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Prediction of Imminent Complications in HIV-1-Infected Patients by Markers of Lymphocyte Apoptosis

Wasmuth, Jan-Christian; Klein, Karl H.; Hackbarth, Frank; Rockstroh, Jürgen K.; Sauerbruch, Tilman; Spengler, Ulrich
JAIDS Journal of Acquired Immune Deficiency Syndromes: January 1st, 2000
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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/μl 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/μl) CD4 counts, as it can reliably assess the risk for imminent complications in such patients.

Address correspondence and reprints requests to Jan-Christian Wasmuth, University of Bonn, Department of General Internal Medicine, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany; email: j-c.wasmuth@uni-bonn.de.

Manuscript received April 1, 1999; accepted October 29, 1999.

© 2000 Lippincott Williams & Wilkins, Inc.