Elevated Labile Iron Levels in CD4 and CD8 T Cells From HIV Positive Individuals With Undetectable Viral Load.

Iron is a key factor at various stages of HIV life cycle and determines the progression of HIV infection. Data about labile cellular iron pool (LIP) in the settings of cART are lacking. Yet LIP is directly related to the generation of reactive oxygen species (ROS), and may contribute to immune activation, dysfunction and exhaustion. Using multiparameter flow cytometry, we evaluated LIP in CD4 and CD8 T-cells from HIV+ patients with sustained viral suppression (SVS) as a result of continuous long-term cART. Based on the recovery of CD4/CD8 ratio two patients' subgroups were defined: A(n=26), CD4/CD8>0.9 and B(n=37), CD4/CD8<0.9, with significantly differing CD4AC (mean 752vs.571 cells/microl, p<0.05). While hemoglobin (Hb) and serum iron (sFe) had recovered in all patients, CD4 and CD8 T cell LIP were significantly higher as compared to controls, both in the subgroup with complete (A) and with incomplete (B) immune recovery (mean CD4DeltaMFI 318.7 and 777.8 vs.157.6; mean CD8DeltaMFI 359.5 and 628.7vs.179.2,ANOVA p<0.05 for both). CD4 LIP correlated inversely with CD4AC (R= -0.4, p <0.01), and both CD4 and CD8 LIP - with CD4/CD8 ratio (R=-0.4, p<0.01). Thus, increased CD4 and CD8 T cell LIP in the settings of SVS and immune recovery is a sensitive marker of residual immune activation and may predict immune exhaustion in long-term cART-treated patients.