Which drug interaction is most likely to reduce protease inhibitor levels?

• A. Rifampin reduces protease inhibitor levels.
• B. Antacids with didanosine reduce absorption of didanosine.
• C. St. John's wort reduces ART levels.
• D. Certain anticonvulsants induce metabolism of ART.

Answer: (A)

Protease inhibitors are broken down by liver enzymes, especially the cytochrome P450 system. When a drug that strongly induces these enzymes is taken with a protease inhibitor, it speeds up the PI’s metabolism, lowering its blood level and risking failure to control the virus.

Rifampin is one of the strongest inducers of CYP3A4 and P-glycoprotein, so coadministration with a protease inhibitor dramatically decreases PI levels. Because of this powerful interaction, rifampin most reliably reduces PI exposure compared with the other options, making it the best answer for this question.

Other options involve effects that aren’t on protease inhibitors themselves or are less potent: antacids with didanosine affect didanosine absorption, not PI levels; St. John’s wort can reduce ART levels but is variable and generally less consistent in lowering PI concentrations; and some anticonvulsants do induce metabolism of ART, but their impact is typically not as strong as rifampin’s induction.