No dose adjustment of Epclusa or atazanavir (ritonavir boosted) is required. Coadministration of atazanavir boosted with ritonavir (300/100 mg once daily) + emtricitabine/tenofovir disoproxil fumarate (200/300 mg once daily) and sofosbuvir/velpatasvir (400 100 mg once daily) had no effect on atazanavir Cmax or AUC but increased Cmin by 40%. There was no change in ritonavir Cmax and a 30% increase in Cmin. Sofosbuvir Cmax and AUC were unchanged, but velpatasvir Cmax, AUC, and Cmin increased by 60%, 140% and 300%. Epclusa has been shown to increase tenofovir exposure, especially when used together with an HIV regimen containing tenofovir disoproxil fumarate and a pharmacokinetic enhancer (ritonavir or cobicistat). The safety of tenofovir disoproxil fumarate in the setting of Epclusa and a pharmacokinetic enhancer has not been established.