Coadministration with rilpivirine/emtricitabine/tenofovir alafenamide has not been studied. Coadministration of rilpivirine (25 mg once daily) and sofosbuvir (400 mg single dose) was studied in 17 subjects. Sofosbuvir Cmax and AUC increased by 21% and 9%, whereas GS-331007 Cmax and AUC increased by 6% and 1%. Rilpivirine Cmax and AUC increased by 5% and 6%, but Cmin decreased by 1%. No dose adjustment of sofosbuvir or rilpivirine is required. In addition, no clinically significant interactions were observed when sofosbuvir was coadministered with emtricitabine or tenofovir alafenamide. Coadministration of emtricitabine (200 mg once daily with efavirenz and tenofovir) and sofosbuvir (400 mg single dose) was studied in 16 subjects. Sofosbuvir Cmax and AUC decreased by 19% and 6%, respectively, with Cmax and AUC of GS-331007 (the major circulating sofosbuvir metabolite) decreasing by 23% and 16%, respectively. Emtricitabine Cmax and AUC decreased by 3% and 1%, but Cmin increased by 4%. Coadministration of ledipasvir/sofosbuvir (90/400 mg once daily) and tenofovir alafenamide (25 mg once daily) increased tenofovir alafenamide AUC by 32%, the pharmacokinetics of ledipasvir/sofosbuvir was not significantly changed.