Bierhoff Marieke, Smolders Elise J, Tarning Joel, Burger David M, Spijker Rene, Rijken Marcus J, Angkurawaranon Chaisiri, McGready Rose, White Nicholas J, Nosten Francois, van Vugt Michèle
Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
Department of Internal Medicine and Tropical Diseases, Amsterdam University Medical Center, location Academic Medical Center Amsterdam, Amsterdam, the Netherlands.
Antivir Ther. 2019;24(7):529-540. doi: 10.3851/IMP3341.
Tenofovir disoproxil fumarate (TDF), the oral prodrug of tenofovir (TFV), is advocated in pregnancy for prevention of mother-to-child transmission (PMCT) with failure of hepatitis B immunoglobulin and vaccination. The pharmacokinetics of TDF monotherapy for PMCT-HBV is important if deployment is to emulate the success of multiple antiretrovirals (ARVs) for PMCT-HIV in resource-constrained settings.
This systematic review followed a protocol and is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) guidelines. We included studies that enrolled pregnant women who received oral TDF therapy as monotherapy or in combination with other ARVs: irrespective of the reason for receiving the drug (for example, HIV, HBV or pre-exposure prophylaxis); and reported pharmacokinetics.
The area under the concentration-time curve (AUC), maximum plasma concentrations (C) and last measurable plasma concentration (C) of TFV were decreased in the second and third trimester compared with first trimester or post-partum. In none of the manuscripts was the non-pregnant HBV threshold of C of 300 ng/ml reached, but the 50% effective concentration (EC) of TFV is lower for treatment of HBV compared with HIV. The TFV concentration in breastfed infants was 0.03% of the recommended infant dose.
Most knowledge of pharmacokinetics of TFV in pregnancy results from studies on HIV involving multiple ARVs. Increased TFV clearance occurred in the second and third trimester when optimal TFV concentrations are required to maximize suppression of HBV in the window before birth. Dose or duration adjustments will be better conceptualized with concurrent analysis of the pharmacokinetics of TFV monotherapy and hepatitis B pharmacodynamics in pregnancy.
替诺福韦酯（TDF）是替诺福韦（TFV）的口服前体药物，在孕期用于预防乙型肝炎免疫球蛋白和疫苗接种失败后的母婴传播（PMCT）。如果要在资源有限的环境中效仿多种抗逆转录病毒药物（ARV）预防母婴传播HIV的成功经验，TDF单药治疗PMCT-HBV的药代动力学就很重要。
本系统评价遵循了一项方案，并根据系统评价和Meta分析的首选报告项目（PRISMA）指南进行报告。我们纳入了招募接受口服TDF单药治疗或与其他ARV联合治疗的孕妇的研究：无论接受药物的原因（例如，HIV、HBV或暴露前预防）；并报告了药代动力学。
与孕早期或产后相比，孕中期和孕晚期TFV的浓度-时间曲线下面积（AUC）、最大血浆浓度（C）和最后可测量血浆浓度（C）均降低。在所有手稿中均未达到非妊娠HBV的C阈值300 ng/ml，但与HIV治疗相比，TFV治疗HBV的50%有效浓度（EC）更低。母乳喂养婴儿体内的TFV浓度为推荐婴儿剂量的0.03%。
孕期TFV药代动力学的大多数知识来自涉及多种ARV的HIV研究。在孕中期和孕晚期，当需要最佳TFV浓度以在出生前窗口期最大限度地抑制HBV时，TFV清除率增加。通过同时分析孕期TFV单药治疗的药代动力学和乙型肝炎药效学，可以更好地理解剂量或疗程调整。
