Abstract & Commentary
A Reassurring Analysis on the Safety of Efavirenz in Pregnancy
By Dean L. Winslow, MD, FACP, FIDSA, Chief, Division of AIDS Medicine, Santa Clara Valley Medical Center; Clinical Professor, Stanford University School of Medicine, is Associate Editor for Infectious Disease Alert.
Dr. Winslow is a speaker for Cubist Pharmaceuticals and GSK, and is a consultant for Siemens Diagnostics
Synopsis: A meta-analysis of 21 studies was conducted. In these studies, there were 39 birth defects in 1437 pregnancies where the mother received efavirenz during the first trimester. The relative risk of defects in women who received efavirenz vs. those who received non-efavirenz-based regimens was 0.85.
Source: Ford N, et al. Safety of efavirenz in first-trimester of pregnancy: an updated systematic review and meta-analysis. AIDS 2011; 25: (epub ahead of print).
An updated meta-analysis of birth defects in infants with first trimester efavirenz exposure was conducted and included published literature up until July 2011. In 21 studies included in the analysis, 39 defects were observed among 1437 women receiving first trimester efavirenz (2% incidence). 316 defects were reported in 8122 live births among women who received first trimester non-efavirenz-containing regimens (2.9% incidence) yielding a relative risk of 0.85 for women receiving first trimester efavirenz. One neural tube defect (myelomengocele) was observed in an infant born to a woman who received efavirenz in the first trimester (0.07% incidence).
Commentary
Concerns about efavirenz-induced fetal effects began after a DuPont teratogenicity trial conducted in cynomolgus monkeys was reported1. In this trial, monkeys were exposed to efavirenz at concentrations similar to those expected in humans receiving the standard 600 mg/day dose. No congenital malformations were observed in 20 control animals, but 3 of 20 efavirenz-exposed infants had major abnormalities. These included anencephaly and unilateral anopthalmia in one monkey, micropthalmia in a second animal, and cleft palate in a third infant monkey.
Retrospective reports have described four cases of CNS malformations in human infants with first trimester efavirenz exposure2. (Three infants had myelomeningocele and one had Dandy-Walker malformation.) It should be pointed out that retrospective case reports of potential teratogenic effects of drug exposures in humans are difficult to interpret since neural tube defects are among the most commonly-observed birth defects (about 1 in 1,000 pregnancies). In many cases these likely represent "background" occurrences rather than events caused by a particular prenatal exposure.
This thorough meta-analysis by Ford et al is reassuring that congenital malformations are not likely to be caused by efavirenz in humans. While avoiding efavirenz use in HIV-infected women during the first trimester of pregnancy is still prudent, it should allay excessive concern when this exposure inadvertently occurs for a short period of time when a woman becomes pregnant while receiving efavirenz.
References
- Nightingale, SL. From the FDA. JAMA 1998;280:1472
- Chersich MF, et al. Efavirenz use during pregnancy and for women of child-bearing potential. AIDS Res Ther 2006; 3:1-6.
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