Trial reportThe Journal of antimicrobial chemotherapy2014
Secondary metabolism pathway polymorphisms and plasma efavirenz concentrations in HIV-infected adults with CYP2B6 slow metabolizer genotypes.
Trial report in The Journal of antimicrobial chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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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
34 citing papers in PubMed, 51 citations in OpenAlex.
- A Cross-Sectional Analysis of the Nicotine Metabolite Ratio and Its Association with Sociodemographic and Smoking Characteristics among People with HIV Who Smoke in South Africa.International journal of environmental research and public health · 2023Trial
- Brain neurotransmitter transporter/receptor genomics and efavirenz central nervous system adverse events.Pharmacogenetics and genomics · 2018Trial
- Race/Ethnicity and the Pharmacogenetics of Reported Suicidality With Efavirenz Among Clinical Trials Participants.The Journal of infectious diseases · 2017Trial
- Population Pharmacokinetic Modeling To Estimate the Contributions of Genetic and Nongenetic Factors to Efavirenz Disposition.Antimicrobial agents and chemotherapy · 2017Trial
- Efavirenz Pharmacokinetics and Pharmacodynamics in HIV-Infected Persons Receiving Rifapentine and Isoniazid for Tuberculosis Prevention.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2015Trial
- 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
- 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
- SLCO1B1 Phenotype and CYP3A5 Polymorphism Significantly Affect Atorvastatin Bioavailability.Journal of personalized medicine · 2021Article
- Influence ofPharmacogenomics and personalized medicine · 2021Article
- Brazilian cohort and genes encoding for drug-metabolizing enzymes and drug transporters.Pharmacogenomics · 2020Article
- Pharmacogenetic interactions between antiretroviral drugs and vaginally administered hormonal contraceptives.Pharmacogenetics and genomics · 2020Article
- Pharmacogenetics and pharmacokinetics of CNS penetration of efavirenz and its metabolites.The Journal of antimicrobial chemotherapy · 2019Article
- Human Genetic Variation and HIV/AIDS in Papua New Guinea: Time to Connect the Dots.Current HIV/AIDS reports · 2018Review
- Drug metabolism and transport gene polymorphisms and efavirenz adverse effects in Brazilian HIV-positive individuals.The Journal of antimicrobial chemotherapy · 2018Article
- Polymorphisms in cytochrome P450 are associated with extensive efavirenz pharmacokinetics and CNS toxicities in an HIV cohort in Botswana.The pharmacogenomics journal · 2018Article
- Effect of CYP2C19, UGT1A8, and UGT2B7 on valproic acid clearance in children with epilepsy: a population pharmacokinetic model.European journal of clinical pharmacology · 2018Article
- Variation in CYP2A6 Activity and Personalized Medicine.Journal of personalized medicine · 2017Review
- Genetic Polymorphisms Affecting the Pharmacokinetics of Antiretroviral Drugs.Clinical pharmacokinetics · 2017Review
- Frequent malaria illness episodes in two Malawian patients on antiretroviral therapy soon after stopping cotrimoxazole preventive therapy.Malawi medical journal : the journal of Medical Association of Malawi · 2017Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
objectivesEfavirenz is widely prescribed for HIV-1 infection, and CYP2B6 polymorphisms 516G→T and 983T→C define efavirenz slow metabolizer genotypes. To identify genetic predictors of higher plasma efavirenz concentrations beyond these two common functional alleles, we characterized associations with mid-dosing interval efavirenz concentrations in 84 HIV-infected adults, all carrying two copies of these major loss-of-function CYP2B6 alleles.
methodsStudy participants had been randomized to efavirenz-containing regimens in prospective clinical trials and had available plasma efavirenz assay data. Analyses focused on secondary metabolism pathway polymorphisms CYP2A6 -48T→G (rs28399433), UGT2B7 735A→G (rs28365062) and UGT2B7 802T→C (rs7439366). Exploratory analyses also considered 196 polymorphisms and 8 copy number variants in 41 drug metabolism/transport genes. Mid-dosing interval efavirenz concentrations at steady-state were obtained ≥8 h but <19 h post-dose. Linear regression was used to test for associations between polymorphisms and log-transformed efavirenz concentrations.
resultsIncreased efavirenz concentrations were associated with CYP2A6 -48T→G in all subjects (P = 3.8 × 10(-4)) and in Black subjects (P = 0.027) and White subjects (P = 0.0011) analysed separately; and with UGT2B7 735 G/G homozygosity in all subjects (P = 0.006) and in Black subjects (P = 0.046) and White subjects (P = 0.062) analysed separately. In a multivariable model, CYP2A6 -48T→G and UGT2B7 735 G/G homozygosity remained significant (P < 0.05 for each). No additional polymorphisms or copy number variants were significantly associated with efavirenz concentrations.
conclusionsAmong individuals with a CYP2B6 slow metabolizer genotype, CYP2A6 and possibly UGT2B7 polymorphisms contribute to even higher efavirenz concentrations.
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