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

• Published in: BMJ global health 2023-12, Vol.8 (Suppl 10), p.A36-A37
• Main Authors: Thomford, Nicholas Ekow, Kellerman, Tracy, Debrah, Oksana, Anyanful, Akwasi, Biney, Robert Peter, Boadi, Dennis, Yahaya, Ewura Seidu, Ekor, Martins, Kyei, George Boateng
• Format: Article
• Language: English
• Subjects: Abstracts of Poster and e-Poster Presentations; Drug interactions; Malaria; Microscopy; Parasites
• ISSN: 2059-7908
• DOI: 10.1136/bmjgh-2023-EDC.88

BackgroundMalaria/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. MethodsTo 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. ResultsMedian 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. ConclusionPharmacogenetic 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.