Long-term effects of protease-inhibitor-based combination therapy on CD4 T-cell recovery in HIV-1-infected children and adolescents

Chang Heok Soh, James M. Oleske, Michael T. Brady, Stephen A. Spector, William Borkowsky, Sandra K. Burchett, Marc D. Foca, Edward Handelsman, Eleanor Jiménez, Wayne M. Dankner, Michael D. Hughes

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

Background: There is limited evidence about longer-term effects of combination antiretroviral therapy that includes protease inhibitors (PIs) on the immunological status of HIV-1-infected children. Better understanding might help to resolve questions on when to initiate treatment. Methods: The change in percentage of CD4-positive T lymphocytes (CD4%) was investigated in 1012 previously treated HIV-1-infected children (aged 0-17 years) who were enrolled in research clinics in the USA before 1996 and followed up to 2000. 702 started PI-based combination therapy. Data analyses ignored subsequent treatment changes. Findings: Among the 1012 children, the median CD4% increased from 22% to 28% between 1996, when PIs were first prescribed, and 2000. For the 702 who started PI-based therapy, the mean CD4% increase after 3 years was largest among participants with the greatest immunosuppression (15.7%, 10.6%, 5.1%, and 2.0% for participants with CD4% before therapy of <5%, 5-14%, 15-24%, and ≥25%; p<0.0001). After adjustment for pre-PI CD4%, the mean increase was largest among the youngest participants (9.2%, 8.0%, and 4.3% for ages <5 years, 5-9 years, and ≥10 years; p=0.001). However, only a minority of significantly immunocompromised participants (33%, 26%, and 49% of those with pre-PI CD4% of <5%, 5-14%, or 15-24%) achieved CD4% values above 25%, whereas 84% of those with pre-PI values above 25% maintained such values. Interpretation: Although PI-based therapy was associated with substantial improvements in CD4%, initiation before severe immunosuppression and at younger ages may be more effective for recovery or maintenance of normal CD4%. Randomised investigation of when to start combination therapy in children, particularly infants, is needed.

Original languageEnglish (US)
Pages (from-to)2045-2051
Number of pages7
JournalLancet
Volume362
Issue number9401
DOIs
StatePublished - Dec 20 2003
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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