Name a common protease inhibitor-based antiretroviral regimen and mention a key interaction with rifampin.

• A. Efavirenz; rifampin increases its levels
• B. Zidovudine; rifampin reduces its absorption
• C. Atazanavir; rifampin has no interaction
• D. Lopinavir/ritonavir; rifampin lowers lopinavir/ritonavir levels; rifabutin may be substituted; monitor

Answer: (D)

Rifampin is a powerful inducer of drug-metabolizing enzymes, especially CYP3A4, and it also affects drug transporters. When a protease inhibitor–based regimen is boosted with ritonavir, that boosting relies on ritonavir’s ability to inhibit metabolism and keep PI levels high. Rifampin’s induction overrides this effect, drastically lowering lopinavir/ritonavir (a common boosted PI combination) levels and risking virologic failure. Because of this, the typical approach is to substitute rifampin with rifabutin (a less potent inducer) and monitor the patient closely for response and toxicity, or adjust the ART regimen accordingly. This is why the statement that rifampin lowers lopinavir/ritonavir levels and that rifabutin may be substituted with monitoring best captures the key interaction.

Other options misstate the interactions: rifampin does not reliably raise efavirenz levels; zidovudine’s absorption is not a major concern with rifampin in the way described; and rifampin does have a significant interaction with atazanavir, so “no interaction” is incorrect.