Rethinking the risk-benefit ratio of efavirenz in HIV-infected children.
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.
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud university medical center, Nijmegen, Netherlands. Electronic address: L.vandewijer@radboudumc.nl.
Lisa
L
Van de Wijer
Department of Psychiatry, Radboud university medical center, Nijmegen, Netherlands.
Arnt F A
AFA
Schellekens
Department of Pharmacy, Radboud university medical center, Nijmegen, Netherlands.
David M
DM
Burger
Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, Netherlands.
Judith R
JR
Homberg
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud university medical center, Nijmegen, Netherlands.
Quirijn
Q
de Mast
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud university medical center, Nijmegen, Netherlands.
Andre J A M
AJAM
van der Ven
D000349:Africa; D000480:Alkynes; D048588:Benzoxazines / Q000378:metabolism / Q000627:therapeutic use* / Q000633:toxicity; D002493:Central Nervous System Diseases / Q000139:chemically induced; D002648:Child; D003071:Cognition / Q000187:drug effects; D003521:Cyclopropanes; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D016017:Odds Ratio; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; C098320:efavirenz