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Recent Phylodynamics of the HIV Epidemic among MSM in the UK
Gareth Hughes*1, A Leigh Brown1, A Rambaut1, S Lycett1, F Lewis2, E Fearnhill3, and UK Collaborative Group on HIV Drug Resistance
1Univ of Edinburgh, Scotland; 2Scottish Agricultural Coll, Inverness, UK; and 3Med Res Council Clinical Trials Unit, London, UK
Background: The structure of sexual contact networks plays
a key role in the epidemiology of sexually transmitted infections. For HIV,
major discrepancies have recently been observed between contact networks and
transmission networks revealed by viral phylogenetics. The high rate of HIV
evolution in principle allows for detailed reconstruction of links between
virus from different individuals but often sampling has been too sparse to
describe the structure of the transmission network. We analyzed a high-density
sample of the U.K. HIV-infected population using recently developed techniques
in phylogenetics to infer the short-term dynamics of the epidemic.
Methods: Protease and reverse transcriptase sequences from 8088
U.K. patients were collected during routine treatment at clinics in London. Genetic distance at third base positions was used to select the subset of patients
with a close link (<5%) to at least 1 other individual. Bayesian Markov
chain Monte Carlo phylogenetics was used to define clusters of individuals,
which were analyzed individually using a relaxed molecular clock in the Bayesian
Ecological Analysis of Statistical Trends (BEAST) program.
Results: A total of 2510 patients (31%) showed a link to at
least one other sequence. A number of clusters were identified among these
sequences. In a subset of 402 individuals from 1 clinic, 10 clusters with 8 or
more individuals and a posterior probability of 1 in the phylogenetic analysis were
detected: analysis using a relaxed molecular clock dated them to the mid to
late 1990s and indicated a high proportion of transmission events occurring within
6 months of infection. Extension of the study to the 2510 patients using
genetic distance approaches has confirmed that all of these clusters are represented
in the larger dataset, with extensive linkage of additional individuals. The
largest cluster in the single clinic study (30 patients) grew to >500
patients in the all-London dataset.
Conclusions: Reconstruction of transmission clusters from
the U.K. HIV epidemic using a dated phylogeny approach has shown the episodic
nature of HIV epidemiology in men who have sex with men (MSM). There is
evidence of multiple clusters of transmissions dating to the late 1990s, a
period when HIV prevalence is known to have doubled. The quantitative
description of the transmission dynamics among MSM suggests “small-world”
network structures exist in this group and will be important for
parameterization of epidemiological models and assisting to design intervention
strategies.
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