Department of Medicine, University of Toronto, Toronto, ON, Canada.
Drugs. 2013 Mar;73(3):229-47. doi: 10.1007/s40265-013-0017-3.
The impact of antiretroviral therapy (ART) on the natural history of HIV-1 infection has resulted in dramatic reductions in disease-associated morbidity and mortality. Additionally, the epidemiology of HIV-1 infection worldwide is changing, as women now represent a substantial proportion of infected adults. As more highly effective and tolerable antiretroviral regimens become available, and as the prevention of mother-to-child transmission becomes an attainable goal in the management of HIV-infected individuals, more and more HIV-positive women are choosing to become pregnant and have children. Consequently, it is important to consider the efficacy and safety of antiretroviral agents in pregnancy. Protease inhibitors are a common class of medication used in the treatment of HIV-1 infection and are increasingly being used in pregnancy. However, several studies have raised concerns regarding pharmacokinetic alterations in pregnancy, particularly in the third trimester, which results in suboptimal drug concentrations and a theoretically higher risk of virologic failure and perinatal transmission. Drug level reductions have been observed with each individual protease inhibitor and dose adjustments in pregnancy are suggested for certain agents. Furthermore, studies have also raised concerns regarding the safety of protease inhibitors in pregnancy, particularly as they may increase the risk of pre-term birth and metabolic disturbances. Overall, protease inhibitors are safe and effective for the treatment of HIV-infected pregnant women. Specifically, ritonavir-boosted lopinavir- and atazanavir-based regimens are preferred in pregnancy, while ritonavir-boosted darunavir- and saquinavir-based therapies are reasonable alternatives. This paper reviews the use of protease inhibitors in pregnancy, focusing on pharmacokinetic and safety considerations, and outlines the recommendations for use of this class of medication in the HIV-1-infected pregnant woman.
抗逆转录病毒疗法（ART）对 HIV-1 感染自然史的影响导致与疾病相关的发病率和死亡率显著降低。此外，由于女性现在占感染成年人的相当大比例，全球 HIV-1 感染的流行病学正在发生变化。随着更有效和更耐受的抗逆转录病毒方案的出现，以及母婴传播的预防成为 HIV 感染者管理的可实现目标，越来越多的 HIV 阳性妇女选择怀孕并生育孩子。因此，考虑抗逆转录病毒药物在怀孕期间的疗效和安全性非常重要。蛋白酶抑制剂是治疗 HIV-1 感染常用的一类药物，在怀孕期间越来越多地被使用。然而，几项研究对妊娠期间药代动力学改变表示担忧，特别是在第三孕期，导致药物浓度不理想，理论上病毒学失败和围产期传播的风险更高。已观察到每个单独的蛋白酶抑制剂的药物水平降低，建议在怀孕期间调整某些药物的剂量。此外，研究还对蛋白酶抑制剂在怀孕期间的安全性表示担忧，特别是因为它们可能增加早产和代谢紊乱的风险。总体而言，蛋白酶抑制剂对治疗 HIV 感染的孕妇是安全有效的。具体而言，利托那韦增强的洛匹那韦/阿扎那韦和阿他那韦为基础的方案在怀孕期间是首选，而利托那韦增强的达芦那韦和沙奎那韦为基础的治疗方案是合理的替代方案。本文回顾了蛋白酶抑制剂在怀孕期间的使用，重点关注药代动力学和安全性方面的考虑，并概述了在 HIV-1 感染孕妇中使用此类药物的建议。
