained undetectable plasma HIV-1 RNA for >104 weeks of HAART. Results: There was a positive correlation between TREC and HIV-1 DNA during HAART, notably at weeks 48 and 80 (P < .004). During the early stage of HAART, TREC levels positively correlated with CD4 + T-lymphocyte percentages (P < .02) and naive CD4 + T-lymphocyte counts (P < .001) and percentages (P = .05). Median TREC levels were consistently equal or higher in slow responders compared with rapid responders (P < .001) despite slow responders having consistently greater quantities of HIV-1 DNA. Conclusion: To maintain adequate levels of CD4 + T-lymphocytes, children with high HIV-1 DNA maintain high levels of TREC while receiving HAART. Thus, a thymic control mechanism is required to maintain new CD4 + T lymphocytes in the presence of persistent virus. Clinical implications: The TREC level is a useful marker of thymic function in HIV-infected children.

Original languageEnglish (US)
Pages (from-to)909-915
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume117
Issue number4
DOIs
StatePublished - Apr 1 2006

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Highly Active Antiretroviral Therapy
CD4 Lymphocyte Count
HIV
HIV-1
T-Lymphocytes
DNA
RNA
Viruses

Keywords

  • CD4 T lymphocytes
  • HAART
  • HIV-1 intracellular DNA
  • T-cell receptor excision circles
  • children
  • immune reconstitution

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Association of CD4 + T-lymphocyte counts and new thymic emigrants in HIV-infected children during successful highly active antiretroviral therapy. / Saitoh, Akihiko; Singh, Kumud K.; Sandall, Sharsti; Powell, Christine A.; Fenton, Terrence; Fletcher, Courtney V; Hsia, Karen; Spector, Stephen A.

In: Journal of Allergy and Clinical Immunology, Vol. 117, No. 4, 01.04.2006, p. 909-915.

Research output: Contribution to journalArticle

Saitoh, Akihiko ; Singh, Kumud K. ; Sandall, Sharsti ; Powell, Christine A. ; Fenton, Terrence ; Fletcher, Courtney V ; Hsia, Karen ; Spector, Stephen A. / Association of CD4 + T-lymphocyte counts and new thymic emigrants in HIV-infected children during successful highly active antiretroviral therapy. In: Journal of Allergy and Clinical Immunology. 2006 ; Vol. 117, No. 4. pp. 909-915.
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AU - Singh, Kumud K.

AU - Sandall, Sharsti

AU - Powell, Christine A.

AU - Fenton, Terrence

AU - Fletcher, Courtney V

AU - Hsia, Karen

AU - Spector, Stephen A.

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AB - Background: In a cohort of children receiving highly active antiretroviral therapy (HAART) with sustained plasma HIV-1 RNA < 50 copies/mL, children who reached undetectable RNA after week 8 (slow responders, median: week 20) had higher HIV-1 intracellular DNA (HIV-1 DNA) and equal or greater CD4 + T-lymphocyte counts compared with children who reached undetectable plasma HIV-1 RNA by week 8 (rapid responders) throughout HAART. Objective: To determine whether levels of T-cell receptor excision circles (TRECs) could explain the apparent inconsistency between the quantity of HIV-1 DNA and CD4 + T-lymphocyte counts in HIV-1-infected children receiving HAART with sustained virologic suppression. Methods: T-cell receptor excision circles and HIV-1 DNA and plasma HIV-1 RNA were quantified longitudinally by PCR in 31 children (median age, 5.6 years) with sustained undetectable plasma HIV-1 RNA for >104 weeks of HAART. Results: There was a positive correlation between TREC and HIV-1 DNA during HAART, notably at weeks 48 and 80 (P < .004). During the early stage of HAART, TREC levels positively correlated with CD4 + T-lymphocyte percentages (P < .02) and naive CD4 + T-lymphocyte counts (P < .001) and percentages (P = .05). Median TREC levels were consistently equal or higher in slow responders compared with rapid responders (P < .001) despite slow responders having consistently greater quantities of HIV-1 DNA. Conclusion: To maintain adequate levels of CD4 + T-lymphocytes, children with high HIV-1 DNA maintain high levels of TREC while receiving HAART. Thus, a thymic control mechanism is required to maintain new CD4 + T lymphocytes in the presence of persistent virus. Clinical implications: The TREC level is a useful marker of thymic function in HIV-infected children.

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