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.

The International Dimension of the U.S. HIV Transmission Network and Onward Transmission of HIV Recently Imported into the United States

“…15,18,19 Here, we found that by including sequences representing the global diversity of HIV, we were able to infer indirect connections between persons within the United States through one or more international sequences. This finding demonstrates the added benefit of including the global diversity of HIV in transmission network analyses, even if the aim of an analysis is local in scope (as suggested by Wertheim et al…”

“…The U.S. isolates were found in MSM residing in the Northeast United States and were linked to five CRF02_AG sequences from Great Britain 15 ; however, these British sequences were not included in the dating analysis, because they were published without associated genotyping year. Notably, these British sequences were interspersed among the U.S. sequences, implying repeated transmission between these countries.…”

“…Transmission networks inferred from genetic sequences allow the study of viral dynamics on a local or national level. [14][15][16][17][18][19] Moreover, these networks provide the means to improve the effect of targeted treatment intervention. 20 Recent work by Wertheim et al 2 has demonstrated how the global diversity of HIV can be efficiently queried for transmission links by comparing genetic distances between isolates.…”

Identifying Transmission Clusters with Cluster Picker and HIV-TRACE

“…[1][2][3][4][5][6] The identification of transmission clusters can support epidemiologically linked transmission events, 7 identify putative transmission chains, 8 and reveal mixing between key risk groups and geographic subpopulations. 9 Transmission clusters of HIV infections are typically defined using either genetic distances among sequences 4 or genetic distances in addition to branch support values (e.g., bootstrap values).…”

Dilemma of concepts and strategies for the prevention of spread of HIV in relation to human behavior, law and human rights

“…However, particularities concerning ethnic communities and immigrants have to be considered (Burns et al, 2009). A study from the UK showed a different dynamics of (clustered) viral transmission in the hetero-sexual risk group (slower dynamics) than that among men having sex with men (MSM), and further reflected the spread of non-B HIV subtypes (Hughes et al, 2009). Different partnership patterns in Africa, for example, reveal that the cultural matrix based on traditional coined behavior can affect the dynamics of the spread of HIV, and sheds light on the problems facing the prevention campaigns in these countries (Halperin and Epstein, 2004;Pettifor et al, 2004).…”