Coadministration of daclatasvir (30 mg once daily) with atazanavir/ritonavir (300/100 mg once daily) or atazanavir/cobicistat (300/150 mg once daily) was studied in 16 HIV/HCV uninfected subjects and compared to historical data. Atazanavir/ritonavir and atazanavir/cobicistat had a similar influence on daclatasvir pharmacokinetics in healthy volunteers and daclatasvir plasma concentrations were in line with previously published data in healthy volunteers (AUCs for reference data vs atazanavir/ritonavir or atazanavir/cobicistat, 14.12 vs 14.18 or 14.30 mg.h/L). When compared to historical data, coadministration of daclatasvir with atazanavir/ritonavir increased atazanavir AUC, Cmax and Cmin by 19%, 11% and 58%, respectively. When compared to historical data, coadministration of daclatasvir with atazanavir/cobicistat increased atazanavir AUC and Cmin by 31% and 100%, and decreased Cmax by 17%.

Coadministration of atazanavir/ritonavir (300/100 mg, once daily) and daclatasvir (60 mg once daily alone or 20 mg once daily with atazanavir/ritonavir) was studied 14 healthy subjects. Dose normalised (to 60 mg) daclatasvir Cmax, AUC and C24 increased 35%, 110% and 265%, respectively. Daclatasvir AUC and C24 for a 30 mg dose were projected to increase by 5% and 83%, while Cmax was projected to decrease by 32%. These data support a dose reduction to 30 mg daclatasvir daily, when given in combination with atazanavir/ritonavir 300/100 mg daily.