Increased HLA-DR expression on peripheral blood monocytes in subsets of subjects with primary HIV infection is associated with elevated CD4 T-cell apoptosis and CD4 T-cell depletion

J Acquir Immune Defic Syndr. 2002 Jun 1;30(2):146-53. doi: 10.1097/00042560-200206010-00002.

Abstract

Whereas T-cell activation parameters of HIV disease have been extensively studied, the activation status of circulating monocytes has received less attention. Sixty-one subjects with primary HIV infection were evaluated by fluorescent-activated cell sorter (FACS) analysis at baseline (pretreatment) for CD4 T-cell count, CD4 T-cell apoptosis, and immune activation. A subset of 15 subjects with marked elevated (3 standard deviations above normal) monocyte DR expression had significantly reduced CD4 T-cell counts at baseline (p <.01) when compared with 46 subjects without monocyte activation. Ten subjects who presented with elevated levels of both CD14/DR, and CD4/CD38, had higher CD4 T-cell apoptosis (p <.001), and lower CD4 T-cell counts (p <.001) and higher baseline plasma HIV RNA (p <.01) than 21 subjects without elevated CD14/DR and CD4/CD38 coexpression. Fifty subjects were subsequently evaluated for immune cell activation over 24 weeks postinitiation of highly active antiretroviral therapy (HAART). A subgroup of 5 subjects who had persistent CD14/DR activation showed continuous depression of CD4 T-cell counts persisting for up to 2 years. The CD4 T-cell counts of this subgroup were significantly lower, at all time points, in comparison to 35 subjects who lacked any persistent expression of monocyte or CD4 T-cell activation (at 24 weeks, p <.002). We conclude that monocyte activation as defined by elevation of CD14/DR expression correlates to CD4 T-cell depletion in primary HIV infection, and is predictive of a poor CD4 T-cell response to HAART in a subset of patients.

Publication types

  • Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ADP-ribosyl Cyclase
  • ADP-ribosyl Cyclase 1
  • Antigens, CD*
  • Antigens, Differentiation / metabolism
  • Antiretroviral Therapy, Highly Active
  • Apoptosis*
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / physiology*
  • Flow Cytometry
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / immunology*
  • HLA-DR Antigens / metabolism*
  • Humans
  • Lipopolysaccharide Receptors / metabolism
  • Lymphocyte Activation
  • Lymphopenia
  • Membrane Glycoproteins
  • Monocytes / immunology*
  • Monocytes / virology
  • NAD+ Nucleosidase / metabolism
  • RNA, Viral / blood

Substances

  • Antigens, CD
  • Antigens, Differentiation
  • HLA-DR Antigens
  • Lipopolysaccharide Receptors
  • Membrane Glycoproteins
  • RNA, Viral
  • ADP-ribosyl Cyclase
  • CD38 protein, human
  • NAD+ Nucleosidase
  • ADP-ribosyl Cyclase 1