T-cell Activation Is Correlated With Monocyte Activation in HCV/HIV Coinfection and Declines During HCV Direct-Acting...

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.

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.

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.

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.