Safety of efavirenz in first-trimester of pregnancy: A systematic review and meta-analysis of outcomes from observational cohorts

Médecins Sans Frontières, University of Cape Town, Cape Town, South Africa.
AIDS (London, England) (Impact Factor: 5.55). 06/2010; 24(10):1461-70. DOI: 10.1097/QAD.0b013e32833a2a14
Source: PubMed


Data on efavirenz safety in first trimester pregnancy are conflicting. We conducted a systematic review and meta-analysis of the available evidence from observational cohorts.
We ran duplicate searches of databases (up to 02 January, 2010) and searchable websites of major HIV conferences (up to February, 2010) to identify observational cohorts reporting birth outcomes among women exposed to efavirenz during the first trimester of pregnancy. Our primary endpoint was birth defects of any kind; secondary outcomes were spontaneous abortions, termination of pregnancy, stillbirths, and preterm delivery.
Sixteen studies met our inclusion criteria, comprising 11 prospective cohorts and five retrospective reviews. Nine prospective studies reported on rates for birth defects both among women exposed to efavirenz-containing regimens (1132 live births) and non-efavirenz-containing regimens (7163 live births) during first trimester, giving a pooled, nonsignificant relative risk of 0.87 [95% confidence interval (CI) 0.61-1.24%, P = 0.45]. Low heterogeneity was observed between studies (I = 0, 95% CI 0-56.3%, P = 0.85). Across all studies (1256 live births), one neural tube defect (meningomyelocele) was observed with first trimester efavirenz exposure, giving a prevalence of 0.08% (95% CI 0.002-0.44%).
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. However, the limited sample size for detection of rare outcomes such as neural tube defects prevents a definitive conclusion.

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    • "Even in this context, our results are reassuring. No congenital abnormalities were noticed, including the child exposed to EFV in the first 5 weeks of gestation [21,22]. Since maternal and neonatal complications due to ART drugs do not seem to be higher in perinatally-infected women, indications should not differ from those commonly recommended in seropositive mothers, for instance HAART should start as soon as possible [15], while stopping ART during pregnancy should be discouraged [12]. "
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    • "If a current ARV regimen is not effective (i.e., suboptimal suppression of viral load), not well tolerated, or associated with significant adverse effects, then it should be modified prior to attempts at conception. Efavirenz (EFV) is the only ARV drug with evidence of teratogenic risk, based on preclinical primate data and retrospective case reports after first trimester human exposure; however, recent data suggest that the risk is likely to be quite low [63]. Nevertheless, in women who are initiating ART prior to attempts to conceive, EFV should be avoided, if possible. "
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