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

Summary:  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.