Close association of CD8 + /CD38 bright with HIV‐1 replication and complex relationship with CD4 + T‐cell count

Background: Measuring lymphocyte activation provides information in addition to CD4 + T‐cell count for immune monitoring of HIV‐1 infected patients. CD38 is a well‐established activation marker that is generally analyzed on the whole population of CD8 + T‐cells. Focusing specifically on CD38 high expression (CD8 + /CD38 bright ) may be an interesting surrogate gating strategy because CD38 bright characterizes principally activated memory cells. Methods: CD8 + /CD38 bright was investigated in 1,353 HIV‐1 infected patients over a one‐year period to establish relevant cutoff values and clarify the relationships of this marker with HIV‐1 RNA viral load (VL) and CD4 + T‐cell count. Results: The CD8 + /CD38 bright (>8,500 CD38 binding site per cells) is well correlated with HIV‐1 VL ( r = 0.87, P < 0.001) in this longitudinal follow‐up of nonimmunodepressed patients that initiated antiviral therapy (ART). In aviremic patients on ART, the marker was highly predictive of VL rebound (sensitivity 93%, specificity 64% for a VL level of detection >200 copies/ml). While the CD8 + /CD38 bright moderately correlated with CD4 + T‐cell count independently of the VL ( r = −0.37, P < 0.001), it increased dramatically in aviremic patient groups that exhibited profound CD4 + T‐cell depletion (median 39% for CD4 + T‐cell counts <50/mm 3 ). This result indicates that other additional immunological and/or viral factors than readily detectable HIV‐1 replication appears to be involved in T‐cell activation of immunodepressed individuals. Conclusions: CD8 + /CD38 bright is an effective marker for monitoring T‐cell activation, which is a central factor of HIV‐1 pathogenesis. This gating strategy requires only a single additional staining in conventional four color CD4 protocols. © 2008 Clinical Cytometry Society