Snijdewind Ingrid J M, Smit Colette, Godfried Mieke H, Bakker Rachel, Nellen Jeannine F J B, Jaddoe Vincent W V, van Leeuwen Elisabeth, Reiss Peter, Steegers Eric A P, van der Ende Marchina E
Department of Internal Medicine, Section Infectious Diseases, Erasmus Medical Center, Rotterdam, The Netherlands.
Stichting HIV Monitoring (SHM), Amsterdam, The Netherlands.
PLoS One. 2018 Jan 19;13(1):e0191389. doi: 10.1371/journal.pone.0191389. eCollection 2018.
The benefits of combination anti-retroviral therapy (cART) in HIV-positive pregnant women (improved maternal health and prevention of mother to child transmission [pMTCT]) currently outweigh the adverse effects due to cART. As the variety of cART increases, however, the question arises as to which type of cART is safest for pregnant women and women of childbearing age. We studied the effect of timing and exposure to different classes of cART on adverse birth outcomes in a large HIV cohort in the Netherlands.
We included singleton HEU infants registered in the ATHENA cohort from 1997 to 2015. Multivariate logistic regression analysis for single and multiple pregnancies was used to evaluate predictors of small for gestational age (SGA, birth weight <10th percentile for gestational age), low birth weight and preterm delivery.
A total of 1392 children born to 1022 mothers were included. Of these, 331 (23.8%) children were SGA. Women starting cART before conception had an increased risk of having a SGA infant compared to women starting cART after conception (OR 1.35, 95% CI 1.03-1.77, p = 0.03). The risk for SGA was highest in women who started a protease inhibitor-(PI) based regimen prior to pregnancy, compared with women who initiated PI-based cART during pregnancy. While the association of preterm delivery and preconception cART was significant in univariate analysis, on multivariate analysis only a non-significant trend was observed (OR 1.39, 95% CI 0.94-1.92, p = 0.06) in women who had started cART before compared to after conception. In multivariate analysis, the risk of low birth weight (OR 1.34, 95% CI 0.94-1.92, p = 0.11) was not significantly increased in women who had started cART prior to conception compared to after conception.
In our cohort of pregnant HIV-positive women, the use of cART prior to conception, most notably a PI-based regimen, was associated with intrauterine growth restriction resulting in SGA. Data showed a non-significant trend in the risk of PTD associated with preconception use of cART compared to its use after conception. More studies are needed with regard to the mechanisms taking place in the placenta during fetal growth in pregnant HIV-positive women using cART. It will only be with this knowledge that we can begin to understand the potential impact of HIV and cART on the fetus, in order to be able to determine the optimal individualised drug regimen for HIV-infected women of childbearing age.
目前，联合抗逆转录病毒疗法（cART）对HIV阳性孕妇的益处（改善孕产妇健康状况及预防母婴传播[pMTCT]）超过了cART带来的不良反应。然而，随着cART种类的增加，对于孕妇和育龄妇女而言，哪种类型的cART最为安全这一问题随之而来。我们在荷兰的一个大型HIV队列中研究了不同类型cART的使用时机和暴露情况对不良出生结局的影响。
我们纳入了1997年至2015年在ATHENA队列中登记的单胎HIV暴露儿童。采用单胎和多胎妊娠的多变量逻辑回归分析来评估小于胎龄儿（SGA，出生体重低于胎龄的第10百分位数）、低出生体重和早产的预测因素。
共纳入了1022名母亲所生的1392名儿童。其中，331名（23.8%）儿童为小于胎龄儿。与受孕后开始cART的女性相比，受孕前开始cART的女性生出小于胎龄儿的风险增加（比值比[OR]为1.35，95%置信区间[CI]为1.03 - 1.77，p = 0.03）。与孕期开始基于蛋白酶抑制剂（PI）的cART的女性相比，孕前开始基于PI方案的女性生出小于胎龄儿的风险最高。虽然在单变量分析中，早产与受孕前cART的关联显著，但在多变量分析中，仅观察到受孕前开始cART的女性有不显著的趋势（OR为1.39，95% CI为0.94 - 1.92，p = 0.06）。在多变量分析中，与受孕后开始cART的女性相比，受孕前开始cART的女性低出生体重风险（OR为1.34，95% CI为0.94 - 1.92，p = 0.11）未显著增加。
在我们的HIV阳性孕妇队列中，受孕前使用cART，尤其是基于PI的方案，与导致小于胎龄儿的宫内生长受限相关。数据显示，与受孕后使用cART相比，受孕前使用cART与早产风险存在不显著的趋势。对于使用cART的HIV阳性孕妇在胎儿生长期间胎盘内发生的机制，还需要更多研究。只有了解这些知识，我们才能开始理解HIV和cART对胎儿的潜在影响，从而能够为感染HIV的育龄妇女确定最佳的个体化药物方案。
