William Short, MD, MPH

The Antiretroviral Pregnancy Registry: 30 Years of Monitoring for Congenital Anomalies

William R. Short MD, MPH, Angela E. Scheuerle MD, Karen Beckerman MD, Lynne Mofenson MD, Vani Vannappagari PhD, Jessica D. Albano PhD, MPH

The Perelman School of Medicine, University of Pennsylvania, Philadelphia PA, USA 
University of Texas Southwestern Medical Center, Dallas, TX, USA
Carl Icahn School of Medicine at Mt Sinai, Bronx, NY, USA
Elizabeth Glaser Pediatric AIDS Foundation, Silver Spring, MD, USA 
Epidemiology and Real-World Evidence, ViiV Healthcare, Research Triangle Park, NC, USA
Syneos Health, Wilmington, NC, USA 

 

Antiretrovirals (ARVs) reduce perinatal transmission of HIV. Due to exclusion of pregnant persons from registrational trials, safety data are limited when a drug is granted Food and Drug Administration approval leaving a critical knowledge gap in data that is needed for safe use of ARVs during pregnancy. In 1989, the Antiretroviral Pregnancy Registry (APR) began monitoring prenatal ARV use to detect an early signal of teratogenicity.

The APR is a voluntary, prospective, exposure-registration cohort study with data from 75 countries. Prevalence of congenital anomalies (CAs) are estimated and compared to both internal (1st trimester vs 2nd/3rd trimester) and external comparator groups (Metropolitan Atlanta Congenital Defect program (MACDP) and Texas Birth Defects Registry (TBDR).

Of the 22,887 evaluable pregnancies enrolled through 31January2023, there were 21,636 live births (LB) with ARV exposure at any time during pregnancy and 631 CAs. Prevalence of CAs was 2.9 % (95% CI: 2.7-3.2) overall, 3.0 % (95% CI: 2.7-3.3) among 1st trimester exposures and 2.8% (95% CI: 2.5-3.2) among 2nd/3rd trimester exposures to ARVs. Prevalence Ratio comparing 1st vs 2nd/3rd trimester exposures was 1.04 (95% CI: 0.89-1.21). Twenty-three ARVs have sufficient 1st trimester exposures to detect at least a 2-fold increase in risk of CAs overall, of which 11 can detect a 1.5-fold increase of overall effects and a 2-fold increased risk of birth defects in the more common classes, cardiovascular and genitourinary systems. See figure 1 for a summary of birth defects among prospective cases with outcomes enrolled in APR with first trimester exposures.

The APR has not found a significant difference in overall CA prevalence compared to two population-based surveillance systems: 2.72/100 LB (95% CI: 2.68-2.76) MACDP and 4.17/100 LB (95% CI: 4.15-4.19) TBDR. Two ARVs, didanosine and nelfinavir, have a modest but statistically significant increased prevalence compared to the MACDP but not the TBDR. The APR independent Advisory Committee concludes, “The Registry finds no significant increases in frequency of defects with first trimester exposures compared to exposures starting later in pregnancy and no pattern to suggest a common cause; however, potential limitations of registries should be recognized”.