Developing a surveillance system for HIV pre-exposure prophylaxis (PrEP) use in pregnancy in Malawi.

BACKGROUND: Pregnant and breastfeeding women are at elevated risk of HIV acquisition. The World Health Organization (WHO) recommends use of oral TDF/FTC and long-acting injectables cabotegravir (CAB-LA) and lenacapavir (LEN) for HIV pre-exposure prophylaxis (PrEP) in pregnancy. However, safety data for emerging regimens remain limited due to the exclusion of pregnant women from early clinical trials and insufficient routine, program-embedded surveillance, especially in resource-constrained settings. In March 2024, as Malawi introduced CAB-LA, the PrEP Pregnancy Registry was established to generate real-world safety data on PrEP exposure during pregnancy.

METHODS: The PrEP Pregnancy Registry provides prospective safety surveillance of pregnant women on PrEP within routine service delivery across Malawi. Guided by the WHO collaborative framework for antiretroviral safety in pregnancy, the Registry was established through a phased process involving the Malawi Ministry of Health, research and implementing partners. Initially implemented at five CAB-LA early-access facilities, it was refined with provider feedback and expanded to 30 additional facilities. The registry utilizes ScanForm, an AI-powered tool that uses optical character recognition technology to digitize and analyze handwritten data. Birth outcomes are measured using WHO's harmonized pharmacovigilance indicators for maternal and infant birth outcomes.

DISCUSSION: The Registry provides a scalable model for real-world pharmacovigilance of PrEP use in pregnancy. The use of ScanForm technology maximizes data quality and ensures integration with existing systems. Resulting evidence will fill critical gaps in PrEP safety data during pregnancy and inform national and global policies for integrating CAB-LA and emerging PrEP regimens into routine maternal health care settings.

TRIAL REGISTRATION NUMBERS: The Pregnancy, Infant and Maternal Health Outcomes (PrIMO) sub-study within the Preventing Infant Infection with Implementation Science in Malawi (PRI3SM) was registered in ClinicalTrials.gov on 05th December 2023 with trial registration number NCT06158126, and the Path to Scale study was registered on 29th March 2024 with trial registration number NCT06319105.