Temporal studies of HIV-1 have demonstrated that HIV-1 undergoes recurrent cycles of escape from autologous Nab [17, 19, 26, 27] , and escape also occurred during infection with a chimeric SIV-HIV-1 (SHIV) virus in response to vaccine-induced Nab [28] . Yet, our knowledge of the specific molecular events that lead to escape remains incomplete. Shifting carbohydrate moieties in and around the outer surface of gp120, as well as changes in the hyper-variable domains, have been proposed as general mechanisms used by HIV-1 and SHIV to alter neutralization epitopes, although most of these studies are based on subtype B Envs. Nab escape in SHIV-infected macaques has been shown to involve glycan changes in the V1, V2, and V3 domains, perhaps by shielding conserved epitopes such as the CD4 binding site [29, 30, 31] . Consistent with this finding, a recent study identified V1V2 as the major determinant of strain-specific autologous Nab in macaques infected with two different strains of SHIV [32] , and this domain was also shown to be the principal determinant of inherent Nab resistance for HIV-1 strain JRFL [10] . Subtype B HIV-1 can also escape from autologous Nab by shifting N-linked carbohydrates on the outer domain of gp120 with little involvement of V1V2 [17] . Others have demonstrated that subtype B viral escape could also occur in the absence of frank changes in glycosylation, with no clear mutational pattern emerging [33] . In experimental SIVmac infection, the emergence of N-and O-linked carbohydrates in the V1 and V4 hypervariable domains has been shown to confer escape from autologous neutralization [34, 35, 36] . Furthermore, the presence of specific glycans in V1 reduced the immunogenicity of SIVmac in the context of an experimental infection [37] . Taken together, these studies hint at the complexity of HIV-1 neutralization and escape, but also suggest that common themes may exist.