Short William R, Patel Parul, Verdier Gustavo, Puga Ana, Vannappagari Vani, de Ruiter Annemiek, Jones Bryn
Department of Medicine, Division of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Medical Arts Building, 3801 Filbert Street, Suite 103, Philadelphia, PA, 19104, USA.
ViiV Healthcare, 406 Blackwell Street, Suite 300, Durham, NC, 27701, USA.
Infect Dis Ther. 2025 Jan;14(1):59-80. doi: 10.1007/s40121-024-01085-z. Epub 2024 Dec 9.
Lowering viral load during pregnancy is regarded as the most important method of reducing human immunodeficiency virus 1 (HIV-1) vertical transmission risk, and minimizing fetal exposure to drugs is a guiding principle during pregnancy. Dolutegravir/lamivudine (DTG/3TC) has demonstrated high efficacy, a high barrier to resistance, and a good safety profile in non-pregnant individuals; however, DTG/3TC is not recommended by perinatal HIV treatment guidelines for initial therapy in pregnant people living with HIV-1 because of limited data on use of the 2-drug regimen during pregnancy. Efficacy and pharmacokinetic data from pregnant individuals using DTG and/or 3TC are reviewed and used to extrapolate anticipated DTG/3TC efficacy in pregnancy. There are robust data on the use of DTG- and 3TC-containing combination regimens, which are recommended by perinatal HIV treatment guidelines during pregnancy, supporting their well-established efficacy and safety in pregnant people living with HIV-1. Updated data from the Tsepamo and Eswatini surveillance studies (> 14,000 DTG exposures from conception) indicate no increased risk of neural tube defects with DTG. Pharmacokinetic data for DTG and 3TC indicate that exposures in pregnancy are within the therapeutically effective range seen in non-pregnant adults. Two studies evaluated DTG/3TC during pregnancy and both reported high virologic suppression rates [HIV-1 ribonucleic acid (RNA) < 50 copies/mL at delivery: 97% (30/31) overall], no events of vertical transmission, and no new safety signals, consistent with the use of DTG-based 3-drug regimens in pregnancy. The use of DTG/3TC during pregnancy is anticipated to be comparably effective and well tolerated for both parental health and prevention of vertical transmission with fetal exposure to fewer antiretrovirals compared with 3- or 4-drug regimens. These considerations are relevant when evaluating use of DTG/3TC in people living with HIV-1 who are pregnant or considering pregnancy in clinical practice and in perinatal HIV treatment guidelines.Video abstract available for this article. Supplementary file1 (MP4 319,147 KB).
降低孕期病毒载量被视为降低人类免疫缺陷病毒1型（HIV-1）垂直传播风险的最重要方法，而尽量减少胎儿对药物的暴露是孕期的一项指导原则。多替拉韦/拉米夫定（DTG/3TC）在非妊娠个体中已显示出高效、高耐药屏障和良好的安全性；然而，由于关于该二联疗法在孕期使用的数据有限，围产期HIV治疗指南不推荐DTG/3TC用于HIV-1感染孕妇的初始治疗。对使用DTG和/或3TC的孕妇的疗效和药代动力学数据进行了综述，并用于推断DTG/3TC在孕期的预期疗效。有关于含DTG和3TC的联合方案使用的可靠数据，围产期HIV治疗指南在孕期推荐这些方案，支持它们在HIV-1感染孕妇中已确立的疗效和安全性。来自Tsepamo和斯威士兰监测研究的最新数据（超过14000例从受孕开始暴露于DTG的病例）表明，DTG不会增加神经管缺陷的风险。DTG和3TC的药代动力学数据表明，孕期的暴露量在非妊娠成人所见的治疗有效范围内。两项研究评估了孕期的DTG/3TC，均报告了高病毒学抑制率[分娩时HIV-1核糖核酸（RNA）<50拷贝/mL：总体为97%（30/31）]，无垂直传播事件，也无新的安全信号，这与孕期使用基于DTG的三联疗法一致。与三联或四联疗法相比，孕期使用DTG/3TC预计对母体健康和预防垂直传播同样有效且耐受性良好，同时胎儿接触的抗逆转录病毒药物更少。在临床实践和围产期HIV治疗指南中评估HIV-1感染孕妇或考虑怀孕的孕妇使用DTG/3TC时，这些考虑因素具有相关性。本文有视频摘要。补充文件1（MP4，319,147 KB）。
