Immunoreconstitution after ritonavir therapy in children with human immunodeficiency virus infection involves multiple lymphocyte lineages

John W. Sleasman, Robert P. Nelson, Maureen M. Goodenow, David Wilfret, Alan Hutson, Michael Baseler, Judy Zuckerman, Philip A. Pizzo, Brigitta U. Mueller

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

Objective: To evaluate lymphocyte reconstitution after protease inhibitor therapy in children with human immunodeficiency virus (HIV) infection. Study design: Forty-four HIV-infected children receiving ritonavir monotherapy followed by the addition of zidovudine and didanosine were evaluated during a phase I/II clinical trial. The cohort had a median age of 6.8 years and advanced disease (57% Centers for Disease Control and Prevention stage C, 73% immune stage 3) and was naive to protease inhibitor therapy. Results: After 4 weeks of therapy, there was a significant increase in CD4+ and CD8+ T cells. CD4+ T cells continued to increase, whereas CD8+ T cells returned to baseline by 24 weeks. Unexpectedly, there was a significant increase in B cells. Changes in CD4+ T-cell subsets revealed an initial increase in CD4+ CD45RO T cells followed by a sustained increase in CD4+ CD45RA T cells. Children <6 years of age had the highest increase in all lymphocyte populations. Significant improvement in CD4+ T-cell counts was observed even in those children whose viral burden returned to pretherapy levels. Conclusions: Early increases in lymphocytes after ritonavir therapy are a result of recirculation, as shown by increases in B cells and CD4+ CD45RO and CD8+ T cells. Children exhibited a high potential to reconstitute CD4+ CD45RA T cells even with advanced disease and incomplete viral suppression.

Original languageEnglish (US)
Pages (from-to)597-606
Number of pages10
JournalJournal of Pediatrics
Volume134
Issue number5
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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