HIV-1 in the United Kingdom: population dynamics and genetic evolution

Background: Phylogenetic characterisation of local HIV-1 epidemics can be used to understand emerging transmission networks. We analysed subtype-unassigned sequences in the UK HIV Drug Resistance Database (UK HIV DRD) to map the emergence and origin of genetically diverse recombinant strains using phylogenetic analyses, near full-length sequencing of plasma HIV-1 and CD4 cell count decline. Methods: 55,556 genotyped pol sequences (protease amino acids 1-99, RT amino acids 1-234) were analysed for evidence of recombination. Near full-length single genome sequencing of plasma HIV-1 was performed on stored specimens from six patients with a putative A1/D novel recombinant strain. Recombination and phylogenetic analyses were performed using RIP, PhyML, jpHMM, Simplot, SCUEAL and FastTree v2.3.1. Evolutionary analysis of putative novel recombinants was performed using Bayesian Evolutionary Analysis by Sampling Trees (BEAST). Geographic screening for additional instances of recombinant structures was performed using HIV BLAST and the Los Alamos National HIV database. Demographic data were available for 50/72 patients. CD4 cell count decline was assessed using linear regression. Results: The proportion of subtype-unassigned HIV-1 strains in the UK HIV DRD increased significantly during 1999-2008 (p