title: Efavirenz, tenofovir and emtricitabine combined with first-line tuberculosis treatment in tuberculosis-HIV-coinfected Tanzanian patients: a pharmacokinetic and safety study.
abstract: BACKGROUND
  To evaluate the effect of rifampicin-based tuberculosis (TB) treatment on the pharmacokinetics of efavirenz/tenofovir/emtricitabine in a fixed-dose combination tablet, and vice versa, in Tanzanian TB-HIV-coinfected patients.
  
  
  METHODS
  This was a Phase II open-label multiple dose pharmacokinetic and safety study. This study was conducted in TB-HIV-coinfected Tanzanian patients who started TB treatment (rifampicin/isoniazid/pyrazinamide/ethambutol) at week 1 to week 8 and continued with rifampicin and isoniazid for another 16 weeks. Antiretroviral treatment (ART) of efavirenz/tenofovir/emtricitabine in a fixed-dose combination tablet was started at week 4 after initiation of TB treatment. A 24-h pharmacokinetic sampling curve was recorded at week 8 (with TB treatment) and week 28 (ART alone). For TB drugs, blood samples at 2 and 5 h post-dose were taken at week 3 (TB treatment alone) and week 8 (with ART).
  
  
  RESULTS
  A total of 25 patients (56% male) completed the study; 21 had evaluable pharmacokinetic profiles. The area under the concentration-time curve 0-24 h post-dose of efavirenz, tenofovir and emtricitabine were slightly higher when these drugs were coadministered with TB drugs; geometric mean ratios (90% CI) were 1.08 (0.90, 1.30), 1.13 (0.93, 1.38) and 1.05 (0.85, 1.29), respectively. For TB drugs, equivalence was suggested for peak plasma concentrations when administered with and without efavirenz/tenofovir/emtricitabine. Adverse events were mostly mild and no serious adverse events or drug discontinuations were reported.
  
  
  CONCLUSIONS
  Coadministration of efavirenz, tenofovir and emtricitabine with a standard first-line TB treatment regimen did not significantly alter the pharmacokinetic parameters of these drugs and was tolerated well by Tanzanian TB patients who are coinfected with HIV.
authors.affiliation: Kilimanjaro Clinical Research Institute, Kilimanjaro Christian Medical Centre, Moshi, Kilimanjaro, Tanzania. hadija.semvua@gmail.com
authors.forename: Hadija H
authors.initials: HH
authors.lastname: Semvua
authors.forename: Charles M
authors.initials: CM
authors.lastname: Mtabho
authors.forename: Quirine
authors.initials: Q
authors.lastname: Fillekes
authors.forename: Jossy
authors.initials: J
authors.lastname: van den Boogaard
authors.forename: Riziki M
authors.initials: RM
authors.lastname: Kisonga
authors.forename: Liberate
authors.initials: L
authors.lastname: Mleoh
authors.forename: Arnold
authors.initials: A
authors.lastname: Ndaro
authors.forename: Elton R
authors.initials: ER
authors.lastname: Kisanga
authors.forename: Andre
authors.initials: A
authors.lastname: van der Ven
authors.forename: Rob E
authors.initials: RE
authors.lastname: Aarnoutse
authors.forename: Gibson S
authors.initials: GS
authors.lastname: Kibiki
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Boeree
authors.forename: David M
authors.initials: DM
authors.lastname: Burger
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D048588:Benzoxazines; D003521:Cyclopropanes; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D000068257:Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; D004977:Ethambutol / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000821:virology; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D010078:Oxazines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D011718:Pyrazinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D012293:Rifampin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000188:drug therapy
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D004338:Drug Combinations; D000068257:Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; D063065:Organophosphonates; D010078:Oxazines; D018894:Reverse Transcriptase Inhibitors; C087181:isoniazid, pyrazinamide, rifampin drug combination; D003841:Deoxycytidine; D011718:Pyrazinamide; D004977:Ethambutol; D000225:Adenine; C098320:efavirenz; D007538:Isoniazid; D012293:Rifampin