Darunavir/Ritonavir with Rifampicin may be hepatotoxic

Ebrahim I., Maartens G., Wiesner L., Orrell C., Smythe W., and McIlleron H

Darunavir/ritonavir administered with rifampicin causes hepatotoxicities in people living with HIV, according to results of a study led by researchers at the department of medicine, the Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa) and the Desmond Tutu HIV Centre at the University of Cape Town. Darunavir/ritonavir-based antiretroviral therapy (ART) is better tolerated and has a higher genetic barrier to resistance compared with second-line lopinavir/ritonavir-based ART for treatment of HIV.

Darunavir, the preferred boosted protease inhibitor in high-income countries, is contraindicated when darunavir/ritonavir is co-administered with rifampicin (a key first-line tuberculosis [TB] treatment), due to its induction of cytochrome P450 (CYP) 3A4, because it causes significant reductions in darunavir metabolism. As a result, rifabutin replaces rifampicin in high-income countries because it is a weaker CYP3A4 inducer that does not reduce PI concentrations; however, rifabutin is not available in most low- to middle-income countries where TB is endemic.

June 17, 2020
Year of publication
Resource types
Journal and research articles
antiretroviral therapy (ART), rifampicin, TB

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