Ledipasvir is an HCV NS5A inhibitor and is part of a fixed-dose drug combination of sofosbuvir and ledipasvir.37 Similar to sofosbuvir, ledipasvir is not metabolized by the cytochrome P450 system (CYP) of enzymes and is a substrate for P-gp. Ledipasvir is an inhibitor of the drug transporters P-gp and breast cancer resistance protein (BCRP) and may increase intestinal absorption of coadministered substrates for these transporters. The use of P-gp inducers is not recommended with ledipasivir/sofosbuvir. The coadministration of ledipasvir/sofosbuvir and ARV regimens containing TDF is associated with increased exposure to TDF, especially when TDF is taken with an HIV PI boosted with either RTV or cobicistat (COBI) (see Table 12 for recommendations on the concomitant use of selected drugs for treatment of HCV and HIV infection). In some patients, alternative HCV or ARV drugs should be considered to avoid increases in TDF exposures. If the drugs are co-administered, the patient should be monitored for potential TDF-associated renal injury by assessing measurements of renal function (i.e., estimated creatinine clearance, serum phosphorus, urine glucose, and urine protein) before HCV treatment initiation and periodically during treatment.