Concordance of HIV transmission risk factors elucidated using viral diversification rate and phylogenetic clustering

Background and objectives Although HIV sequence clustering is routinely used to identify subpopulations experiencing elevated transmission, it over-simplifies transmission dynamics and is sensitive to methodology. Complementarily, viral diversification rates can be used to approximate historical transmission rates. Here, we investigated the concordance and sensitivity of HIV transmission risk factors identified by phylogenetic clustering, viral diversification rate, changes in viral diversification rate and a combined approach. Methodology Viral sequences from 9848 people living with HIV in British Columbia, Canada, sampled between 1996 and February 2019, were used to infer phylogenetic trees, from which clusters were identified and viral diversification rates of each tip 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 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, a resident of health authority E, previous injection drug use, previous hepatitis C virus infection or a high recent viral load. In a sensitivity analysis, models based on cluster membership had wider confidence intervals and lower concordance of significant effects than viral diversification rate for lower sampling rates. Conclusions and implications Viral diversification rate complements phylogenetic clustering, offering a means of evaluating transmission dynamics to guide provision of treatment and prevention services. Lay Summary Understanding HIV transmission dynamics within clusters can help prioritize public health resource allocation. We compared socio-demographic and clinical risk factors associated with phylogenetic cluster membership and viral diversification rate, a historical branching rate, in order to assess their relative concordance and sampling sensitivity.