ArticleThe Journal of antimicrobial chemotherapy2019
Pharmacogenetics and pharmacokinetics of CNS penetration of efavirenz and its metabolites.
Article in The Journal of antimicrobial chemotherapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 17 citations in OpenAlex.
- Blood and cerebrospinal fluid biomarker changes in patients with HIV-associated neurocognitive impairment treated with lithium: analysis from a randomised placebo-controlled trial.Journal of neurovirology · 2023Trial
- Efavirenz metabolism and CNS toxicity in Ugandan children: impact of CYP2B6 genotype and plasma metabolite profiles.Frontiers in pharmacology · 2026Article
- Interactions between ABC gene polymorphisms and processing speed in predicting depression severity.BMC psychiatry · 2025Article
- Pharmacogenetics of Breast Cancer Treatments: A Sub-Saharan Africa Perspective.Pharmacogenomics and personalized medicine · 2022Review
- Pharmacogenetics of tenofovir and emtricitabine penetration into cerebrospinal fluid.Southern African journal of HIV medicine · 2021Article
- Barriers to Implementing Clinical Pharmacogenetics Testing in Sub-Saharan Africa. A Critical Review.Pharmaceutics · 2020Review
- The neurologic phenotype of South African patients with HIV-associated neurocognitive impairment.Neurology. Clinical practice · 2020Article
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundThere are limited data on the pharmacogenetics and pharmacokinetics of the CNS penetration of efavirenz.
objectivesWe investigated genetic polymorphisms associated with CSF concentrations of efavirenz and its metabolites and explored the relationships with neurocognitive performance.
methodsWe included 47 HIV-infected South African black adults with and without HIV-associated neurocognitive disorder on efavirenz/tenofovir/emtricitabine and collected paired plasma-CSF samples. We considered 2049 SNPs, including SNPs known to affect plasma efavirenz exposure, from potentially relevant genes (ABCC5, ABCG2, ABCB1, SLCO2B1, SCLO1A2, ABCC4, CYP2B6 and CYP2A6) and 880 met a linkage disequilibrium (LD)-pruning threshold.
resultsWe identified 9 slow, 21 intermediate and 17 extensive metabolizers. The CYP2B6 983 genotype in multivariate analyses predicted log10-transformed concentrations of plasma efavirenz (β = 0.38, P = 2.7 × 10-03), plasma 7-hydroxy-efavirenz (β = 0.59, P = 3.7 × 10-03), plasma 8-hydroxy-efavirenz:efavirenz ratio (β = -0.31, P = 1.8 × 10-04) and CSF efavirenz (β = 0.36, P = 0.01). Lower plasma 7-hydroxy-efavirenz concentrations were independently associated with CYP2A6 rs10853742 (β = -0.55, P = 3.5 × 10-05), ABCB1 rs115780656 (β = -0.65, P = 4.1 × 10-05) and CYP2A6 -48A→C (β = -0.59, P = 0.01). CYP2A6 -48A→C was independently associated with higher CSF 8-hydroxy-efavirenz:efavirenz ratio (β = 0.54, P = 0.048). CYP2B6 rs2279345 polymorphism was associated with lower plasma 7-hydroxy-efavirenz:efavirenz ratio in multivariate analyses (P < 0.05). No polymorphisms were associated with CSF:plasma ratios of efavirenz, plasma or CSF concentrations of 8-hydroxy-efavirenz or neurocognitive performance.
conclusionsWe identified novel genetic associations with plasma efavirenz, plasma 7-hydroxy-efavirenz, plasma 7-hydroxy-efavirenz:efavirenz ratio, plasma 8-hydroxy-efavirenz:efavirenz ratio, CSF efavirenz and CSF 8-hydroxy-efavirenz:efavirenz ratio.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.