Infectious Diseases Department, Mater Misericordia University Hospital, Dublin, Republic of Ireland.
School of Medicine and Medicinal Science, University College Dublin, Republic of Ireland; and.
Ther Drug Monit. 2020 Apr;42(2):229-244. doi: 10.1097/FTD.0000000000000735.
To date, therapeutic drug monitoring (TDM) has played an important role in the management of pregnant HIV patients on highly active antiretroviral therapy. Historically, in pregnant women living with HIV, the third agent in triple therapy has been either non-nucleoside reverse transcriptase inhibitors or protease inhibitors (PIs). PIs have been the preferred agents because of their robustness from the perspective of viral resistance and the dominant drug class for the management of HIV during pregnancy for the previous decade. As with many drugs used during pregnancy, pharmacokinetic changes decrease exposure to these agents as the pregnancy progresses. This can lead to viral escape at the time of pregnancy and ultimately increase the risk of mother-to-child transmission (MTCT) of HIV. TDM has been well-established for this class of highly active antiretroviral therapy, and appropriate dose adjustment studies have been performed. At present, there is a shift from the traditional treatment paradigm in pregnancy to a new drug class, integrase strand transfer inhibitors (INSTIs). Although INSTIs are affected by pharmacokinetic changes during pregnancy, they do not harbor the same issues with viral escape as seen with PIs at birth and in general eliminate the need for boosting with additional agents like ritonavir (r) and cobicistat (c) [bar elvitegravir (EVG)] that can lead to interactions with treatment of other common infections in HIV, including tuberculosis. Furthermore, INSTIs are the most successful medication for rapidly reducing the viral load (VL) in HIV patients, a useful factor where VL may be unknown, or in late presenters. These merits make INSTIs the best choice in pregnancy, although their use has been hindered in recent years by a report of neural tube defects from a large African study with dolutegravir (DTG). New data from Botswana and Brazil indicate that this risk is less significant than previously reported, necessitating further data to shed light on this critical issue. Current international guidelines including DHHS, EACS, WHO, and BHIVA (for patients with VLs >100,000 copies/mL or late presenters) now recommend INSTIs as first-line agents. The role of TDM in INSTIs shifts to cases of insufficient viral suppression with standard adherence measures, cases of drug-drug interactions, or cases where EVG/c is continued throughout pregnancy, and thus remains an important aspect of HIV care in pregnancy.
迄今为止，治疗药物监测（TDM）在管理接受高效抗逆转录病毒治疗的妊娠 HIV 患者方面发挥了重要作用。从历史上看，在感染 HIV 的孕妇中，三联疗法中的第三种药物是非核苷类逆转录酶抑制剂或蛋白酶抑制剂（PI）。PI 一直是首选药物，因为从病毒耐药性的角度来看，它们具有稳健性，并且在过去十年中一直是管理妊娠期间 HIV 的主要药物类别。与许多在妊娠期间使用的药物一样，随着妊娠的进展，药物代谢动力学的变化会降低这些药物的暴露量。这可能导致在妊娠期间病毒逃逸，并最终增加 HIV 母婴传播（MTCT）的风险。TDM 已经在这一类高效抗逆转录病毒治疗中得到很好的建立，并且已经进行了适当的剂量调整研究。目前，妊娠治疗模式正在从传统模式向新的药物类别整合酶链转移抑制剂（INSTIs）转变。尽管 INSTIs 会受到妊娠期间药物代谢动力学变化的影响，但它们不会像 PI 那样在出生时和通常情况下出现病毒逃逸问题，而且通常不需要额外的增效剂（如ritonavir [r] 和 cobicistat [c] [bar elvitegravir [EVG]）来增强疗效，这些增效剂可能会与 HIV 治疗其他常见感染（包括结核病）的药物相互作用。此外，INSTIs 是降低 HIV 患者病毒载量（VL）最有效的药物，在 VL 未知或晚期患者中，这是一个有用的因素。这些优点使得 INSTIs 成为妊娠的最佳选择，尽管近年来由于一项来自大型非洲 dolutegravir（DTG）研究的神经管缺陷报告，其使用受到了阻碍。来自博茨瓦纳和巴西的新数据表明，这种风险比之前报道的要小，因此需要进一步的数据来阐明这一关键问题。目前的国际指南包括 DHHS、EACS、WHO 和 BHIVA（VL>100,000 拷贝/mL 或晚期患者）现在推荐 INSTIs 作为一线药物。在标准依从性措施下病毒抑制不足、药物相互作用或 EVG/c 在整个妊娠期间持续使用的情况下，TDM 在 INSTIs 中的作用发生转变，因此仍然是妊娠 HIV 护理的一个重要方面。
