Coadministration of sofosbuvir and emtricitabine (200 mg once daily) had no effect on emtricitabine (Cmax and AUC decreased by 3% and 1%, Cmin increased by 4%). Sofosbuvir Cmax decreased by 19% and 6%, whereas GS-331007 Cmax and AUC decreased by 23% and 16%. No dose adjustment of sofosbuvir or emtricitabine is required when sofosbuvir and emtricitabine are used concomitantly.

The interaction between sofosbuvir and emtricitabine was evaluated in clinical trials and no dose adjustment is needed for either drug. 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 GS-331007 Cmax and AUC decreasing by 23% and 16%, respectively. No effect on the pharmacokinetic parameters of emtricitabine was observed.

Coadministration of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (150/150/200/10 mg once daily) and ledipasvir/sofosbuvir (90/400 mg once daily) was studied in 30 HIV/HCV-negative subjects. Ledipasvir AUC, Cmax and Ctrough increased by 79%, 65% and 93%, respectively. Sofosbuvir AUC and Cmax  increased by 47% and 28% with the AUC, Cmax and Ctrough of GS-331007 increasing by 48%, 29% and 66%, respectively. Elvitegravir AUC and Ctrough increased by 11% and 46%, with Cmax decreasing by 2%. Cobicistat AUC, Cmax and Ctrough increased by 53%, 23% and 225%, respectively. Emtricitabine AUC and Ctrough decreased by 3% and 5%, with Cmax increasing by 3%. AUC and Cmax of tenofovir alafenamide decreased by 14% and 9%; tenofovir AUC, Cmax and Ctrough increased by 27%, 17% and 33%, respectively. The increase in ledipasvir and sofosbuvir are within the safety window. In addition, the increase in elvitegravir and cobicistat are considered as not clinically relevant based on the safety window. No dose adjustments are needed.

No dose adjustment of ledipasvir/sofosbuvir and Genvoya is warranted upon co-administration. Coadministration of ledipasvir/sofosbuvir (90-400 mg once daily) and Genvoya was studied. Ledipasvir AUC ,Cmin and Cmax increased by 79%, 93% and 65%, respectively. Sofosbuvir AUC and Cmax increased by 47% and 28%. The AUC and Cmin of GS-331007 (the predominant circulating metabolite of sofosbuvir) increased by 48% and 66% with no change in Cmax; there no change in the AUC, Cmin or Cmax of the metabolite GS-566500. Elvitegravir AUC and Cmax were unchanged, but Cmin increased by 46%. Cobicistat AUC and Cmin increased by 53% and 225%, but Cmax was unchanged. There was no change in the AUC, Cmin and Cmax of emtricitabine, nor in the AUC and Cmax of tenofovir alafenamide.

Based on drug interaction studies conducted with the components of Genvoya, no clinically significant drug interactions have been either observed or are expected when Genvoya is combined with ledipasvir and sofosbuvir. Coadministration of ledipasvir/sofosbuvir (90/400 mg once daily) and elvitegravir/cobicistat (150/150 mg once daily, as Genvoya) decreased elvitegravir Cmax by 2% and increased AUC and Cmin by 11% and 46% (n=30). Tenofovir alafenamide Cmax and AUC decreased by 10% and 14%. Ledipasvir Cmax, AUC, and Cmin increased by 65%, 79%, and 93%. Sofosbuvir Cmax and AUC increased by 28% and 47%, with the Cmax, AUC, and Cmin of GS-331007 (the predominant circulating metabolite of sofosbuvir) increasing by 29%, 484%, and 66%, respectively.