Figure 1.

Mechanisms of ritonavir boosting and cobicistat boosting. (A) Ritonavir inhibits CYP3A in both the liver and gut and demonstrates time-dependent inhibition followed by induction of P-gp in the gut. Ritonavir also inhibits CYP2D6 in the liver while inducing CYP1A2, CYP2C9, CYP2C19, and CYP2B6. (B) Cobicistat boosts TAF plasma exposures by inhibiting efflux transporters (P-gp and BCRP) in gut enterocytes, enhancing oral bioavailability. Cobicistat boosts protease and integrase inhibitors by selectively inhibiting CYP3A metabolism in the liver and intestinal tract and by inhibiting efflux transporters (to a smaller extent). BRCP, breast cancer resistance protein; CYP, cytochrome P450; P-gp, P-glycoprotein; TAF, tenofovir alafenamide.