Surveillance of ARV safety in pregnancy and breastfeeding: towards a new framework

• Published in: Journal of the International AIDS Society 2022-07, Vol.25 (S2), p.e25922-n/a
• Main Authors: Renaud, Françoise, Mofenson, Lynne M., Bakker, Charlotte, Dolk, Helen, Leroy, Valeriane, Namiba, Angelina, Sahin, Leyla, Shapiro, Roger, Slogrove, Amy, Thorne, Claire, Vicari, Marissa, Low‐Beer, Daniel, Doherty, Meg
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Adolescent; adverse pregnancy outcomes; AIDS; Anti-Retroviral Agents - adverse effects; Anti-Retroviral Agents - therapeutic use; Antiretroviral drugs; antiretrovirals; Antiviral agents; Birth defects; Breast Feeding; Child; Clinical trials; Cohort Studies; Collaboration; Complications and side effects; Data collection; Data entry; Drug therapy; Drugs; Europe; Evaluation; Female; Gestational age; Health aspects; HIV; HIV infection; HIV Infections - drug therapy; HIV Infections - epidemiology; HIV Infections - prevention & control; Human immunodeficiency virus; Humans; Infant; Infants; Methods; North America; Pharmaceutical industry; Pharmaceutical research; Pharmacovigilance; Pregnancy; Pregnant women; Premature birth; Prevention; Product safety; Public health; Risk assessment; Safety; Safety regulations; Sentinel health events; Stillbirth; Supplement; Surveillance; Testing; Womens health
• ISSN: 1758-2652; 1758-2652
• DOI: 10.1002/jia2.25922

Introduction As new antiretrovirals (ARVs), including long‐acting ARVs for treatment and prevention, are approved and introduced, surveillance during pregnancy must become the safety net for evaluating birth outcomes, especially those that are rare and require large numbers of observations. Historically, drug pharmacovigilance in pregnancy has been limited and fragmented between different data sources, resulting in inadequate data to assess risk. The International Maternal Pediatric Adolescent AIDS Clinical Trials Network and World Health Organization convened a Workshop which reviewed strengths and weaknesses of existing programs and discussed an improved framework to integrate existing safety data sources and promote harmonization and digitalization. Discussion This paper highlights that although robust sources of safety data and surveillance programs exist, key challenges remain, including unknown denominators, reporting bias, under‐reporting (e.g. in voluntary registries), few data sources from resource‐limited settings (most are in North America and Europe), incomplete or inaccurate data (e.g. within routine medical records). However, recent experiences (e.g. with safety signals) and current innovations (e.g. electronic record use in resource‐limited settings and defining adverse outcomes) provide momentum and building blocks for a new framework for active surveillance of ARV safety in pregnancy. A public health approach should be taken using data from existing sources, including registries of pregnancy ARV exposure and birth defects; observational surveillance and cohort studies; clinical trials; and real‐world databases. Key facilitators are harmonization and standardization of outcomes, sharing of materials and tools, and data linkages between programs. Other key facilitators include the development of guidance to estimate sample size and duration of surveillance, ensuring strategic geographic diversity, bringing partners together to share information and engaging the community of women living with HIV. Conclusions Looking ahead, critical steps to safely introduce new ARVs include (1) adopting harmonized standards for measuring adverse maternal, birth and infant outcomes; (2) establishing surveillance centres of excellence in areas with high HIV prevalence with harmonized data collection and optimized electronic health records linking maternal/infant data; and (3) creating targets and evaluation goals for reporting progress on implementation and qu