Increased incidence of miscarriage with efavirenz use

Despite being contraindicated in pregnancy an increasing number of women are becoming pregnant while receiving efavirenz-containing regimens.

A poster authored by Esau Joao and co-workers from the Hospital dos Servidores do Estado, Rio de Janeiro, Brazil, reported findings from a case note review to evaluate adverse pregnancy outcomes after exposure to efavirenz during the first trimester among women in their cohort.

The authors found 969 women had received any ARV prophylaxis or treatment in pregnancy between January 1996 and December 2006. 19.6% became pregnant while receiving ART. 776 women were unexposed at conception, 47 received mono or dual therapy with nucleosides, 36 ART with efavirenz and 107 women received other ART regimens. The median duration of exposure to efavirenz and other ART regimens were 13 and 19 weeks respectively.

There was 0.4% incidence of miscarriage among women receiving no ART at conception; 2.1% with mono or dual nucleosides; 11.1% with efavirenz-containing ART and 4.8% with other ART, p<0.005.

Additionally, the authors reported 19/874 (2.2%) congenital abnormalities (background population in Rio de Janeiro in 2004, 0.8%), 17 occurred in infants born to women without any ARV exposure at conception.

Two birth defects were observed in infants born to women receiving ART in the first trimester: one infant exposed to NVP+3TC+ d4T was born with patent foramen ovale, pulmonary valve stenosis and mitral valve hypoplasia and another exposed to AZT+ 3TC+EFV was born with pulmonary valve stenosis.

The authors suggested that the higher rate (11.1%) of miscarriage that occurred among women receiving efavirenz at conception in this cohort could actually represent early congenital malformations.

Comment

These data should be treated with extreme caution. The miscarriage rate reported from this notes review is extremely low (1.38%). It is generally thought that approximately 30% of conceptions are miscarried.

The potential for biased reporting is very high and this is more likely to be seen with efavirenz than other antiretroviral drugs.

Although the congenital anomaly rate is reported to be more than twice the background for Rio de Janeiro (2.2% v 0.8%) the later figure is only about one third of the normally cited of congenital malformations and 2.2% is a more realistic figure.

Joao E, Calvert G, Sidi L et al. Increased incidence of spontaneous abortion during first trimester exposure to efavirenz. 4th IAS conference, Sydney, 2007. Poster abstract TUPEB113.