Abigail Zuger, MD

First-trimester AZT raised the risk for cardiac malformations, but other commonly used antiretrovirals were reconfirmed to be safe during pregnancy.

The increasing use of antiretrovirals (ARVs) worldwide means that more and more women will be on combination treatment when they conceive. And although the drugs' success in preventing mother-to-child HIV transmission is incontrovertible, their safety during pregnancy is still being evaluated.

Now, researchers have assessed the prevalence of birth defects in more than 13,000 ARV-exposed infants born in France between 1994 and 2010. Most of the mothers were from sub-Saharan Africa and had well-controlled HIV infection; only 2% were intravenous drug users.

Overall, 5388 (41.1%) of the infants had first-trimester exposure to one or more ARVs (rising from 19.1% in 1994–1996 to 51.7% in 2005–2010). The total rate of birth defects was 4.4% or 7.0%, depending on which of two classification systems was used. Several significant independent associations between first-trimester use of individual drugs and birth defects emerged:

• AZT use was associated with increased risk for congenital heart disease, primarily ventricular and atrial septal defects and patent ductus arteriosus.
• Efavirenz use was associated with increased risk for neurological defects as defined by one classification system but not the other. These defects included white matter anomalies, subependymal cyst, and partial agenesis of the corpus callosum.
• Use of either ddI or indinavir was associated with head and neck defects.

No associations were found for any of the other drugs in common use today, including abacavir, tenofovir, FTC, nevirapine, or protease inhibitors.

Citation(s):

Sibiude J et al. Association between prenatal exposure to antiretroviral therapy and birth defects: An analysis of the French Perinatal Cohort Study (ANRS CO1/CO11). PLoS Med 2014 Apr; 11:e1001635.

Mofenson LM and Watts DH.Safety of pediatric HIV elimination: The growing population of HIV- and antiretroviral-exposed but uninfected infants. PLoS Med 2014 Apr; 11:1001636.