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Impact of HIV-1 infection and highly active antiretroviral therapy on the kinetics of CD4(+) and CD8(+) T cell turnover in HIV-infected patients

  1. Author:
    Lempicki, R. A.
    Kovacs, J. A.
    Baseler, M. W.
    Adelsberger, J. W.
    Dewar, R. L.
    Natarajan, V.
    Bosche, M. C.
    Metcalf, J. A.
    Stevens, R. A.
    Lambert, L. A.
    Alvord, W. G.
    Polis, M. A.
    Davey, R. T.
    Dimitrov, D. S.
    Lane, H. C.

  2. Author Address

    NIAID, Lab Immunoregulat, Clin & Mol Retrovirol Sect, NIH, Bldg 10, Room 11S231, Bethesda, MD 20892 USA. NIAID, Lab Immunoregulat, Clin & Mol Retrovirol Sect, NIH, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Clin Serv Program, Frederick, MD 21702 USA. Data Management Serv Inc, Comp Serv, Frederick, MD 21702 USA. Data Management Serv Inc, Stat Serv, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, Frederick, MD 21702 USA. NIAID, Ctr Clin, Dept Crit Care Med, NIH, Bethesda, MD 20892 USA. NIAID, Lab Immunoregulat, Clin & Mol Retrovirol Sect, NIH, Bethesda, MD 20892 USA. Lane HC NIAID, Lab Immunoregulat, Clin & Mol Retrovirol Sect, NIH, Bldg 10, Room 11S231, Bethesda, MD 20892 USA.
    1. Year: 2000
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 97
    2. 25
    3. Pages: 13778-13783
  4. Type of Article: Article
  1. Abstract:

    To evaluate the effects of HIV infection on T cell turnover, we examined levels of DNA synthesis in lymph node and peripheral blood mononuclear cell subsets by using ex vivo labeling with BrdUrd. Compared with healthy controls (n = 67), HIV-infected patients (n = 57) had significant increases in the number and fraction of dividing CD4(+) and CD8(+) T cells. Higher percentages of dividing CD4+ and CD8(+) T cells were noted in patients with the higher viral burdens. No direct correlation was noted between rates of T cell turnover and CD4(+) T cell counts. Marked reductions in CD4+ and CD8(+) T cell proliferation were seen in 11/11 patients 1-12 weeks after initiation of highly active antiretroviral therapy (HAART). These reductions persisted for the length of the study (16-72 weeks). Decreases in naive T cell proliferation correlated with increases in the levels of T cell receptor rearrangement excision circles. Division of CD4(+) and CD8(+) T cells increased dramatically in association with rapid increases in HIV-1 viral loads in 9/9 patients 5 weeks after termination of HAART and declined to pre-HAART-termination levels 8 weeks after reinitiation of therapy. These data are consistent with the hypothesis that HIV-1 infection induces a viral burden- related, global activation of the immune system, leading to increases in lymphocyte proliferation.

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