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

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Authors: Canini, L; Imamura, M; Kawakami, Y.; Uprichard, S. L.; Cotler, S. J.; Dahari, H; Chayama, K
Article Title: HCV kinetic and modeling analyses project shorter durations to cure under combined therapy with daclatasvir and asunaprevir in chronic HCV-infected patients
Abstract: BACKGROUND amp; AIMS: High 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. METHODS: HCV 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, lt;1 virus copy in the extracellular body fluid. Patients with HCVlt;15 IU/ml at week 1 (n = 27) were excluded from modeling analysis due to insufficient HCV RNA data points. RESULTS: Eighty 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 HCVlt;15 IU/ml at days 14 and 28 might have been cured with 6 and 8 weeks of therapy, respectively. There was a trend (p = 0.058) between younger age and shorter time to cure. CONCLUSION: Modeling 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.
Journal Title: PloS one
Volume: 12
Issue: 12
ISSN: 1932-6203; 1932-6203
Publisher: Unknown  
Journal Place: United States
Date Published: 2017
Start Page: e0187409
Language: eng
DOI/URL:

10.1371/journal.pone.0187409
Notes: LR: 20180105; JID: 101285081; 0 (Antiviral Agents); 0 (BMS-790052); 0 (Imidazoles); 0 (Isoquinolines); 0 (Sulfonamides); S9X0KRJ00S (asunaprevir); 2017/06/26 00:00 [received]; 2017/10/19 00:00 [accepted]; 2017/12/08 06:00 [entrez]; 2017/12/08 06:00 [pubmed]; 2018/01/06 06:00 [medline]; epublish