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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Quantifying the impact of nevirapine-based prophylaxis strategies to prevent mother-to-child transmission of HIV-1: a combined pharmacokinetic, pharmacodynamic, and viral dynamic analysis to predict clinical outcomes.
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Quantifying the impact of nevirapine-based prophylaxis strategies to prevent mother-to-child transmission of HIV-1: a combined pharmacokinetic, pharmacodynamic, and viral dynamic analysis to predict clinical outcomes.

机译：量化基于奈韦拉平的预防策略对预防HIV-1母婴传播的影响：组合的药代动力学，药效学和病毒动力学分析可预测临床结果。

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摘要

Single-dose nevirapine (sd-NVP) and extended NVP prophylaxis are widely used in resource-constrained settings to prevent vertical HIV-1 transmission. We assessed the pharmacokinetics of sd-NVP in 62 HIV-1-positive pregnant Ugandan woman and their newborns who were receiving sd-NVP prophylaxis to prevent mother-to-child HIV-1 transmission. Based on these data, we developed a mathematical model system to quantify the impact of different sd-NVP regimens at delivery and of extended infant NVP prophylaxis (6, 14, 21, 26, 52, 78, and 102 weeks) on the 2-year risk of HIV-1 transmission and development of drug resistance in mothers and their breast-fed infants. Pharmacokinetic parameter estimates and model-predicted HIV-1 transmission rates were very consistent with other studies. Predicted 2-year HIV-1 transmission risks were 35.8% without prophylaxis, 31.6% for newborn sd-NVP, 19.1% for maternal sd-NVP, and 19.7% for maternalewborn sd-NVP. Maternal sd-NVP reduced newborn infection predominately by transplacental exchange, providing protective NVP concentrations to the newborn at delivery, rather than by maternal viral load reduction. Drug resistance was frequently selected in HIV-1-positive mothers after maternal sd-NVP. Extended newborn NVP prophylaxis further decreased HIV-1 transmission risks, but an overall decline in cost-effectiveness for increasing durations of newborn prophylaxis was indicated. The total number of infections with resistant virus in newborns was not increased by extended newborn NVP prophylaxis. The developed mathematical modeling framework successfully predicted the risk of HIV-1 transmission and resistance development and can be adapted to other drugs/drug combinations to a priori assess their potential in reducing vertical HIV-1 transmission and resistance spread.
机译：单剂量奈韦拉平（sd-NVP）和延长的NVP预防措施广泛用于资源紧张的环境，以防止HIV-1垂直传播。我们评估了62例HIV-1阳性孕妇乌干达妇女及其新生儿中sd-NVP的药代动力学，这些孕妇正在接受sd-NVP预防以防止母婴HIV-1传播。根据这些数据，我们开发了一个数学模型系统来量化不同的sd-NVP方案在分娩时和延长的婴儿NVP预防（6、14、21、26、52、78和102周）对2-母亲及其母乳喂养的婴儿一年中HIV-1传播和耐药性发展的风险。药代动力学参数估计值和模型预测的HIV-1传播率与其他研究非常一致。预测的2年HIV-1传播风险为35.8％，无预防措施，新生儿sd-NVP为31.6％，母亲sd-NVP为19.1％，母亲/新生儿sd-NVP为19.7％。孕妇的sd-NVP主要通过胎盘交换减少新生儿感染，从而在分娩时为新生儿提供保护性的NVP浓度，而不是通过减少孕妇的病毒载量。在母亲sd-NVP后，HIV-1阳性母亲经常选择耐药性。扩大新生儿NVP预防可进一步降低HIV-1传播风险，但表明随着新生儿预防时间的延长，成本效益总体下降。延长新生儿NVP预防措施不会增加新生儿感染抗病毒的总数。发达的数学模型框架成功地预测了HIV-1传播和耐药性发展的风险，并且可以适用于其他药物/药物组合，以事前评估其减少垂直HIV-1传播和耐药性传播的潜力。

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