Immune activation correlates better than HIV plasma viral load with CD4 T-cell decline during HIV infection

This study addressed the role of T-cell immune activation in determining HI V-I plasma viral load and CD4(+) T-cell blood levels during HIV-I infection . A decrease of blood CD4 levels and CD4/CD8 ratios and an increase of CD8 levels in both treated (n = 35) and untreated (n = 19) HIV-positive individ uals were more strongly correlated to immune activation (log percentage of HLA-DR(+)CD3(+) cells; R = -0.78, R = -0.77. and R = 0.58, respectively: p < .0001) than to CD4 T-cell proliferation (log percentage of Ki-67(+)CD4(+) cells R = -0.57 [p < .0001], R = -0.48 [p < .001]. and R = 0.37 [p < .01]. respectively) or to viral load (R = -0.36 [P < .01], R = -0.23 [p = .09], R = 0.13 [p = .35], respectively). Because almost half of the Ki-67(+)CD4() cells were also positive for CTLA-4 (a marker for activated nonproliferat ing cells), the correlation of CD4 levels to Ki-67 expression is only parti ally related to cell proliferation and more likely represents mainly immune activation of the cells without proliferation. Taken together, these resul ts suggest that immune activation is the major determinant of CD4 decline a nd should therefore be considered central for the monitoring of HIV infecti on and its outcome after antiviral treatment.