Increased immune activation precedes the inflection point of CD4 T cells and the increased serum virus load in human immunodeficiency virus infection.

The temporal relationship of serum levels of human immunodeficiency virus (HIV) RNA and of immune activation products in 10 HIV-seropositive persons who showed an accelerated decline (inflection point) in CD4 T cell counts and went on to develop AIDS and in 10 matched controls without inflection point were examined. Cases and controls did not differ statistically at the baseline time point for this study. CD4 cell inflection points occurred 18-30 months before AIDS development. Serum levels of soluble tumor necrosis factor receptor II, soluble interleukin-2 receptor, beta2-microglobulin, and neopterin increased significantly > or = 6 months before the CD4 cell inflection point. In contrast, increases in mean HIV RNA levels occurred at the time of the CD4 cell inflection point. These data are consistent with the view that in vivo immune activation precedes the increases in virus load and is followed by an accelerated and rapid loss of CD4 lymphocytes.