Molecular phylodynamics of the heterosexual HIV epidemic in the United Kingdom

Abstract

The heterosexual risk group has become the largest HIV infected group in the United Kingdom during the last 10 years, but little is known of the network structure and dynamics of viral transmission in this group. The overwhelming majority of UK heterosexual infections are of non-B HIV subtypes, indicating viruses originating among immigrants from sub-Saharan Africa. The high rate of HIV evolution, combined with the availability of a very high density sample of viral sequences from routine clinical care has allowed the phylodynamics of the epidemic to be investigated for the first time. Sequences of the viral protease and partial reverse transcriptase coding regions from 11,071 patients infected with HIV of non-B subtypes were studied. Of these, 2774 were closely linked to at least one other sequence by nucleotide distance. Including the closest sequences from the global HIV database identified 296 individuals that were in UK-based groups of 3 or more individuals. There were a total of 8 UK-based clusters of 10 or more, comprising 143/2774 (5%) individuals, much lower than the figure of 25% obtained earlier for men who have sex with men (MSM). Sample dates were incorporated into relaxed clock phylogenetic analyses to estimate the dates of internal nodes. From the resulting time-resolved phylogenies, the internode lengths, used as estimates of maximum transmission intervals, had a median of 27 months overall, over twice as long as obtained for MSM (14 months), with only 2% of transmissions occurring in the first 6 months after infection. This phylodynamic analysis of non-B subtype HIV sequences representing over 40% of the estimated UK HIV-infected heterosexual population has revealed heterosexual HIV transmission in the UK is clustered, but on average in smaller groups and is transmitted with slower dynamics than among MSM. More effective intervention to restrict the epidemic may therefore be feasible, given effective diagnosis programmes.

Figure 1. Time-scaled Bayesian MCMC phylogenies of clusters of ≥10 patients.

Red dots indicate the most recent common ancestor (MRCA) of UK transmission clusters as defined against analysis with global diversity. The scale bar is in calendar years. Grey lines indicate non-UK-based segments of the phylogeny, black lines indicate UK-based lineages. A) Subtype A. Scale bar indicates calendar years. B) Subtype C. Scale bar indicates 2 calendar years.

Figure 2. Distribution of cluster size.

Frequency of UK-based clusters, as defined in the text, of size 2 or higher, identified by subtype. A) Non-B subtypes (this study). B) Subtype B .

Figure 3. Power law plot of UK-based non-B subtype clusters.

Log-log plot of numbers of individuals with k contacts (N(k)) against the number of contacts (k). Individuals are assumed to be in contact within the clusters only if the time to the most recent common ancestor of their virus sequences is less than or equal to 5 years. The best fit to a power law (straight line in log-log space) has R² = 0.95 (95% CI: 0.84–0.99), p<10⁻⁶, and shape parameter (negative gradient) α = 2.1.

Figure 4. Histogram of internal branch lengths from time-scaled trees representing minimum transmission intervals.

A) Non-B subtype UK transmission clusters, as defined in the text. B) Subtype B transmission clusters from MSM in London .