title: Reversible reduction of nevirapine plasma concentrations during rifampicin treatment in patients coinfected with HIV-1 and tuberculosis.
abstract: BACKGROUND
  Nevirapine (NVP) plasma levels are reduced in patients receiving rifampicin (RFM) for tuberculosis (TB) treatment. We determined variations over time of the pharmacokinetic parameters of NVP in patients who receive RFM.
  
  
  METHODS
  HIV-1-infected patients with CD4+ T-lymphocyte count <or=100 cells per microliter and TB diagnosis received standard anti-TB therapy and a fixed-dose combination of stavudine, lamivudine, and NVP. Full NVP pharmacokinetic curves were calculated at 4 (T1) and 10 weeks (T2) of combined therapy and at 4 (T3) and 26 weeks after termination of anti-TB therapy.
  
  
  RESULTS
  In 16 enrolled subjects, the median value of the area under the curve of NVP was reduced by 25.6% at T1 compared with NVP alone (43.7 vs. 58.7 microg x mL(-1) x h(-1); P = 0.02). The reduction was only 7.5% at T2 (54.3 vs. 58.7 microg x mL(-1) x h(-1); P = 0.17). The median C trough was reduced of 19.5% at T1 compared with T3 (3.3 vs. 4.2 microg/mL; P = 0.02) and of 7.1% at T2 compared with T3 (3.9 vs. 4.2 microg/mL; P = 0.17). The proportion of subjects with C trough values <or=3 microg/mL was 31.2% (5 of 16), 40.0% (6 of 15), and 7.7% (1 of 13) at T1, T2, and T3, respectively.
  
  
  CONCLUSIONS
  The reduction of the area under the curve of NVP during concomitant RFM treatment substantially decreases over time.
authors.affiliation: Institute of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy. amatteelli@bsnet.it
authors.forename: Alberto
authors.initials: A
authors.lastname: Matteelli
authors.forename: Nuccia
authors.initials: N
authors.lastname: Saleri
authors.forename: Paola
authors.initials: P
authors.lastname: Villani
authors.forename: Victor
authors.initials: V
authors.lastname: Bonkoungou
authors.forename: Anna Cristina C
authors.initials: AC
authors.lastname: Carvalho
authors.forename: Seni
authors.initials: S
authors.lastname: Kouanda
authors.forename: Marie J
authors.initials: MJ
authors.lastname: Sanou
authors.forename: Jacques
authors.initials: J
authors.lastname: Simporé
authors.forename: Laura
authors.initials: L
authors.lastname: Monno
authors.forename: Giampiero
authors.initials: G
authors.lastname: Carosi
authors.forename: Mario
authors.initials: M
authors.lastname: Regazzi
authors.forename: Mathurin
authors.initials: M
authors.lastname: Dembele
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D019259:Lamivudine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011446:Prospective Studies; D012293:Rifampin / Q000008:administration & dosage*; D018119:Stavudine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy*
chemical_list: D019380:Anti-HIV Agents; D000904:Antibiotics, Antitubercular; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine; D012293:Rifampin