Soluble T-Cell Immunoglobulin Mucin Domain-3 Is Associated With Hepatitis C Virus Coinfection and Low-Grade Inflammation During Chronic Human Immunodeficiency Virus Infection

Abstract

In well-treated HIV infection, 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. Tim-3 can be cleaved to soluble Tim-3 (sTim-3) that may serve as a soluble marker of immune exhaustion. We measured sTim-3 with ELISA DuoSets in a cross-sectional cohort of 1010 People with HIV (PWH) on ART and 76 controls from the COCOMO study, and in a longitudinal cohort of 60 PWH before and during ART. In the cross-sectional cohort, levels of sTim-3 were elevated in PWH on ART compared to controls, especially in HCV-coinfected individuals, and were associated with HCV viremia and inflammation. In the longitudinal cohort, pre-treatment sTim-3 correlated with HIV viral load and decreased after ART initiation. Pre-treatment sTim-3 correlated inversely with CD4 counts, but did not predict immunological response in multivariable analyses. Levels of sTim-3 decreased after ART initiation. In a cross-sectional cohort, levels of sTIM-3 was higher in PWH than in controls and were independently associated with HCV coinfection and hsCRP, representing a potential link between immune exhaustion, inflammation and risk of comorbidities.