PHARMABIOME | Fellow: Dr Nicholas Ekow Thomford | Pharmacomicrobiomics in malaria-HIV co-infection (MHC) treatment outcome: finding causal therapeutic variation in artemisinin-based combination therapy (ACT) and antiretroviral therapy (ART) in a Ghanaian population

PROJECT DETAILS

 
Abstract:

Malaria is common in human immunodeficiency virus (HIV) patients and both are severe public health challenges in sub-Saharan countries such as Ghana. They both represent a significant cause of morbidity and mortality in sub-Sahara Africa. The treatment of malaria in HIV patients results in well recognised adverse drug events which potentially affects parasite clearance and viral suppression. There is a prevalence of 11-30% of malaria in HIV patients from individual studies in Ghana. Treating malaria in HIV patients involves artemisinin-based combination therapy (ACT) in patients who are already taking anti-retroviral therapy (ART).  Combination of ACTs and ARTs to treat malaria in HIV patients could result in drug-drug interactions which could lead to low levels of ACTs and ARTs and eventually breed resistance. The mechanism of reported adverse events and why not everyone gets them is unknown. This proposed study is hypothesizing that the therapeutic outcomes and associated adverse events are due to variations/polymorphisms in genes involved in metabolising ACTs and ARTs and those that affect gut microbiome composition.  We aim to quantitatively measure drug concentrations in patients who are on ACTs and ARTs and determine any associated polymorphism in drug metabolising enzymes and gut microbiome composition genes. We will enrol and recruit patients with malaria only, HIV without malaria and MHC patients on ACTs and ARTs over a period for this study. In the process we will  create biorepository with clinical and demographic data for future studies. The results and knowledge emanating from this study could result in (i) development of new ACT regimen for HIV patients (ii) personalized medicine if specific polymorphisms are found.

Summary of results

Several genetic variations were observed in drug metabolisng enzymes which affected the plasma drug concentration of ACT howerver, the concentrations were high enough to have an effect on the parasite as observed in day three parasetimia. There are clear signs of ACT-ART interaction observed under pharmacogenomics influence (yet to be published daa). The biorepository has been established where we have blood samples, stool samples, plasma, serum and DNA samples stored in freezers.  

Publication(s)

i.       Thomford, N.E., Kellermann, T., Biney, R.P. Dixon, C., Badu Nyarko, S., Ateko, R.O., Ekor, M. & Kyei. G. B. (2024). Therapeutic efficacy of generic artemether–lumefantrine in the treatment of uncomplicated malaria in Ghana: assessing anti-malarial efficacy amidst pharmacogenetic variations. Malaria Journal, 23, 125. https://doi.org/10.1186/s12936-024-04930-1.


ii.       Thomford, N.E., Abraham, S.A., Badu Nyarko, S. & Biney R.P. (2024). A consideration of CYP2D6 genetic variations in the Ghanaian population as a potential ‘culprit’ for the tramadol “abuse crisis”. BMC Medical Genomics, 17(1),28. https://doi.org/10.1186/s12920-023-01773-8.

iii.      Thomford, N.E., Dampson, F.N., Adjei, G., Eliason, S., Ekor, M. & Kyei, G.B. (2023). Psychometric assessment of HIV stigma in patients attending a tertiary facility: an initial validation of the Berger HIV stigma scale in a Ghanaian perspective. Plos One, 18(4), e0282193. https://doi.org/10.1371/ journal.pone.0282193.

iv.       Thomford, N.E., Anyanful, A., Ateko, R.O., Blackhurst, D., Biney, R.P., Boadi, D., Badu Nyarko, S., Ekor, M. & Kyei, G.B. (2023). Apolipoprotein E genetic variation, atherogenic index and cardiovascular disease risk assessment in an African population: An analysis of HIV and malaria patients in Ghana. PLoS One, 18(5), e0284697. https://doi.org/10.1371/journal. pone.0284697.

v.       Sarpong, E., Acheampong, D.O., Fordjour, G.N.R., Anyanful, A., Aninagyei,, E., Tuoyire D.A., Blackhurst, D., Kyei, G.B., Ekor, M. & Thomford, N.E. (2022). Zero malaria: A mirage or reality for a population of sub-Saharan Africa in health transition. Malaria Journal, 21,314. https://doi.org/10.1186/s12936-022-04340-1.