title: Plasma pharmacokinetics of once-daily abacavir- and lamivudine-containing regimens and week 96 efficacy in HIV-infected Thai children.
abstract: BACKGROUND
  Abacavir and lamivudine are approved for once-daily use in HIV-infected adults. Limited pharmacokinetic (PK) data for abacavir and lamivudine in children are available.
  
  
  METHODS
  A crossover study to compare PK of once- versus twice-daily abacavir and lamivudine was conducted in virologically suppressed HIV-infected Thai children aged <18years, with bodyweight of at least 14 kg, HIV RNA <50 copies/mL and HLA-B*5701 negative. Abacavir and lamivudine daily doses by bodyweight were 300 and 150 mg for 14-<20 kg, 450 and 300 mg for 20-<25 kg, and 600 and 300 mg for ≥25 kg, respectively. Originator abacavir and lamivudine scored tablets were administered. Intensive PK sampling was performed after 14 days of each dose. PK parameters were determined using non-compartmental analysis.
  
  
  RESULTS
  Thirty children (57% male) were enrolled, 10 per weight band. Median (IQR) age was 8.8 (6.6-11.3) years and bodyweight was 21.9 (19.2-30.6) kg. The geometric means (GM) AUC0-24 of once- and twice-daily abacavir were 14.43 and 10.65 mg.h/L, respectively. The geometric mean ratio (GMR) of AUC0-24 for once- versus twice-daily abacavir dosing was 1.36 [90% confidence interval (CI) 1.11-1.66]. The GM AUC0-24 of once- and twice-daily lamivudine were 17.70 and 18.11 mg.h/L, respectively. The GMR of AUC0-24 for once- versus twice-daily lamivudine dosing was 0.98 (90% CI 0.84-1.14). At 96 weeks, 90% had HIV RNA <50 copies/mL and there were no serious adverse events.
  
  
  CONCLUSIONS
  Abacavir exposure was greater with once-daily dosing, while lamivudine once- and twice-daily exposures were bioequivalent. Once-daily abacavir and lamivudine using weight-band dosing is a treatment option for children.
authors.affiliation: HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT) , Thai Red Cross AIDS Research Centre , Bangkok , Thailand.
authors.forename: Torsak
authors.initials: T
authors.lastname: Bunupuradah
authors.affiliation: Department of Pediatrics, Faculty of Medicine , Chulalongkorn University , Bangkok , Thailand.
authors.forename: Passorn
authors.initials: P
authors.lastname: Punyahotra
authors.affiliation: Program for HIV Prevention and Treatment (PHPT/IRD174), Faculty of Associated Medical Sciences, Chiang Mai, Thailand; Harvard School of Public Health, Boston, USA.
authors.forename: Tim R
authors.initials: TR
authors.lastname: Cressey
authors.affiliation: HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT) , Thai Red Cross AIDS Research Centre , Bangkok , Thailand.
authors.forename: Amornrat
authors.initials: A
authors.lastname: Srimuan
authors.affiliation: HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT) , Thai Red Cross AIDS Research Centre , Bangkok , Thailand.
authors.forename: Narukjaporn
authors.initials: N
authors.lastname: Thammajaruk
authors.affiliation: HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT) , Thai Red Cross AIDS Research Centre , Bangkok , Thailand.
authors.forename: Jiratchaya
authors.initials: J
authors.lastname: Sophonphan
authors.affiliation: HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT) , Thai Red Cross AIDS Research Centre , Bangkok , Thailand.
authors.forename: Chulalak
authors.initials: C
authors.lastname: Sriheara
authors.affiliation: Radboud Institute for Health Sciences (RIHS) , Nijmegen , the Netherlands.
authors.forename: David M
authors.initials: DM
authors.lastname: Burger
authors.affiliation: HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Thai Red Cross AIDS Research Centre, Bangkok, Thailand; Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Thanyawee
authors.initials: T
authors.lastname: Puthanakit
authors.affiliation: HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Thai Red Cross AIDS Research Centre, Bangkok, Thailand; SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand; US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD; Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
keywords: HIV-infected children; abacavir; lamivudine; once-daily; pharmacokinetics