T-cell homeostasis alteration in HIV-1 infected subjects with low CD4 T-cell count despite undetectable virus load during HAART

AIDS. 2006 Oct 24;20(16):2033-41. doi: 10.1097/01.aids.0000247588.69438.fd.


Objective: To investigate the pathogenesis of low CD4 T-cell count in subjects who are immunological non responders (InR) to HAART.

Design: Thirty-five HIV-positive subjects on HAART for at least 1 year, all with undetectable HIV-1 RNA, were studied. Patients were defined as InR according to a CD4 cell increase < 20% from CD4 cell baseline or CD4 cell count < 200/microl; subjects with a CD4 T-cell increase > 20% from baseline and a CD4 cell count > 200/microl were defined as immunological responders (IR). We performed a comprehensive study to characterize the immune response of InR.

Methods: The immunological phenotype of peripheral blood mononuclear cells, thymic naive T cells, T-cell receptor Vbeta repertoire, serum concentration of interleukin (IL)-7, the expression of IL-7Ralpha on naive and memory CD4 and CD8 T cells, and regulatory T cells (Treg) were studied.

Results: In InR a significant reduction (P < 0.0001) of naive and thymic naive CD4 T cells was associated with a reduced expression of IL-7Ralpha in both cell subsets, with an increased serum concentration of IL-7 was observed. Furthermore, an increased immune activation with a reduced Treg frequency and increased number of expansions of Vbeta families was observed.

Conclusions: The reduced expression of IL-7Ralpha associated with the persistent immune activation and the alteration of Treg frequencies in part explains the low level of CD4 T cells observed in InR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • Female
  • Flow Cytometry
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1*
  • Homeostasis / immunology
  • Humans
  • Immunophenotyping
  • Interleukin-7 / blood
  • Male
  • Middle Aged
  • Receptors, Antigen, T-Cell, alpha-beta / blood
  • Receptors, Interleukin-7 / blood
  • T-Lymphocyte Subsets / immunology
  • Viral Load


  • Interleukin-7
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Interleukin-7