Biomarkers of inflammation, coagulation and microbial translocation in HIV/HCV co-infected patients in the SMART study

Abstract

Background: Previous results from the SMART study showed that HIV/viral hepatitis co-infected persons with impaired liver function are at increased risk of death following interruption of antiretroviral therapy (ART).

Objectives: To investigate the influence of fibrosis and ART interruption on levels of biomarkers of inflammation, coagulation and microbial translocation in HIV/HCV co-infected persons in the SMART study.

Study design: All HIV/HCV co-infected persons with stored plasma at study entry and at six months of follow-up were included (N=362). D-dimer, IL-6, sCD14 and hepatic synthesized coagulation markers were measured and compared according to the liver fibrosis marker hyaluronic acid (HA) at study entry. Percent difference in changes in biomarker levels from study entry to month 6 was compared between randomization groups and according to study entry HA levels.

Results: At study entry, persons with elevated HA (>75ng/mL vs. ≤75ng/mL) had higher median (IQR) levels of IL-6 [4.14pg/mL (2.60-6.32) vs. 2.74pg/mL (1.88-3.97)] and soluble CD14 [2163ng/mL (1952-2916) vs. 1979ng/mL (1742-2310)] (p<0.001). Elevated HA was also associated with alterations of both pro- and anti-coagulation markers but the overall coagulation profile was not affected. Interruption of ART lead to a particularly pronounced increase in IL-6 levels in persons with elevated HA levels (p=0.01 for interaction between randomization group and continuous HA level).

Conclusions: HIV/HCV co-infected persons with impaired liver function are in an enhanced pro-inflammatory state which is further exacerbated upon interruption of ART.

Keywords: Coagulation; HIV; Hepatitis; Inflammation; Microbial translocation.