Coadministration of methadone (30-130 mg once daily) and sofosbuvir (400 mg once daily) was studied in 14 subjects. When compared to historical controls, sofosbuvir Cmax decreased by 5% and AUC increased by 30%, whereas GS-331007 Cmax decreased by 27% and AUC increased by 4%. No effect on the pharmacokinetic parameters of methadone was observed (R-methadone AUC increased by 1%, Cmax and Cmin decreased by 1% and 4%; S-methadone Cmax, AUC and Cmin all decreased by 5%). Sofosbuvir is a prodrug and formation of its active metabolite is unlikely to be affected by comedications. No dose adjustment of sofosbuvir or methadone is required.