Background: An increase in non-B HIV-1 infections among men who have sex with men (MSM) in the United Kingdom (UK)
has created opportunities for novel recombinants to arise and become established. We used molecular mapping to
characterize the importance of such recombinants to the UK HIV epidemic, in order to gain insights into transmission
dynamics that can inform control strategies.
Methods and Results: A total of 55,556 pol (reverse transcriptase and protease) sequences in the UK HIV Drug Resistance
Database were analyzed using Subtype Classification Using Evolutionary Algorithms (SCUEAL). Overall 72 patients shared
the same A1/D recombination breakpoint in pol, comprising predominantly MSM but also heterosexuals and injecting drug
users (IDUs). In six MSM, full-length single genome amplification of plasma HIV-1 RNA was performed in order to
characterize the A1/D recombinant. Subtypes and recombination breakpoints were identified using sliding window and
jumping profile hidden markov model approaches. Global maximum likelihood trees of gag, pol and env genes were drawn
using FastTree version 2.1. Five of the six strains showed the same novel A1/D recombinant (8 breakpoints), which has been
classified as CRF50_A1D. The sixth strain showed a complex CRF50_A1D/B/U structure. Divergence dates and
phylogeographic inferences were determined using Bayesian Evolutionary Analysis using Sampling Trees (BEAST). This
estimated that CRF50_A1D emerged in the UK around 1992 in MSM, with subsequent transmissions to heterosexuals and
IDUs. Analysis of CRF50_A1D/B/U demonstrated that around the year 2000 CRF50_A1D underwent recombination with a
subtype B strain.
Conclusions: We report the identification of CRF50_A1D, a novel circulating recombinant that emerged in UK MSM around
1992, with subsequent onward transmission to heterosexuals and IDUs, and more recent recombination with subtype B.
These findings highlight the changing dynamics of HIV transmission in the UK and the converging of the two previously
distinct MSM and heterosexual epidemics.