Impact of lopinavir-ritonavir or nevirapine on bedaquiline exposures and potential implications for patients with tuberculosis-HIV coinfection

Antimicrob Agents Chemother. 2014 Nov;58(11):6406-12. doi: 10.1128/AAC.03246-14. Epub 2014 Aug 11.


Concomitant treatment of tuberculosis (TB) and HIV is recommended and improves outcomes. Bedaquiline is a novel drug for the treatment of multidrug-resistant (MDR) TB; combined use with antiretroviral drugs, nevirapine, or ritonavir-boosted lopinavir (LPV/r) is anticipated, but no clinical data from coinfected patients are available. Plasma concentrations of bedaquiline and its M2 metabolite after single doses were obtained from interaction studies with nevirapine or LPV/r in healthy volunteers. The antiretrovirals' effects on bedaquiline and M2 pharmacokinetics were assessed by nonlinear mixed-effects modeling. Potential dose adjustments were evaluated with simulations. No significant effects of nevirapine on bedaquiline pharmacokinetics were identified. LPV/r decreased bedaquiline and M2 clearances to 35% (relative standard error [RSE], 9.2%) and 58% (RSE, 8.4%), respectively, of those without comedication. As almost 3-fold (bedaquiline) and 2-fold (M2) increases in exposures during chronic treatment with LPV/r are expected, dose adjustments are suggested for evaluation. Efficacious, safe bedaquiline dosing for MDR-TB patients receiving antiretrovirals is important. Modeling results suggest that bedaquiline can be coadministered with nevirapine without dose adjustments. The predicted elevation of bedaquiline and M2 levels during LPV/r coadministration may be a safety concern, and careful monitoring is recommended. Further data are being collected in coinfected patients to determine whether dose adjustments are needed. (These studies have been registered at under registration numbers NCT00828529 [study C110] and NCT00910806 [study C117].).

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use
  • Antitubercular Agents / therapeutic use
  • Coinfection / drug therapy
  • Diarylquinolines* / blood
  • Diarylquinolines* / pharmacokinetics
  • Diarylquinolines* / therapeutic use
  • Drug Combinations
  • Drug Interactions
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / drug effects
  • Humans
  • Lopinavir / therapeutic use*
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / drug effects
  • Nevirapine / therapeutic use*
  • Ritonavir / therapeutic use*
  • Tuberculosis / complications
  • Tuberculosis / drug therapy*
  • Tuberculosis / microbiology
  • Young Adult


  • Anti-HIV Agents
  • Antitubercular Agents
  • Diarylquinolines
  • Drug Combinations
  • lopinavir-ritonavir drug combination
  • Lopinavir
  • bedaquiline
  • Nevirapine
  • Ritonavir

Associated data