Birth defects following efavirenz exposure in a South African Hospital

Although efavirenz is FDA pregnancy category D, the teratogenic risk is still uncertain. The Antiretroviral Pregnancy Registry has recorded birth defects in 14/477 (2.9%) live births.

Data from the MRC Centre of Epidemiology for Child Health, UCL Institute of Child Health, University College London, showed birth defects occurred in 5/205 (2.4%) infants with early pregnancy exposure.

A paper in the January 2010 edition of AIDS authored by Ebrahim Bera and colleagues describes findings from a regional South African cohort of pregnant women exposed to efavirenz. This is the largest study to date of efavirenz based HAART exposure from the second trimester onwards.

This study evaluated data from the Efavirenz in Pregnancy Registry which was set up in January 2006. The registry is prospective and based at Frere Hospital in East London, a referral hospital for a large area of the Eastern Cape. Women who conceived on efavirenz and presented in the first trimester were offered the choice of termination of pregnancy (to 20 weeks gestation) or switched to another drug. Women who presented at 14 weeks or later and eligible for HAART were initiated on an efavirenz-based regimen.

The investigators reported that between 1 January 2006 and 31 December 2008, 744 women were initiated on efavirenz-based regimens from the second trimester onward. Of these, 89 women were still pregnant at the time of evaluation and 32 were lost to follow up.

During the same period, 220 women conceived while receiving efavirenz based HAART and 42 nevirapine-based HAART. Of this group, 17 and seven women were still pregnant and eight and two women were lost to follow up receiving efavirenz and nevirapine respectively.

The investigators classified women who had received efavirenz-base HAART throughout the entire first trimester as complete first trimester exposure and those who substituted efavirenz for another drug as partial first trimester exposure.

The 623 women initiated on efavirenz in pregnancy were a median age of 28 (IQR 25-32) years with median of 9 (IQR 4-13) weeks of HAART. Birth defects occurred in 16 live births, a prevalence of 2.6% (95% CI 1.5-4.2). The 195 women who conceived while receiving efavirenz were a median age of 30 (27-34) years, with a median of 39 (37-40) weeks of HAART. Birth defects occurred in 5/184 live births and 1/4 stillbirths, a prevalence of 3.3% (95% CI 1.2-7.0). The investigators noted that 93% of this group, received efavirenz based HAART for longer than one month before conception and all pregnancies were unintended.

There were no significant differences in the prevalence of birth defects between the first and second/third trimester exposure (prevalence ratio 1.27; 95%CI: 0.5-3.20; p=0.301). Neither were there differences between complete (4/131; 3.1%) and partial (2/53; 3.8%) efavirenz exposure (prevalence ratio 0.81: 95% CI: 0.15-4.29; p=0.556).

The investigators also observed a birth defect in 1/33 live nevirapine exposed infants, a prevalence of 3.0% (95% CI 0.1-15.8). The prevalence ratio of birth defects following conception on efavirenz compared to nevirapine was 1.08; 95% CI: 0.13-8.65; p=0.69. However the numbers of nevirapine exposures are too small to draw any conclusions.

The investigators suggested that these data provide some reassurance on second/third line trimester efavirenz use for pregnant women. There were too few first trimester exposures in this study to make any recommendations concerning the safety or teratogenicity of efavirenz during this period.

COMMENT

This data adds to, and is consistent with, the existing experience of first trimester exposure to efavirenz. This study also provides significant new data on second and third trimester only exposure that is generally reassuring.

Bera E et al. Birth defects following exposure to efavirenz-based antiretroviral therapy during pregnancy: a study at a regional South African hospital. AIDS 24(2):283-289, January 2010.