Pharmacogenetics of Efavirenz in HIV Therapy

Efavirenz remains a cornerstone non-nucleoside reverse transcriptase inhibitor in global antiretroviral regimens, valued for once-daily dosing and potent viral suppression. Its metabolism is chiefly mediated by the cytochrome P450 enzyme CYP2B6, whose genetic variants govern inter-individual differences in drug clearance, plasma exposure and risk of central nervous system toxicity. Common loss-of-function alleles such as CYP2B6*6 and CYP2B6*18 are associated with slower efavirenz elimination, elevated steady-state concentrations and an increased incidence of adverse neuropsychiatric effects at standard doses. Conversely, extensive metabolisers may require higher or unadjusted dosing to maintain therapeutic levels and prevent virological failure. Population-specific allele frequencies drive regional variability in both efficacy and safety profiles, highlighting the need for tailored dosing guidelines. Integration of pharmacogenetic testing with therapeutic drug monitoring and physiologically-based pharmacokinetic modelling supports precision dosing approaches, particularly where co-medications and physiological factors further modify efavirenz pharmacokinetics. Ultimately, pharmacogenetic insights into CYP2B6 and related pathways aim to optimise virological control while minimising adverse events across diverse patient populations.

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Pharmacogenetics of Efavirenz in HIV Therapy publication trend

The graph below shows the total number of articles in pharmacogenetics of efavirenz in hiv therapy across all publications each year (not limited to Nature Index journals).

Technical terms

Pharmacogenetics: The study of how inherited genetic differences influence individual responses to drugs, including efficacy and risk of adverse effects.

CYP2B6: A member of the cytochrome P450 enzyme family that metabolises efavirenz and other medications; genetic variants alter its metabolic activity.

Single nucleotide polymorphism (SNP): A variation at a single base pair in the genome that can affect gene function and drug metabolism.

Physiologically-based pharmacokinetic (PBPK) model: A computational simulation that predicts drug absorption, distribution, metabolism and excretion using physiological parameters and enzyme kinetics.

Non-nucleoside reverse transcriptase inhibitor (NNRTI): A class of antiretroviral drugs that bind directly to HIV reverse transcriptase, blocking viral replication without requiring intracellular activation.

References

1. A Physiologically-Based Pharmacokinetic Simulation to Evaluate Approaches to Mitigate Efavirenz-Induced Decrease in Levonorgestrel Exposure with a Contraceptive Implant. Pharmaceutics (2024).
2. Functional significance of CYP2B6 gene rare allelic variants identified in Japanese individuals. Biochemical Pharmacology (2024).
3. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2B6 and Efavirenz‐Containing Antiretroviral Therapy. Clinical Pharmacology & Therapeutics (2019).
4. CYP2B6*6, CYP2B6*18, Body weight and sex are predictors of efavirenz pharmacokinetics and treatment response: population pharmacokinetic modeling in an HIV/AIDS and TB cohort in Zimbabwe. BMC Pharmacology and Toxicology (2015).
5. Pharmacogenetics of cytochrome P450 2B6 (CYP2B6): advances on polymorphisms, mechanisms, and clinical relevance. Frontiers in Genetics (2013).
6. CYP2B6 Functional Variability in Drug Metabolism and Exposure Across Populations—Implication for Drug Safety, Dosing, and Individualized Therapy. Frontiers in Genetics (2021).