Impact of HIV-1 Infection and Highly Active Antiretroviral Therapy on the Kinetics of CD4+and CD8+T Cell Turnover in HIV-Infected Patients

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.