Efavirenz in pregnancy: update of systemic review and meta-analysis

Polly Clayden HIV i-Base

A systematic review and meta-analysis by Nathan Ford and colleagues, to February 2010, showed no increase in overall birth defects with efavirenz (EFV) use in the first trimester of pregnancy compared to other antiretrovirals or the general population. [1,2] But, the authors were unable to come to a definitive conclusion concerning the risk of rare outcomes such as neural tube defects due to the limited number of reports.

The same authors recently updated the meta-analysis to July 2011 and these findings were published ahead of print as a research letter in AIDS. [3]

This update found 181 additional live births with first trimester efavirenz exposure.

Across 21 studies, included in the analysis, 39 defects were reported among live births to 1437 women. The pooled prevalence of birth defects was 2% (95% CI, 0.82-3.18%) and ranged from 0% to 22.6%. There was one neural tube defect (myelomeningocele), an incidence proportion of 0.07% (95% CI, 0.002-0.39%). Prevalence appeared to be higher in developed countries compared to developing ones, p=0.015.

An analysis of the 11 studies that reported birth defects among women receiving EFV-containing regimens (38 defects from 1289 live births) vs non-EFV regimens (316 defects from 8122 live births) gave a relative risk of 0.85 (95% CI, 0.61-1.20).

There was variable reporting of secondary outcomes across the studies: 8 reported spontaneous abortion (prevalence range 0% to 16.05%); 8 stillbirth (prevalence range 0% to 13.3%), 5 preterm delivery (prevalence range 9.1% to 18.2%) and 10 termination of pregnancy (prevalence range 0% to 33.7%). From the three studies that reported termination of pregnancy for EFV-exposed vs non-exposed pregnancies, the relative risk for termination of pregnancy with EFV exposure was 2.81 (95% CI, 0.94-8.36).

The authors wrote that this expanded review confirms the findings from their previous meta-analysis. The pooled prevalence of defects for first trimester EFV-exposed births of 2% is similar to that reported for first trimester non-EFV exposed births in the Antiretroviral Pregnancy Registry of 2.9% and in the general population of 6%. They note that the incidence of neural tube defects of 0.07% remains low.

They add that the main limitation of the review is the small sample size, with over 80% of the data coming from just four studies where prospective reporting of birth outcomes has been established. With data for only 181 found for the update in the 18 months since the original review, “Prospective surveillance systems particularly in developing countries are needed to improve data reporting and inform the assessment of rare birth defects”, they wrote.


That there were data for, what would work out as, an average of ten efavirenz-exposed pregnancies reported per month since the previous analysis definitely highlights the authors conclusion.

If more countries go down the same path as Malawi and recommend universal efavirenz-based HAART (lifelong from initiation) for pregnant women, it is hoped that there will be good surveillance systems with these programmes to help to improve the numbers.


  1. Ford N et al. Safety of efavirenz in first trimester of pregnancy: a systematic review and meta-analysis of outcomes from observational cohorts. AIDS 2010; 24:1461-70.
  2. Clayden P. Pregnancy outcomes with efavirenz. HTB June 2010
  3. Ford N et al. Safety of efavirenz in first-trimester of pregnancy: an updated systematic review and meta-analysis. AIDS DOI:10.1097/QAD.0b013e32834cdb71

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