Ledipasvir/sofosbuvir has been shown to increase tenofovir exposure, especially when used together with an HIV regimen containing tenofovir disoproxil fumarate and a pharmacokinetic enhancer (ritonavir). The safety of tenofovir disoproxil fumarate in the setting of ledipasvir/sofosbuvir and a pharmacokinetic enhancer has not been established. The potential risks and benefits associated with co-administration of ledipasvir/sofosbuvir with tenofovir disoproxil fumarate given in conjunction with a boosted HIV protease inhibitor (e.g. atazanavir) should be considered, particularly in patients at increased risk of renal dysfunction. Patients receiving ledipasvir/sofosbuvir concomitantly with tenofovir disoproxil fumarate and a boosted HIV protease inhibitor should be monitored for tenofovir-associated adverse reactions. Refer to tenofovir disoproxil fumarate Summary of Product Characteristics for recommendations on renal monitoring. 

Coadministration of ledipasvir/sofosbuvir and regimens containing tenofovir and a HIV protease inhibitor/ritonavir may increase tenofovir concentrations. The safety of increased tenofovir concentrations in the setting of ledipasvir/sofosbuvir and a HIV protease inhibitor/ritonavir has not been established. Consider alternative HCV or antiretroviral therapy to avoid increases in tenofovir exposures. If coadministration is necessary, monitor for tenofovir-associated adverse reactions. Refer to tenofovir-DF prescribing information for recommendations on renal monitoring.