Pharmacokinetics, pharmacogenetics, and toxicity of co-administered efavirenz and isoniazid
Background: CYP2B6 slow metabolisers have higher efavirenz concentrations, which are further increased by isoniazid inhibiting efavirenz’s accessory metabolic pathway. Objectives: We investigated the association between CYP2B6 genotype and toxicity in people living with HIV (PLWH) on isoniazid and...
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AOSIS
2025-03-01
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| Series: | Southern African Journal of HIV Medicine |
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| Online Access: | https://sajhivmed.org.za/index.php/hivmed/article/view/1661 |
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| author | Jessica Taylor Gary Maartens Simiso Sokhela Nomathemba Chandiwana Godspower Akpomiemie Francois Venter Phumla Sinxadi |
| author_facet | Jessica Taylor Gary Maartens Simiso Sokhela Nomathemba Chandiwana Godspower Akpomiemie Francois Venter Phumla Sinxadi |
| author_sort | Jessica Taylor |
| collection | DOAJ |
| description | Background: CYP2B6 slow metabolisers have higher efavirenz concentrations, which are further increased by isoniazid inhibiting efavirenz’s accessory metabolic pathway.
Objectives: We investigated the association between CYP2B6 genotype and toxicity in people living with HIV (PLWH) on isoniazid and efavirenz.
Method: We enrolled participants from the efavirenz arm of the ADVANCE trial (reference no.: NCT03122262), who received isoniazid and consented to genotyping. We compared efavirenz concentrations on and off isoniazid, stratified by CYP2B6 genotype. We explored associations between the CYP2B6 genotype and efavirenz concentrations on isoniazid; and changes over 24 weeks in lipids, alanine aminotransferase (ALT), fasting plasma glucose (FPG), sleep quality, and Modified Mini Screen (MMS) scores.
Results: A total of 168 participants, median age 31 years, 57% female, had classifiable CYP2B6 genotypes. Efavirenz concentrations on isoniazid were higher (pseudo-median difference 0.49 µg/mL (95% confidence interval [CI] [0.19–0.91]) and associated with increases in total and high-density lipoprotein (HDL)-cholesterol. CYP2B6 slow metabolisers had higher efavirenz concentrations on isoniazid than extensive metabolisers (β = 1.66 [95% CI 0.98–2.34]). CYP2B6 slow metabolisers had greater increases in total (β = 0.44 mmol/L [95% CI 0.01–0.86]) and HDL-cholesterol (β = 0.39 mmol/L [95% CI 0.21–0.57]) than extensive metabolisers. There were no associations between efavirenz concentrations or CYP2B6 genotype, and change in ALT, FPG, low-density lipoprotein (LDL)-cholesterol, triglycerides, sleep quality, or MMS scores.
