title: Pharmacokinetic interaction between rifampicin and ritonavir-boosted atazanavir in HIV-infected patients.
abstract: BACKGROUND
  Tuberculosis (TB) is a common opportunistic infection among HIV-infected people, and rifampicin is an important drug for the treatment of TB. However, administration of rifampicin in combination with antiretroviral therapy, particularly protease inhibitors, is difficult because of drug-drug interactions.
  
  
  METHODS
  We have performed a prospective study in three HIV-infected patients with TB treated with a rifampicin-containing regimen (rifampicin 600 mg per day) and antiretroviral therapy including only nucleoside reverse transcriptase inhibitors (NRTIs) plus atazanavir 300 mg once a day (qd) and ritonavir 100 mg qd, to evaluate whether the inducing effect of rifampicin on the drug-metabolizing enzyme cytochrome P450 (CYP) 3A4 could be overcome by the inhibitory effect of ritonavir. A complete pharmacokinetic evaluation of the steady-state concentrations of atazanavir and ritonavir was performed.
  
  
  RESULTS
  In all three cases, more than 50% of the time the atazanavir level was below the minimum recommended trough plasma level (150 ng/mL according to current pharmacokinetic guidelines) to inhibit HIV wild-type replication.
  
  
  CONCLUSIONS
  These results strongly indicate that the administration of rifampicin with a combination of atazanavir 300 mg qd plus ritonavir 100 mg qd must be avoided because subtherapeutic concentrations of atazanavir are produced.
authors.affiliation: Infectious Diseases, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain. mallolas@clinic.ub.es
authors.forename: J
authors.initials: J
authors.lastname: Mallolas
authors.forename: M
authors.initials: M
authors.lastname: Sarasa
authors.forename: M
authors.initials: M
authors.lastname: Nomdedeu
authors.forename: A
authors.initials: A
authors.lastname: Soriano
authors.forename: Y
authors.initials: Y
authors.lastname: López-Púa
authors.forename: J L
authors.initials: JL
authors.lastname: Blanco
authors.forename: E
authors.initials: E
authors.lastname: Martínez
authors.forename: J M
authors.initials: JM
authors.lastname: Gatell
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy*; D000328:Adult; D000904:Antibiotics, Antitubercular / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D000069446:Atazanavir Sulfate; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011446:Prospective Studies; D011725:Pyridines / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012293:Rifampin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019438:Ritonavir / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014376:Tuberculosis / Q000188:drug therapy
chemical_list: D000904:Antibiotics, Antitubercular; D065607:Cytochrome P-450 Enzyme Inhibitors; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D019438:Ritonavir; D012293:Rifampin