The Role of Integrated HBV DNA in the Quest for a Cure in HIV/HBV co-infection.

Purpose: This review highlights the importance of Hepatitis B virus (HBV) integrated into the host genome (iDNA) to functional cure and how human immunodeficiency virus (HIV) may affect HBV integration.

Recent findings: Functional cure of chronic hepatitis B infection is characterized by durable loss of hepatitis B surface antigen (HBsAg) from blood after treatment discontinuation. Because HBsAg is transcribed from two intrahepatic sources, covalently closed circular DNA (cccDNA) or iDNA, functional cure requires elimination or silencing of both sources. It is not clear how HIV affects HBV integration, but since HIV enhances HBV replication and leads to increased DNA breaks through oxidative stress, people with HIV and HBV may have more integration events. HBV integration into the human genome is a random and ongoing process that occurs during all phases of chronic HBV infection (CHB). iDNA is important for maintaining HBsAg expression despite antiviral therapy. In studies without HIV, higher levels of HBV replication are associated with increased integration events. Higher HBV DNA levels in HIV/HBV co-infected individuals may contribute to increased HBV integration. HIV worsens CHB by weakening immune responses, promoting oxidative stress, and activating cellular pathways that enhance HBV replication and integration.