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

Guillaume Giraud1,2, Barbara Testoni3,4

  • 1Université Claude-Bernard Lyon 1, Inserm, UMR 1350 PaThLiv, Lyon, F-69003, France. guillaume.giraud@inserm.fr.

Current HIV/AIDS Reports
|December 17, 2025
PubMed

Insights

Human immunodeficiency virus (HIV) co-infection accelerates chronic hepatitis B (HBV) progression. Understanding HBV covalently closed circular DNA (cccDNA) persistence is key for developing HBV cure strategies in co-infected patients.

Area of Science:

  • Hepatology
  • Virology
  • Immunology

Background:

  • Chronic hepatitis B (HBV) infection poses a significant health burden.
  • HIV co-infection exacerbates HBV progression, increasing liver disease severity and mortality risk.
  • HBV covalently closed circular DNA (cccDNA) is crucial for viral persistence and a major barrier to HBV cure.

Purpose of the Study:

  • To review the role of HBV cccDNA in viral persistence.
  • To highlight knowledge gaps regarding cccDNA in HIV/HBV co-infection.
  • To discuss implications for achieving an HBV cure in co-infected individuals.

Main Methods:

  • Literature review focusing on HBV cccDNA.
  • Analysis of studies on HIV/HBV co-infection and antiviral therapy (ART).
  • Examination of immune responses and biomarkers in co-infected patients.

Main Results:

  • ART in HIV/HBV co-infected patients does not eliminate transcriptionally active cccDNA.
  • Hepatitis B surface antigen (HBsAg) loss post-ART suggests immune reconstitution may overcome HBV immune tolerance.
  • Significant questions persist regarding virus-virus interactions, liver microenvironment, and serum biomarkers of the HBV reservoir.

Conclusions:

  • Further research with advanced models and larger cohorts is essential to elucidate HIV/HBV interactions.
  • Understanding cccDNA biology is critical for developing novel HBV cure strategies.
  • Improved clinical management and access to HBV cure options are needed for co-infected individuals.
Abstract

Keywords:
BiomarkersFunctional cureHBVHIVcccDNA

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