|
|
Abstract
IMPACT OF NELFINAVIR (NFV) AND ITS ACTIVE METABOLITE M8 TROUGH LEVELS (TL) ON VIROLOGIC RESPONSE FROM PRIMARY HIV-1 VERTICALLY INFECTED CHILDREN TREATED WITH STAVUDINE (D4T), DIDANOSINE (DDI) AND NFV IN THE PENTA 7 STUDY
A. Compagnucci1, Y. Saïdi1, A. Faye2, L. Ciria Calavia3, D.M. Gibb4, S. Girard1, M.H. Quernin6, L. Harper4, Giaquinto5, E. Jacqz-Aigrain6, on behalf of the Paediatric European Network for Treatment of AIDS (PENTA) Committees
1INSERM SC10, Villejuif, France, 2Pédiatrie Générale, Hôpital R. Debré, Paris, France, 3Hospital Son Dureta, Palma de Mallorca, Spain, 4MRC CTU, London, UK, 5Universita de Padova, Italy, 6Pharmacologie Pédiatrique et Pharmacogénétique, Hôpital R. Debré, Paris, France
Background: The impact of antiretroviral combination therapy with d4T,ddI and NFV was evaluated in 20 primary HIV-1 vertically infected children aged less than 3 months. Viral load decrease was 2.06 log at week 4 and was sustained up to week 12 but did not continue further. The incomplete viral suppression (HIV-1 RNA < 400 copies) in 70% of the infants even with high doses of NFV (150 mg/kg/day as powder or crushed tablets) and the presence of genotypic resistance mutations represent a great concern. Pharmacological issues may explain virologic response .
Objectives and methods : To investigate the relationship between virologic response at week 48 and early pharmacologic parameters, NFV concentrations and M8 from plasma samples taken through follow-up were analysed. M8/NFV “Metabolic ratio” (MR) was calculated. Samples taken between 0 and 1.5 hours and beyond 10.5 after dosing were considered as TL.
Results: Fourteen infants had 39 (range 1-5) TL up to week 12. At week 4, Mean (SD) NFV, M8 were 392(416), 694(745) in responders and 636(455), 388(432) in non responders. No significant differences in NFV and M8 were found between the two groups. Mean(SD) MR was 1.72(0.09) and 0.62(0.32) in responders and non responders respectively (p=0.005). Similar trend was observed when all TL between week 4 and week 12 were analysed.
Conclusions: In infants treated during HIV-1 primary infection, NFV TL and M8 were highly variable. MR values were different between responders and non responders at week 48. These findings even with a small number of infants reinforce the need to undertake further pharmacokinetic studies in very young children. The role of this metabolic ratio in virologic response needs to be elucidated.
The 2nd IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
1095
Suggested Citation
" A. Compagnucci , et al.
IMPACT OF NELFINAVIR (NFV) AND ITS ACTIVE METABOLITE M8 TROUGH LEVELS (TL) ON VIROLOGIC RESPONSE FROM PRIMARY HIV-1 VERTICALLY INFECTED CHILDREN TREATED WITH STAVUDINE (D4T), DIDANOSINE (DDI) AND NFV IN THE PENTA 7 STUDY.
Poster:
The 2nd IAS Conference on HIV Pathogenesis and Treatment:
Abstract no.
1095"
|
|
|