Kakkar Fatima, Boucoiran Isabelle, Lamarre Valerie, Ducruet Thierry, Amre Devendra, Soudeyns Hugo, Lapointe Normand, Boucher Marc
Division of Infectious Diseases, CHU Sainte-Justine, Montréal, Canada;
Department of Pediatrics, Faculty of Medicine, Université de Montréal, Montreal, Canada.
J Int AIDS Soc. 2015 Jun 5;18(1):19933. doi: 10.7448/IAS.18.1.19933. eCollection 2015.
The risk of pre-term birth (PTB) associated with the use of protease inhibitors (PIs) during pregnancy remains a subject of debate. Recent data suggest that ritonavir boosting of PIs may play a specific role in the initiation of PTB, through an effect on the maternal-fetal adrenal axis. The primary objective of this study is to compare the risk of PTB among women treated with boosted PI versus non-boosted PIs during pregnancy.
Between 1988 and 2011, 705 HIV-positive women were enrolled into the Centre Maternel et Infantile sur le SIDA mother-infant cohort at Centre Hospitalier Universitaire Sainte-Justine in Montreal, Canada. Inclusion criteria for the study were: 1) attendance at a minimum of two antenatal obstetric visits and 2) singleton live birth, at 24 weeks gestational or older. The association between PTB (defined as delivery at <37 weeks gestational age), antiretroviral drug exposure and maternal risk factors was assessed retrospectively using logistic regression.
A total of 525 mother-infant pairs were included in the analysis. Among them, PI-based combination anti-retroviral therapy was used in 37.4%, boosted PI based in 24.4%, non-nucleoside reverse transcriptase inhibitor (NNRTI) or nucleoside reverse transcriptase inhibitor based in 28.1%, and no treatment was given in 10.0% of cases. Overall, 13.5% of women experienced PTB. Among women treated with antiretroviral therapy, the risk of PTB was significantly higher among women who received boosted versus non-boosted PI (OR 2.01, 95% CI 1.02-3.97). This remained significant after adjusting for maternal age, delivery CD4 count, hepatitis C co-infection, history of previous PTB, and parity (aOR 2.17, 95% CI 1.05-4.51). There was no increased risk of PTB with the use of unboosted PIs as compared to NNRTI- or NRTI-based regimens.
While previous studies on the association between PTB and PI use have generally considered all PIs the same, our results would indicate a possible role of ritonavir boosting as a risk factor for PTB. Further work is needed to understand the pathophysiologic mechanisms involved, and to identify the safest ARV regimens to be used in pregnancy.
孕期使用蛋白酶抑制剂（PI）与早产（PTB）风险仍是一个存在争议的话题。近期数据表明，利托那韦增强的PI可能通过对母胎肾上腺轴的影响在早产起始中发挥特定作用。本研究的主要目的是比较孕期接受增强PI治疗的女性与未接受增强PI治疗的女性的早产风险。
1988年至2011年间，705名HIV阳性女性被纳入加拿大蒙特利尔圣贾斯汀大学中心医院的母婴艾滋病母婴队列研究。该研究的纳入标准为：1）至少进行两次产前产科检查；2）单胎活产，孕周24周或以上。使用逻辑回归回顾性评估早产（定义为孕周<37周分娩）、抗逆转录病毒药物暴露与母亲风险因素之间的关联。
共有525对母婴纳入分析。其中，37.4%使用基于PI的联合抗逆转录病毒疗法，24.4%使用增强PI，28.1%使用非核苷类逆转录酶抑制剂（NNRTI）或核苷类逆转录酶抑制剂，10.0%的病例未接受治疗。总体而言，13.5%的女性发生早产。在接受抗逆转录病毒治疗的女性中，接受增强PI治疗的女性早产风险显著高于未接受增强PI治疗的女性（比值比2.01，95%置信区间1.02 - 3.97）。在调整母亲年龄、分娩时CD4细胞计数、丙型肝炎合并感染、既往早产史和产次后，这一差异仍具有统计学意义（校正后比值比2.17，95%置信区间1.05 - 4.51）。与基于NNRTI或NRTI的治疗方案相比，使用未增强PI并未增加早产风险。
虽然先前关于早产与PI使用之间关联的研究通常将所有PI视为相同，但我们的结果表明利托那韦增强可能是早产的一个风险因素。需要进一步开展工作以了解其中涉及的病理生理机制，并确定孕期使用的最安全抗逆转录病毒治疗方案。
