Role of cccDNA in the Quest for HBV Cure- Implications for HIV-HBV Coinfection.

PURPOSE OF REVIEW: HIV co-infection worsens chronic hepatitis B progression, leading to more aggressive disease and higher risk of liver-related death. This review addresses the role of HBV cccDNA, responsible for viral persistence, and the related gaps in knowledge in the perspective of obtaining an HBV cure with special focus on HIV/HBV co-infection.

RECENT FINDINGS: HIV/HBV co-infected patients under ART show persistence of transcriptionally active cccDNA. High incidence of HBsAg loss after ART initiation suggests that intrahepatic immune reconstitution might break immune-tolerance to HBV. Open questions remain on the interaction between the two viruses and the liver microenvironment and on the role of emerging serum biomarkers of HBV liver reservoir in co-infected individuals. To clarify HIV/HBV interactions, more advanced models and larger patient cohorts are needed. Insights into cccDNA biology will guide innovative therapies, improving clinical management and access to new HBV cure strategies for co-infected individuals.