Evaluation of the impact of highly active antiretroviral therapy on immune recovery in antiretroviral naive patients

Lena Al-Harthi, J. Voris, B. K. Patterson, S. Becker, J. Eron, K. Y. Smith, R. D'Amico, D. Mildvan, J. Snidow, B. Pobiner, L. Yau, A. Landay

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Objectives. To examine the extent of immune reconstitution in treatment-naive patients with CD4 T-cell counts < 500 cells/μL following 48 weeks of highly active antiretroviral therapy (HAART). Methods. Thirteen antiretroviral naive patients were evaluated longitudinally for 48 weeks on HAART utilizing immune functional and lymphocyte phenotyping assays, including lymphocyte proliferation assay, flow cytometric evaluation of cell surface markers, and delayed type hypersensitivity skin tests. Virologic responses were monitored using commercially available viral load assays and gag/pol mRNA quantification using simultaneous immunophenotyping/UltraSensitive fluorescence in situ hybridization (ViroTect In Cell HIV-1 Detection Kit; Invirion, Frankfort, MI). Thymic function was evaluated for a subset of four patients using real-time polymerase chain reaction (PCR) for T-cell receptor excision circle (TREC) quantification and thymic scans using computerized axial tomography (CT) of the thymus. Results. HAART initiation resulted in a significant decline in plasma viremia and percentage of infected peripheral blood cells, and a rise in CD4 T cells from a baseline median of 207 cells/μL to a week-48 median of 617 cells/μL. The rise was predominately in CD4 memory cells. Naive T cells also increased in number, but at a slower rate. Activated (HLA-DR CD38) CD4 and CD8 T cells were elevated at baseline (24 and 62%, respectively) and declined by week 48 (17 and 36%, respectively) but did not reach normal levels. The number of Fas CD4 T cells increased from a baseline median of 169 to 381 cells/μL at week 48. Both soluble interleukin (IL)-2 and tumour necrosis factor (TNF) II receptors declined by week 48. HIV p24 lymphocyte proliferation assay responses were transiently detected in three patients. TREC values increased from a median 6400 copies/μg at baseline to a week-48 median value of 26 697 copies/μg. Conclusion. Immune functional reconstitution was not achieved in these HAART naive patients.

Original languageEnglish (US)
Pages (from-to)55-65
Number of pages11
JournalHIV Medicine
Volume5
Issue number1
DOIs
StatePublished - Jan 2004
Externally publishedYes

Keywords

  • Antiretroviral naice patients
  • HAART
  • HIV
  • Immune reconstitution
  • T-cell receptor excision circules(TRECs)
  • Thymic index

ASJC Scopus subject areas

  • Health Policy
  • Infectious Diseases
  • Pharmacology (medical)

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