Understanding the HIV pandemic in Malawi using genomic, structural and geographic data.

HIV remains a devastating disease and is particularly common in sub-Saharan Africa. In countries like Malawi prevalence is nearly 9% in adults and it is a substantial public health burden. In this project we will characterise the extent and variability of the HIV outbreak through sequencing and evolutionary methods.

Our overall aim is to use the abundant knowledge of HIV's biology - specifically from the perspectives of the viral genome, proteome and structure-function relationships - to characterise the HIV pandemic in Malawi. We will combine this information with evolutionary and geographic data to understand the epidemiology of HIV in this heavily affected area.

We will draw extensively on our combined expertise in molecular evolution, protein structure analysis and geographic analysis. Although the degree of sequence variation in HIV is extensive, due to error-prone replication and selection from the immune system, it is not without limit. We will identify the limitations on HIV's variability, and characterise the evolutionary trajectories in Malawi.

We will identify and quantify the limits of viral change. Combined with the knowledge of evolutionary selection and geography we will be able to identify drug escape and target effective interventions.

The result of this project will be a novel characterisation of ongoing dynamics of HIV infection in Malawi and in particular the role of human dispersal in shaping genetic diversity of HIV and its role in altering adaptive landscapes. This will have implications for future transmission and control.