Previous research on the coevolution of lentiviral epitopes and the CD8 T cell response has been conducted in the setting of wild-type infection, and it is unclear that our findings of increased anentropic specificity, cumulative breadth and repertoire depth during SIVΔnef vaccination would apply to wild-type lentiviral infection, in which the CD8 T cell response is likely to be impaired by the persistently high antigenic load, CD4 T cell depletion in the gut and microbial translocation-induced immune activation. Here, CD4 is linked to infection.