Advancing HIV cure: insights from developing chronic hepatitis b therapies for functional cure

Area of Science:

• Hepatology
• Virology
• Immunology

Background:

• Hepatitis B virus (HBV) establishes persistent infections due to stable nuclear forms and host genome integration.
• Complete eradication of HBV is challenging, similar to HIV, necessitating novel therapeutic strategies.

Purpose of the Study:

• To review recent advancements in therapies aimed at achieving a functional cure (FC) for chronic Hepatitis B (CHB).
• To highlight emerging treatment modalities beyond the current standard-of-care.

Main Methods:

• Review of current literature on experimental and emerging therapies for CHB.
• Analysis of the efficacy of nucleos(t)ide analogues (NA), PegIFN-α, capsid-assembly modulators (CAMs), siRNAs, and antisense oligonucleotides.
• Evaluation of treatment strategies for achieving functional cure.

Main Results:

• Standard therapies (NA, PegIFN-α) are insufficient for functional cure alone.
• NA cessation, with or without PegIFN-α, improves FC rates and reduces relapse.
• Newer CAMs show potential for cccDNA effects and HBsAg reduction; bepirovirsen demonstrates modest FC rates possibly via innate immune induction.

Conclusions:

• Functional cure for CHB requires combination therapies.
• Therapies must inhibit viral replication, reduce HBsAg, and enhance the host antiviral immune response.
• Addressing persistent cccDNA, integrated DNA, and HBsAg-induced immune dysfunction is crucial for FC.