Abstract
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.
