ArticleBMC pharmacology & toxicology2015
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.
Article in BMC pharmacology & toxicology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 77 citations in OpenAlex.
- Meta-analysis of the associations of CYP2B6-516G>T polymorphisms with efavirenz-induced central nervous system side effects and virological outcome in HIV-infected adults.The pharmacogenomics journal · 2020Pooled it
- Pharmacokinetics of efavirenz in patients on antituberculosis treatment in high human immunodeficiency virus and tuberculosis burden countries: A systematic review.British journal of clinical pharmacology · 2018Pooled it
- A population pharmacokinetic model is beneficial in quantifying hair concentrations of ritonavir-boosted atazanavir: a study of HIV-infected Zimbabwean adolescents.BMC pharmacology & toxicology · 2020Trial
- Population Pharmacokinetic Modeling To Estimate the Contributions of Genetic and Nongenetic Factors to Efavirenz Disposition.Antimicrobial agents and chemotherapy · 2017Trial
- Why Did I Stop? Barriers and Facilitators to Uptake and Adherence to ART in Option B+ HIV Care in Lilongwe, Malawi.PloS one · 2016Trial
- Immunological Determinants of Oncogenic Virus-Driven Cancers in Africa: Mechanisms, Co-Infections and Public Health Challenges.Pathogens (Basel, Switzerland) · 2026Review
- Africa finally has its own drug-regulation agency - and it could transform the continent's health.Nature · 2025Article
- Population Pharmacokinetic-Pharmacogenetic (PopPK-PGx) Model of Efavirenz in HIV-1-Infected Patients.Cureus · 2025Article
- PBPK Modeling of Lamotrigine and Efavirenz during Pregnancy: Implications for Personalized Dosing and Drug-Drug Interaction Management.Pharmaceutics · 2024Article
- Severe efavirenz associated neurotoxicity: A retrospective cohort study.Southern African journal of infectious diseases · 2023Article
- Pharmacogenetics of Breast Cancer Treatments: A Sub-Saharan Africa Perspective.Pharmacogenomics and personalized medicine · 2022Review
- Predictors of Efavirenz Plasma Exposure, Auto-Induction Profile, and Effect of Pharmacogenetic Variations among HIV-Infected Children in Ethiopia: A Prospective Cohort Study.Journal of personalized medicine · 2021Article
- Large variability in plasma efavirenz concentration in Papua New Guinea HIV/AIDS patients associated with high frequency of CYP2B6 516T allele.Clinical and translational science · 2021Article
- Associations between Antiretrovirals and Cognitive Function in Women with HIV.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Article
- CYP2B6 Functional Variability in Drug Metabolism and Exposure Across Populations-Implication for Drug Safety, Dosing, and Individualized Therapy.Frontiers in genetics · 2021Review
- Association ofPharmacogenomics and personalized medicine · 2021Article
- PromotingInternational journal of environmental research and public health · 2020Review
- A review of clinical pharmacogenetics Studies in African populations.Personalized medicine · 2020Review
- Impact of Population and Pharmacogenetics Variations on Efavirenz Pharmacokinetics and Immunologic Outcomes During Anti-Tuberculosis Co-Therapy: A Parallel Prospective Cohort Study in Two Sub-Sahara African Populations.Frontiers in pharmacology · 2020Article
- Heterogeneity in neurocognitive change trajectories among people with HIV starting antiretroviral therapy in Rakai, Uganda.Journal of neurovirology · 2019Observational
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEfavirenz (EFV) therapeutic response and toxicity are associated with high inter-individual variability attributed to variation in its pharmacokinetics. Plasma concentrations below 1 μg/ml may result in virologic failure and above 4 μg/ml, may result in central nervous system adverse effects. This study used population pharmacokinetics modeling to explore the influence of demographic and pharmacogenetic factors including efavirenz-rifampicin interaction on EFV pharmacokinetics, towards safer dosing of EFV.
methodsPatients receiving an EFV-based regimen for their antiretroviral therapy and a rifampicin-containing anti-TB regimen were recruited. EFV plasma concentrations were measured by HPLC and genomic DNA genotyped for variants in the CYP2B6, CYP2A6 and ABCB1 genes. All patients were evaluated for central nervous system adverse effects characterised as sleep disorders, hallucinations and headaches using the WHO ADR grading system. A pharmacokinetic model was built in a forward and reverse procedure using nonlinear mixed effect modeling in NONMEM VI followed by model-based simulations for optimal doses.
resultsCYP2B6*6 and *18 variant alleles, weight and sex were the most significant covariates explaining 55% of inter-individual variability in EFV clearance. Patients with the CYP2B6*6TT genotype had a 63% decrease in EFV clearance despite their CYP2B6*18 genotypes with females having 22% higher clearance compared to males. There was a 21% increase in clearance for every 10 kg increase in weight. The effect of TB/HIV co-treatment versus HIV treatment only was not statistically significant. No clinically relevant association between CYP2B6 genotypes and CNS adverse effects was seen, but patients with CNS adverse effects had a 27% lower clearance compared to those without. Model- based simulations indicated that all carriers of CYP2B6*6 TT genotype would be recommended a dose reduction to 200 mg/day, while the majority of extensive metabolisers may be given 400 mg/day and still maintain therapeutic levels.
conclusionThis study showed that screening for CYP2B6 functional variants has a high predictability for efavirenz plasma levels and could be used in prescribing optimal and safe EFV doses.
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