Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Stat Methods Med Res. 2019 Feb;28(2):599-612. doi: 10.1177/0962280217732597. Epub 2017 Oct 3.
Combination antiretroviral regimens have achieved tremendous success in reducing perinatal HIV transmission, and have become standard of care in pregnant women with HIV. However, the large variety of combination antiretroviral regimens utilized in practice raises the question of whether some of these highly potent drugs pose other risks to the pregnancy or infant. While HIV-infected pregnant women are almost always exposed to multiple antiretrovirals concurrently, standard safety screening strategies typically consider each individual antiretroviral separately, which fails to account for potential confounding due to simultaneous exposure to other antiretrovirals. In this paper, we evaluate a hierarchical modeling approach which groups antiretrovirals by drug class to screen for the safety of antiretrovirals taken during pregnancy, while still providing individual antiretroviral drug effect estimates. In simulation studies, we observed that the hierarchical approach may be advantageous as compared to considering each antiretroviral drug separately or simultaneously evaluating all antiretrovirals in a fixed effect model, particularly when there is prior evidence suggesting drugs from the same class behave similarly on the outcome. The characteristics of the hierarchical approach are illustrated in an application evaluating risk of preterm birth using a study including over 2000 pregnancies representing over 100 antiretroviral combinations, each involving up to three drug classes.
联合抗逆转录病毒疗法在降低母婴传播方面取得了巨大成功,已成为 HIV 感染孕妇的标准治疗方法。然而,实践中使用的联合抗逆转录病毒疗法种类繁多,这引发了一个问题,即这些高效药物是否会对妊娠或婴儿造成其他风险。虽然感染 HIV 的孕妇通常同时接触多种抗逆转录病毒药物,但标准的安全性筛选策略通常会分别考虑每种单独的抗逆转录病毒药物,而没有考虑到同时接触其他抗逆转录病毒药物可能产生的混杂因素。在本文中,我们评估了一种分层建模方法,该方法按药物类别对抗逆转录病毒药物进行分组,以筛选妊娠期使用的抗逆转录病毒药物的安全性,同时仍提供个体抗逆转录病毒药物效果估计。在模拟研究中,我们观察到与分别考虑每种抗逆转录病毒药物或同时在固定效应模型中评估所有抗逆转录病毒药物相比,分层方法可能具有优势,特别是当有先前的证据表明来自同一类别的药物在结局上表现相似时。该分层方法的特点在一项应用中得到了说明,该应用评估了使用一项包括 2000 多例妊娠的研究评估早产风险,该研究涉及超过 100 种抗逆转录病毒药物组合,每种组合涉及多达三种药物类别。
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