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  • PA-113 Pharmacogenomics of drug-drug interactions in malaria-HIV con-infections: effects on generic artemether-lumefantrine therapy used in Ghana for malaria treatment

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PA-113 Pharmacogenomics of drug-drug interactions in malaria-HIV con-infections: effects on generic artemether-lumefantrine therapy used in Ghana for malaria treatment
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  1. Nicholas Ekow Thomford1,2,3,
  2. Tracy Kellerman4,
  3. Oksana Debrah5,
  4. Akwasi Anyanful2,3,
  5. Robert Peter Biney6,
  6. Dennis Boadi1,
  7. Ewura Seidu Yahaya6,
  8. Martins Ekor6,
  9. George Boateng Kyei7,8
  1. 1Pharmacogenomics and Genomic Medicine Research Group, Ghana
  2. 2Division of Human Genetics, Department of Pathology, Faculty of Health Sciences, University of Cape Town, South Africa
  3. 3Biomedical and Clinical Research Centre, College of Health and Allied Sciences, University of Cape Coast, Ghana
  4. 4Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, South Africa
  5. 5Department of Chemical Pathology, School of Medical Sciences, College of Health and Allied Sciences, University of Cape Coast, Ghana
  6. 6Department of Pharmacology, School of Medical Sciences, College of Health and Allied Sciences, University of Cape Coast, Ghana
  7. 7Department of Virology, Noguchi Memorial Institute for Medical Research, University of Ghana, Ghana
  8. 8Department of Medicine, Washington University School of Medicine, USA

Abstract

Background Malaria/HIV co-infection (MHC) is a public health challenge which may present with worse health outcomes due to interactions. Coadministration of artemether lumefantrine (ALU) and antiretroviral therapy may have potential drug-drug interactions that can affect the course of treatment for both diseases. Generic ALU medications are used in Ghana for malaria treatment after RDT or microscopy diagnosis. ALU is metabolized by the enzymes CYP2B6, CYP3A4/5, CYP2A6 and UGTs which can be affected by pharmacogenetics. A better understanding of the effects of MHC on ALU drugs could help prompt treatment, and control of malarial parasites among HIV-infected patients. This study evaluated effects of MHC on ALU drugs used in antimalarial treatment and pharmacogenetic influences on their efficacy.

Methods To compare metabolite profiles and treatment outcome in patients on generic ALU for uncomplicated malaria and MHC, this study has recruited about 218 participants. However, we currently have complete preliminary metabolite and genomic data on 52 participants. Blood was taken for microscopy, genotyping using iPLEX Gold microarray and PCR-RFLP, and metabolite analysis using LC-MS/MS.

Results Median parasite density was 2119.42/uL, 760.10/uL, 0/uL and 0/uL on days 1,2,3 and 7 for malaria-only participants and 7322.52/uL, 3928.60/uL, 0/uL and 0/uL for MHC participants. Plasma concentrations of dihydroartemisinin (DHA) ranged from 3.30–35.85ng/ml. Desbutyl-lumefantrine (DBL) concentrations ranged from 7.8ng/ml-40.44ng/ml on days 3 and 7. Decreased concentrations of lumefantrine, DBL and DHA were observed across CYP2B6 *1/*1, CYP2B6 *1/*18/*1/*6, CYP3A5 *1/* and CYP3A5 *1/*3/*1/*6/1*/*7 carriers for MHC participants. However, MHC carriers of non-functional haplotypes CYP2B6*6/*6 or *6/*18 or *18/*18 showed increase in lumefantrine, DBL, artemether and DHA concentrations.

Conclusion Pharmacogenetic variations affected ALU plasma concentrations although blood parasites were eliminated by day 3 in malaria monoinfected and MHC participants. This however shows there is potential drug-drug interactions between ALU-ART components which can influence the progression of either disease.

https://doi.org/10.1136/bmjgh-2023-EDC.88

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