Living in a house of cards: re-evaluating CD8+ T-cell immune correlates against HIV

The Merck STEP and the Thai RV144 human immunodeficiency virus (HIV) vaccine trials confirmed that we still have a long way to go before developing a prophylactic HIV vaccine. The main issue at hand is that we have yet to identify an immunological correlate of protection against HIV. While many question the T-cell-based approach towards vaccine development, it is likely that T cells will be a necessary part of any vaccine strategy. CD8+ T cells remain an attractive option because of their ability to specifically recognize and eliminate virally infected host cells. In this review, we recapitulate the evidence for CD8+ T cells as an immunological correlate against HIV, but more importantly, we assess the means by which we evaluate their antiviral capacity. To achieve a breakthrough in the domain of T-cell-based HIV vaccine development, it has become abundantly clear that we must overhaul our system of immune monitoring and come up with a 'rational' tactic to evaluate the efficacy of HIV-specific CD8+ T cells.