title: Pharmacokinetics and 48-week efficacy of nevirapine: 400 mg versus 600 mg per day in HIV-tuberculosis coinfection receiving rifampicin.
abstract: BACKGROUND
  We aim here to determine the appropriate dose of nevirapine (NVP) in Thai HIV-tuberculosis (TB)-coinfected patients receiving rifampicin.
  
  
  METHODS
  Thirty-two HIV-infected adults with CD4+ T-cell counts <200 cells/mm3 and active TB, receiving rifampicin for 2-6 weeks were randomized to receive either NVP 400 mg (NVP400) or 600 mg (NVP600) per day plus two nucleoside reverse transcriptase inhibitors; a 2-week NVP lead-in was performed at 200 mg once daily (OD) and 200 mg twice daily, respectively. Plasma NVP levels were determined at weeks 2, 4 and 12. Twelve-hour pharmacokinetics (PK) were obtained (n=20) at week 4.
  
  
  RESULTS
  Baseline body weight was comparable. There were more patients with NVP plasma concentration at 12 h (C12) <3.1 mg/l at week 2 in NVP400 than in NVP600 (79% versus 19%, respectively; P=0.002). However, the proportions were comparable at weeks 4 and 12. From week 4, 12 h PK studies showed that NVP400 had lower median NVP area under the plasma concentration-0-12 h (AUC0-12 h, maximum concentration in plasma (Cmax) and C12 than NVP600 (P<0.05). Four patients in NVP600 developed NVP hypersensitivity. At week 48, the median CD4+ T-cell count rise and proportion with viral load <50 copies/ml (intention-to-treat analysis 56% versus 50% and as-treated analysis 75% versus 89%) were comparable.
  
  
  CONCLUSIONS
  In rifampicin-treated patients, 200 mg NVP OD lead-in led to a significant short-term suboptimal NVP C12 level, while NVP 400 mg lead-in then 600 mg/day was associated with a high rate of NVP hypersensitivity. Forty-eight week efficacy was comparable. Thus, NVP 600 mg/day in rifampicin-treated patients is not recommended.
authors.affiliation: HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Anchalee
authors.initials: A
authors.lastname: Avihingsanon
authors.forename: Weerawat
authors.initials: W
authors.lastname: Manosuthi
authors.forename: Pacharee
authors.initials: P
authors.lastname: Kantipong
authors.forename: Charoen
authors.initials: C
authors.lastname: Chuchotaworn
authors.forename: Saiyud
authors.initials: S
authors.lastname: Moolphate
authors.forename: Waraporn
authors.initials: W
authors.lastname: Sakornjun
authors.forename: Meena
authors.initials: M
authors.lastname: Gorowara
authors.forename: Norio
authors.initials: N
authors.lastname: Yamada
authors.forename: Hideki
authors.initials: H
authors.lastname: Yanai
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mitarai
authors.forename: Nobukatsu
authors.initials: N
authors.lastname: Ishikawa
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.forename: Praphan
authors.initials: P
authors.lastname: Phanuphak
authors.forename: David
authors.initials: D
authors.lastname: Burger
authors.forename: Kiat
authors.initials: K
authors.lastname: Ruxrungtham
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D006801:Humans; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D012293:Rifampin / Q000008:administration & dosage / Q000627:therapeutic use; D013785:Thailand; D016896:Treatment Outcome; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy
chemical_list: D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; D012293:Rifampin