Service de gynécologie-obstétrique, AP-HP Hôpital Louis Mourier, Colombes.
Université de Paris, INSERM UMR1137, IAME, Paris.
AIDS. 2021 Feb 2;35(2):219-226. doi: 10.1097/QAD.0000000000002719.
Following an alert on neural tube defects and dolutegravir, we sought to evaluate if the exposure integrase strand transfer inhibitors (INSTIs) at conception was associated with birth defects or other adverse pregnancy outcomes.
In the prospective national French Perinatal Cohort (EPF), we studied birth defects and other perinatal outcomes by matching each pregnant woman exposed to INSTIs with a pregnant woman exposed to darunavir/ritonavir receiving the same backbone of nucleoside reverse transcriptase inhibitors and matched for other characteristics such as age, geographic origin, centre and year of delivery.
Among 808 women exposed to INSTIs during pregnancy (raltegravir = 703, dolutegravir = 57 and elvitegravir = 48), we reported a slightly higher rate of birth defects in infants exposed at conception to raltegravir (6.7%) vs. infants exposed to raltegravir later in pregnancy: 2.9% if initiated during pregnancy as first-line, and 2.5% as second-line treatment, P =0.04. When compared with matched controls, raltegravir exposure at conception was not significantly associated with birth defects: 6.4 vs. 2.3%, P = 0.08. There was no cluster of birth defect type and no neural tube defects were observed. Other perinatal outcomes, such as preterm birth and stillbirths, did not differ significantly between raltegravir-exposed women and matched counterparts. No difference in any outcome was observed for elvitegravir/cobicistat or dolutegravir.
We found a nonsignificant trend for an association between exposure to raltegravir at conception and birth defects, which needs to be evaluated by larger prospective surveillance data, as these drugs are increasingly prescribed in women living with HIV.
在神经管缺陷和多替拉韦发出警报后，我们评估了整合酶链转移抑制剂（INSTIs）在受孕时的暴露是否与出生缺陷或其他不良妊娠结局相关。
在前瞻性全国法国围产期队列（EPF）中，我们通过将每个暴露于 INSTIs 的孕妇与接受相同核苷逆转录酶抑制剂骨干的暴露于达芦那韦/利托那韦的孕妇相匹配，研究了出生缺陷和其他围产期结局，并对年龄、地理来源、中心和分娩年份等其他特征进行了匹配。
在 808 名怀孕期间暴露于 INSTIs 的女性（raltegravir = 703，dolutegravir = 57，elvitegravir = 48）中，我们报告了暴露于 raltegravir 的婴儿出生缺陷率略高，在受孕时暴露于 raltegravir（6.7%）与怀孕后期暴露于 raltegravir的婴儿（如果在怀孕时作为一线治疗开始使用，发生率为 2.9%，二线治疗为 2.5%，P = 0.04）。与匹配的对照组相比，受孕时暴露于raltegravir 与出生缺陷无显著相关性：6.4%比 2.3%，P = 0.08。未观察到出生缺陷类型的聚类，也未观察到神经管缺陷。 raltegravir 暴露组与对照组在早产和死产等其他围产期结局方面无显著差异。elvitegravir/cobicistat 或 dolutegravir 也未观察到任何结局的差异。
我们发现暴露于raltegravir 在受孕时与出生缺陷之间存在非显著趋势，需要通过更大的前瞻性监测数据进行评估，因为这些药物在感染艾滋病毒的女性中越来越多地被处方。
