title: Compatibility of next-generation first-line antiretrovirals with rifampicin-based antituberculosis therapy in resource limited settings.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: aDivision 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.
authors.forename: Gary
authors.initials: G
authors.lastname: Maartens
authors.forename: Marta
authors.initials: M
authors.lastname: Boffito
authors.forename: Charles W
authors.initials: CW
authors.lastname: Flexner
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000409:Alanine; D000480:Alkynes; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D048588:Benzoxazines / Q000627:therapeutic use*; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6; D004347:Drug Interactions; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006575:Heterocyclic Compounds, 3-Ring / Q000627:therapeutic use*; D006801:Humans; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D012293:Rifampin / Q000008:administration & dosage* / Q000627:therapeutic use; D000068698:Tenofovir / Q000031:analogs & derivatives; D000099226:Dolutegravir
chemical_list: D000225:Adenine; D000409:Alanine; D000480:Alkynes; D044966:Anti-Retroviral Agents; D000995:Antitubercular Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6; D006575:Heterocyclic Compounds, 3-Ring; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D012293:Rifampin; D000068698:Tenofovir; D000099226:Dolutegravir; C585599:CYP2B6 protein, human; C442442:tenofovir alafenamide; C098320:efavirenz