The European Pregnancy and Paediatric HIV Cohort Collaboration includes data from 24,963 pregnancies ending in singleton live births between 2002 and 2015. Cohorts in Belgium, Denmark, Germany, Ireland, Italy, the Netherlands, Poland, Romania, Spain, Sweden, Switzerland, Thailand, Ukraine and the United Kingdom provided data.
In 1200 pregnancies (4.8%), the mother received efavirenz at the time of conception or during the first three months of pregnancy; in 7537 pregnancies (30.2%) she received a non-efavirenz regimen; and in 16,226 pregnancies (65%) she did not receive antiretroviral treatment at this stage.
There were 412 infants with at least one birth abnormality, including 34 infants with two or three abnormalities. The overall prevalence was 1.7%. Limb/musculoskeletal and congenital heart defects were the most commonly reported.
Among infants exposed to efavirenz, the prevalence of birth defects (1.6%, 95% CI 0.96-2.5%) was not statistically significantly higher than among infants not exposed to any antiretrovirals (1.3%, 65% CI 1.1-1.5%) or a non-efavirenz regimen (2.4%, 95% CI 2.1-2.8%).
After adjustment for other factors that could skew the results, the risk of birth defects was 40% lower in infants exposed to efavirenz than in those exposed to other antiretrovirals, but this was not statistically significant (adjusted odds ratio 0.61, 95% confidence interval 0.36-1.03).
Among children with congenital heart defects, almost half in the non-efavirenz group and a third in the efavirenz group had also been exposed to zidovudine. Studies have had divergent findings on the question of whether heart abnormalities are associated with zidovudine exposure or not.
Pre-term birth was more common in infants with birth defects (25%) than infants without defects (11%). There was no association with low birth weight.
“Overall, our results demonstrate evidence of the safety of efavirenz when used from the start of pregnancy with no clinically relevant differences in the risk of birth defects compared with infants exposed to non-efavirenz based regimens or non-exposed to antiretroviral therapy,” Professor Martinez de Tejada concludes.