HIV Protease Inhibitor Use During Pregnancy Is Associated With Decreased Progesterone Levels, Suggesting a Potential Mechanism Contributing to Fetal Growth Restriction

被引:93
作者
Papp, Eszter [1 ]
Mohammadi, Hakimeh [1 ]
Loutfy, Mona R. [2 ,3 ]
Yudin, Mark H. [3 ,4 ]
Murphy, Kellie E. [3 ,5 ]
Walmsley, Sharon L. [1 ,3 ]
Shah, Rajiv [4 ]
MacGillivray, Jay [4 ]
Silverman, Michael [3 ,6 ]
Serghides, Lena [1 ,2 ]
机构
[1] Univ Hlth Network, Toronto Gen Res Inst, Toronto, ON, Canada
[2] Womens Coll Hosp, Womens Coll Res Inst, Toronto, ON, Canada
[3] Univ Toronto, Toronto, ON, Canada
[4] St Michaels Hosp, Toronto, ON M5B 1W8, Canada
[5] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada
[6] Rouge Valley Hosp, Lakeridge Hlth, Ajax, ON, Canada
基金
加拿大健康研究院;
关键词
progesterone; protease inhibitors; lopinavir; small for gestational age; low birth weight; HIV; pregnancy; ANTIRETROVIRAL THERAPY; INFECTED WOMEN; PRETERM DELIVERY; PREMATURE DELIVERY; PREVENTION; PREECLAMPSIA; RITONAVIR; EXPOSURE; OUTCOMES; RISK;
D O I
10.1093/infdis/jiu393
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:10 / 18
页数:9
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