CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Immune activation set point during early HIV infection predicts subsequent CD4 T-cell changes independent of viral load

Although generalized T-cell activation is an important factor in chronic HIV dis-ease pathogenesis, its role in primary infection remains poorly defined. To in-vestigate the effect of immune activation on T-cell changes in subjects with early HIV infection, and to test the hypothesis that an immunologic activation “set point” is established early in the natural history of HIV disease, a prospective cohort of acutely infected adults was performed. The median density of CD38 molecules on CD4 and CD8 T cells was measured longitudinally in 68 antiretroviral-un-treated individuals and 83 antiretroviral-treated individuals. At study entry, T-cell activation was positively associated with viremia, with CD8 T-cell activation levels increasing exponentially at plasma HIV RNA levels more than 10 000 copies/mL. Among untreated patients, the level of CD8 T-cell activation varied widely among individuals but often remained stable within a given individual. CD8 T-cell activation and plasma HIV RNA levels over time were independently asso-ciated with the rate of CD4 T-cell loss in untreated individuals. These data indi-cate that immunologic activation set point is established early in HIV infection, and that this set point determines the rate at which CD4 T cells are lost over time