Critical Review: What Dose of Rifabutin Is Recommended With Antiretroviral Therapy?

Since the advent of combination antiretroviral therapy to successfully treat HIV infection, drug-drug interactions (DDIs) have become a significant problem as many antiretrovirals (ARVs) are metabolized in the liver. Antituberculous therapy traditionally includes rifamycins, particularly rifampicin. Rifabutin (RBT) has shown similar efficacy as rifampicin but induces CYP3A4 to a lesser degree and is less likely to have DDIs with ARVs. We identified 14 DDI pharmacokinetic studies on HIV monoinfected and HIV-tuberculosis coinfected individuals, and the remaining studies were healthy volunteer studies. Although RBT may be coadministered with most nonnucleoside reverse transcriptase inhibitors, identifying the optimal dose with ritonavir-boosted or cobicistat-boosted protease inhibitors is challenging because of concern about adverse effects with increased RBT exposure. Limited healthy volunteer studies on other ARV drug classes and RBT suggest that dose modification may be unnecessary. The paucity of data assessing clinical tuberculosis endpoints concurrently with RBT and ARV pharmacokinetics limits evidence-based recommendations on the optimal dose of RBT within available ARV drug classes.