First-line ART for pregnant and breastfeeding women and ARV drugs for their infants

Consolidated ARV guidelines, June 2013

Rationale and supporting evidence: Safety of EFV in pregnancy

Early data suggesting birth defects, including anencephaly, microphthalmia and cleft palate among primates with EFV exposure in utero (141) and some isolated case reports and retrospective clinical data on neural tube defects among humans (142) have led to concern about using EFV in the first trimester of pregnancy or in non-pregnant women with childbearing potential.

The United States Food and Drug Administration and European Medicines Agency advise against using EFV in the first trimester and in women of childbearing potential unless the potential benefits outweigh the potential risks; however, the British HIV Association recently changed its recommendation to allow EFV to be used in the first trimester (143).

Because the risk of neural tube defects is limited to the first five to six weeks of pregnancy and because pregnancy is rarely recognized this early, especially in resource-limited settings, any potential risk of neural tube defects with the use of EFV would be primarily in women who become pregnant while already receiving EFV.

Evaluation of prospectively collected data in humans is reassuring; an updated systematic review and meta-analysis, including the Antiretroviral Pregnancy Registry (47 134) , reported outcomes for 1502 live births to women receiving EFV in the first trimester and found no increase in overall birth defects and no elevated signal for EFV compared with other ARV exposure in pregnancy (140). With one identified neural tube defect, the estimated prevalence from the systematic review continues to be about 7 per 10 000 population (0.07%), which is comparable to the estimates of 0.02–0.2% in the general population in the USA (138).

Because neural tube defects are relatively rare events and there are limited exposures in the Antiretroviral Pregnancy Registry and in the meta-analyses, current available data are sufficient to rule out a potential increased risk greater than three-fold or up to 0.21% (the more limited data available for the 2010 guidelines were sufficient to rule out a 10-fold increased risk).

Although the Guidelines Development Group emphasized that better data on birth defects are needed, it felt confident that this potential low risk should be balanced against the programmatic advantages and the clinical benefit of EFV in preventing HIV infection in infants and for the mother’s health.