Due to its inductive effect on drug transporters, Rifampin causes a decrease in Cmax and AUC of plasma TAF. Intracellular Tenofovir concentrations were higher than those seen when patients used tenofovir disoproxil fumarate, and as such, further study is recommended before a final determination can be made on the clinical management of possible interactions between Tenofovir Alafenamide and Rifampin.
Tenofovir Alafenamide versus Rifampin
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Study Design
In this study healthy volunteers aged 18-65 years received Tenofovir Alafenamide (TAF)/Emtricitabine (FTC) 25/200mg daily for 28 days with food. After, volunteers were given Tenofovir Alafenamide/Emtricitabine and Rifampin (RIF) 600mg daily for 28 days. Lastly, Tenofovir Disoproxil Fumarate (TDF) 300mg daily was given for 28 days with food. Pharmacokinetic parameters were measured on days 28 for Tenofovir Alafenamide/Emtricitabine, 56 for Tenofovir Alafenamide/Emtricitabine and Rifampin and 84 for Tenofovir Disoproxil Fumarate. Plasma concentrations for Tenofovir Alafenamide, Tenofovir, Emtricitabine, intracellular Tenofovir (TFV) diphosphate and Emtricitabine triphosphate were measured by LC-MS methods.
Study Results
Plasma TAF and TFV geometric mean ratios (GMR, TAF+RIF vs TAF) and 90% confidence intervals (CI) for the main PK parameters were calculated, as well as IC TFV-DP GMR (90%CI). For TAF+RIF vs TAF, the Cmax and AUC GMR (90% CI) for Plasma TAF were 0.55 (0.43-0.71) and 0.53 (0.36-0.79) respectively. Mean TFV-DP AUC was 122,920 on PK2 versus 24,247 h*fmol/million-cells on PK3. Plasma TFV/IC TFV-DP AUC ratio was unchanged by RIF co-administration (0.001). FTC-TP PK parameters were not affected by RIF. All polymorphisms were in Hardy-Weinberg equilibrium and no associations were made after correction for multiple comparisons.
Study Conclusions
Relative to TAF 25mg daily, following administration of TAF + RIF daily, plasma TAF Cmax and AUC were decreased by 45% and 47%, respectively, while intracellular TFV-DP concentrations were decreased by 40%. The authors’ suggested that this was evidence that RIF affected TAF absorption but not clearance. However, IC TFV-DP concentrations were still 82% higher on average than those achieved by standard dose TDF. These data support further study of TAF when co-administered with RIF in patients with HIV and tuberculosis.
References
Cerrone, M, Alfarisi, O, Neary, M. Rifampin effect on tenofovir alafenamide (taf) plasma/intracellular pharmacokinetics. Conference On Retroviruses And Opportunistic Infections. Boston. 2018; March 2018.
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