HBV/HIV Coinfection: Impact on the Development and Clinical Treatment of Liver Diseases

Abstract

Hepatitis B virus (HBV) infection is a common contributor to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Approximately 10% of people with human immunodeficiency virus (HIV) also have chronic HBV co-infection, owing to shared transmission routes. HIV/HBV coinfection accelerates the progression of chronic HBV to cirrhosis, end-stage liver disease, or hepatocellular carcinoma compared to chronic HBV mono-infection. HBV/HIV coinfection alters the natural history of hepatitis B and renders the antiviral treatment more complex. In this report, we conducted a critical review on the epidemiology, natural history, and pathogenesis of liver diseases related to HBV/HIV coinfection. We summarized the novel therapeutic options for these coinfected patients.

Keywords: clinical treatment; coinfection; hepatitis B virus; human immunodeficiency virus; liver disease.

Figure 1

Mechanism of virus-targeted agents. Though undergoing different life cycles, HBV and HIV share some similarities in their life cycles, which are important for the development of dual antiviral drugs for HBV and HIV. Activated nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) are capable of disturbing the functions of both HIV reverse transcriptase and HBV polymerase by competing with natural nucleotide substrates for joining into DNA chains, resulting in the chain termination and viral replication. Cyclophilin A (Cyp A) plays a crucial role in the replication of various viruses, including HBV and HIV. Thus, cyclophilins inhibitor could be a potential option for anti-HIV and anti-HBV strategy.

Figure 2

Mechanism of host-targeted agents. Pattern-recognition receptors are activated when the virus invades, leading to the production of interferon (IFN). IFN interacts with its cognate receptors and activates receptor-associated kinases, contributing to the activation of the STAT family to form a transcription factor complex or a homo-/heterodimer. The transcription factor complex and the homo-/heterodimer bind to the ISRE and GAS promoter elements, respectively, and encode numerous viral restriction factors with potent inhibition potential on viral replication. Consequently, immunomodulators offer a rational option for treating HBV and HIV infection. Additionally, the adaptive immune response is also a promising target for novel therapeutic interventions owing to the key position of T cells in viral infection control. Regardless of HBV or HIV infection, virus-specific T cells have been found to have a distinct dysfunction. And the PD-1/PD-L1 axis plays an important role in the pathogenic process of viruses. Considering that high expression levels of PD-1 and PD-L1 are usually related to unsatisfactory immune response, agents based on the PD-1/PD-L1 axis might be able to reverse this immune suppression consequence and exert corresponding antiviral effects. Hence, immune checkpoint inhibitor targeting the PD-1/PD-L1 axis can be another option for treating HBV/HIV coinfection.