The Impact of Clinical, Demographic and Risk Factors on Rates of HIV Transmission: A Population-based Phylogenetic Analysis in British Columbia, Canada

Background. The diversification of human immunodeficiency virus (HIV) is shaped by its transmission history. We therefore used a population based province wide HIV drug resistance database in British Columbia (BC), Canada, to evaluate the impact of clinical, demographic, and behavioral factors on rates of HIV transmission. Methods. We reconstructed molecular phylogenies from 27 296 anonymized bulk HIV pol sequences representing 7747 individuals in BC-about half the estimated HIV prevalence in BC. Infections were grouped into clusters based on phylogenetic distances, as a proxy for variation in transmission rates. Rates of cluster expansion were reconstructed from estimated dates of HIV seroconversion. Results. Our criteria grouped 4431 individuals into 744 clusters largely separated with respect to risk factors, including large established clusters predominated by injection drug users and more-recently emerging clusters comprising men who have sex with men. The mean log(10) viral load of an individual's phylogenetic neighborhood (composed of 5 other individuals with shortest phylogenetic distances) increased their odds of appearing in a cluster by >2-fold per log(10) viruses per milliliter. Conclusions. Hotspots of ongoing HIV transmission can be characterized in near real time by the secondary analysis of HIV resistance genotypes, providing an important potential resource for targeting public health initiatives for HIV prevention.