HCV kinetic and modeling analyses project shorter durations to cure under combined therapy with daclatasvir and asunaprevir in chronic HCV-infected patients

Background & aimsHigh cure rates are achieved in HCV genotype-1b patients treated with daclatasvir and asunaprevir, DCV/ASV. Here we analyzed early HCV kinetics in genotype-1b infected Japanese subjects treated with DCV/ASV and retrospectively projected, using mathematical modeling, whether shorter treatment durations might be effective.MethodsHCV RNA levels were measured frequently during DCV/ASV therapy in 95 consecutively treated patients at a single center in Japan. Mathematical modeling was used to predict the time to cure, i.e, ResultsEighty nine of the 95 included patients (94%) achieved cure, 3 (3%) relapsed due to treatment-emergent resistance, and 3 (3%) completed therapy but were lost during follow up. Model fits from 68 patients with sufficient data points indicate that after a short pharmacological delay (15.4 min [relative standard error, rse = 26%]), DCV/ASV effectiveness in blocking HCV production was 0.999 [rse~0%], HCV half-life in blood was t1/2 = 1.7 hr [rse = 21%], and HCV-infected cell loss rate was 0.391/d [rse = 5%]. Modeling predicted that 100% and 98.5% of patients who had HCVConclusionModeling early HCV kinetics under DCV/ASV predicts that most patients would achieve cure with short treatment durations, suggesting that 24 weeks of DCV/ASV treatment can be significantly shortened.