Evaluating the safety of prenatal HIV PrEP use: Perinatal outcomes from three cohort studies in Western Kenya.

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.