Objective Chronic viral infections, HCV and HIV, are characterized by systemic inflammation. Yet the relative levels, drivers and correlates of inflammation in these settings are not well defined. Methods We studied seventy-nine HIV-infected patients who had been receiving antiretroviral therapy (ART) for more than two years and had suppressed plasma HIV levels (<50 copies/ml). Two patient groups: HCV+/HIV+, HCV−/HIV+, and a control group comprised of healthy volunteers (n=20) were examined. Markers of systemic inflammation (IL-6, IP-10, sTNF-RI, and sTNF-RII), monocyte/macrophage activation (sCD163, sCD14, and neopterin), intestinal epithelial barrier loss (I-FABP and LPS), and coagulation (D-dimers) were analyzed. CD4+ naïve T cells and CD4+ recent thymic emigrants (RTE) were enumerated. Results Plasma levels of IP-10, neopterin, and sCD163 were higher in HCV/HIV co-infection than in HIV monoinfection and were positively correlated with indices of hepatic damage (AST, ALT, and APRI). Levels of I-FABP were comparably increased in both HIV monoinfection and HIV/HCV co-infection but LPS concentrations were highest in HCV/HIV co-infection suggesting impaired hepatic clearance of LPS. Plasma HCV levels were related to no inflammatory indices but for sCD163. In co-infected subjects, a previously recognized relationship of CD4+ naïve T cell and RTE counts to hepatocellular injury was defined more mechanistically by an inverse relationship to sCD163. Conclusion Hepatocellular injury in HCV/HIV co-infection is linked to elevated levels of certain inflammatory cytokines and an apparent failure to clear systemically translocated microbial products. A related decrease in CD4+ naïve T cells and recent thymic emigrants also merits further exploration.

Whereas we could find no relationship between HCV infection and most indices of CD4⁺ T-cell homeostasis or activation, CD4⁺ RTEs are diminished in the circulation of HCV coinfected persons and appear to be related to indices of ongoing hepatic damage or inflammation.

The level of proinflammatory markers was assessed in HIV-infected patients that were coinfected with hepatitis C virus (HCV) and had failed to restore the CD4+ T cell counts (immunological nonresponders, INR) during the antiretroviral therapy (ART). Among four patient groups (HIV+HCV− and HIV+HCV+ subjects with the concordant response to ART; HIV+HCV− and HIV+HCV+ subjects that were INR), the greatest systemic inflammation was in the latter group. The maximum difference was between the subjects HIV+HCV−INR and HIV+HCV+ INR: the blood of coinfected patients contained significantly higher concentrations of the IP-10, sCD163, sTNF-RI, and sTNF-RII and of bacterial lipopolysaccharide. Systemic inflammation in HIV/HCV coinfected patients with the discordant response to ART is probably caused by a breach of hepatic barrier for the intestine products.

No abstract