'Modeling' relationships among HIV-1 replication, immune activation and CD4+ T-cell losses using adjusted correlative analyses

Michael M. Lederman, Leslie A. Kalish, David Asmuth, Eberhard Fiebig, Maria Mileno, Michael P. Busch

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Objective: To model the relationships among HIV-1 replication, immune activation and CD4+ T-cell losses in HIV-1 infection. Methods: Cross-sectional analysis of baseline data from the Viral Activation by Transfusion Study. Comparisons of unadjusted and adjusted correlative analyses to establish models for mechanisms of cell loss in AIDS. Results: Using these analyses, significant correlations were found among plasma levels of tumor necrosis factor alpha (TNFα) and its type two receptor (TNFrII), interleukin-6 (IL-6), β2-microglobulin, expression of CD38 and HLA-DR on CD8+ T lymphocytes and plasma levels of HIV-1 RNA. When correlations among these indices were adjusted for possible intermediary correlations, the relationship between HIV-1 RNA levels and all plasma markers of immune activation could be accounted for by the correlation between plasma HIV-1 RNA and plasma TNFrII levels. In addition, the negative correlations that both HIV-1 RNA levels and TNFrII levels had with CD4+ T-cell counts were partially accounted for by the correlations of HIV-1 RNA and TNFrII with CD38 expression on CD8+ T cells. In persons with advanced disease (CD4+ T cells < 50 x 106/l) IL-6 levels were inversely correlated with CD4+ T-cell counts. Conclusions: This analysis is consistent with a model wherein HIV-1 replication induces TNFα expression that induces multiple other indices of immune activation. In this model, HIV-1 replication and TNFα expression induce CD4+ T-cell losses at least in part through mechanisms reflected in heightened CD38 expression. (C) 2000 Lippincott Williams and Wilkins.

Original languageEnglish (US)
Pages (from-to)951-958
Number of pages8
JournalAIDS
Volume14
Issue number8
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • Anemia
  • B2-microglobulin
  • CD38
  • Cell loss
  • Cytokines
  • HIV
  • Immune activation
  • Immune deficiency
  • Interleukin-6
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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