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Safety of Efavirenz in the First Trimester of Pregnancy: An Updated Systematic Review and Meta-Analysis

Publication year: 
Corporate author: 
Ford, Nathan [et al.]
Publication details: 
USA, Wolters Kluwer Health, 2014
Publication in: 
AIDS 2014, 28 (Suppl 2):S123–S131

Introduction: Primate studies and some observational human data have raised concern
regarding an association of first-trimester efavirenz exposure with central nervous
system congenital anomalies. The objective of this review is to update evidence on
efavirenz safety in HIV-infected pregnant women to inform revision of the 2013 WHO
guidelines for antiretroviral therapy in low and middle-income countries.

Design: A systematic review and meta-analysis.
Methods: We searched for studies reporting birth outcomes among women exposed to
efavirenz during the first trimester of pregnancy up to 10 January 2014. Relative risks of congenital anomalies comparing women exposed to efavirenz and nonefavirenz-based
antiretroviral regimens were pooled using random effects meta-analysis.

Results: Twenty-three studies were included in this review, among which 21 reported
the birth outcomes of 2026 live births among women exposed to efavirenz during the
first trimester of pregnancy. Forty-four congenital anomalies were reported, giving a
pooled proportion of 1.63% [95% confidence interval (95% CI) 0.78–2.48], with only
one neural tube defect. Twelve studies reported birth outcomes of women exposed to
efavirenz or nonefavirenz-containing regimens during the first trimester of pregnancy.
Pooled analysis found no differences in overall risks congenital anomalies between
these two groups (relative risk 0.78, 95% CI 0.56–1.08). The incidence of neural tube
defects was low, 0.05% (95% CI <0.01–0.28), and similar to incidence in the general

Discussion: This updated analysis found no evidence of an increased risk of overall or
central nervous system congenital anomalies associated with first-trimester exposure to
efavirenz, similar to previous systematic reviews. This review contributed to the
evidence base for the revised 2013 WHO guidelines on antiretroviral therapy, which
recommend that efavirenz can be included as part of first-line therapy in adults
regardless of sex, and that it can be used throughout pregnancy, including during
the first trimester. However, because of the low incidence of central nervous system
anomalies in the overall population and relatively small number of exposures in the
current literature, continued birth outcomes prospective surveillance is warranted.