Observational studyBritish journal of clinical pharmacology2015
Pharmacogenetics of plasma efavirenz exposure in HIV-infected adults and children in South Africa.
Observational study in British journal of clinical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 82 citations in OpenAlex.
- CYP2B6 Genotype and Weight Gain Differences Between Dolutegravir and Efavirenz.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Trial
- Influence of CYP2B6 activity score on the pharmacokinetics and safety of single dose efavirenz in healthy volunteers.The pharmacogenomics journal · 2020Trial
- Why Did I Stop? Barriers and Facilitators to Uptake and Adherence to ART in Option B+ HIV Care in Lilongwe, Malawi.PloS one · 2016Trial
- Pharmacokinetics of Efavirenz in Pregnancy and Postpartum with and Without First-line Tuberculosis Drugs: Results from IMPAACT P1026s.Clinical pharmacokinetics · 2026Article
- Efavirenz metabolism and CNS toxicity in Ugandan children: impact of CYP2B6 genotype and plasma metabolite profiles.Frontiers in pharmacology · 2026Article
- Body weight changes in people with HIV starting dolutegravir versus efavirenz-based regimens in a large cohort in rural Tanzania.AIDS (London, England) · 2025Observational
- Sub- and supratherapeutic efavirenz plasma concentrations with risk for HIV therapy failure are mainly genetically explained in Ugandan children: The prospective GENEFA cohort study.British journal of clinical pharmacology · 2025Article
- Pharmacokinetics, pharmacogenetics, and toxicity of co-administered efavirenz and isoniazid.Southern African journal of HIV medicine · 2025Article
- Drug-induced hepatotoxicity and association with slow acetylation variants NAT2*5 and NAT2*6 in Cameroonian patients with tuberculosis and HIV co-infection.BMC infectious diseases · 2024Article
- Towards Evidence-Based Implementation of Pharmacogenomics in Southern Africa: Comorbidities and Polypharmacy Profiles across Diseases.Journal of personalized medicine · 2023Article
- Pharmacogenetic Aspects of Drug Metabolizing Enzymes and Transporters in Pediatric Medicine: Study Progress, Clinical Practice and Future Perspectives.Paediatric drugs · 2023Review
- Weight gain on dolutegravir: Association is not the same as causation.Southern African journal of HIV medicine · 2023Article
- Polymorphisms at CYP enzymes, NR1I2 and NR1I3 in association with virologic response to antiretroviral therapy in Brazilian HIV-positive individuals.The pharmacogenomics journal · 2022Article
- Pharmacogenetics of Breast Cancer Treatments: A Sub-Saharan Africa Perspective.Pharmacogenomics and personalized medicine · 2022Review
- Potential challenges to sustained viral load suppression in the HIV treatment programme in South Africa: a narrative overview.AIDS research and therapy · 2021Review
- AntiRetroviral Therapy In Second-line: investigating Tenofovir-lamivudine-dolutegravir (ARTIST): protocol for a randomised controlled trial.Wellcome open research · 2021Article
- Inter-ethnic genetic variations and novel variant identification in the partial sequences ofPeerJ · 2021Article
- Association ofPharmacogenomics and personalized medicine · 2021Article
- The Pharmacogenetics of Efavirenz Metabolism in Children: The Potential Genetic and Medical Contributions to Child Development in the Context of Long-Term ARV Treatment.New directions for child and adolescent development · 2020Review
- Drug resistance after cessation of efavirenz-based antiretroviral treatment started in pregnancy.Southern African journal of HIV medicine · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
aimsGenetic factors, notably CYP2B6 516G→T [rs3745274] and 983T→C [rs28399499], explain much of the interindividual variability in efavirenz pharmacokinetics, but data from Africa are limited. We characterized relationships between genetic polymorphisms and plasma efavirenz concentrations in HIV-infected Black South African adults and children.
methodsSteady-state mid-dosing interval efavirenz concentrations were measured. We genotyped 241 polymorphisms in genes potentially relevant to efavirenz metabolism and transport, including ABCB1, CYP2A6, CYP2B6, CYP3A4, CYP3A5, NR1I2 and NR1I3.
resultsAmong 113 participants (59 adults and 54 children), minor allele frequencies for CYP2B6 516G→T, 983T→C, and 15582C→T [rs4803419] were 0.36, 0.07, and 0.09, respectively. Based on composite CYP2B6 15582/516/983 genotype, there were 33 extensive metabolizer, 62 intermediate metabolizer and 18 slow metabolizer genotypes. Median (IQR) mid-dose efavirenz concentrations were 1.44 (1.21-1.93) µg ml(-1), 2.08 (1.68-2.94) µg ml(-1) and 7.26 (4.82-8.34) µg ml(-1) for extensive, intermediate and slow metabolizers, respectively. In univariate analyses, a model that included composite genotype best predicted efavirenz concentrations (β = 0.28, 95% CI 0.21, 0.35, P = 2.4 × 10(-11)). Among individual CYP2B6 polymorphisms, 516G→T best predicted efavirenz concentrations (β = 0.22, 95% CI 0.13, 0.30, P = 1.27 × 10(-6)). There was also associations with 983T→C (β = 0.27, 95% CI 0.10, 0.44, P = 0.002) and 15582C→T (β = 0.11, 95% CI 0.01, 0.22, P = 0.04). Associations were consistent in adults and children. No other polymorphisms were independently associated with efavirenz concentrations.
conclusionsComposite CYP2B6 genotype based on CYP2B6 516G→T, 983T→C, and 15582C→T best described efavirenz exposure in HIV-infected Black South African adults and children.
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