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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

2000; National Academy of Sciences; Volume: 97; Issue: 25 Linguagem: Inglês

10.1073/pnas.250472097

1091-6490

Richard A. Lempicki, Joseph A. Kovacs, Michael Baseler, Joseph W. Adelsberger, Robin Dewar, Ven Natarajan, Marjorie Bosche, Julia A. Metcalf, Randy Stevens, Laurie Lambert, W. Gregory Alvord, Michael A. Polis, Richard T. Davey, Dimiter S. Dimitrov, H. Clifford Lane,

HIV-related health complications and treatments

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 naïve 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.