%0 Journal Article
%9 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES
%A Cressey, T. R.
%A Punyawudho, B.
%A Le Coeur, S.
%A Jourdain, Gonzague
%A Saenjum, C.
%A Capparelli, E. V.
%A Jittayanun, K.
%A Phanomcheong, S.
%A Luvira, A.
%A Borkird, T.
%A Puangsombat, A.
%A Aarons, L.
%A Sukrakanchana, P. O.
%A Urien, S.
%A Lallemant, Marc
%A Phpt-5 Study Team
%T Assessment of nevirapine prophylactic and therapeutic dosing regimens for neonates
%D 2017
%L fdi:010070375
%G ENG
%J JAIDS - Journal of Acquired Immune Deficiency Syndromes
%@ 1525-4135
%K nevirapine ; mother-to-child transmission ; Thailand ; pharmacokinetics
%K THAILANDE
%M ISI:000405556900009
%N 5
%P 554-560
%U https://www.documentation.ird.fr/hor/fdi:010070375
%> https://www.documentation.ird.fr/intranet/publi/2017/08/010070375.pdf
%V 75
%W Horizon (IRD)
%X Background: Nevirapine (NVP) is a key component of antiretroviral prophylaxis and treatment for neonates. We evaluated current World Health Organization (WHO) weight-band NVP prophylactic dosing recommendations and investigated optimal therapeutic NVP dosing for neonates. Methods: The PHPT-5 study in Thailand assessed the efficacy of "Perinatal Antiretroviral Intensification" to prevent mother-to-child transmission of HIV in women with <8 weeks of antiretroviral treatment before delivery (NCT01511237). Infants received a 2-week course of zidovudine/lamivudine/NVP (NVP syrup/once daily: 2 mg/kg for 7 days; then 4 mg/kg for 7 days). Infant samples were assessed during the first 2 weeks of life. NVP population pharmacokinetics (PK) parameters were estimated using nonlinear mixed-effects models. Simulations were performed to estimate the probability of achieving target NVP trough concentrations for prophylaxis (>0.10 mg/L) and for therapeutic efficacy (>3.0 mg/L) using different infant dosing strategies. Results: Sixty infants (55% male) were included. At birth, median (range) weight was 2.9 (2.3-3.6) kg. NVP concentrations were best described by a 1-compartment PK model. Infant weight and postnatal age influenced NVP PK parameters. Based on simulations for a 3-kg infant, >= 92% would have an NVP trough >0.1 mg/L after 48 hours through 2 weeks using the PHPT-5 and WHO-dosing regimens. For NVP-based therapy, a 6-mg/kg twice daily dose produced a trough >3.0 mg/L in 87% of infants at 48 hours and 80% at 2 weeks. Conclusion: WHO weight-band prophylactic guidelines achieved target concentrations. Starting NVP 6 mg/kg twice daily from birth is expected to achieve therapeutic concentrations during the first 2 weeks of life.
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