'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 Citations (Scopus)

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

Fingerprint

HIV-1
T-Lymphocytes
RNA
Tumor Necrosis Factor-alpha
CD4 Lymphocyte Count
Virus Activation
HLA-DR Antigens
HIV Infections
Interleukin-2
Interleukin-6
Acquired Immunodeficiency Syndrome
Cross-Sectional Studies
Biomarkers

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

Cite this

'Modeling' relationships among HIV-1 replication, immune activation and CD4+ T-cell losses using adjusted correlative analyses. / Lederman, Michael M.; Kalish, Leslie A.; Asmuth, David; Fiebig, Eberhard; Mileno, Maria; Busch, Michael P.

In: AIDS, Vol. 14, No. 8, 2000, p. 951-958.

Research output: Contribution to journalArticle

Lederman, Michael M. ; Kalish, Leslie A. ; Asmuth, David ; Fiebig, Eberhard ; Mileno, Maria ; Busch, Michael P. / 'Modeling' relationships among HIV-1 replication, immune activation and CD4+ T-cell losses using adjusted correlative analyses. In: AIDS. 2000 ; Vol. 14, No. 8. pp. 951-958.
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AU - Lederman, Michael M.

AU - Kalish, Leslie A.

AU - Asmuth, David

AU - Fiebig, Eberhard

AU - Mileno, Maria

AU - Busch, Michael P.

PY - 2000

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N2 - 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.

AB - 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.

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KW - Cytokines

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KW - Immune activation

KW - Immune deficiency

KW - Interleukin-6

KW - Tumor necrosis factor

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