Immune activation predicts morbidity during HCV and HIV infection, though mechanisms underlying immune activation are unclear. Plasma autotaxin and its enzymatic product, lysophosphatidic-acid (LPA), are elevated during HCV infection, and LPA activates immunocytes, but whether this contributes to immune activation is unknown.
We evaluated plasma autotaxin, IL-6, sCD14, sCD163, and Mac2-Binding Protein (Mac2BP) during HCV, HIV and HCV-HIV infection, and in uninfected controls, before and after HIV ART and IFN-free HCV therapy.
We observed greater plasma autotaxin levels in HCV and HCV-HIV-infected compared to uninfected participants, primarily those with higher AST/PLT ratio index. Autotaxin levels correlated with IL-6, sCD14, sCD163, Mac2BP, and LPA in HCV-infected, and with Mac2BP in HCV-HIV-infected participants, while in HIV infection sCD14 correlated with Mac2BP. Autotaxin, LPA and sCD14 levels normalized, while sCD163 and Mac2BP levels partially normalized within 6 months of starting IFN-free HCV therapy. sCD163 and IL-6 levels normalized within 6 months of starting HIV ART. In vitro, LPA activated monocytes.
These data indicate elevated autotaxin levels and soluble markers of immune activation during HCV infection are partially reversible within 6 months of IFN-free HCV treatment, and autotaxin may be causally linked to immune activation during HCV and HCV-HIV infection.