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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    ABSTRACT: Background In the Highly Active Antiretroviral Therapy (HAART) era, the prognosis of children perinatally infected with HIV-1 has significantly improved, so the number of perinatally-infected females entering child-bearing age and experiencing motherhood is increasing. Methods A description of the medical history and pregnancy outcomes of women with perinatal acquired HIV-1 infection enrolled in the Italian Register for HIV infection in Children. Results Twenty-three women had 29 pregnancies. They had started an antiretroviral therapy at a median of 7.7 years (interquartile range, IQR 2.3 - 11.4), and had experienced a median of 4 therapeutic regimens (IQR 2–6). Twenty women (87%) had taken zidovudine (AZT) before pregnancy, in 14 cases as a starting monotherapy. In 21 pregnancies a protease inhibitor-based regimen was used. At delivery, the median of CD4+ T lymphocytes was 450/μL (IQR 275–522), and no viral load was detectable in 15 cases (reported in 21 pregnancies). Twenty-eight children were delivered through caesarean section (median gestational age: 38 weeks, IQR 36–38, median birth weight: 2550 grams, IQR 2270 – 3000). Intravenous AZT was administered during delivery in 26 cases. All children received oral AZT (median: 42 days, IQR 31 – 42), with no adverse events reported. No child acquired HIV-1 infection. Conclusions Despite a long history of maternal infection, multiple antiretroviral regimens and, perhaps, the development of drug-resistant viruses, the risk of mother-to-child transmission does not seem to have increased among the second-generation of HIV-1 exposed infants.
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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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    ABSTRACT: Women living with HIV have fertility desires and intentions that are similar to those of uninfected women, and with advances in treatment most women can realistically plan to have and raise children to adulthood. Although HIV may have adverse effects on fertility, recent studies suggest that antiretroviral therapy may increase or restore fertility. Data indicate the increasing numbers of women living with HIV who are becoming pregnant, and that many pregnancies are unintended and contraception is underutilized, reflecting an unmet need for preconception care (PCC). In addition to the PCC appropriate for all women of reproductive age, women living with HIV require comprehensive, specialized care that addresses their unique needs. The goals of PCC for women living with HIV are to prevent unintended pregnancy, optimize maternal health prior to pregnancy, improve maternal and fetal outcomes in pregnancy, prevent perinatal HIV transmission, and prevent HIV transmission to an HIV-uninfected sexual partner when trying to conceive. This paper discusses the rationale for preconception counseling and care in the setting of HIV and reviews current literature relevant to the content and considerations in providing PCC for women living with HIV, with a primary focus on well-resourced settings.
    Full-text · Article · Oct 2012 · Infectious Diseases in Obstetrics and Gynecology
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    • "First-trimester exposure to efavirenz is believed to be associated with an increased risk of congenital abnormalities [14, 15], although one systematic review disagrees [16]. In these data, 522 (72%) of pregnancies were exposed to efavirenz. "
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