Understanding the dynamics within HIV transmission clusters is critical information that can help prioritize public health resource allocation. Although HIV sequence clustering is routinely used to identify subpopulations experiencing elevated transmission, there’s a risk of over-simplifying transmission dynamics within clusters as well as the risk that clustering methodology influences outcomes.
In a newly published study written by BC-CfE researchers, led by PhD student Angela McLaughlin, researchers investigated the similarities and sensitivities of HIV transmission risk factors as identified by phylogenetic clustering, viral diversification rate, changes in viral diversification rate, and a combined approach. Other authors of the study include BC-CfE Executive Director and Physician-in-Chief Dr. Julio Montaner, BC-CfE Senior Medical Director Dr. Rolando Barrios, BC-CfE Laboratory Director Dr. Zabrina Brumme, and BC-CfE Molecular Epidemiology and Evolutionary Genetics Group Senior Research Scientist Dr. Jeff Joy.
The study, titled, “Concordance of HIV transmission risk factors elucidated using viral diversification rate and phylogenetic clustering,”compared sociodemographic and clinical risk factors associated with belonging to phylogenetic clusters, elevated viral diversification rates, and historical branching rates in order to assess their relative concordance and sampling sensitivity.
The methodology for this study inferred phylogenetic trees based on HIV sequence data. From the resulting trees, clusters were identified and viral diversification rates were calculated. Factors associated with heightened transmission risk were compared across models of cluster membership, viral diversification rate, changes in diversification rate, and viral diversification rate among clusters.
Results from this comparison revealed viruses within larger clusters had higher diversification rates and lower changes in diversification rate than those within smaller clusters. However, rates within individual clusters, independent of size, varied widely.
Risk factors for both cluster membership and elevated viral diversification rate included being male, young, living in certain locations in BC, previous injection drug use, previous hepatitis C virus infection, or a high recent viral load.
This study shows how knowledge of viral diversification rate complements phylogenetic clustering, and offers a means of better evaluating transmission dynamics to guide provision of treatment and prevention services.
This work is important because it advances our understanding of HIV transmission dynamics beyond whether viruses are clustered (linked through recent transmission events) or not. In recent years, our group has been laying the groundwork towards understanding how viral diversification rate – a relatively new metric in the field of genomic epidemiology – should be appropriately interpreted, and in this study, how it compares to a commonly applied clustering method. We have shown that the sociodemographic and clinical risk factors associated with clustering and viral diversification rate are similar, yet diversification rate within clusters can be widely variable. A modelling approach that combines clustering and diversification rate is ideal in order to identify subpopulations at the highest risk of transmission and infection, and further projects are underway to fine tune this approach.
– Lead author Angela McLaughlin