A novel finding is that Nab resistant Envs at 28-months utilized distinct Env sub-regions to block the same Nab pool. This provided a striking example of convergent, intra-patient evolution during early infection. One pathway was heavily dependent on the V5 domain, while the other exhibited V1V2 and gp41 codependence. The V5 domains of these two Envs contained the same predicted glycosylation shift (Fig. 7A : green and white spheres in 28-PL3.1 and 28-PL5.1) but differed in primary amino acid sequence (Fig. 4C) . This raises the possibility that the V5dependent Env contained mutations that directly confer epitope escape, while the V1V2-dependent Env retained the target but escaped through indirect mechanisms. In addition, both V1V2 and the regions flanking V5 are proximal to the CD4 binding site and could therefore alter its exposure, as has been proposed for changes in V2 and V5 in the context of a SHIV infection [30] . Thus, in examining a single subject in great detail, we have uncovered remarkable flexibility in the pathways of viral escape during early infection. These results further highlight how the plasticity of the Env hyper-variable domains coupled with complex conformational interactions could provide numerous options for escape.