In contrast to subject 185F, Nab escape in 205F was driven predominantly by changes in the V1V2 domain ( Fig. 8A and B) . A preference for potential glycan shifts in V1V2 became evident from the spatial representation of gp120, where in the 14-month Env, four predicted glycosylation site changes are observed in V1 alone (Fig. 8A : green and white spheres in Env 14-PB5.4). The importance of V1V2 for escape was further illustrated by the demonstration that two predicted glycan sites, one in V1 and one in V2, influenced neutralization by two Mabs derived from this same subject. Thus, this study is the first to identify specific mutations that confer autologous Nab resistance at the single antibody level. This made possible several observations that were not apparent from polyclonal plasma. First, a single substitution can confer resistance against multiple antibody specificities within an individual. While we did not formally show that glycosylation at the substituted site was responsible for resistance against Mabs 6.4C and 13.6A, there is strong evidence from other studies to support that this is the case. Second, different pathways of escape also operate at the single antibody level. Resistance against 13.6A could be achieved either by addition of the predicted glycan site in V2 or by loss of the predicted glycan site in V1. Interestingly, only the modification of V2 was retained in subsequent escape variants, suggesting that it could have been more advantageous in terms of escape and or maintenance of replication fitness. Third, mutations that confer escape from multiple monoclonal antibody specificities do not necessarily confer escape from the entire polyclonal Nab milieu in plasma. The V2 modification in the 8-month Env conferred complete resistance against 6.4C and 13.6A at 10 mg/ ml, but only partial escape from patient plasma ( Fig. S5 and data not shown). This finding suggests that escape determinants mapped against plasma will only reflect the dominant Nab specificities that are present at relatively high concentration (able to inhibit virus infectivity at greater than a 1:100 dilution in our assay), but other lower titer Nab specificities could also drive escape mutations. The relative contributions of different antibody specificities in plasma will undoubtedly vary among subjects, and potentially even within a subject over time, resulting in the need for customized escape pathways that are driven by each dominant Nab response. Thus, to derive a complete picture of autologous Nab and escape, it will be necessary to recover and characterize individual Mabs with different specificities, as was done here and recently by others to dissect the B cell response in subjects with neutralization breadth [9] . These studies demonstrate how the HIV-1 subtype C Env is uniquely equipped to respond to the current immune response of each individual host by adjusting its pathways of escape.