Pharmacokinetics and Drug-Drug Interactions of Isoniazid and Efavirenz in Pregnant Women Living With HIV in High TB Incidence Settings: Importance of Genotyping

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dc.contributor.authorGausi, Kamunkhwalaen_ZA
dc.contributor.authorWiesner, Lubbeen_ZA
dc.contributor.authorNorman, Jenniferen_ZA
dc.contributor.authorWallis, Carole Len_ZA
dc.date.accessioned2022-04-30T10:53:11Z
dc.date.available2022-04-30T10:53:11Z
dc.date.issued2020
dc.descriptionGausi, K., Wiesner, L., Norman, J., Wallis, C.L., Onyango-Makumbi, C., Chipato, T., Haas, D.W., Browning, R., Chakhtoura, N., Montepiedra, G., Aaron, L., McCarthy, K., Bradford, S., Vhembo, T., Stranix-Chibanda, L., Masheto, G.R., Violari, A., Mmbaga, B.T., Aurpibul, L., Bhosale, R., Nevrekhar, N., Rouzier, V., Kabugho, E., Mutambanengwe, M., Chanaiwa, V., Nyati, M., Mhembere, T., Tongprasert, F., Hesseling, A., Shin, K., Zimmer, B., Costello, D., Jean-Philippe, P., Sterling, T.R., Theron, G., Weinberg, A., Gupta, A., Denti, P. and (2021), Pharmacokinetics and Drug-Drug Interactions of Isoniazid and Efavirenz in Pregnant Women Living With HIV in High TB Incidence Settings: Importance of Genotyping. Clin. Pharmacol. Ther., 109: 1034-1044. https://doi.org/10.1002/cpt.2044
dc.description.abstractThe World Health Organization guidelines recommend that individuals living with HIV receive ≥ 6 months of isoniazid preventive therapy, including pregnant women. Yet, plasma isoniazid exposure during pregnancy, in the antiretroviral therapy era, has not been well-described. We investigated pregnancy-induced and pharmacogenetic-associated pharmacokinetic changes and drug-drug interactions between isoniazid and efavirenz in pregnant women. Eight hundred forty-seven women received isoniazid for 28 weeks, either during pregnancy or at 12 weeks postpartum, and 786 women received efavirenz. After adjusting for NAT2 and CYP2B6 genotype and weight, pregnancy increased isoniazid and efavirenz clearance by 26% and 15%, respectively. Isoniazid decreased efavirenz clearance by 7% in CYP2B6 normal metabolizers and 13% in slow and intermediate metabolizers. Overall, both isoniazid and efavirenz exposures were reduced during pregnancy, but the main determinants of drug concentration were NAT2 and CYP2B6genotypes, which resulted in a five-fold difference for both drugs between rapid and slow metabolizers.en_ZA
dc.format.extent11 pages
dc.identifier.issn0009-9236
dc.identifier.otherdoi.org/10.1002/cpt.2044
dc.identifier.urihttp://hdl.handle.net/10019.1/125170
dc.language.isoen_ZAen_ZA
dc.publisherJohn Wiley & Sons, Ltd
dc.rights.holderAuthors retain copyright
dc.subjectPharmacokineticsen_ZA
dc.subjectIsoniaziden_ZA
dc.subjectEfavirenzen_ZA
dc.subjectPregnanten_ZA
dc.subjectHIVen_ZA
dc.subjectTBen_ZA
dc.titlePharmacokinetics and Drug-Drug Interactions of Isoniazid and Efavirenz in Pregnant Women Living With HIV in High TB Incidence Settings: Importance of Genotypingen_ZA
dc.typeArticleen_ZA
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