1. Rethinking the risk-benefit ratio of efavirenz in HIV-infected children.
- Author
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Van de Wijer L, Schellekens AFA, Burger DM, Homberg JR, de Mast Q, and van der Ven AJAM
- Subjects
- Africa, Alkynes, Benzoxazines metabolism, Benzoxazines toxicity, Central Nervous System Diseases chemically induced, Child, Cognition drug effects, Cyclopropanes, HIV Infections blood, Humans, Odds Ratio, Benzoxazines therapeutic use, HIV Infections drug therapy, HIV-1 drug effects, Reverse Transcriptase Inhibitors therapeutic use
- Abstract
The non-nucleoside reverse transcriptase inhibitor efavirenz is part of the WHO guidelines for preferred first-line treatment of HIV-1-infected adults, pregnant and lactating women, and children. Efavirenz is well known to cause CNS toxicity. Although good data for CNS toxicity are available for adults, the opposite is true for children. Paediatric studies on this topic frequently suffer from small sample sizes or absence of thorough neuropsychiatric assessments. In this Personal View, we focus on two knowledge gaps of CNS toxicity of efavirenz in children. First, plasma concentrations of efavirenz are difficult to predict in children because of immaturity of and genetic variation in metabolic enzymes. Second, efavirenz exerts a lysergide (LSD)-like effect on brain serotonergic pathways and affects CNS metabolic pathways, including mitochondrial function. Whether these effects interfere with normal brain development is unknown. These uncertainties underline the imminent need for better monitoring of mental health and neurocognitive development in children given and exposed to efavirenz., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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