title: Nevirapine or efavirenz for tuberculosis and HIV coinfected patients: exposure and virological failure relationship.
abstract: OBJECTIVE
  We describe nevirapine and efavirenz exposure on and off tuberculosis treatment and consequences for virological efficacy and tolerance in patients included in the ANRS 12146/12214-CARINEMO trial.
  
  
  METHODS
  Participants were randomly selected to receive either nevirapine at 200 mg twice daily (n = 256) or efavirenz at 600 mg daily (n = 270), both combined with two nucleoside analogues. Blood samples were drawn 12 h after nevirapine or efavirenz administration, while on tuberculosis treatment and after tuberculosis treatment discontinuation. In 62 participants, samples taken 12 h after drug administration were drawn weekly for the first month of ART. Sixteen participants participated in an extensive pharmacokinetic study of nevirapine. Concentrations were compared with the therapeutic ranges of 3000-8000 ng/mL for nevirapine and 1000-4000 ng/mL for efavirenz.
  
  
  RESULTS
  Nevirapine concentrations at the end of the first week of treatment (on antituberculosis drugs) did not differ from concentrations off tuberculosis treatment, but declined thereafter. Concentrations at steady-state were 4111 ng/mL at week 12 versus 6095 ng/mL at week 48 (P < 0.0001). Nevirapine concentrations <3000 ng/mL were found to be a risk factor for virological failure. Efavirenz concentrations were higher on than off tuberculosis treatment (2700 versus 2450 ng/mL, P < 0.0001).
  
  
  CONCLUSIONS
  The omission of the 2 week lead-in dose of nevirapine prevented low concentrations at treatment initiation but did not prevent the risk of virological failure. Results support the WHO recommendation to use efavirenz at 600 mg daily in patients on rifampicin-based antituberculosis therapy.
authors.affiliation: Instituto Nacional de Saúde, Ministry of Health, Maputo, Mozambique Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil nbhatt.mz@gmail.com.
authors.forename: Nilesh B
authors.initials: NB
authors.lastname: Bhatt
authors.affiliation: Epicentre, Paris, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Baudin
authors.affiliation: Instituto Nacional de Saúde, Ministry of Health, Maputo, Mozambique.
authors.forename: Bindiya
authors.initials: B
authors.lastname: Meggi
authors.affiliation: Epicentre, Paris, France.
authors.forename: Carlota
authors.initials: C
authors.lastname: da Silva
authors.affiliation: Assistance Publique Hôpitaux de Paris, Bicêtre Hospital, Hôpitaux Universitaires Paris Sud, Clinical Pharmacy, Paris, France EA4123, Faculty of Pharmacy, University Paris Sud, Paris, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Barrail-Tran
authors.affiliation: Assistance Publique Hôpitaux de Paris, Bicêtre Hospital, Hôpitaux Universitaires Paris Sud, Clinical Pharmacy, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Furlan
authors.affiliation: Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Grinsztejn
authors.affiliation: Epicentre, Paris, France.
authors.forename: Maryline
authors.initials: M
authors.lastname: Bonnet
authors.affiliation: Assistance Publique Hôpitaux de Paris, Bicêtre Hospital, Hôpitaux Universitaires Paris Sud, Clinical Pharmacy, Paris, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Taburet
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D000995:Antitubercular Agents / Q000627:therapeutic use; D048588:Benzoxazines / Q000627:therapeutic use*; D003521:Cyclopropanes; D004361:Drug Tolerance; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000627:therapeutic use*; D016896:Treatment Outcome; D014376:Tuberculosis / Q000150:complications* / Q000188:drug therapy
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D019829:Nevirapine; C098320:efavirenz
keywords: TB/HIV coinfection; drug–drug interactions; efavirenz; nevirapine