Setting an appropriately high enough bar when evaluating the safety of antiretroviral drugs for use in pregnancy.
Setting an appropriately high enough bar when evaluating the safety of antiretroviral drugs for use in pregnancy.
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在评估妊娠期使用的抗逆转录病毒药物的安全性时，设定足够高的标准。
DOI：
10.1007/s15010-020-01396-6
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发表时间：
2020
期刊：
影响因子：
7.5
通讯作者：
Slogrove,AmyL
中科院分区：
文献类型：
--
作者：
Powis,KathleenM;Slogrove,AmyL
我们饶有兴趣地阅读了Floridia及其同事于2020年1月1日在线发表的题为“暴露于整合酶抑制剂，蛋白酶抑制剂和非核苷逆转录酶抑制剂的HIV-1女性的妊娠和新生儿结局：一项观察性研究”的原始论文。作者比较了感染艾滋病毒的妇女在怀孕期间使用三联抗逆转录病毒疗法的各种孕产妇和分娩结局。由于所有治疗方案均包含两种核苷类逆转录酶抑制剂，因此对治疗方案中的第三类抗逆转录病毒药物（整合酶链转移抑制剂（INSTI）、蛋白酶抑制剂（PI）和非核苷类逆转录酶抑制剂（NNRTI））进行了比较。Floridia及其同事报告的分析的一个关键优势是，80%的妊娠结局评估涉及前瞻性入组的女性，最大限度地减少了选择偏倚的机会。作者报告称，在妊娠和关注的结局中使用三类药物（INSTI、NNRTI和PI）之间没有任何重大差异。显然，这对接受孕前咨询或初次产前检查的艾滋病毒感染妇女来说是非常令人放心的，因为有效的抗逆转录病毒治疗对预防孕产妇艾滋病毒疾病进展和婴儿艾滋病毒感染至关重要。在引用研究局限性时，作者正确地指出了样本量小，特别是在怀孕期间接受INSTI的妇女群体中。重要的是，在调整后的低出生体重决定因素分析中，使用NNRTI和PI的点估计值表明，与使用NRTI相比，低出生体重的风险更高。然而，小样本量导致不精确性，如宽置信区间所示。与其得出三种药物类别与低出生体重结局之间无差异的结论，不如报告证据不足，以得出ARV类别与LBW之间是否存在差异的结论。在过去十年中，联合国艾滋病规划署的估计表明，感染艾滋病毒的怀孕妇女人数没有下降，估计每年有130万人[1]。越来越多的妇女在怀孕期间接受抗逆转录病毒治疗（ART），估计2018年全球不到60%。虽然这无疑有助于将婴儿感染艾滋病毒的人数减少60%以上，从2000年的45万多人减少到2018年的估计16万人，但妊娠期使用抗逆转录病毒药物的安全性尚未得到系统和严格的研究。2018年，博茨瓦纳的一份报告指出，在怀孕前开始使用基于整合酶链转移酶的治疗方案与神经管缺陷之间可能存在关联[2]，因此重点关注了妊娠期抗逆转录病毒药物的安全性监测。在此背景下，与未感染艾滋病毒的妇女所生婴儿相比，有许多报告称，子宫内暴露于艾滋病毒和抗逆转录病毒药物的婴儿的出生结局不良，感染性发病率和死亡率较高，生长较差，发育迟缓[3-5]。比较抗逆转录病毒治疗方案的安全性是非常重要的，
We read with interest the original paper entitled “Pregnancy and neonatal outcomes in women with HIV-1 exposed to integrase inhibitors, protease inhibitors and non-nucleoside reverse transcriptase inhibitors: an observational study”, published by Floridia and colleagues online on 1-Jan-2020. The authors compared a wide variety of maternal and birth outcomes based upon use of triple antiretroviral regimens in pregnancy among women living with HIV. Since all regimens contained a backbone of two nucleoside reverse transcriptase inhibitors, comparison was made between the third antiretroviral drug class in the regimen, integrase strand transfer inhibitors (INSTIs) versus protease inhibitors (PIs) versus non-nucleoside reverse transcriptase inhibitors (NNRTIs). A key strength of the analyses reported by Floridia and colleagues is the fact that 80% of the pregnancy outcomes evaluated involved women prospectively enrolled, minimizing the chance of selection bias. The authors reported the absence of any major differences between the use of the three drug classes, INSTIs, NNRTIs, and PIs in pregnancy and outcomes of interest. Clearly, this can be very reassuring to women living with HIV undergoing preconception counseling or during an initial antenatal visit, as efficacious antiretroviral regimens are essential to preventing both maternal HIV disease progression and infant HIV acquisition. In citing study limitations, the authors correctly note the small sample sizes, particularly with respect to the group of women receiving INSTIs in pregnancy. Importantly, in the adjusted analysis of determinants of low birth weight, the point estimates for NNRTI and PI use indicate a higher risk of low birth weight compared with INSTI use. Yet the small sample size contributes to imprecision, as noted in the wide confidence intervals. Rather than a conclusion of no difference between the three drug classes and the outcome of low birth weight, it would be more appropriate to report insufficient evidence to conclude whether there is a difference or not by ARV class in association with LBW. In the last decade, UNAIDS estimates indicate that there has been no decline in the number of women living with HIV who experience pregnancy, an estimated 1.3 million annually [1]. Increasingly, a larger proportion of these women are accessing antiretroviral treatment (ART) in pregnancy, estimated at just under 60% globally in 2018 [1]. While this has unquestionably contributed to the greater than 60% reduction in infant acquisition of HIV, from over 450,000 in 2000 to an estimated 160,000 in 2018, the safety of antiretroviral use in pregnancy has not been systematically and rigorously studied. In 2018, with a report from Botswana of a possible association between use of integrase strand transfer inhibitor-based treatment regimens initiated prior to conception and neural tube defects [2], a spotlight was placed on safety monitoring of antiretroviral use in pregnancy. Against this backdrop, there have been numerous reports of adverse birth outcomes, higher rates of infectious morbidity and mortality, poorer growth and development delays among infants exposed in utero to both HIV and antiretroviral drugs compared with infants born to women without HIV [3–5]. It is incredibly important to compare the safety of antiretroviral treatment regimens used