Meta-analysis suggests efavirenz does not increase risk of birth abnormalities

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Treatment with efavirenz during the first three months of pregnancy does not increase the risk of birth abnormalities, according to the results of a systematic review and meta-analysis published in the online edition of AIDS.

The prevalence of neural tube defects in infants exposed to efavirenz during the first three months of gestation was 0.08% – well within the range seen in the wider population.

“Our systematic review of the available evidence to date found no increased risk of overall birth defects among women exposed to efavirenz during the first trimester of pregnancy compared with exposure to other antiretroviral drugs,” comment the investigators.


systematic review

A review of the findings of all studies which relate to a particular research question and which conform to pre-determined selection criteria. 

observational study

A study design in which patients receive routine clinical care and researchers record the outcome. Observational studies can provide useful information but are considered less reliable than experimental studies such as randomised controlled trials. Some examples of observational studies are cohort studies and case-control studies.

relative risk

Comparing one group with another, expresses differences in the risk of something happening. For example, in comparison with group A, people in group B have a relative risk of 3 of being ill (they are three times as likely to get ill). A relative risk above 1 means the risk is higher in the group of interest; a relative risk below 1 means the risk is lower. 

sample size

A study has adequate statistical power if it can reliably detect a clinically important difference (i.e. between two treatments) if a difference actually exists. If a study is under-powered, there are not enough people taking part and the study may not tell us whether one treatment is better than the other.


Studies aim to give information that will be applicable to a large group of people (e.g. adults with diagnosed HIV in the UK). Because it is impractical to conduct a study with such a large group, only a sub-group (a sample) takes part in a study. This isn’t a problem as long as the characteristics of the sample are similar to those of the wider group (e.g. in terms of age, gender, CD4 count and years since diagnosis).

However, they note that most of the observational studies included in their analysis were small and often had other limitations.

The international team of investigators conducted their analysis because there are conflicting data about the use of efavirenz and the risk of birth abnormalities during pregnancy.

Treatment guidelines have adopted a cautious approach towards the use of the drug by pregnant women. Some recommend that the use of the drug should be avoided during the first trimester, whereas others state that the drug should not be used at all during pregnancy. Irrespective of these guidelines, many HIV-positive women become pregnant when taking the drug, so a better understanding of its potential risks is needed.

A literature search identified a total of 16 observational studies reporting on the incidence of birth abnormalities in women taking efavirenz during the first trimester of pregnancy. Most (eleven) of these studies were prospective, five were retrospective, and nine were conducted in resource-limited settings.

There were a total of 1132 live births amongst women treated with efavirenz during the first three months of therapy, and 35 birth abnormalities were recorded.

Of the 7163 women who took a combination of antiretroviral drugs that did not include efavirenz in the first trimester, a total of 289 birth abnormalities were observed.

The investigators’ statistical analysis showed that therapy which included efavirenz did not increase the risk of birth abnormalities (relative risk, 0.87; 95% CI: 0.61 to 1.24, p = 0.45).

Overall, the incidence of birth abnormalities amongst women who received efavirenz was 2.9%. The investigators note that this is very close “to the ranges reported in the general population; 2.7% in the United States, 2-5% in France, and 2.5-8% in South Africa.”

Only one efavirenz-exposed infant was born with neural tube defects, providing an incidence rate of 0.08%, “giving a point prevalence that is within the range reported among the general population in the United Kingdom (0.14%).”

“These data should provide reassurance to healthcare providers confronted with women who become pregnant while on efavirenz,” conclude the investigators.

However, they note that the quality of the studies included in their analysis was “low.” Five studies failed to consider potential bias, and only three studies adjusted for potentially confounding factors. Moreover, the studies were limited by their small sample size and event rate.

The investigators call for the establishment of registries, especially in African countries, to report on the outcomes of infants exposed to efavirenz in the first trimester.


Ford N et al. Safety of efavirenz in first-trimester of pregnancy: a systematic review and meta-analysis of outcomes from observational studies. AIDS, advance online publication, DOI: 10.1097/QAD.0b013e32833a2a14, 2010.