INCREASED IMMUNE ACTIVATION PRECEDES THE INFLECTION POINT OF CD4 T-CELLS AND THE INCREASED SERUM VIRUS LOAD IN HUMAN-IMMUNODEFICIENCY-VIRUSINFECTION

The temporal relationship of serum levels of human immunodeficiency vi rus (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 wi thout inflection point were examined. Cases and controls did not diffe r statistically at the baseline time point for this study. CD4 cell in flection points occurred 18-30 months before AIDS development. Serum l evels of soluble tumor necrosis factor receptor II, soluble interleuki n-2 receptor, beta(2-)microglobulin, and neopterin increased significa ntly greater than or equal to 6 months before the CD4 cell inflection point, In contrast, increases in mean HIV RNA levels occurred at the t ime of the CD4 cell inflection point, These data are consistent with t he view that in vivo immune activation precedes the increases in virus load and is followed by an accelerated and rapid loss of CD4 lymphocy tes.