TY - JOUR
T1 - Soluble T-Cell Immunoglobulin Mucin Domain-3 Is Associated With Hepatitis C Virus Coinfection and Low-Grade Inflammation During Chronic Human Immunodeficiency Virus Infection
AU - Hoel, Hedda
AU - Ueland, Thor
AU - Hove-Skovsgaard, Malene
AU - Hartling, Hans Jakob
AU - Gelpi, Marco
AU - Benfield, Thomas
AU - Ullum, Henrik
AU - Michelsen, Annika E
AU - Aukrust, Pål
AU - Nielsen, Susanne Dam
AU - Trøseid, Marius
N1 - © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
PY - 2020/2
Y1 - 2020/2
N2 - Background: In well treated human immunodeficiency virus infection (HIV), there is a residual immune activation and immune exhaustion that may contribute to increased risk of comorbidities. T-cell immunoglobulin mucin domain-3 (Tim-3) is an inhibitory molecule involved in HIV-associated T-cell dysfunction. The Tim-3 can be cleaved to soluble Tim-3 (sTim-3) that may serve as a soluble marker of immune exhaustion.Methods: We measured sTim-3 with enzyme-linked immunosorbent assay DuoSets in a cross-sectional cohort of 1010 people with HIV (PWH) on antiretroviral therapy (ART), and 76 controls from the Copenhagen Co-Morbidity in HIV Infection (COCOMO) study, and in a longitudinal cohort of 60 PWH before and during ART.Results: In the cross-sectional cohort, levels of sTim-3 were elevated in PWH on ART compared with controls, especially in hepatitis C virus (HCV)-coinfected individuals, and were associated with HCV viremia and inflammation. In the longitudinal cohort, pretreatment sTim-3 correlated with HIV viral load and decreased after ART initiation. Pretreatment sTim-3 correlated inversely with CD4 counts, but it did not predict immunological response in multivariable analyses.Conclusions: Levels of sTim-3 decreased after ART initiation. In a cross-sectional cohort, levels of sTIM-3 were higher in PWH than in controls and were independently associated with HCV coinfection and high-sensitivity C-reactive protein, representing a potential link between immune exhaustion, inflammation, and risk of comorbidities.
AB - Background: In well treated human immunodeficiency virus infection (HIV), there is a residual immune activation and immune exhaustion that may contribute to increased risk of comorbidities. T-cell immunoglobulin mucin domain-3 (Tim-3) is an inhibitory molecule involved in HIV-associated T-cell dysfunction. The Tim-3 can be cleaved to soluble Tim-3 (sTim-3) that may serve as a soluble marker of immune exhaustion.Methods: We measured sTim-3 with enzyme-linked immunosorbent assay DuoSets in a cross-sectional cohort of 1010 people with HIV (PWH) on antiretroviral therapy (ART), and 76 controls from the Copenhagen Co-Morbidity in HIV Infection (COCOMO) study, and in a longitudinal cohort of 60 PWH before and during ART.Results: In the cross-sectional cohort, levels of sTim-3 were elevated in PWH on ART compared with controls, especially in hepatitis C virus (HCV)-coinfected individuals, and were associated with HCV viremia and inflammation. In the longitudinal cohort, pretreatment sTim-3 correlated with HIV viral load and decreased after ART initiation. Pretreatment sTim-3 correlated inversely with CD4 counts, but it did not predict immunological response in multivariable analyses.Conclusions: Levels of sTim-3 decreased after ART initiation. In a cross-sectional cohort, levels of sTIM-3 were higher in PWH than in controls and were independently associated with HCV coinfection and high-sensitivity C-reactive protein, representing a potential link between immune exhaustion, inflammation, and risk of comorbidities.
KW - Hepatitis C
KW - HIV
KW - Immune exhaustion
KW - Soluble
KW - Tim-3
UR - http://www.scopus.com/inward/record.url?scp=85083736061&partnerID=8YFLogxK
U2 - 10.1093/ofid/ofaa033
DO - 10.1093/ofid/ofaa033
M3 - Journal article
C2 - 32055642
SN - 2328-8957
VL - 7
SP - ofaa033
JO - Open Forum Infectious Diseases
JF - Open Forum Infectious Diseases
IS - 2
M1 - ofaa033
ER -