In efforts to develop an effective
vaccine, sterilizing immunity to primate lentiviruses has only been achieved by the use of live attenuated viruses carrying major deletions in nef and other accessory genes. Although live attenuated
HIV vaccines are unlikely to be developed due to a myriad of safety concerns, opportunities exist to better understand the correlates of immune protection against
HIV infection by studying rare cohorts of long-term survivors infected with attenuated, nef-deleted HIV strains such as the Sydney blood bank cohort (SBBC). Here, we review studies of viral evolution, pathogenicity, and immune responses to
HIV infection in SBBC members. The studies show that potent, broadly neutralizing anti-
HIV antibodies and robust CD8+ T-cell responses to
HIV infection were not necessary for long-term control of
HIV infection in a subset of SBBC members, and were not sufficient to prevent HIV sequence evolution, augmentation of pathogenicity and eventual progression of
HIV infection in another subset. However, a persistent T-helper proliferative response to
HIV p24 antigen was associated with long-term control of
infection. Together, these results underscore the importance of the host in the eventual outcome of
infection. Thus, whilst generating an effective antibody and CD8+ T-cell response are an essential component of
vaccines aimed at preventing primary
HIV infection, T-helper responses may be important in the generation of an effective therapeutic
vaccine aimed at blunting chronic
HIV infection.