Higher nelfinavir concentrations improve response in children

David Burger from the University Medical Centre in Nijmegen, Holland, presented data from a pharmacokinetic substudy of the PENTA 5 trial, in which naïve children received nelfinavir plus two nucleosides.

All participating children received NFV 25-30 mg/kg TID or 45-55 mg/kg BID with food. Trough samples were taken between week 20 and 80. NFV troughs <0.8 mg/L were considered subtherapeutic. Viral load <50 copies/mL was measured at week 24 and 48.

Forty-four children were enrolled in this substudy of which data from 32 were evaluable (22 boys, 10 girls). The investigators reported an average trough of 2.1mg/L (n=18; CV: 66%) for children receiving NFV BID and 1.7 mg/L (n=14; CV 90%) for those receiving the drug TID.

Seven (22%) children had a subtherapeutic NFV trough (0.10-0.53 mg/L) and the researchers reported no difference between the children with subtherapeutic and therapeutic concentrations with regard to: gender, baseline HIV-1 RNA, daily NFV dose and dose frequency. Viral load less than 50 copies/mL was reported in 43% and 295 at weeks 24 and 48 respectively.

However of the 25 children with a NFV trough concentration above 0.8mg/mL, 72% and 80% had HIV RNA <50 copies/mL at weeks 24 (p=0.20) and 48 (p=0.02) respectively.

The investigators concluded TDM of NFV appears to have the same relevance in children as in adults and a target of 0.8mg/L improves treatment outcome in children.

Burger D, Bergshoeff A, de Groot R et al. Maintaining the nelfinavir trough concentration above 0.8 mg/L significantly improves virological response in HIV-1-infected children. Abstract 10. Poster 3.3.