A 30-year-old HIV-positive woman with tuberculosis is on lopinavir-ritonavir-based antiretroviral therapy. Which rifamycin should be chosen to treat her TB, and why?

• A Rifampicin, because it gives the highest bactericidal activity
• B Rifabutin, because it is a weaker inducer of cytochrome CYP3A4 ✓
• C Rifapentine, because weekly dosing suits directly observed therapy
• D Rifampicin plus boosted ritonavir dose escalation

Explanation

All rifamycins induce hepatic cytochrome enzymes through pregnane X receptor activation, but rifabutin is a substantially weaker inducer and is also metabolised by CYP3A4. This permits continued use of protease inhibitors such as lopinavir-ritonavir without unacceptable loss of antiretroviral levels. Rifampicin reduces protease inhibitor concentrations drastically and cannot be co-administered. Rifapentine interacts even more strongly with ritonavir boosting.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.

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