Significance An HIV vaccine must induce antibodies [broadly neutralizing antibodies (bnAbs)] that neutralize many viral variants. Determining pathways of antibody affinity maturation that have led to specific bnAbs and tracking coevolution in an infected individual of virus and antibody will define characteristics of immunogens that might elicit broad responses. We have followed, in an infected individual, one round of coevolution of viral envelope with antibodies from a single lineage. Insertions into a loop (V5) in gp120 of autologous viruses allowed escape from neutralization by antibodies in this lineage; antibody affinity maturation shifted the relative orientation of the light- and heavy-chain variable domains, allowing binding to envelopes with augmented V5. The results illustrate a mechanism of affinity maturation through mutation outside the antigen combining site.