Coadministration has not been studied but no effect on sofosbuvir or GS-331007 is expected. No dose adjustment of Vemlidy or sofosbuvir is required.

Based on drug interaction studies conducted with Vemlidy, no clinically significant drug interactions have been observed with sofosbuvir.

Coadministration of ledipasvir/sofosbuvir (once daily) with rilpivirine/emtricitabine/tenofovir alafenamide (25/200/25 mg, daily, study 1) or elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (150/150/200/10 mg, daily, study 2) was studied in 40 (study 1) and 30 (study 2) healthy volunteers in a crossover trial. In study 1, tenofovir alafenamide AUC and Cmax increased by 32% and 3%, respectively. Tenofovir AUC, Cmax and Cmin increased by 75%, 62% and 85%, respectively. Ledipasvir AUC and Cmin increased by 2% and Cmax increased by 1%. Sofosbuvir AUC increased by 5% while Cmax fell by 4%. Finally, the sofosbuvir metabolite GS-331007 AUC and Cmax increased by 8% and Cmin increased by 10%. In study 2, tenofovir alafenamide AUC and Cmax decreased by 14.3% and Cmax decreased by 9.5%. Tenofovir AUC, Cmax and Cmin increased by 27%, 17% and 33%, respectively. Ledipasvir AUC, Cmax and Cmin increased by 79%, 65% and 93%, respectively. Sofosbuvir AUC and Cmax increased by 47% and 28%, respectively. GS-331007 AUC, Cmax and Cmin increased by 48%, 29% and 66%, respectively. Despite the increases in tenofovir exposure seen in this study, the mean tenofovir AUC is still five times lower than that seen with tenofovir-DF administration, so these exposures are safe. Likewise, the increases in ledipasvir, sofosbuvir and GS-113007 are within safe limits. The authors therefore conclude that ledipasvir/sofosbuvir may be safely coadministered with rilpivirine/emtricitabine/tenofovir-alafenamide or elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, without dose adjustment.