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Case 2: Antiretrovirals and Tuberculosis Therapy

You answered:

C Rifampin will significantly lower darunavir and ritonavir levels.

This answer is correct. Rifampin is a strong inducer of hepatic cytochrome P-450 isoenzymes, particularly CYP 3A4, and it will significantly lower ritonavir and darunavir levels. Overall, the estimated impact of rifampin is a 75% decrease or more in the area under the curve (AUC) concentration for all protease inhibitors. Thus, coadminstration of rifampin and protease inhibitors is not recommended. In comparison, rifabutin has significantly less impact on the CYP 3A4 enzymes in the liver. Thus, rifabutin is generally preferred over rifampin when combining anti-tuberculosis therapy with antiretroviral therapy. Of note, the protease inhibitors cause a significant increase in rifabutin levels and thus rifabutin dose adjustments are required when used with a protease inhibitor.


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