Close association of CD8+/CD38 bright with HIV-1 replication and complex relationship with CD4+ T-cell count

Cytometry B Clin Cytom. 2009 Jul;76(4):249-60. doi: 10.1002/cyto.b.20467.

Abstract

Background: Measuring lymphocyte activation provides information in addition to CD4(+) T-cell count for immune monitoring of HIV-1 infected patients. CD38 is a well-established activation marker that is generally analyzed on the whole population of CD8(+) T-cells. Focusing specifically on CD38 high expression (CD8(+)/CD38(bright)) may be an interesting surrogate gating strategy because CD38(bright) characterizes principally activated memory cells.

Methods: CD8(+)/CD38(bright) was investigated in 1,353 HIV-1 infected patients over a one-year period to establish relevant cutoff values and clarify the relationships of this marker with HIV-1 RNA viral load (VL) and CD4(+) T-cell count.

Results: The CD8(+)/CD38(bright) (>8,500 CD38 binding site per cells) is well correlated with HIV-1 VL (r = 0.87, P < 0.001) in this longitudinal follow-up of nonimmunodepressed patients that initiated antiviral therapy (ART). In aviremic patients on ART, the marker was highly predictive of VL rebound (sensitivity 93%, specificity 64% for a VL level of detection >200 copies/ml). While the CD8(+)/CD38(bright) moderately correlated with CD4(+) T-cell count independently of the VL (r = -0.37, P < 0.001), it increased dramatically in aviremic patient groups that exhibited profound CD4(+) T-cell depletion (median 39% for CD4(+) T-cell counts <50/mm(3)). This result indicates that other additional immunological and/or viral factors than readily detectable HIV-1 replication appears to be involved in T-cell activation of immunodepressed individuals.

Conclusions: CD8(+)/CD38(bright) is an effective marker for monitoring T-cell activation, which is a central factor of HIV-1 pathogenesis. This gating strategy requires only a single additional staining in conventional four color CD4 protocols.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / metabolism*
  • Anti-Retroviral Agents / therapeutic use
  • Biomarkers / analysis
  • Biomarkers / blood
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology*
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Case-Control Studies
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Infections / pathology
  • HIV Infections / virology
  • HIV-1 / immunology
  • HIV-1 / physiology*
  • Humans
  • Longitudinal Studies
  • Lymphocyte Activation / immunology
  • Lymphocyte Activation / physiology
  • Male
  • Membrane Glycoproteins / metabolism*
  • RNA, Viral / analysis
  • RNA, Viral / blood
  • Sensitivity and Specificity
  • Viral Load
  • Virus Replication / immunology*

Substances

  • Anti-Retroviral Agents
  • Biomarkers
  • Membrane Glycoproteins
  • RNA, Viral
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1