A Tale of Two Viruses: Immunological Insights Into HCV/HIV Coinfection.

Samaa T Gobran,Petronela Ancuta,Naglaa H Shoukry

doi:10.3389/fimmu.2021.726419

Abstract

Nearly 2.3 million individuals worldwide are coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Odds of HCV infection are six times higher in people living with HIV (PLWH) compared to their HIV-negative counterparts, with the highest prevalence among people who inject drugs (PWID) and men who have sex with men (MSM). HIV coinfection has a detrimental impact on the natural history of HCV, including higher rates of HCV persistence following acute infection, higher viral loads, and accelerated progression of liver fibrosis and development of end-stage liver disease compared to HCV monoinfection. Similarly, it has been reported that HCV coinfection impacts HIV disease progression in PLWH receiving anti-retroviral therapies (ART) where HCV coinfection negatively affects the homeostasis of CD4+ T cell counts and facilitates HIV replication and viral reservoir persistence. While ART does not cure HIV, direct acting antivirals (DAA) can now achieve HCV cure in nearly 95% of coinfected individuals. However, little is known about how HCV cure and the subsequent resolution of liver inflammation influence systemic immune activation, immune reconstitution and the latent HIV reservoir. In this review, we will summarize the current knowledge regarding the pathogenesis of HIV/HCV coinfection, the effects of HCV coinfection on HIV disease progression in the context of ART, the impact of HIV on HCV-associated liver morbidity, and the consequences of DAA-mediated HCV cure on immune reconstitution and HIV reservoir persistence in coinfected patients.

Highlights

Hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) are two chronic viral infections that affect millions worldwide
Other indirect mechanisms include the enhancement of HCV RNA replication via the HIV accessory proteins Vpr [167] and Nef [168]; the accumulation in the liver of HIV-specific CD8+ T cells creating a state of inflammation and tissue damage in coinfected patients [181, 182]; and functional alterations of HCVspecific immune responses in the presence of HIV coinfection [150, 169]
This T cell activation may facilitate de novo infection, especially since the concentrations of antiretroviral drugs reaching lymphoid tissues are low [210]. Another theory is the possibility that impaired HIV-specific cell-mediated immunity, responsible for clearance of HIV-infected cells, contributes to HIV reservoir persistence. This immune suppression may be a consequence of chronic HCV coinfection where higher frequencies of peripheral regulatory T cells (Tregs) and IL-10 producing cells were detected as compared to HIV monoinfected subjects [203]

Summary

A Tale of Two Viruses

Reviewed by: Bertram Bengsch, University of Freiburg Medical Center, Germany Carey Shive, Louis Stokes Cleveland VA Medical Center, United States. HIV coinfection has a detrimental impact on the natural history of HCV, including higher rates of HCV persistence following acute infection, higher viral loads, and accelerated progression of liver fibrosis and development of end-stage liver disease compared to HCV monoinfection. It has been reported that HCV coinfection impacts HIV disease progression in PLWH receiving anti-retroviral therapies (ART) where HCV coinfection negatively affects the homeostasis of CD4+ T cell counts and facilitates HIV replication and viral reservoir persistence. We will summarize the current knowledge regarding the pathogenesis of HIV/HCV coinfection, the effects of HCV coinfection on HIV disease progression in the context of ART, the impact of HIV on HCV-associated liver morbidity, and the consequences of DAA-mediated HCV cure on immune reconstitution and HIV reservoir persistence in coinfected patients

INTRODUCTION

Findings

CONCLUSION