The Antiretroviral Pregnancy Registry: Three decades of prospective monitoring for birth defects

Pharmacoepidemiol Drug Saf. 2024 Jun;33(6):e5801. doi: 10.1002/pds.5801.

Abstract

Purpose: Antiretrovirals (ARVs) are life-saving drugs used for the treatment and prevention of HIV infection and antiviral drugs (AVs) for the treatment of chronic HBV infection. ARVs have proven highly effective in reducing perinatal HIV transmission, however the risk of birth defects from prenatal exposure to ARVs/AVs is an ongoing concern. The Antiretroviral Pregnancy Registry (APR), an international, prospective exposure-registration cohort study, monitors ARV and AV use in pregnancy for early signals of teratogenicity. This communication reports results of 30-years' experience of ARV/AV exposure during pregnancy and lessons learned through continuous quality improvement.

Methods and results: Birth defect prevalence is estimated and compared to internal and external groups. Statistical inference is based on exact methods for binomial proportions. Between 2006 and 2023, cumulative enrollment more than tripled from 6893 to 25 960 pregnancies and ARVs/AVs monitored increased from 29 to 222. Through January 2023, there were 21 636 live births and 631 outcomes with birth defects, for overall prevalence of 2.9/100 live births (95% CI 2.7, 3.2). The birth defect prevalence was 3.0% (95% CI 2.7%, 3.3%) among first trimester exposures and 2.8% (95% CI 2.5%, 3.2%) among second/third trimester exposures (prevalence ratio 1.04 [95% CI 0.89, 1.21]).

Conclusions: Birth defect prevalence is not statistically significantly different between first trimester ARV/AV pregnancy exposures compared to second/third trimester exposures and is also not different from two population-based surveillance systems: 2.72/100 live births reported in the Metropolitan Atlanta Congenital Defects Program (MACDP); and 4.17/100 live births from the Texas Birth Defects Registry (TBDR).

Keywords: HIV; PrEP; antiretroviral; birth defects; hepatitis B; pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Drug-Induced* / epidemiology
  • Abnormalities, Drug-Induced* / etiology
  • Adult
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / therapeutic use
  • Anti-Retroviral Agents / therapeutic use
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use
  • Cohort Studies
  • Congenital Abnormalities / epidemiology
  • Female
  • HIV Infections* / drug therapy
  • HIV Infections* / epidemiology
  • Humans
  • Infant, Newborn
  • Pregnancy
  • Pregnancy Complications, Infectious* / drug therapy
  • Pregnancy Complications, Infectious* / epidemiology
  • Prevalence
  • Prospective Studies
  • Registries*
  • Young Adult

Substances

  • Anti-Retroviral Agents
  • Anti-HIV Agents
  • Antiviral Agents