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一种评估妊娠期间暴露于复杂抗逆转录病毒药物方案的安全性的分层建模方法。

A hierarchical modeling approach for assessing the safety of exposure to complex antiretroviral drug regimens during pregnancy.

机构信息

Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

出版信息

Stat Methods Med Res. 2019 Feb;28(2):599-612. doi: 10.1177/0962280217732597. Epub 2017 Oct 3.


DOI:10.1177/0962280217732597
PMID:28969502
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5818331/
Abstract

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.

摘要

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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[2]
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[3]
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[4]
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[6]
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[7]
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引用本文的文献

[1]
First-trimester exposure to newer antiretroviral agents and congenital anomalies in a US cohort.

AIDS. 2024-9-1

[2]
Do contemporary antiretrovirals increase the risk of end-stage liver disease? Signals from patients starting therapy in the North American AIDS Cohort Collaboration on Research and Design.

Pharmacoepidemiol Drug Saf. 2022-2

[3]
Association of maternal antiretroviral use with microcephaly in children who are HIV-exposed but uninfected (SMARTT): a prospective cohort study.

Lancet HIV. 2019-11-15

[4]
Approaches for incorporating environmental mixtures as mediators in mediation analysis.

Environ Int. 2018-12-17

[5]
Cardiac status of perinatally HIV-infected children: assessing combination antiretroviral regimens in observational studies.

AIDS. 2018-10-23

[6]
Surveillance monitoring for safety of in utero antiretroviral therapy exposures: current strategies and challenges.

Expert Opin Drug Saf. 2016-11

本文引用的文献

[1]
Timing of initiation of antiretroviral therapy and adverse pregnancy outcomes: a systematic review and meta-analysis.

Lancet HIV. 2016-11-16

[2]
Surveillance monitoring for safety of in utero antiretroviral therapy exposures: current strategies and challenges.

Expert Opin Drug Saf. 2016-11

[3]
Maternal Lopinavir/Ritonavir Is Associated with Fewer Adverse Events in Infants than Nelfinavir or Atazanavir.

Infect Dis Obstet Gynecol. 2016

[4]
Is protease inhibitors based antiretroviral therapy during pregnancy associated with an increased risk of preterm birth? Systematic review and a meta-analysis.

Reprod Health. 2016-4-5

[5]
Atazanavir exposure in utero and neurodevelopment in infants: a comparative safety study.

AIDS. 2016-5-15

[6]
Antiretroviral exposure during pregnancy and adverse outcomes in HIV-exposed uninfected infants and children using a trigger-based design.

AIDS. 2016-1-2

[7]
Fibroblast growth factor 23: associations with antiretroviral therapy in patients co-infected with HIV and hepatitis C.

HIV Med. 2016-5

[8]
Association between in utero zidovudine exposure and nondefect adverse birth outcomes: analysis of prospectively collected data from the Antiretroviral Pregnancy Registry.

BJOG. 2016-5

[9]
Lopinavir and atazanavir in pregnancy: comparable infant outcomes, virological efficacies and preterm delivery rates.

HIV Med. 2016-1

[10]
Pregnancy outcomes following exposure to efavirenz-based antiretroviral therapy in the Republic of Congo.

New Microbiol. 2015-4

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