Phylogenetic structure in African HIV-1 subtype C revealed by selective sequential pruning

Subtype C is the most prevalent clade in the HIV-1 pandemic. Previous studies suggested that African HIV-1 subtype C lacks a well-defined phylogenetic structure. Here we show that, by sequential pruning of ambiguously positioned taxa, a well-defined intrasubtype C phylogenetic structure becomes apparent, with 52% African HIV-1 subtype C isolates analyzed in envelope sequences branching within 11 clusters, also supported in a tree of full-length genomes, and all with geographical associations. Among 46 viruses recently transmitted in South Africa, 70% branched within 7 clusters (41% in the largest one) and 15% additional isolates were intercluster recombinants. Choice of the outgroup sequence and inclusion of intrasubtype recombinant viruses in the analyses could greatly affect support of clusters. The identification of clusters comprising a large proportion of African HIV-1 subtype C viruses may have implications for the design of vaccines intended for use in areas where subtype C is prevalent.