Epclusa has been shown to increase tenofovir exposure (P-gp-inhibition). The increase in tenofovir exposure (AUC and Cmax) was around 40-80% during co-treatment with Epclusa and tenofovir disoproxil fumarate/emtricitabine as part of various HIV regimens. Coadministration of elvitegravir/cobicistat/emtricitabine/tenofovir-DF (150/150/200/300 mg, once daily) with sofosbuvir/velpatasvir (400/100 mg, once daily) was studied. Elvitegravir and sofosbuvir pharmacokinetics were unchanged. Cobicistat and velpatasvir Cmin increased by 70% and 40%, respectively. No dose adjustment of Epclusa or elvitegravir/ cobicistat/emtricitabine/ tenofovir disoproxil fumarate is required. Patients receiving tenofovir disoproxil fumarate and Epclusa concomitantly should be monitored for adverse reactions associated with tenofovir disoproxil fumarate. Refer to the elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil Summary of Product Characteristics for recommendations on renal monitoring. 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. The potential risks and benefits associated with co-administration of Epclusa with the fixed-dose combination tablet containing elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate or tenofovir disoproxil fumarate given in conjunction with a boosted HIV protease inhibitor (e.g. atazanavir or darunavir) should be considered, particularly in patients at increased risk of renal dysfunction. Patients receiving Epclusa concomitantly with elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate or with tenofovir disoproxil fumarate and a boosted HIV protease inhibitor should be monitored for tenofovir-associated adverse reactions.