Objective:The aim of the study was to compare accepted surrogate markers of HIV disease progression with markers of lymphocyte apoptosis in their ability to predict short-term disease progression.Methods:In all, 40 HIV-positive patients were studied prospectively and observed during follow-up for HIV-related adverse clinical events. Ex vivo apoptosis was measured with the markers CD95 expression, annexin V binding, and Apostain dye uptake by flow cytometry at baseline. Established markers of disease progression (CD4 count, HIV-RNA level, and CD8/38 count), CD8, B-cell, and natural killer (NK) cell counts were determined by standard procedures at baseline and after 6 months.Results:In HIV-infected patients, CD95 expression and annexin V binding showed significantly elevated apoptosis in peripheral blood lymphocytes and all lymphocyte subsets at baseline compared with HIV-negative, healthy controls. Apostain failed to differentiate between HIV-infected patients and healthy controls. HIV-related complications could be predicted by CD4 and CD8/38 counts, but not HIV viral load as assessed by relative operating characteristic (ROC) analysis (CD4,p= .003; CD8/38,p= .031). A similar or even better diagnostic accuracy was found for CD95 expression in total lymphocytes (p< .001), the CD4+(p= .003) and CD8+(p= .005) T-cell subsets and for annexin V binding in CD4+T cells (p= .005). When patients with CD4 counts <200 cells/&mgr;l were analyzed separately, only annexin V binding in CD4+T cells, but none of the other prognostic markers could predict complications (p= .001).Conclusion:Determination of annexin V binding on CD4+T cells may be a useful tool to monitor HIV-infected patients with low (<200 cells/&mgr;l) CD4 counts, as it can reliably assess the risk for imminent complications in such patients.