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 le vels of DNA synthesis in lymph node and peripheral blood mononuclear cell s ubsets by using ex vivo labeling with BrdUrd. Compared with healthy control s (n = 67), HIV-infected patients (n = 57) had significant increases in the number and fraction of dividing CD4(+) and CD8(+) T cells. Higher percenta ges of dividing CD4+ and CD8(+) T cells were noted in patients with the hig her 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 c ell proliferation were seen in 11/11 patients 1-12 weeks after initiation o f highly active antiretroviral therapy (HAART). These reductions persisted for the length of the study (16-72 weeks). Decreases in naive T cell prolif eration correlated with increases in the levels of T cell receptor rearrang ement excision circles. Division of CD4(+) and CD8(+) T cells increased dra matically in association with rapid increases in HIV-1 viral loads in 9/9 p atients 5 weeks after termination of HAART and declined to pre-HAART-termin ation levels 8 weeks after reinitiation of therapy. These data are consiste nt with the hypothesis that HIV-1 infection induces a viral burden-related, global activation of the immune system, leading to increases in lymphocyte proliferation.