Modelling hepatitis D virus RNA and HBsAg dynamics during nucleic acid polymer monotherapy suggest rapid turnover of HBsAg
Hepatitis D virus (HDV) requires hepatitis B surface antigen (HBsAg) for its assembly and release. Current HBV treatments are only marginally effective against HDV because they fail to inhibit HBsAg production/secretion. However, monotherapy with the nucleic acid polymer REP 2139-Ca is accompanied by rapid declines in both HBsAg and HDV RNA. We used mathematical modeling to estimate HDV-HBsAg-host parameters and to elucidate the mode of action and efficacy of REP 2139-Ca against HDV in 12 treatment-naive HBV/HDV co-infected patients. The model accurately reproduced the observed decline of HBsAg and HDV, which was simultaneous. Median serum HBsAg half-life (t1/2) was estimated as 1.3 [0.9-1.8] days corresponding to a pretreatment production and clearance of ~10^8 [10^7.7-10^8.3] IU/day. The HDV-infected cell loss was estimated to be 0.052 [0.035-0.074] days-1 corresponding to an infected cell t1/2=13.3 days. The efficacy of blocking HBsAg and HDV production were 98.2 [94.5-99.9]% and 99.7 [96.0-99.8]%, respectively. In conclusion, both HBsAg production and HDV replication are effectively inhibited by REP 2139-Ca. Modeling HBsAg kinetics during REP 2139-Ca monotherapy indicates a short HBsAg half-life (1.3 days) suggesting a rapid turnover of HBsAg in HBV/HDV co-infection.
Louis Shekhtman, Scott J. Cotler, Leeor Hershkovich, Susan L. Uprichard, Michel Bazinet, Victor Pantea, Valentin Cebotarescu, Lilia Cojuhari, Pavlina Jimbei, Adalbert Krawczyk, Ulf Dittmer, Andrew Vaillant, Harel Dahari