T-Cell Activation Is Correlated With Monocyte Activation In Hcv/Hiv Coinfection And Declines During Hcv Direct-Acting Antiviral Therapy

Background. Immune activation markers associate with morbidity and mortality in HIV and hepatitis C virus (HCV) infection. We investigated how T-cell and monocyte activation are related over the course of HCV direct-acting antiviral (DAA) therapy during HCV/HIV coinfection.Methods. Peripheral blood mononuclear cells from AIDS Clinical Trials Group (ACTG) A5329 participants and a single-site separate cohort treated with DAAs were analyzed for central memory (CM)/effector memory (EM) T-cell subsets, monocyte subsets, and cell activation (CD38 and HLA-DR expression) before, during, and after therapy.Results. Before therapy, classical and inflammatory monocyte subset HLA-DR expression positively correlated with absolute counts and frequencies of CD38(+)HLA-DR+-expressing CD4(+) and CD8 T cells and corresponding CM and EM subsets. After therapy initiation, CD38(+)HLA-DR+ co-expression on CD4(+) and CD8(+) memory T cells decreased by 12 weeks and 36 weeks, and plasma sCD14 positively correlated with CD38(+)HLA-DR+ CD4(+) and CD4(+)CM T-cell frequencies. Monocyte subset activation remained similar over time.Conclusions. During HCV/HIV coinfection, memory T-cell activation is associated with monocyte subset activation, consistent with related underlying mechanisms. Following therapy initiation, memory T-cell, but not monocyte, activation decreased. Residual CD4(+) T-cell activation after therapy completion is associated with sCD14, potentially linking the remaining CD4(+) T-cell activation to residual factors driving activation in antiretroviral therapy-controlled HIV.