Pharmacokinetic study of once-daily versus twice-daily abacavir and lamivudine in HIV type-1-infected children aged 3- Paediatric European Network for Treatment of AIDS (PENTA)  1 Collaborators, Affiliations Expand Collaborators Paediatric European Network for Treatment of AIDS (PENTA): Evelyne Jacqz-Aigrain, Linda Harrison, Wei Zhao, Alexandra Compagnucci, Hannah Castro, Laura Farrelly, Yacine Saidi, Djamel Hamadache, Steven Welch, Uwe Wintergerst, Silvia Forcat, Ghenima Hadjou, Ghislaine Firtion, Wendy Snowden, Carlo Giaquinto, Diana Gibb, David Burger, J-P Aboulker, C Brothers, D Burger, A Compagnucci, C Giaquinto, D M Gibb, E Jacqz-Aigrain, W Snowdon, D Burger, H Castro, A Compagnucci, L Farrelly, C Giaquinto, D M Gibb, E Jacqz-Aigrain, H Lyall, C Pharo, M Le Provost, Y Saïdi, W Snowden, W Zhao, E Jacqz-Aigrain, K Adkison, C Brothers, C Pharo, I Song, W Snowden, N Thoofer, J Yeo, D Burger, P Clayden, T R Cressey, E Jacqz-Aigrain, S Khoo, J M Tréluyer, J-P Aboulker, A Babiker, A-B Bohlin, K Butler, G Castelli-Gattinara, P Clayden, A Compagnucci, J Darbyshire, M Debré, A Faye, R de Groot, M della Negra, D Duicelescu, C Giaquinto, D M Gibb, I Grosch-Wörner, C Kind, M Lallemant, J Levy, H Lyall, M Marczynska, M J Mellado Peña, D Nadal, T Niehues, C Peckham, J T Ramos Amador, L Rosado, C Rudin, H Scherpbier, M Sharland, M Stevanovic, P A Tovo, G Tudor-Williams, N Valerius, A S Walker, U Wintergerst Affiliation 1 penta@ctu.mrc.ac.uk PMID: 20516550 PMCID: PMC3827580 DOI: 10.3851/IMP1532 Free PMC article Item in Clipboard

Abstract

Background: Once-daily dosing of abacavir and lamivudine has been approved for adults, but paediatric data are insufficient. We conducted a pharmacokinetic study of once-daily and twice-daily abacavir and lamivudine in children aged 3-<36 months.

Methods: Children with stable HIV type-1 (HIV-1) RNA levels after 12 weeks treatment with twice-daily abacavir (8 mg/kg) with or without lamivudine (4 mg/kg) underwent plasma pharmacokinetic sampling. Children then switched to once-daily abacavir (16 mg/kg) with or without lamivudine (8 mg/kg), and sampling was repeated 4 weeks later. The area under the plasma concentration-time curve over 24 h (AUC(0-24)) and the maximum concentration (C(max)) were compared using geometric mean ratios (GMRs); 90% confidence intervals (CIs) within the range of 0.80-1.25 were considered bioequivalent.

Results: A total of 18 children (4, 6 and 8 in the 3-<12, 12-<24 and 24-<36 month age ranges, respectively) provided pharmacokinetic data for abacavir (17 for lamivudine). The GMR of AUC(0-24), once-daily versus twice-daily, was 1.07 (90% CI 0.92-1.23) for abacavir and 0.91 (90% CI 0.79-1.06) for lamivudine. C(max) almost doubled on once-daily versus twice-daily dosing: abacavir and lamivudine GMRs were 2.04 (90% CI 1.73-2.42) and 1.78 (90% CI 1.52-2.09), respectively. At baseline, 12, 24 and 48 weeks, 89%, 94%, 100% and 89% of children had HIV-1 RNA<400 copies/ml, respectively.

Conclusions: Bioequivalence was demonstrated on AUC(0-24) between twice-daily and once-daily abacavir; very similar AUC(0-24) values were seen for twice-daily and once-daily lamivudine. Given that viral load suppression rates were maintained, these data suggest that once-daily abacavir and lamivudine might be an option for children aged 3-<36 months.

Figures

Figure 1

PENTA 15 participant flow ABC, abacavir; Cmax, maximum plasma concentration; Cmin, minimum plasma concentration; HIV-1, HIV type-1; PK, pharmacokinetic; 3TC, lamivudine; ±, with or without.

Figure 2

Geometric mean plasma concentrations with 95% confidence intervals Geometric means (95% confidence interval) of plasma concentrations of (A) abacavir and (B) lamivudine.