US study explores congenital anomaly risk on newer antiretrovirals

A long-term study of infants born to pregnant people living with HIV found no elevation in the rate of congenital anomalies among infants who were exposed in utero to any of a number of antiretrovirals that have been commonly prescribed in the U.S. since 2012, when compared to the rate among infants who were not exposed to those antiretrovirals.

About This Study

“First-trimester exposure to newer antiretroviral agents and congenital anomalies in a U.S. cohort” was published online on June 12, 2024, in AIDS. The lead author is Kelly Fung, M.S., of the Department of Epidemiology at Harvard T.H. Chan School of Public Health in Boston, Massachusetts.

Key Research Findings

In this prospective cohort study, researchers used U.S. medical records to analyze the relationship between fetal exposure to newer HIV medications during the first trimester of pregnancy and later congenital infant anomalies. Participants were 2,034 infants born between 2012 and 2022 to 1,670 birthing parents living with HIV. The majority of adult-infant pairs were people of color (70%) and 66% had an annual household income of <$20,000/year at baseline.

Exposures were to rilpivirine (14% of infants), darunavir (13% of infants), elvitegravir (10% of infants), dolutegravir (9% of infants), raltegravir (8% of infants) and bictegravir (3% of infants). Some drugs were boosted with ritonavir or cobicistat, and many parents also took tenofovir (disoproxil fumarate or alafenamide).

Congenital anomalies were found among 135 infants (7% of total), with 32% having a cardiovascular, 27% a musculoskeletal, and 18% a central nervous system defect. The risk of being born with an anomaly did not differ substantially between infants exposed to the drugs of interest and those exposed to other HIV medications.

Discussion Highlights and Implications for Practice

The overall rate of anomalies in this study is higher than the latest rate of 2.9 per 100 live births reported by the Antiretroviral Pregnancy Registry. However, the registry is based on physicians’ voluntary reporting, likely leading to an undercount, the researchers pointed out.

Study limitations reported included a yes/no definition of medication exposure, a relatively small number of birthing parents on certain antiretrovirals, and few infants with anomalies. Thus, safety signals for rare birth defects or for antiretrovirals to which few infants were exposed may have been missed. All participants were born live, so potential relationships between medications and miscarriages or infants born dead were not captured.

While this study shows the safety of recent antiretrovirals during pregnancy, the authors said that more research involving birthing parents’ entire antiretroviral therapy regimens and larger cohorts are needed to conclusively establish the safety of all drugs used to treat HIV during pregnancy.

By Barbara Jungwirth