Co-administration of tenofovir disoproxil with sofosbuvir/velpatasvir/voxilaprevir has been shown to increase plasma concentrations of tenofovir, especially when used together with an HIV regimen containing tenofovir disoproxil and a pharmacokinetic enhancer (ritonavir or cobicistat). Increased plasma concentrations of tenofovir resulting from co-administration of tenofovir disoproxil, sofosbuvir/velpatasvir/voxilaprevir and may increase adverse reactions related to tenofovir disoproxil, including renal disorders. The safety of tenofovir disoproxil when used with sofosbuvir/velpatasvir/voxilaprevir and a pharmacokinetic enhancer (e.g. ritonavir or cobicistat) has not been established. The combination should be used with caution with frequent renal monitoring. The potential risks and benefits associated with co-administration should be considered, particularly in patients at increased risk of renal dysfunction. Patients receiving sofosbuvir/velpatasvir/voxilaprevir concomitantly with tenofovir disoproxil and a boosted HIV protease inhibitor should be monitored for adverse reactions related to tenofovir disoproxil. Concomitant administration of sofosbuvir/velpatasvir and efavirenz is expected to decrease plasma concentrations of velpatasvir. Co-administration of sofosbuvir/velpatasvir with efavirenz-containing regimens is not recommended. Coadministration of sofosbuvir/velpatasvir/voxilaprevir (400/100/100 mg once daily, plus 100 mg voxilaprevir) and emtricitabine/tenofovir disoproxil (200/245 mg once daily with darunavir/ritonavir (800/100 mg once daily) had no effect on sofosbuvir AUC but decreased Cmax by 30%; there was no effect on AUC and Cmax of GS-331007 (the prominent circulating metabolite of sofosbuvir). Velpatasvir AUC, Cmax and Cmin were unaltered. Voxilaprevir AUC, Cmax and Cmin increased by 143%, 72% and 300%, respectively. There was no change in the AUC and Cmax of darunavir, but Cmin decreased by 34%; ritonavir AUC and Cmax increased by 45% and 60% but Cmin was unaltered; there was no change in AUC, Cmax and Cmin of emtricitabine. Tenofovir AUC, Cmax and Cmin increased by 39%, 48% and 47%, respectively.

Coadministration increases tenofovir concentrations. Coadministration of sofosbuvir/velpatasvir/voxilaprevir (400/100/100 mg once daily, plus 100 mg voxilaprevir) and tenofovir-DF (300 mg once daily) in the presence of darunavir/ritonavir increased tenofovir Cmax, AUC and Cmin by 48%, 39% and 47%, respectively (n=29). Monitor patients receiving Truvada concomitantly with Vosevi (sofosbuvir/velpatasvir/voxilaprevir) for adverse reactions associated with TDF.