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

Abstract

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.

• Authors: Ann W N Auma, Carey Shive, Sofi Damjanovska, Corinne Kowal, Daniel E Cohen, Debika Bhattacharya, Beverly Alston-Smith, Melissa Osborne, Robert Kalayjian, Ashwin Balagopal, Mark Sulkowski, David Wyles, Donald D Anthony
• Journal: Open forum infectious diseases (Open Forum Infect Dis) Vol. 8 Issue 4 Pg. ofab079 (Apr 2021) ISSN: 2328-8957 [Print] United States
• PMID: 33880389 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.