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



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.