HIV protease inhibitor use during pregnancy is associated with decreased progesterone levels, suggesting a potential mechanism contributing to fetal growth restriction.
HIV protease inhibitor use during pregnancy is associated with decreased progesterone levels, suggesting a potential mechanism contributing to fetal growth restriction.
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DOI：
10.1093/infdis/jiu393
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发表时间：
2015-01-01
期刊：
影响因子：
--
通讯作者：
Serghides L
中科院分区：
文献类型：
--
作者：
Papp E;Mohammadi H;Loutfy MR;Yudin MH;Murphy KE;Walmsley SL;Shah R;MacGillivray J;Silverman M;Serghides L
背景：妊娠期间使用基于蛋白酶抑制剂（PI）的联合抗逆转录病毒治疗（cART）以预防围产期人类免疫缺陷病毒（HIV）传播。 然而，PI的使用与不良出生结局相关，包括早产和小于胎龄儿（SGA）出生。这些结果背后的机制尚不清楚。我们假设PI通过改变孕酮水平而导致这些不良事件。方法：体外评估PI对滋养层孕酮产生的影响。 使用小鼠妊娠模型来评估基于PI的cART对妊娠结果和体内孕酮水平的影响。对27例HIV感染者和17例未感染HIV的孕妇的血浆标本进行了预后水平评估。结果：PI（利托那韦，洛匹那韦，阿扎那韦），而不是核苷类逆转录酶抑制剂（NRTI）或非核苷类逆转录酶抑制剂减少体外滋养层孕酮的产生。 在妊娠小鼠中，基于PI的cART而不是双重NRTI治疗与显著降低的孕酮水平相关，孕酮水平与胎儿体重直接相关。补充黄体酮可显着改善胎儿体重。我们观察到，与对照组相比，接受基于PI的cART的HIV感染妇女的孕酮水平较低，婴儿较小。在HIV感染的妇女中，孕激素水平与出生体重百分位数显著相关。结论：我们的数据表明，妊娠期使用PI可能导致孕酮水平降低，从而导致不良的出生结局。
Background. Protease inhibitor (PI)–based combination antiretroviral therapy (cART) is administered during pregnancy to prevent perinatal human immunodeficiency virus (HIV) transmission. However, PI use has been associated with adverse birth outcomes, including preterm delivery and small-for-gestational-age (SGA) births. The mechanisms underlying these outcomes are unknown. We hypothesized that PIs contribute to these adverse events by altering progesterone levels. Methods. PI effects on trophoblast progesterone production were assessed in vitro. A mouse pregnancy model was used to assess the impact of PI-based cART on pregnancy outcomes and progesterone levels in vivo. Progesterone levels were assessed in plasma specimens from 27 HIV-infected and 17 HIV-uninfected pregnant women. Results. PIs (ritonavir, lopinavir, and atazanavir) but not nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors reduced trophoblast progesterone production in vitro. In pregnant mice, PI-based cART but not dual-NRTI therapy was associated with significantly lower progesterone levels that directly correlated with fetal weight. Progesterone supplementation resulted in a significant improvement in fetal weight. We observed lower progesterone levels and smaller infants in HIV-infected women receiving PI-based cART, compared with the control group. In HIV-infected women, progesterone levels correlated significantly with birth weight percentile. Conclusions. Our data suggest that PI use in pregnancy may lead to lower progesterone levels that could contribute to adverse birth outcomes.
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