The Pharmacogenetics of Efavirenz Metabolism in Children: The Potential Genetic and Medical Contributions to Child Development in the Context of Long‐Term ARV Treatment

Abstract

Efavirenz (EFV) is a well‐known, effective anti‐retroviral drug long used in first‐line treatment for children and adults with HIV and HIV/AIDS. Due to its narrow window of effective concentrations, between 1 and 4 μg/mL, and neurological side effects at supratherapeutic levels, several investigations into the pharmacokinetics of the drug and its genetic underpinnings have been carried out, primarily with adult samples. A number of studies, however, have examined the genetic influences on the metabolism of EFV in children. Their primary goal has been to shed light on issues of appropriate pediatric dosing, as well as the manifestation of neurotoxic effects of EFV in some children. Although EFV is currently being phased out of use for the treatment of both adults and children, we share this line of research to highlight an important aspect of medical treatment that is relevant to understanding the development of children diagnosed with HIV.

Introduction to the Issue

“…To project useful arenas of future research, Penner et al. (Chapter 6, this issue; Penner et al, 2020) and Tan et al (Chapter 7, this issue; Tan et al, 2020) have conducted reviews in two diverse yet relevant topics: the potential of community‐based interventions to mitigate the direct and indirect effects of HIV on adolescent mental health; and the role of genetics, both at the population and individual level, in the determination of anti‐retroviral dosage for optimal treatment delivery for children across all ages and in different parts of the world. Both of these reviews are timely as we should continue to extend our focus on the farther outcomes of sustainable treatments that are culturally and individually appropriate for the long haul.…”

“…Tan et al. (Chapter 7, this issue; Tan et al, 2020) attempt to illustrate this argument using the case of Efavirenz, a former first‐line drug for pediatric HIV, the metabolism of which is highly affected by gene variants whose population distributions differ from one world region to the next. Optimal dosage, in other words, may differ from one nation or race to another.…”