Immune Activation Response in Chronic HIV-Infected Patients: Influence of Hepatitis C Virus Coinfection

Abstract

ObjectivesWe have analyzed the parameters (bacterial translocation, immune activation and regulation, presence of HCV coinfection) which could be implicated in an inappropriate immune response from individuals with chronic HIV infection. The influence of them on the evolution of CD4+ T cell count has been investigated.Patients and methodsSeventy HIV-infected patients [monoinfected by HIV (n = 20), HCV-coinfected (with (n = 25) and without (n = 25) liver cirrhosis)] and 25 healthy controls were included. Median duration of HIV infection was 20 years. HIV- and HCV-related parameters, as well as markers relative to bacterial translocation, monocyte and lymphocyte activation and regulation were considered as independent variables. Dependent variables were the increase of CD4+ T cell count during the follow-up (12 months).ResultsIncreased values of bacterial translocation, measured by lipopolysaccharide-binding protein, monocyte and lymphocyte activation markers and T regulatory lymphocytes were detected in HIV-monoinfected and HIV/HCV coinfected patients. Serum sCD14 and IL-6 were increased in HIV/HCV-coinfected patients with liver cirrhosis in comparison with those with chronic hepatitis or HIV-monoinfected individuals. Time with undetectable HIV load was not related with these parameters. The presence of cirrhosis was negatively associated with a CD4+ T cell count increase.ConclusionIn patients with a chronic HIV infection, a persistent increase of lipopolysaccharide-binding protein and monocyte and lymphocyte modifications are present. HCV-related cirrhosis is associated with more elevated serum concentrations of monocyte-derived markers. Cirrhosis influences the continued immune reconstitution of these patients.

HIV infection and immune activation

“…A small study reported evidence of higher tissue factor activity (measured as microparticles tissue factor), a procoagulant factor, and associated CD4 T cell activation in HCV patients both mono- and HIV-coinfected suggesting a potential mechanism of immune activation and coagulopathy that may predispose to cardiovascular disease [86]. In another prospective study, immune activation markers were compared between HIV monoinfecetd and HIV/HCV coinfected (with and without cirrhosis) ART treated patients with suppressed plasma HIV viremia during 12 months [87]. HIV patients with chronic hepatitis and cirrhosis had higher concentrations of serum sCD14 and IL-6 and incomplete CD4 restoration.…”

“…HIV patients with chronic hepatitis and cirrhosis had higher concentrations of serum sCD14 and IL-6 and incomplete CD4 restoration. Although the percent of activated CD4+ and CD8+ T cells and Treg were higher in HIV-infected patients compared to healthy controls, no significant differences were observed among the groups of HIV patients [87]. In a different study, biomarkers of inflammation including INFa were found to be higher in HCV/HIV co-infected patients compared to HCV mono-infected patients but importantly, some decreased after successful sustained virologic suppression (SVR) of hepatitis C [88].…”

The proportion of different interleukin‐17‐producing T‐cell subsets is associated with liver fibrosis in chronic hepatitis C

“…Much evidence has suggested that elevated plasmatic levels of soluble CD14 (sCD14) are indicative of bacterial translocation . Recent studies have demonstrated a relationship between sCD14 and hepatic disease outcomes in chronically HCV‐infected individuals . In this study, sCD14 concentrations were not only elevated in plasma from naive and therapy failed CHC patients (Fig.…”

Bacterial translocation and clinical progression of HCV‐related cirrhosis in HIV‐infected patients

“…These studies have suggested that high levels of BT markers are frequently found in HIV/HCV‐coinfected patients, underpinning the severity of the underlying liver fibrosis. Besides, HIV/HCV‐coinfected patients with decompensated cirrhosis had higher levels of BT and immune activation markers in one study . Because of the above‐mentioned reasons, it is reasonable to speculate that BT might contribute to a worse clinical outcome in HIV‐infected patients with advanced liver disease due to HCV.…”

“…Besides, HIV/HCV-coinfected patients with decompensated cirrhosis had higher levels of BT and immune activation markers in one study. 13 Because of the above-mentioned reasons, it is reasonable to speculate that BT might contribute to a worse clinical outcome in HIV-infected patients with advanced liver disease due to HCV. Thus, our objective was to assess whether BT impacts on the clinical outcome of compensated cirrhosis in HIV/HCV-coinfected patients.…”