Cd14(Bright)Cd16(-) Monocytes And Scd14 Level Negatively Associate With Cd4-Memory T-Cell Frequency And Predict Hcv-Decline On Therapy

During HIV+ hepatitis C virus (HCV)(+) coinfection CD14(bright)CD16(-) monocytes produce soluble immune-activation markers that predict disease progression and poor response to interferon (IFN)-alpha treatment. We evaluated relationships among immune activation, monocyte phenotype, CD4-memory T cells, and HCV-, cytomegalovirus-, and cytomegalovirus/Epstein-Barr virus/influenzaspecific IFN-gamma-response before and during IFN-alpha treatment. Effector-memory and central-memory CD4 T-cell frequencies were lower in HCV+HIV+ donors than in uninfected donors and correlated negatively with HCV level, CD14(bright)CD16(-) monocytes, and plasma sCD14. sCD14 and CD14(bright)CD16(-) monocytes negatively correlated with IFN-alpha-dependent HCV decline. CD4 effector-memory T cells positively associated with cytomegalovirus/Epstein-Barr virus/influenza (CEF)-specific IFN-gamma response, while sCD14 negatively associated with both CD4 effector-memory T cells and CEF-specific IFN-gamma response. These data support a role for memory-CD4 T cells in HCV containment and link immune activation and CD14(bright)CD16(-)-monocyte frequency to the failure of IFN-dependent HCV clearance.