Purpose of review: We discuss recent studies giving insight into the promise of cell-mediated immunity for prophylactic HIV vaccine strategies, and challenges to be overcome for this approach to succeed.
Recent findings: Advances in understanding of events in very early HIV infection and their importance in viral pathogenesis emphasize the rapidity with which vaccine-induced T-cell responses must act to modulate CD4 cell destruction, but also reveal an early window of opportunity when foci of infection are limited and could potentially be eliminated. Super-infection with diverse HIV strains is now appreciated to be relatively common, indicating that cell-mediated responses in most infected individuals do not confer protection. Recent studies suggest that T-cell correlates of good control of HIV replication may be a consequence rather than a cause of containment of viraemia. Analysis of features of HIV-specific T-cell responses restricted by human leukocyte antigen alleles associated with differential prognosis of infection is giving insight into correlates of protection. The importance of efficacious responses, escape from which incurs high fitness costs, is increasingly appreciated.
Summary: There are many challenges to be overcome before the promise of cell-mediated immunity for HIV vaccines is realized.