Abstract
(1) Background: The role of hepatitis C virus (HCV) co-infection on the T-cell homeostasis disturbances in human immunodeficiency virus (HIV)-infected patients as well as its reversion after HCV eradication with direct acting antivirals (DAAs) therapy has not been yet clarified. We extensively analyzed the effect of HCV co-infection on immune parameters of HIV pathogenesis and its evolution after HCV eradication with DAAs. (2) Methods: Seventy individuals were included in the study—25 HIV-monoinfected patients, 25 HIV/HCV-coinfected patients and 20 HIV and HCV seronegative subjects. All patients were on antiretroviral therapy and undetectable HIV-viremia. Immune parameters, such as maturation, activation, apoptosis, senescence and exhaustion of T-cells were assessed by flow cytometry. Cross-sectional and longitudinal (comparing pre- and post-DAAs data in HIV/HCV coinfected patients) analyses were performed. Univariate and multivariate (general linear model and canonical discriminant analysis -CDA-) analyses were used to assess differences between groups. (3) Results—The CDA was able to clearly separate HIV/HCV coinfected from HIV-monoinfected patients, showing a more disturbed T-cells homeostasis in HIV/HCV patients, especially activation and exhaustion of T-cells. Interestingly, those perturbations were more marked in HIV/HCV patients with increased liver stiffness. Eradication of HCV with DAAs restored some but not all the T-cells homeostasis disturbances, with activation and exhaustion of effector CD8 T-cells remaining significantly increased three months after HCV eradication. (4) Conclusions—HCV co-infection significantly impacts on several immune markers of HIV pathogenesis, especially in patients with increased liver stiffness. Eradication of HCV with DAAs ameliorates but does not completely normalize these alterations. It is of utmost relevance to explore other mechanisms underlying the immune damage observed in HIV/HCV coinfected patients with control of both HIV and HCV replication.
Highlights
The UNAIDS (Joint United Nations Programme on HIV and AIDS) estimates that around 37.9 million people were living with human immunodeficiency virus (HIV) in 2018 [1] and 71 million people were chronically infected with hepatitis C virus (HCV) [2]
There were no significant differences between HIV and HIV/HCV groups in terms of age, gender, time since HIV diagnosis, time on antiretroviral therapy (ART), CD4 counts and HIV transmission route
The main findings of our study are—(a) the presence of HCV coinfection significantly impacts on several immune parameters in patients with HIV infection, especially on T-cells activation and exhaustion; (b) The impact on immune parameters is more marked in HIV/HCV coinfected patients with increased liver stiffness; (c) eradication of HCV with direct acting antivirals (DAAs)-based therapy does not completely restore the T-cells homeostasis perturbations observed in HIV/HCV coinfected patients
Summary
The UNAIDS (Joint United Nations Programme on HIV and AIDS) estimates that around 37.9 million people were living with human immunodeficiency virus (HIV) in 2018 [1] and 71 million people were chronically infected with hepatitis C virus (HCV) [2]. Co-infection poses an additional stress on host immune system and, as a consequence, each virus can aggravate the normal clinical course of the concomitant infection It is well known the negative impact of HIV on the HCV progression—higher levels of HCV load [6], faster liver disease progression [7,8] and hepatocellular carcinoma (HCC) [9]. Most previous studies have analyzed only a limited number of parameters, focusing mainly on T cell activation [17,27,28] or apoptosis [21], in cohorts of patients undergoing anti-HCV treatment with IFN-α and ribavirin and the results obtained maybe biased by the immunomodulatory effect of IFN-α [29]. We have performed an in-depth analysis of several immune parameters related to HIV infection pathogenesis, in a well-defined cohort of HIV/HCV coinfected patients before and after HCV eradication with the new DAAs-based therapy
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