Ravidasvir is a NS5A inhibitor that exhibits potent pan-genotypic inhibition of Hepatitis C virus (HCV) replication in vitro. Sofosbuvir plus ravidasvir (SOF/RDV) has shown excellent efficacy and safety in genotype 4 HCV-infected adults in Egypt. SOF/RDV is currently under study in HCV patients (+/- HIV) from South East Asia, where prevalent genotypes are 3, 1 and 6. We assessed the pharmacokinetics (PK) of RDV in this population and the impact of SOF/RDV treatment on the concentrations of commonly prescribed antiretrovirals (ARV) in HIV/HCV co-infected adults.
Data were analyzed within the ongoing phase II/III trial assessing the efficacy, safety, tolerance, and PK of SOF/RDV in HCV (+/- HIV)-infected adults in Thailand and Malaysia (NCT01671982). To determine the PK of RDV in Asian adults, 25 HCV mono-infected patients had intensive steady-state 24-hour blood sampling. RDV PK parameters were calculated using non-compartmental analysis. To assess possible drug-drug interactions in HIV/HCV co-infected patients, mid-dose or trough ARV drug concentrations were measured before (week 0) and after SOF/RDV treatment initiation (Week 4), and compared with Wilcoxon signed-rank tests.
Of the 25 subjects with intensive PK data: 21 were male (84%) and 21 non-cirrhotic (4 cirrhotic). Median age (range) was 49.2 (21.2-64.0) years, weight was 65.5 (46.2-88.3) kg and body mass index 23.3 (18.3-30.9) kg/m2. Median RDV AUC0-24h, Cmax and C24 were 17.3 (3.2-69.9) µg.hr/mL, 2.3 (0.4-6.4) µg/mL and 0.11 (0.03-1.63) µg/mL, respectively. Sixty-five HIV/HCV co-infected subjects were included: median age (range) was 42.9 (23.4-61.5) years and weight 62.0 (45.0-100) kg. Tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), efavirenz (EFV) and nevirapine (NVP) were the most commonly prescribed ARVs in HIV/HCV co-infected patients. A total of 47 subjects had tenofovir (TFV) ARVs concentrations before and after SOF/RDV treatment, 34 had FTC, 51 had EFV and 7 had NVP. Mid-dose tenofovir (TFV) concentrations were significantly higher with concomitant SOF/RDV treatment, while mid-dose FTC, EFV and trough NVP concentrations were not significantly different (Table).
SOF/RDV had no significant impact on FTC, EFV and NVP concentrations. TFV concentrations were slightly higher with SOF/RDV use but the magnitude is likely not clinically significant. The intensive PK data will aid the development of a population PK model to evaluate the impact of ARVs on RDV exposure.