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Compatibility of next-generation first-line antiretrovirals with rifampicin-based antituberculosis therapy in
Gary Maartens1, Marta Boffito, Charles W Flexner
1aDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, South Africa bSt Stephen's AIDS Trust and Imperial College, Chelsea and Westminster Hospital, London, UK cDivisions of Clinical Pharmacology and Infectious Diseases, Departments of Medicine, Pharmacology and Molecular Sciences, and International Health, Johns Hopkins University, Baltimore, Maryland, USA.
Purpose Of Review:
Reduced dose efavirenz, dolutegravir, and/or tenofovir alafenamide (TAF) are likely to be used in the next generation of first-line antiretroviral therapy in resource limited settings, where HIV-associated tuberculosis is common. Rifampicin, which is a key component of first-line antituberculosis therapy, is a potent inducer of many drug transporters and metabolising enzymes. We reviewed the literature for potential or actual drug--drug interactions between these antiretrovirals and rifampicin.
Recent Findings:
Dose adjustments of standard dose efavirenz are not necessary with rifampicin, because auto-induction of CYP2B6 by efavirenz counteracts the induction of rifampicin. However, patients with extensive metabolizer CYP2B6 genotypes have lower efavirenz concentrations and may have less auto-induction of CYP2B6; the additive inducing effects of rifampicin on CYP2B6 could result in clinically significant reductions of efavirenz concentrations. Doubling the dose of dolutegravir overcomes induction by rifampicin. TAF is more prone to be the victim in drug--drug interactions than tenofovir disoproxil fumarate. Interactions between TAF and rifampicin have not been studied, but there is likely to be significant interaction.
Summary:
Further research on drug--drug interactions between rifampicin and the next generation of first-line antiretrovirals will be needed before they can be recommended in patients with HIV-associated tuberculosis.