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J Virus Erad. 2015 Jul 1;1(3):185-91.

Plasma pharmacokinetics of once-daily abacavir- and lamivudine-containing regimens and week 96 efficacy in HIV-infected Thai children.

Author information

1
HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT) , Thai Red Cross AIDS Research Centre , Bangkok , Thailand.
2
Department of Pediatrics, Faculty of Medicine , Chulalongkorn University , Bangkok , Thailand.
3
Program for HIV Prevention and Treatment (PHPT/IRD174), Faculty of Associated Medical Sciences, Chiang Mai, Thailand; Harvard School of Public Health, Boston, USA.
4
Radboud Institute for Health Sciences (RIHS) , Nijmegen , the Netherlands.
5
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.
6
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.

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.

CONCLUSION:

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.

KEYWORDS:

HIV-infected children; abacavir; lamivudine; once-daily; pharmacokinetics

PMID:
27482411
PMCID:
PMC4946738

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