A Phylodynamic Study of HIV Transmission Networks in Europe

Tracking HIV-1 transmission patterns on an epidemic scale is of increasing social relevance as the WHO reports no decline in the incidence of newly diagnosed HIV-1 infections. This study tests the pan-European mixing hypothesis and investigates differences in network structure and epidemic growth rates across HIV-1 subtypes and modes of transmission and determines intra versus inter patient genetic diversity by examining 46000 HIV-1 pol gene sequences sampled from 30000 patients collected by the EuResist consortium. The guiding principle is that evolutionary change occurs on the same time scale as disease spread, allowing the estimation of transmission linkage between patients. Sequences are subtyped using COMET and REGA and aligned with ClustalW. A transmission graph is inferred from the pairwise distance matrix via thresholding sequence similarity as measured using log-det. An optimal threshold is identified based on edge density and a novel graph theoretic metric, graph coagulation. The pan-mixing hypothesis is tested using a modified form of the assortativity coefficient. Since a transmission edge is also an edge on the underlying contact network, transmission clusters are a subgraph of the contact network motivating their quantification using social network measures. These network measures are then used to help identify a threshold at which transmission clusters form a good approximation of a social network. Growth rates within these transmission clusters are estimated from divergence times in phylogenetic trees reconstructed using Bayesian MCMC. The optimal threshold is significantly different for each HIV subtype suggesting differences in the contact dynamics of groups invaded by different strains. Transmission clusters exhibit high country wise assortativity suggesting endemic transmission as opposed to pan-mixing. The IVDA show high assortativity with other transmission types along with a higher node centrality, suggesting that they are important bridging elements of the epidemic. There is significant intra patient diversity which could allow for an exploratory study in intra-patient transmission