title: Pharmacokinetics of and short-term virologic response to low-dose 400-milligram once-daily raltegravir maintenance therapy.
abstract: Because studies showed similar viral suppression with lower raltegravir doses and because Asians usually have high antiretroviral concentrations, we explored low-dose raltegravir therapy in Thais. Nineteen adults on raltegravir at 400 mg twice daily (BID) with HIV RNA loads of <50 copies/ml were randomized to receive 400 mg once daily (QD) or 800 mg QD for 2 weeks, followed by the other dosing for 2 weeks. Intensive pharmacokinetic analyses were performed, and HIV RNA was monitored. Two patients were excluded from the 400-mg QD analysis due to inevaluable pharmacokinetic data. The mean patient weight was 58 kg. Mean pharmacokinetic values were as follows: for raltegravir given at 400 mg BID, the area under the concentration-time curve from 0 to 12 h (AUC₀₋₁₂) was 15.6 mg/liter-h and the minimum plasma drug concentration (C(trough)) was 0.22 mg/liter; for raltegravir given at 800 mg QD, the AUC₀₋₂₄ was 33.6 mg/liter-h and the C(trough) was 0.06 mg/liter; and for raltegravir given at 400 mg QD, the AUC₀₋₂₄ was 18.6 mg/liter-h and the C(trough) was 0.08 mg/liter. The HIV RNA load was <50 copies/ml at each dose level. Compared to the adjusted AUC₀₋₂₄ for Westerners on raltegravir at 400 mg BID, Thais on the same dose had double the AUC₀₋₂₄ and those on raltegravir at 400 mg QD had a similar AUC₀₋₂₄. More patients had a C(trough) of <0.021 mg/liter on raltegravir at 400 mg QD (9/17 patients) than on raltegravir at 800 mg QD (1/19 patients) or 400 mg BID (0/19 patients). Seventeen patients used raltegravir at 400 mg QD for a median of 35 weeks; two had confirmed HIV RNA loads between 50 and 200 copies/ml, and both had low C(trough) values. Low-dose raltegravir could be a cost-saving option for maintenance therapy in Asians or persons with low body weight. However, raltegravir at 400 mg QD was associated with a low C(trough) and with a risk for HIV viremia. Raltegravir at 200 or 300 mg BID should be studied, but new raltegravir formulations will be needed.
authors.affiliation: The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), The Thai Red Cross AIDS Research Centre, Bangkok, Thailand. jintanat.a@hivnat.org
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
authors.forename: Meena
authors.initials: M
authors.lastname: Gorowara
authors.forename: Anchalee
authors.initials: A
authors.lastname: Avihingsanon
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kerr
authors.forename: Nadine
authors.initials: N
authors.lastname: van Heesch
authors.forename: Chuleeporn
authors.initials: C
authors.lastname: Khongpetch
authors.forename: Anuntaya
authors.initials: A
authors.lastname: Uanithirat
authors.forename: Andrew
authors.initials: A
authors.lastname: Hill
authors.forename: Kiat
authors.initials: K
authors.lastname: Ruxrungtham
authors.forename: David M
authors.initials: DM
authors.lastname: Burger
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D019540:Area Under Curve; D001835:Body Weight / Q000502:physiology; D015331:Cohort Studies; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D019428:HIV Integrase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D008875:Middle Aged; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D000068898:Raltegravir Potassium; D012044:Regression Analysis; D012984:Software; D013785:Thailand; D019562:Viral Load
chemical_list: D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D012367:RNA, Viral; D000068898:Raltegravir Potassium