HIV-hepatitis B virus coinfection: epidemiology, pathogenesis, and treatment

Abstract

: HIV infection has a significant impact on the natural history of chronic hepatitis B virus (HBV) infection, with increased levels of HBV DNA, accelerated progression of liver disease and increased liver-associated mortality compared with HBV monoinfection. Widespread uptake and early initiation of HBV-active antiretroviral therapy has substantially improved the natural history of HIV-HBV coinfection but the prevalence of liver disease remains elevated in this population. In this paper, we review recent studies examining the natural history and pathogenesis of liver disease and seroconversion in HIV-HBV coinfection in the era of HBV-active antiretroviral therapy and the effects of HIV directly on liver disease. We also review novel therapeutics for the management of HBV with a particular emphasis on clinical strategies being developed for an HBV cure and an HIV cure and their impact on HIV-HBV coinfected individuals.

Figure 1. Prevalence of chronic hepatitis B amongst HIV infected individuals

Prevalence rates reported in the last 5 years from studies that included a minimum of 100 HIV-infected individuals are shown in graduated colours (filled and crosses). The number of HIV infected individuals surveyed in each study is represented by the size of the grey circles. Many regions have not formally evaluated prevalence and these regions are represented in white. Created using EMMa ECDC map maker^[237].

Figure 2. Hepatitis B (HBV) replication

HBV enters the hepatocyte upon binding to the putative sodium taurocholate co-transporting polypeptide (NTCP) receptor. Following entry and uncoating, relaxed circular (rc) DNA and then covalently closed circular (ccc) DNA minichromosome is formed. cccDNA is then transcribed into pregenomic RNA (pgRNA) and ultimately HBV DNA (following reverse transcription) which can be blocked by nucleos(t)ide reverses transcriptase inhibitors (NRTIs). HBsAg is coded for by preS1 and preS2/S from separate RNA transcripts and is produced even in the presence of NRTIs. HBV can also become integrated into the host genome and produce HBsAg.

Figure 3. Effects of HIV and HBV on the liver and circulating HBV-specific immune cells

1. HIV has been shown to directly infected hepatocytes, hepatic stellate cells (HSC) or Kupffer cells while 2. HBV only infects hepatocytes. 3. HIV can also significantly impair the integrity of the gastrointestinal tract leading to elevated levels of lipopolysaccharide (LPS). LPS can directly activate Kupffer cells and HSC leading to increased intrahepatic inflammation and fibrosis. 4. In HBV infection, liver disease can also be mediated by migration from the blood to the liver of HBV specific and non-HBV specific T cells, CXCR6+ NK cells (by chemokines CXCL10 and CXCL16 respectively) and monocytes (by chemokine CCL2). (adapted with permission from Chang et al^[238])