Prediction of imminent complications in HIV-1-infected patients by markersof lymphocyte apoptosis

Objective: The aim of the study was to compare accepted surrogate markers o f HIV disease progression with markers of lymphocyte apoptosis in their abi lity to predict short-term disease progression. Methods: In all, 40 HIV-positive patients were studied prospectively and ob served during follow-up for HIV-related adverse clinical events. Ex vivo ap optosis was measured with the markers CD95 expression, annexin V binding, a nd Apostain dye uptake by flow cytometry at baseline. Established markers o f disease progression (CD4 count, HIV-RNA level, and CD8/38 count), CD8, B- cell, and natural killer (NK) cell counts were determined by standard proce dures at baseline and after 6 months. Results: In HIV-infected patients, CD95 expression and annexin V binding sh owed significantly elevated apoptosis in peripheral blood lymphocytes and a ll lymphocyte subsets at baseline compared with HIV-negative, healthy contr ols. Apostain failed to differentiate between HIV-infected patients and hea lthy controls. HIV-related complications could be predicted by CD4 and CD8/ 38 counts, but not HIV viral load as assessed by relative operating charact eristic (ROC) analysis (CD4, p = .003; CD8/38, p = .031). A similar or even better diagnostic accuracy was found for CD95 expression in total lymphocy tes (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/mu 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 u seful tool to monitor HIV-infected patients with low (<200 cells/mu l) CD4 counts, as it can reliably assess the risk for imminent complications in su ch patients.