ArticlePloS one2014
Pharmacogenetic-based efavirenz dose modification: suggestions for an African population and the different CYP2B6 genotypes.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 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
- Initiation of dolutegravir vs efavirenz on 12- and 24-month weight, body mass index, blood pressure, and incident hypertension: A target trial emulation.Annals of epidemiology · 2026Trial
- Variability of efavirenz plasma concentrations among pediatric HIV patients treated with efavirenz based combination antiretroviral therapy in Dar es Salaam, Tanzania.BMC pharmacology & toxicology · 2018Trial
- Pharmacokinetic and Pharmacodynamic Comparison of Once-Daily Efavirenz (400 mg vs. 600 mg) in Treatment-Naïve HIV-Infected Patients: Results of the ENCORE1 Study.Clinical pharmacology and therapeutics · 2015Trial
- Article
- Decision-making and role preferences for receiving individual pharmacogenomic research results among participants at a Ugandan HIV research institute.BMC medical ethics · 2025Article
- 'Research ethics · 2024Article
- Article
- Research Participants' Preferences for Individual Results of Pharmacogenomics Research: A Case of a Ugandan HIV Research Institute.Journal of empirical research on human research ethics : JERHRE · 2023Article
- Genetic and non-genetic factors influencing efavirenz population pharmacokinetics among human immunodeficiency virus-1-infected children in Ethiopia.CPT: pharmacometrics & systems pharmacology · 2023Article
- Effect of pharmacogenetic variations on praziquantel plasma concentration and safety outcomes among school children in Rwanda.Scientific reports · 2023Article
- Pharmacogenomics of Hypertension in Africa: Paving the Way for a Pharmacogenetic-Based Approach for the Treatment of Hypertension in Africans.International journal of hypertension · 2023Review
- 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
- Strategies for Implementation Research to Investigate the Negative Pharmacokinetic Interaction Between Efavirenz and Dolutegravir.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Article
- Association ofPharmacogenomics and personalized medicine · 2021Article
- Effect of Pharmacogenetics Variations on Praziquantel Plasma Concentrations and Schistosomiasis Treatment Outcomes Among Infected School-Aged Children in Tanzania.Frontiers in pharmacology · 2021Article
- Influence ofPharmacogenomics and personalized medicine · 2021Article
- Ethnogeographic and inter-individual variability of human ABC transporters.Human genetics · 2020Article
- 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
- Antiretroviral concentration measurements as an additional tool to manage virologic failure in resource limited settings: a case control study.AIDS research and therapy · 2019Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
Abstract
backgroundPharmacogenetics contributes to inter-individual variability in pharmacokinetics (PK) of efavirenz (EFV), leading to variations in both efficacy and toxicity. The purpose of this study was to assess the effect of genetic factors on EFV pharmacokinetics, treatment outcomes and genotype based EFV dose recommendations for adult HIV-1 infected Ugandans.
methodsIn total, 556 steady-state plasma EFV concentrations from 99 HIV infected patients (64 female) treated with EFV/lamivudine/zidovidine were analyzed. Patient genotypes for CYP2B6 (*6 & *11), CYP3A5 (*3,*6 & *7) and ABCB1 c.4046A>G, baseline biochemistries and CD4 and viral load change from baseline were determined. A one-compartment population PK model with first-order absorption (NONMEM) was used to estimate genotype effects on EFV pharmacokinetics. PK simulations were performed based upon population genotype frequencies. Predicted AUCs were compared between the product label and simulations for doses of 300 mg, 450 mg, and 600 mg.
resultsEFV apparent clearance (CL/F) was 2.2 and 1.74 fold higher in CYP2B6*6 (*1/*1) and CYP2B6*6 (*1/*6) compared CYP2B6*6 (*6/*6) carriers, while a 22% increase in F1 was observed for carriers of ABCB1 c.4046A>G variant allele. Higher mean AUC was attained in CYP2B6 *6/*6 genotypes compared to CYP2B6 *1/*1 (p<0.0001). Simulation based AUCs for 600 mg doses were 1.25 and 2.10 times the product label mean AUC for the Ugandan population in general and CYP2B6*6/*6 genotypes respectively. Simulated exposures for EFV daily doses of 300 mg and 450 mg are comparable to the product label. Viral load fell precipitously on treatment, with only six patients having HIV RNA >40 copies/mL after 84 days of treatment. No trend with exposure was noted for these six patients.
conclusionResults of this study suggest that daily doses of 450 mg and 300 mg might meet the EFV treatment needs of HIV-1 infected Ugandans in general and individuals homozygous for CYP2B6*6 mutation, respectively.
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