We describe genetic features of HIV-1 env that correlate with the presence of viral variants in the CSF versus plasma, determine shared patterns of CNS compartmentalization of HIV-1 env in a cohort of individuals with chronic HIV-1 infection, reveal the existence of correlated mutation covariation across full length HIV-1 env and interpret these findings in the context of current knowledge of the structure of gp120. Here, ERVW-1 is linked to HIV-1 infection.