Birth Defects After Exposure to Efavirenz-Based Antiretroviral Therapy at Conception/First Trimester of Pregnancy: A Multicohort Analysis.

BACKGROUND

To investigate the association between efavirenz (EFV) use during conception or first trimester (T1) of pregnancy and the occurrence of birth defects.

SETTING

Seven observational studies of pregnant HIV-positive women across 13 European countries and Thailand.

METHODS

Individual-level data were pooled on singleton pregnancies included in participating cohorts in 2002-2015. Birth defects were coded according to ICD-10 and the EUROCAT classification. We performed mixed-effects logistic regression models to assess the association between EFV exposure in utero and likelihood of birth defects.

RESULTS

We included 24,963 live births from 21,093 women. At conception, 30.2% (7537) women were on a non-EFV-based regimen, 4.8% (1200) on EFV, and 65% (16,226) were unexposed to antiretroviral therapy (ART). There were 412 infants with ≥1 birth defect, a prevalence of 1.65% (95% confidence interval: 1.50 to 1.82). Limb/musculoskeletal and congenital heart defects were the most common defects reported. Birth defects were present in 2.4%, 1.6%, and 1.3% of infants exposed to non-EFV, EFV, and unexposed to ART during conception/T1 (P = 0.135), respectively. The association between exposure to ART during conception/T1 and birth defects remained nonsignificant in adjusted analyses, as did exposure to EFV versus non-EFV (adjusted odds ratio 0.61; 95% confidence interval: 0.36 to 1.03, P = 0.067). Among the 21 birth defects in 19 infants on EFV, no neural tube defects were reported.

CONCLUSIONS

Prevalence of birth defects after exposure to EFV-based compared with non-EFV-based ART in conception/T1 was not statistically different in this multicohort study, and even lower. EFV is at least as safe as other ART drugs currently recommended for antenatal use.