15th Conference on Retroviruses and Opportunistic Infections Boston, Massachusetts - February 3-6, 2008

Conf Retrovir Opportunistic Infect 2008 Feb 3-6;15: (abstract no. 13)

Gareth Hughes¹, 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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2008-02-03
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