Role of Nucleic Acid Polymers and Entry Inhibitors in Functional Cure Strategies for HBV

Hepatitis B virus (HBV) infection is one of the most common viral infections worldwide with an estimated 2 billion people exposed to HBV and 240 million with active chronic infection. Despite this, less than 1% of patients with chronic HBV infection receive treatment, and less than 3% of those achieve functional cure with traditional therapies. This review summarizes recent advances in the treatment of chronic HBV utilizing nucleic acid polymers (NAP) and entry inhibitors (EI). A recent phase 2 study evaluating the use of NAP following tenofovir and pegylated interferon (PEG-IFN) demonstrated increased rates of functional cure which persisted in 35% of patients after 48 weeks of follow-up. In addition, the EI Myrcludex B has demonstrated HBsAg response in up to 40% of patients when used in combination with PEG-IFN at week 72. Functional cure is considered the “holy grail” of treatment, and many new therapies are under investigation for the treatment of chronic HBV. As we work towards functional cure for chronic HBV, NAPs and EIs have shown efficacy in reducing HBV DNA and HBsAg levels and have emerged as potential therapeutic agents that may lead to a functional cure for HBV.