T-cell Activation Is Correlated With Monocyte Activation in HCV/HIV Coinfection and Declines During HCV Direct-Acting Antiviral Therapy
Open Access
- 18 February 2021
- journal article
- research article
- Published by Oxford University Press (OUP) in Open Forum Infectious Diseases
- Vol. 8 (4), ofab079
- https://doi.org/10.1093/ofid/ofab079
Abstract
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.Funding Information
- AbbVie
- AIDS Clinical Trials Group (UM1 AI106701, UM1 AI068634)
- Statistical and Data Management Center (CFAR AI 36219, IK2CX001471, BX001894, CX001791, K24DA034621, D43TW010319)
This publication has 41 references indexed in Scilit:
- Accuracy of Fibroscan, Compared With Histology, in Analysis of Liver Fibrosis in Patients With Hepatitis B or C: A United States Multicenter StudyClinical Gastroenterology and Hepatology, 2015
- Hepatic Decompensation in Antiretroviral-Treated Patients Co-Infected With HIV and Hepatitis C Virus Compared With Hepatitis C Virus–Monoinfected PatientsAnnals of Internal Medicine, 2014
- Elevated sCD163 in plasma but not cerebrospinal fluid is a marker of neurocognitive impairment in HIV infectionAIDS, 2013
- Monocyte Activation in HIV/HCV Coinfection Correlates with Cognitive ImpairmentPLOS ONE, 2013
- Shared monocyte subset phenotypes in HIV-1 infection and in uninfected subjects with acute coronary syndromeBlood, 2012
- Hepatitis C Virus Core Protein Induces Homotolerance and Cross‐Tolerance to Toll‐Like Receptor Ligands by Activation of Toll‐Like Receptor 2The Journal of Infectious Diseases, 2010
- High Levels of Chronic Immune Activation in the T-Cell Compartments of Patients Coinfected with Hepatitis C Virus and Human Immunodeficiency Virus Type 1 and on Highly Active Antiretroviral Therapy Are Reverted by Alpha Interferon and Ribavirin TreatmentJournal of Virology, 2009
- Immunological recovery and antiretroviral therapy in HIV-1 infectionThe Lancet Infectious Diseases, 2006
- Influence of Human Immunodeficiency Virus Infection on the Course of Hepatitis C Virus Infection: A Meta‐AnalysisClinical Infectious Diseases, 2001
- Human immunodeficiency virus infection modified the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosisJournal of Hepatology, 1997