HCV coinfection contributes to HIV pathogenesis by increasing immune exhaustion in CD8 T-cells

Marcial García,Beatriz Álvarez,Norma Rallón,José M Benito,Rosa García,Miguel Górgolas,Javier García-Samaniego,Lishomwa C Ndhlovu,Noelia Rodríguez,Alfonso Cabello,Clara Restrepo

doi:10.1371/journal.pone.0173943

Abstract

BackgroundThere are several contributors to HIV-pathogenesis or insufficient control of the infection. However, whether HIV/HCV-coinfected population exhibits worst evolution of HIV-pathogenesis remains unclear. Recently, some markers of immune exhaustion have been proposed as preferentially upregulated on T-cells during HIV-infection. Herein, we have analyzed T-cell exhaustion together with several other contributors to HIV-pathogenesis that could be affected by HCV-coinfection.Patients and methodsNinety-six patients with chronic HIV-infection (60 HIV-monoinfected and 36 HIV/HCV-coinfected), and 20 healthy controls were included in the study. All patients were untreated for both infections. Several CD4 and CD8 T-cell subsets involved in HIV-pathogenesis were investigated. Non-parametric tests were used to establish differences between groups and associations between variables. Multivariate linear regression was used to ascertain the variables independently associated with CD4 counts.ResultsHIV-patients presented significant differences compared to healthy controls in most of the parameters analyzed. Both HIV and HIV/HCV groups were comparable in terms of age, CD4 counts and HIV-viremia. Compared to HIV group, HIV/HCV group presented significantly higher levels of exhaustion (Tim3+PD1- subset) in total CD8+ T-cells (p = 0.003), and higher levels of exhaustion in CD8+HLADR+CD38+ (p = 0.04), CD8+HLADR-CD38+ (p = 0.009) and CD8+HLADR-CD38- (p = 0.006) subsets of CD8+ T-cells. Interestingly these differences were maintained after adjusting by CD4 counts and HIV-viremia.ConclusionsWe show a significant impact of HCV-coinfection on CD8 T-cells exhaustion, an important parameter associated with CD8 T-cell dysfunction in the setting of chronic HIV-infection. The relevance of this phenomenon on immunological and/or clinical HIV progression prompts HCV treatment to improve management of coinfected patients.

Highlights

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) are two of the most relevant persistent infections afflicting the human population, with 37 and 150 million chronically infected individuals worldwide respectively [1]
Both HIV and HIV/HCV groups were comparable in terms of age, CD4 counts and HIV-viremia
We show a significant impact of HCV-coinfection on CD8 T-cells exhaustion, an important parameter associated with CD8 T-cell dysfunction in the setting of chronic HIV-infection

Summary

Introduction

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) are two of the most relevant persistent infections afflicting the human population, with 37 and 150 million chronically infected individuals worldwide respectively [1] Coinfection with both viruses is common due to the existence of shared transmission routes [2] and as much as 20–30% of HIV positive patients are coinfected with HCV [1]. Since the introduction of highly active antiretroviral therapy (HAART), the clinical prognosis for HIV patients has markedly improved and, as a result, HCV infection is a leading cause of morbidity and mortality in HIV/HCV coinfected individuals [7] This coinfection is probably associated with more rapid progression of HIV disease, but data on the impact of HCV coinfection on HIV disease progression and mortality are controversial [8,9,10,11]. We have analyzed T-cell exhaustion together with several other contributors to HIV-pathogenesis that could be affected by HCV-coinfection

Methods

Results

Conclusion