Assessment of Nevirapine Prophylactic and Therapeutic Dosing Regimens for Neonates.
Assessment of Nevirapine Prophylactic and Therapeutic Dosing Regimens for Neonates.
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DOI：
10.1097/qai.0000000000001447
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发表时间：
2017-08-15
期刊：
影响因子：
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通讯作者：
PHPT-5 study team
中科院分区：
文献类型：
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作者：
Cressey TR;Punyawudho B;Le Coeur S;Jourdain G;Saenjum C;Capparelli EV;Jittayanun K;Phanomcheong S;Luvira A;Borkird T;Puangsombat A;Aarons L;Sukrakanchana PO;Urien S;Lallemant M;PHPT-5 study team
奈韦拉平（NVP）是新生儿抗逆转录病毒预防和治疗的关键成分。我们评估了目前WHO体重带NVP的预防性剂量建议，并研究了新生儿NVP的最佳治疗剂量。泰国的PHPT-5研究评估了“围产期抗逆转录病毒强化”在分娩前接受抗逆转录病毒治疗<8周的妇女中预防艾滋病毒母婴传播的功效（NCT01511237）。婴儿接受为期2周的齐多夫定/拉米夫定/NVP [NVP糖浆/每日1次：2 mg/kg，连续7天；然后4 mg/kg，连续7天。在出生后的前两周对婴儿样本进行评估。采用非线性混合效应模型估计NVP群体PK参数。通过模拟来估计使用不同的婴儿给药策略达到NVP预防目标谷浓度（>0.10 mg/L）和治疗效果（>3.0 mg/L）的概率。包括60名婴儿（55%为男性）。出生时，中位（范围）体重为2.9 (2.3-3.6)kg。NVP浓度最好用单室PK模型来描述。婴儿体重和出生后年龄影响NVP PK参数。根据对3公斤婴儿的模拟，在使用PHPT-5和who给药方案的48小时至2周后，≥92%的婴儿NVP将达到bb0 0.1 mg/L。对于基于nvp的治疗，6mg /kg每日两次的剂量在87%的婴儿48小时和80%的婴儿2周内产生了3.0 mg/L的峰值。世卫组织体重带预防指南达到了目标浓度。从出生开始，每天两次，起始剂量为6mg /kg，预计在出生后的前两周内达到治疗浓度。
Nevirapine (NVP) is a key component of antiretroviral prophylaxis and treatment for neonates. We evaluated current WHO weight-band NVP prophylactic dosing recommendations and investigated optimal therapeutic NVP dosing for neonates. 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 PK parameters were estimated using non-linear 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. 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 one compartment PK model. Infant weight and post-natal age influenced NVP PK parameters. Based on simulations for a 3-kg infant, ≥92% would have a 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. 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.