The use of mathematical modeling and response-guided therapy (RGT) to reduce patient treatment duration without sacrificing efficacy is well documented in hepatitis C virus research. HCV research is relatively mature with well-established drugs for treatment and over 20 years of data and applications. It now requires larger studies for application and refinement. In contrast, HDV research is in the early stages of research for treatments and cure or SVR (sustained virological response). The mathematical models needed to predict time to cure* during HDV antiviral therapy requires the additional consideration of viral kinetics of both HDV and hepatitis B (since HDV is dependent on hepatitis B surface antigen). Treatments may impact the suppression, elimination, and interplay of either or both viruses. [*defined as <1 copy of HDV in total extracellular body fluid.]

 

As for 2023 the only treatments for HDV are pegylated-Interferon alpha (pegIFN-α ) and bulevirtide (BLV), an HDV entry blocker. However, pegIFN-α is suboptimal even after 5 years of treatment (Hepatology 2014) and BLV has only been conditionally approved in Europe since 2021.

 

In a recent study of BLV, we predicted that cure could be achieved (J Hep 2022). In this study of 3 patients, two of them were predicted to reach cure.* In a follow up, one of them remained HDV undetectable 72 weeks after discontinuing treatment of BLV suggesting viral cure.
[J Hepatology 2022). In another study of 7 patients treated with BLV, a mathematical (viral kinetic) model was used to predict the number of weeks of treatment in individualized BLV therapy. The model predicted that cure could have been achieved after  ~100 weeks of BLV treatment (EASL 2023). Using RGT, individualized treatment schedules predicted each patient had the potential to achieve HDV cure based on differing durations of treatment.

 

In a 2017 study, our mathematical modeling approach (and RGT) predicted that 2 of the 12 patients treated with investigational Lonafarnib + Ritonavir (LOWR HDV-3 for 24 weeks), would have achieved a cure.* if treatment was extended to 48-51 weeks (AASLD Oral Talk, 2017).