Safety of efavirenz in the first trimester of pregnancy: An updated systematic review and meta-analysis

Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa.
AIDS (London, England) (Impact Factor: 5.55). 09/2011; 25(18):2301-4. DOI: 10.1097/QAD.0b013e32834cdb71
Source: PubMed


Evidence of the risk of birth defects with efavirenz use is limited. We updated a meta-analysis of birth defects in infants with first trimester efavirenz exposure up to July 2011. In 21 studies, there were 39 defects among live births in 1437 women receiving first trimester efavirenz [2.0%, 95% confidence interval (CI) 0.82-3.18]. The relative risk of defects comparing women on efavirenz-based (1290 live births) and nonefavirenz-based regimens (8122 live births) was 0.85 (95% CI 0.61-1.20). One neural tube defect was observed (myelomeningocele), giving an incidence of 0.07% (95% CI 0.002-0.39).

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Available from: Lynne M Mofenson, Aug 29, 2014
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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.
    BMC Infectious Diseases 05/2014; 14(1):277. DOI:10.1186/1471-2334-14-277 · 2.61 Impact Factor
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    • "Efavirenz showed teratogenicity in animal models, but the most recent guidance from the World Health Organization and the British HIV Association does permit continued use of efavirenz in pregnancy [18] [19]. This is because of evidence from a meta-analysis of outcomes in pregnant women treated with efavirenz showing no excess of birth abnormalities [20]. Nevirapine has been associated with severe skin reactions in a minority of patients, including Stevens-Johnsons syndrome, particularly if used in patients with high CD4 counts [7]; hepatotoxicity is an additional issue [21]. "
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    ABSTRACT: Unlike other nonnucleoside reverse transcriptase inhibitors, etravirine is only approved for use in treatment-experienced patients. In the DUET 1 and 2 trials, 1203 highly treatment-experienced patients were randomized to etravirine or placebo, in combination with darunavir/ritonavir and optimized background treatment. In these trials, etravirine showed significantly higher rates of HIV RNA suppression when compared with placebo (61% versus 40% at Week 48). There was no significant rise of lipids or neuropsychiatric adverse events, but there was an increase in the risk of rash with etravirine treatment. In the SENSE trial, which evaluated etravirine and efavirenz in 157 treatment-naïve patients in combination with 2 nucleoside analogues, there was a lower risk of lipid elevations and neuropsychiatric adverse events with etravirine when compared to efavirenz. Etravirine has been evaluated in three randomized switching studies. In the SSAT029 switch trial, 38 patients who had neuropsychiatric adverse events possibly related to efavirenz showed an improvement in these after switching to etravirine. The Swiss Switch-EE recruited 58 individuals without neuropsychiatric adverse events who were receiving efavirenz, and no benefit was shown when switching to etravirine. In the Spanish ETRA-SWITCH trial (), there were improvements in lipids when individuals switched from a protease inhibitor to etravirine. These switching trials were conducted in patients with full HIV RNA suppression: <50 copies/mL and with no history of virological failure or resistance to therapy. The results from these three randomized switching studies suggest a possible new role for etravirine, in combination with two nucleoside analogues, as a switching option for those with HIV RNA suppression but who are reporting adverse events possibly related to antiretroviral therapy. However a large well-powered trial would need to be conducted to strengthen the evidence from the pilot studies conducted so far.
    AIDS research and treatment 02/2014; 2014:636584. DOI:10.1155/2014/636584
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    • "We aimed at developing nanoparticles containing a combination of RAL, an integrase inhibitor and efavirenz, a NNRTI. Although there are concerns about the use of efavirenz as a microbicide due to resistance issues and teratogenicity [107] [108], we used it as a model NNRTI to establish a proof-of-concept. We fabricated PLGA nanoparticles containing a combination of raltegravir and efavirenz (RAL-EFV-NPs) using simple and scalable emulsion-solvent evaporation technique [109]. "
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    Biomaterials 05/2013; 34(26). DOI:10.1016/j.biomaterials.2013.05.012 · 8.56 Impact Factor
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