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CYP2B6*6 genotype and high efavirenz plasma concentration but not nevirapine are associated with low lumefantrine plasma exposure and poor treatment response in HIV-malaria-coinfected patients

The Pharmacogenomics Journal volume 16, pages 88–95 (2016)Cite this article

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Abstract

We investigated the influence of efavirenz (EFV)- or nevirapine (NVP)-based antiretroviral therapy (ART) on lumefantrine plasma exposure in HIV-malaria-coinfected patients and implication of pharmacogenetic variations. A total of 269 HIV patients with uncomplicated falciparum malaria on NVP-based ART (NVP-arm), EFV-based ART (EFV-arm) or not receiving ART (control-arm) were enrolled and treated with artemether-lumefantrine. Day-7 lumefantrine, baseline EFV and NVP plasma concentrations, and CYP2B6*6,*18, CYP3A4*1B, CYP3A5*3,*6,*7, ABCB1 c.3435C>T and ABCB1 c.4036A>G genotypes were determined. The median day-7 lumefantrine plasma concentration was significantly lower in the EFV-arm compared with that in NVP- and control-arm. High EFV plasma concentrations and CYP2B6*6/*6 genotype significantly correlated with low lumefantrine plasma concentrations and high rate of recurrent parasitemia. No significant effect of NVP-based ART on lumefantrine exposure was observed. In conclusion, owing to long-term CYP3A induction, EFV-based ART cotreatment significantly reduces lumefantrine plasma exposure leading to poor malaria treatment response, which is more pronounced in CYP2B6 slow metabolizers.

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Acknowledgements

We are grateful to study participants Dorisia Nanage and Lilleba Bohman for their dedicated technical assistance. This study was supported by grants from the Swedish International Development Cooperation Agency Programme (SIDA MALARIA-2010/2012, Contribution no: 7500051601).

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Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania

    B A Maganda

  2. Unit of Pharmacology and Therapeutics, School of Pharmacy, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania

    O M S Minzi, E Ngaimisi & A A R Kamuhabwa

  3. Division of Clinical Pharmacology, Department of Laboratory of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden

    E Aklillu

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  1. B A Maganda
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Correspondence to E Aklillu.

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Maganda, B., Minzi, O., Ngaimisi, E. et al. CYP2B6*6 genotype and high efavirenz plasma concentration but not nevirapine are associated with low lumefantrine plasma exposure and poor treatment response in HIV-malaria-coinfected patients. Pharmacogenomics J 16, 88–95 (2016). https://doi.org/10.1038/tpj.2015.37

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