Background: The global spread of HIV-1 has been accompanied by the emergence of genetically distinct viral strains. Over
the past two decades subtype C viruses, which predominate in Southern and Eastern Africa, have spread rapidly throughout
parts of South America. Phylogenetic studies indicate that subtype C viruses were introduced to South America through a
single founder event that occurred in Southern Brazil. However, the external route via which subtype C viruses spread to the
South American continent has remained unclear.
Methodology/Principal Findings: We used automated genotyping to screen 8,309 HIV-1 subtype C pol gene sequences
sampled within the UK for isolates genetically linked to the subtype C epidemic in South America. Maximum likelihood and
Bayesian approaches were used to explore the phylogenetic relationships between 54 sequences identified in this screen,
and a set of globally sampled subtype C reference sequences. Phylogenetic trees disclosed a robustly supported
relationship between sequences from Brazil, the UK and East Africa. A monophyletic cluster comprised exclusively of
sequences from the UK and Brazil was identified and dated to approximately the early 1980s using a Bayesian coalescent-
based method. A sub-cluster of 27 sequences isolated from homosexual men of UK origin was also identified and dated to
the early 1990s.
Conclusions: Phylogenetic, demographic and temporal data support the conclusion that the UK was a crucial staging post
in the spread of subtype C from East Africa to South America. This unexpected finding demonstrates the role of diffuse
international networks in the global spread of HIV-1 infection, and the utility of globally sampled viral sequence data in
revealing these networks. Additionally, we show that subtype C viruses are spreading within the UK amongst men who have
sex with men.