<p>Inclusion and exclusion criteria by study cohort.</p>

Existing data support the safety of daily oral tenofovir disoproxil fumarate (TDF)-based HIV pre-exposure prophylaxis (PrEP) use in pregnancy, yet ongoing monitoring is needed. We analyzed data from three recently completed HIV PrEP safety and implementation studies (PrIMA, PrIMA-X, and mWACh-PrEP) that enrolled women who were offered and/or initiated TDF-based HIV PrEP at routine health clinics in Western Kenya to summarize perinatal outcomes following HIV PrEP use in pregnancy. Data were included in the analysis from participants who were ≥ 15 years, HIV-negative, enrolled ≤32 weeks gestation and remained pregnant until at least 24 weeks gestation. We summarized the frequency of each pregnancy outcome (stillbirth, preterm birth, low birthweight, neonatal death, congenital anomalies) by study cohort, HIV PrEP exposure status (any vs. none), and timing of first HIV PrEP exposure (first, second, or third trimester). Poisson regression models were used to assess associations between adverse outcomes and HIV PrEP exposure timing and duration, adjusting for maternal age, primigravity, and clustering by study cohort. A total of N = 4389 women were included in the analysis (29.8% with HIV PrEP exposure). The median age was 24.1 years, and median gestational age at enrollment was 24 weeks. Most women (83.4%) were married and 39.4% had a partner of unknown HIV status. Among HIV PrEP-exposed pregnancies (n = 1310), most initiated HIV PrEP in the second trimester (56.2%). We found no appreciable differences in perinatal outcomes between pregnancies with and without any HIV PrEP exposure, though HIV PrEP-exposed pregnancies had lower frequency of low birthweight (1.9% vs. 2.5%, adjusted prevalence ratio [aPR]=0.77, 95% CI 0.61-0.97). Among pregnancies with any HIV PrEP exposure, preterm birth was less frequent among those with any PrEP use in the first trimester (aPR = 0.49, 95% CI 0.42-0.57) and third-trimester (aPR = 0.74, 95% CI 0.61-0.88), compared to those with no PrEP use in those trimesters; low birth weight was also less frequent among in pregnancies with third-trimester HIV PrEP initiation compared to second trimester initiation (aPR = 0.74, 95% CI 0.61-0.88). All other perinatal outcomes were comparable by timing of HIV PrEP exposure. These findings support current guidelines recommending daily oral TDF-based HIV PrEP for pregnant and lactating women at risk of HIV.现有数据支持妊娠期每日口服基于富马酸替诺福韦二吡呋酯（tenofovir disoproxil fumarate, TDF）的HIV暴露前预防（pre-exposure prophylaxis, PrEP）的安全性，但仍需开展持续监测。本研究分析了三项近期完成的HIV PrEP安全性与实施性研究（PrIMA、PrIMA-X及mWACh-PrEP）的数据，这些研究在肯尼亚西部的常规卫生诊所中为符合入组条件的女性提供并/或启动基于TDF的HIV PrEP，旨在总结妊娠期使用HIV PrEP后的围产期结局。分析纳入的参与者需满足年龄≥15岁、HIV阴性、入组时孕周≤32周且至少妊娠至24周。研究人员按研究队列、HIV PrEP暴露状态（任何暴露vs. 未暴露）以及首次HIV PrEP暴露的孕周（妊娠早、中、晚期）对各项妊娠结局（死胎、早产、低出生体重、新生儿死亡、先天性畸形）的发生频率进行了总结。使用泊松回归模型评估不良结局与HIV PrEP暴露时机及持续时长的关联，并校正产妇年龄、初产情况以及研究队列的聚类效应。本分析共纳入4389名女性，其中29.8%存在HIV PrEP暴露。受试者的中位年龄为24.1岁，入组时的中位孕周为24周。大多数女性（83.4%）已婚，39.4%的性伴侣HIV感染状态未知。在存在HIV PrEP暴露的妊娠（n=1310）中，多数在妊娠中期启动HIV PrEP（56.2%）。研究未观察到任何HIV PrEP暴露组与未暴露组的围产期结局存在显著差异，但暴露组的低出生体重发生率更低（1.9% vs. 2.5%，校正患病率比（adjusted prevalence ratio, aPR）=0.77，95%置信区间（confidence interval, CI）0.61~0.97）。在存在任何HIV PrEP暴露的妊娠中，与未在对应孕周使用PrEP的受试者相比，妊娠早期（aPR=0.49，95%置信区间0.42~0.57）或妊娠晚期（aPR=0.74，95%置信区间0.61~0.88）使用任何PrEP的受试者早产发生率更低；与妊娠中期启动PrEP的受试者相比，妊娠晚期启动PrEP的妊娠的低出生体重发生率也更低（aPR=0.74，95%置信区间0.61~0.88）。其余围产期结局的发生频率均与HIV PrEP暴露时机无显著关联。本研究结果支持当前指南推荐，即为存在HIV感染风险的妊娠期及哺乳期女性提供每日口服基于TDF的HIV PrEP。