Abstract
Systemic inflammation, endothelial dysfunction and coagulopathy are of high clinical relevance in the management of people living with HIV (PLWH), and even more in patients coinfected with hepatitis C virus (HCV). It has been suggested a significant impact of HCV coinfection on these conditions. However, HCV can be eradicated in most patients with the new direct-acting antivirals (DAAs) therapy. We have analyzed the effect of HCV on systemic inflammation, endothelial activation and coagulopathy in PLWH and its evolution after HCV eradication with DAAs. Twenty-five HIV/HCV coinfected (HIV/HCV group), 25 HIV monoinfected (HIV group) and 20 healthy controls (HC) were included in the study. All patients were on ART and HIV suppressed. Levels of fourteen markers of systemic inflammation, endothelial activation and coagulopathy (IL-1ß, IL-6, IL-12p70, IL-8, TNFα, D-dimer, Eotaxin, IL-18, IP-10, monocyte chemotactic protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1), TNFα receptor 1 (TNFR1), vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1)) were measured on plasma at baseline and after DAAs-mediated HCV eradication. Non-parametric tests were used to establish inter/intra-group differences. At baseline, the HIV/HCV group showed increased levels of IL-18 (p = 0.028), IP-10 (p < 0.0001), VCAM-1 (p < 0.0001) and ICAM-1 (p = 0.045), compared to the HC and HIV groups, with the highest levels for IL18 and IP10 observed in HIV/HCV patients with increased liver stiffness (≥7.1 KPa). Eradication of HCV with DAAs-based therapy restored some but not all the evaluated parameters. VCAM-1 remained significantly increased compared to HC (p = 0.001), regardless of the level of basal liver stiffness in the HIV/HCV group, and IP-10 remained significantly increased only in the HIV/HCV group, with increased level of basal liver stiffness compared to the HC and to the HIV groups (p = 0.006 and p = 0.049, respectively). These data indicate that DAAs therapy in HIV/HCV co-infected patients and HCV eradication does not always lead to the normalization of systemic inflammation and endothelial dysfunction conditions, especially in cases with increased liver stiffness.
Highlights
Among people living with HIV (PLWH), the advent of combination antiretroviral therapy has reduced the incidence of morbidity and mortality, improving life expectancy [1].despite successful cART, there is evidence of the existence of a state of persistent systemic inflammation [2,3], and a heightened incidence of several comorbidities, including cardiovascular events, diabetes mellitus, kidney and liver diseases and cancer [3,4], which has been associated with that state of heightened inflammation [5]
The baseline clinical characteristics of HIV and the HIV/hepatitis C virus (HCV) groups of patients are summarized in HCV genotype 1 and 28% HCV genotype 4
The main findings of our study are: (a) HCV coinfection in PLWH significantly impacts on several bio- markers associated to inflammation and endothelial activation; (b) The alterations of these markers in HIV/HCV coinfected patients are more marked in patients with increased liver stiffness; (c) the eradication of HCV with
Summary
Among people living with HIV (PLWH), the advent of combination antiretroviral therapy (cART) has reduced the incidence of morbidity and mortality, improving life expectancy [1].despite successful cART, there is evidence of the existence of a state of persistent systemic inflammation [2,3], and a heightened incidence of several comorbidities, including cardiovascular events, diabetes mellitus, kidney and liver diseases and cancer [3,4], which has been associated with that state of heightened inflammation [5]. The effect of HCV on different aspects of HIV disease pathogenesis has been explored, and previous studies have shown an increase in T-cells homeostasis disturbances in PLWH coinfected with HCV [9,10]. Since HCV infection is associated with a state of chronic inflammation [11], an additive effect of HCV co-infection in PLWH might be expected. Previous studies have shown that patients coinfected with HIV and HCV present higher levels of soluble markers of systemic inflammation [12,13,14,15,16], monocyte activation [13,15,16] and endothelial dysfunction [12,16]
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