Conclusion: CYP2B6 slow metabolisers on isoniazid and efavirenz had greater efavirenz concentrations and increases in total and HDL-cholesterol. We found no association between CYP2B6 genotype or efavirenz concentrations and sleep or psychiatric symptoms. |
| format | Article |
| id | doaj-art-bf06b57596ec4b24b52697500111b248 |
| institution | DOAJ |
| issn | 1608-9693 2078-6751 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | AOSIS |
| record_format | Article |
| series | Southern African Journal of HIV Medicine |
| spelling | doaj-art-bf06b57596ec4b24b52697500111b2482025-08-20T03:06:40ZengAOSISSouthern African Journal of HIV Medicine1608-96932078-67512025-03-01261e1e1110.4102/sajhivmed.v26i1.1661893Pharmacokinetics, pharmacogenetics, and toxicity of co-administered efavirenz and isoniazidJessica Taylor0Gary Maartens1Simiso Sokhela2Nomathemba Chandiwana3Godspower Akpomiemie4Francois Venter5Phumla Sinxadi6Division of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape TownDivision of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape TownEzintsha, Wits Health Consortium, Faculty of Health Sciences, University of the Witwatersrand, JohannesburgEzintsha, Wits Health Consortium, Faculty of Health Sciences, University of the Witwatersrand, JohannesburgEzintsha, Wits Health Consortium, Faculty of Health Sciences, University of the Witwatersrand, JohannesburgEzintsha, Wits Health Consortium, Faculty of Health Sciences, University of the Witwatersrand, JohannesburgDivision of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; and, SAMRC/UCT Platform for Pharmacogenomics Research and Translation, South African Medical Research Council, Cape TownBackground: CYP2B6 slow metabolisers have higher efavirenz concentrations, which are further increased by isoniazid inhibiting efavirenz’s accessory metabolic pathway. Objectives: We investigated the association between CYP2B6 genotype and toxicity in people living with HIV (PLWH) on isoniazid and efavirenz. Method: We enrolled participants from the efavirenz arm of the ADVANCE trial (reference no.: NCT03122262), who received isoniazid and consented to genotyping. We compared efavirenz concentrations on and off isoniazid, stratified by CYP2B6 genotype. We explored associations between the CYP2B6 genotype and efavirenz concentrations on isoniazid; and changes over 24 weeks in lipids, alanine aminotransferase (ALT), fasting plasma glucose (FPG), sleep quality, and Modified Mini Screen (MMS) scores. Results: A total of 168 participants, median age 31 years, 57% female, had classifiable CYP2B6 genotypes. Efavirenz concentrations on isoniazid were higher (pseudo-median difference 0.49 µg/mL (95% confidence interval [CI] [0.19–0.91]) and associated with increases in total and high-density lipoprotein (HDL)-cholesterol. CYP2B6 slow metabolisers had higher efavirenz concentrations on isoniazid than extensive metabolisers (β = 1.66 [95% CI 0.98–2.34]). CYP2B6 slow metabolisers had greater increases in total (β = 0.44 mmol/L [95% CI 0.01–0.86]) and HDL-cholesterol (β = 0.39 mmol/L [95% CI 0.21–0.57]) than extensive metabolisers. There were no associations between efavirenz concentrations or CYP2B6 genotype, and change in ALT, FPG, low-density lipoprotein (LDL)-cholesterol, triglycerides, sleep quality, or MMS scores. Conclusion: CYP2B6 slow metabolisers on isoniazid and efavirenz had greater efavirenz concentrations and increases in total and HDL-cholesterol. We found no association between CYP2B6 genotype or efavirenz concentrations and sleep or psychiatric symptoms.https://sajhivmed.org.za/index.php/hivmed/article/view/1661hivisoniazidefavirenzcyp2b6neurotoxicity. |
| spellingShingle | Jessica Taylor Gary Maartens Simiso Sokhela Nomathemba Chandiwana Godspower Akpomiemie Francois Venter Phumla Sinxadi Pharmacokinetics, pharmacogenetics, and toxicity of co-administered efavirenz and isoniazid Southern African Journal of HIV Medicine hiv isoniazid efavirenz cyp2b6 neurotoxicity. |
| title | Pharmacokinetics, pharmacogenetics, and toxicity of co-administered efavirenz and isoniazid |
| title_full | Pharmacokinetics, pharmacogenetics, and toxicity of co-administered efavirenz and isoniazid |
| title_fullStr | Pharmacokinetics, pharmacogenetics, and toxicity of co-administered efavirenz and isoniazid |
| title_full_unstemmed | Pharmacokinetics, pharmacogenetics, and toxicity of co-administered efavirenz and isoniazid |
| title_short | Pharmacokinetics, pharmacogenetics, and toxicity of co-administered efavirenz and isoniazid |
| title_sort | pharmacokinetics pharmacogenetics and toxicity of co administered efavirenz and isoniazid |
| topic | hiv isoniazid efavirenz cyp2b6 neurotoxicity. |
| url | https://sajhivmed.org.za/index.php/hivmed/article/view/1661 |
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