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Large Meta-analysis Finds No Link between Efavirenz (Sustiva) and Birth Defects

A meta-analysis of 16 studies looking at more than 8000 live births to HIV positive mothers found that using efavirenz (Sustiva, also in the Atripla combination pill) during the first trimester of pregnancy was not associated with an increased risk of birth abnormalities, according to a report in the June 19, 2010 issue of AIDS.

Current antiretroviral treatment guidelines recommend that HIV positive pregnant women should not take efavirenz because animal studies indicated a small risk of congenital abnormalities, or birth defects. This recommendation was strongest for the first 3 months of gestation, the period when fetal organs are formed.

Nathan Ford from Médecins Sans Frontièresand colleagues performed a systematic review and meta-analysis of available evidence regarding the link between efavirenz and pregnancy outcomes.

The study authors searched medical literature databases through January 2010 and searchable websites of major HIV conferences through February 2010 to identify observational cohort studies reporting birth outcomes among women exposed to efavirenz during the first trimester of pregnancy.

The primary endpoint was birth defects of any kind. The researchers also looked at neural tube defects (a type of birth defect seen in efavirenz animal studies), spontaneous abortions or miscarriages, induced abortions or pregnancy terminations, stillbirths, and preterm deliveries.


  • 16 studies met the inclusion criteria, including 11 prospective cohort studies and 5 retrospective reviews; about half were conducted in resource-limited settings.
  • 9 prospective studies reported birth defect rates among babies born to women exposed or not exposed to efavirenz-containing regimens during the first trimester.
  • 35 birth abnormalities were reported among 1132 live births to women exposed to efavirenz during early pregnancy.
  • 289 birth defects were reported among 7163 live births to non-efavirenz-exposed women.
  • The overall incidence rate of birth defects among babies born to women exposed to efavirenz was about 3% -- within ranges reported for the general population in both industrialized and developing countries.
  • Across all studies, 1 neural tube defect (meningomyelocele) was observed with first trimester efavirenz exposure, for an incidence rate of 0.08%.
  • The pooled relative risk of birth defects among women who used efavirenz during early pregnancy was 0.87, not significantly different from the rate among unexposed women (P = 0.45).

Based on these findings, the study authors concluded, "We 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."

"Prevalence of overall birth defects with first trimester efavirenz exposure was similar to the ranges reported in the general population," they continued. "However, the limited sample size for detection of rare outcomes such as neural tube defects prevents a definitive conclusion."

Investigator affiliations: Médecins Sans Frontières, South Africa; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa; Pediatric, Adolescent and Maternal AIDS Branch, Center for Research for Mothers and Children, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD; London School of Hygiene and Tropical Medicine, London, UK; Faculty of Health Sciences, Simon Fraser University, Vancouver, Canada; Red Cross Children's hospital, Cape Town, South Africa; Faculty of Health Sciences, University of Ottawa, Canada; Geneva University Hospital, HIV Unit, Service of Infectious Diseases, Geneva, Switzerland.



N Ford, L Mofenson, K Kranzer, and others. Safety of efavirenz in first-trimester of pregnancy: a systematic review and meta-analysis of outcomes from observational cohorts. AIDS 24(10):1461-1470. June 19, 2010.