Research Article: Episodic Sexual Transmission of HIV Revealed by Molecular Phylodynamics

Date Published: March 18, 2008

Publisher: Public Library of Science

Author(s): Fraser Lewis, Gareth J Hughes, Andrew Rambaut, Anton Pozniak, Andrew J. Leigh Brown, Christopher Pilcher

Abstract: BackgroundThe structure of sexual contact networks plays a key role in the epidemiology of sexually transmitted infections, and their reconstruction from interview data has provided valuable insights into the spread of infection. For HIV, the long period of infectivity has made the interpretation of contact networks more difficult, and major discrepancies have been observed between the contact network and the transmission network 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. The aim of this study was to analyze a high-density sample of an HIV-infected population using recently developed techniques in phylogenetics to infer the short-term dynamics of the epidemic among men who have sex with men (MSM).Methods and FindingsSequences of the protease and reverse transcriptase coding regions from 2,126 patients, predominantly MSM, from London were compared: 402 of these showed a close match to at least one other subtype B sequence. Nine large clusters were identified on the basis of genetic distance; all were confirmed by Bayesian Monte Carlo Markov chain (MCMC) phylogenetic analysis. Overall, 25% of individuals with a close match with one sequence are linked to 10 or more others. Dated phylogenies of the clusters using a relaxed clock indicated that 65% of the transmissions within clusters took place between 1995 and 2000, and 25% occurred within 6 mo after infection. The likelihood that not all members of the clusters have been identified renders the latter observation conservative.ConclusionsReconstruction of the HIV transmission network using a dated phylogeny approach has revealed the HIV epidemic among MSM in London to have been episodic, with evidence of multiple clusters of transmissions dating to the late 1990s, a period when HIV prevalence is known to have doubled in this population. The quantitative description of the transmission dynamics among MSM will be important for parameterization of epidemiological models and in designing intervention strategies.

Partial Text: Sexually transmitted infections spread through an often complex network of sexual contacts [1]. The characteristics of such a network play a vital role in determining both short-term dynamics and longer-term equilibrium prevalence of disease [2,3]. Early epidemiological modelling of the HIV epidemic among men who have sex with men (MSM) identified primary infection, when infectivity might be highest [4], as a potential driver of the epidemic [5], but empirical evidence to support this has been lacking. The reconstruction of contact networks from interview data has provided valuable insights into epidemics of sexually transmitted infections such as Chlamydia [6] and gonorrhoea [7], and has been applied in studies of some HIV-infected populations [8,9]. However, the interpretation of the contact network in the context of HIV infection is more problematic because of the long period of infectivity and the low average risk of infection per contact [10]. Although in some cases it has been shown that the reconstructed HIV transmission network maps closely onto the contact network [11,12] in other cases the transmission network was not reflected by the contact network [13,14].

We have made use of sequence data obtained for resistance genotyping for the largest clinical centre treating patients with HIV in London to reconstruct the transmission network in this population. In contrast to previous studies based on sparsely sampled populations, by examining all pairwise comparisons among sequences from more than 2,000 patients, we were able to identify a subset of 402 subtype B pairs with a genetic distance of 5% or less. Detailed phylogenetic analysis identified a number of large clusters among these patients, which together comprised 25% of this group. “Dated phylogeny” analysis of these clusters [28] revealed an episodic pattern, with many of the transmissions within them occurring within a short space of time.



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