Briceño-Patiño Natalia, Prieto María Camila, Manrique Paula, Calderon-Ospina Carlos-Alberto, Gómez Leonardo
School of Medicine and Health Sciences, Universidad del Rosario, Bogota 111221, Colombia.
Research Group in Applied Biomedical Sciences (UR Biomed), School of Medicine and Health Sciences, Universidad del Rosario, Bogota 111221, Colombia.
Pharmaceutics. 2025 Jul 15;17(7):913. doi: 10.3390/pharmaceutics17070913.
Pregnancy introduces significant physiological changes that alter the pharmacokinetics (PK) of antiretroviral therapy (ART), impacting its safety and efficacy in HIV-positive women. Optimizing ART during pregnancy is critical to maintaining maternal virological suppression and preventing mother-to-child transmission (MTCT) of HIV. This review evaluates the impact of pregnancy-induced PK changes on ART and proposes strategies for tailored regimens to improve outcomes. A comprehensive review of published literature was conducted, focusing on PK adaptations during pregnancy and their implications for different ART classes, including protease inhibitors (PIs), integrase strand transfer inhibitors (INSTIs), and nucleoside reverse transcriptase inhibitors (NRTIs). Key studies were analyzed to assess drug exposure, efficacy, and safety. Pregnancy significantly alters the PK of antiretrovirals, with increased hepatic metabolism, renal clearance, and changes in plasma protein binding leading to reduced drug exposure. For example, drugs like lopinavir and atazanavir require dose adjustments, while dolutegravir maintains efficacy despite reduced plasma levels. Integrase inhibitors demonstrate favorable virological suppression, although cobicistat-boosted regimens show subtherapeutic levels. Tailored approaches, such as therapeutic drug monitoring (TDM), optimize ART efficacy while minimizing toxicity. Pregnancy-specific PK changes necessitate evidence-based ART adjustments to ensure virological suppression and reduce MTCT risk. Incorporating TDM, leveraging pharmacogenomic insights, and prioritizing maternal and neonatal safety are critical for personalized ART management. Further research into long-acting formulations and global guideline harmonization is needed to address disparities in care and improve outcomes for HIV-positive pregnant women.
怀孕会引发显著的生理变化，这些变化会改变抗逆转录病毒疗法（ART）的药代动力学（PK），影响其在HIV阳性女性中的安全性和疗效。孕期优化ART对于维持母亲病毒学抑制及预防HIV母婴传播（MTCT）至关重要。本综述评估了怀孕引起的PK变化对ART的影响，并提出了调整治疗方案以改善治疗效果的策略。我们对已发表的文献进行了全面综述，重点关注孕期的PK适应性变化及其对不同ART类别（包括蛋白酶抑制剂（PIs）、整合酶链转移抑制剂（INSTIs）和核苷类逆转录酶抑制剂（NRTIs））的影响。对关键研究进行了分析，以评估药物暴露、疗效和安全性。怀孕会显著改变抗逆转录病毒药物的PK，肝脏代谢增加、肾脏清除率提高以及血浆蛋白结合的变化导致药物暴露减少。例如，洛匹那韦和阿扎那韦等药物需要调整剂量，而多替拉韦尽管血浆水平降低仍能维持疗效。整合酶抑制剂显示出良好的病毒学抑制效果，尽管考比司他增强方案显示出低于治疗水平。采用治疗药物监测（TDM）等定制方法可优化ART疗效，同时将毒性降至最低。孕期特定的PK变化需要基于证据调整ART，以确保病毒学抑制并降低MTCT风险。纳入TDM、利用药物基因组学见解以及优先考虑母婴安全对于个性化ART管理至关重要。需要进一步研究长效制剂并统一全球指南，以解决护理差异并改善HIV阳性孕妇的治疗效果。
