Project Leader: Dr Machel Leuschner
https://orcid.org/0000-0003-1901-5416

The incidence of therapeutic drug failure or adverse effects to standard therapeutic doses as a result of patient variability continue to be a major problem in clinical practice. Human immunodeficiency virus (HIV) prevalence is the highest in South Africa, however there is limited information on the pharmacogenomics of first-line antiretroviral treatment in this genetically diverse population. Considering the double disease burden of both infectious and noncommunicable diseases in South Africa, personalised pharmacotherapy to optimise dose response and to prevent unwanted side-effects is imperative.

South African Pharmacogenomics of first-line antiretroviral treatment

The umbrella project will aim to gather data on the pharmacogenomics of the first-line antiretroviral regimen of tenofovir disoproxil fumarate-lamivudine-dolutegravir. The main objective is to build a predictive model determining the strength of relationships between different variables with risk stratification and prediction of treatment response. Genetic variants of UGT1A1, ABCC2-MRP2,SLC22A6, SLC22A1, SLC22A2 associated with the metabolism and transport of the first-line regimen will be assessed in this study. The epigenetics, specifically DNA-methylation of CpG islands associated with these genes, together with the measured phenotype and related patient demographics, adverse drug effects and lifestyle will be incorporated into the predictive model.

Collaborators:  Dr Tracey Hurrell, CSIR NextGen Health

Applicable research levels: Basic and Regulatory sciences research at MSc or PhD level

Minimum skillsets at MSc and PhD levels: Skillsets required depend on the different parts of the project and will be communicated as the project is rolled out.

Students: The project is in its conceptualisation phase and a funding application has been submitted