After the success of combination antiretroviral therapy (cART) to treat HIV infection, the next great frontier is to cure infected persons, a formidable challenge. HIV persists in a quiescent state in resting CD4+ T cells, where the replicative enzymes targeted by cART are not active. Although low levels of HIV transcripts are detectable in these resting cells, little to no viral protein is produced, rendering this reservoir difficult to detect by the host CD8+ T cell response. However, recent advances suggest that this state of latency might be pharmacologically reversed, resulting in viral protein expression without the adverse effects of massive cellular activation. Emerging data suggest that with this approach, infected cells will not die of viral cytopathic effects, but might be eliminated if HIV-specific CD8+ T cells can be effectively harnessed. Here, we address the antiviral properties of HIV-specific CD8+ T cells and how these cells might be harnessed to greater effect toward achieving viral eradication or a functional cure.
R. Brad Jones, Bruce D. Walker
Barriers to CTL-mediated elimination of persistent viral reservoirs.
Shown is a representation of the major barriers preventing CTL from effectively recognizing and eliminating HIV-infected cells. These issues will likely have to be solved in parallel in order to achieve reductions in the viral reservoir. For example, the enhancement of T cell function by blockade of immune checkpoints can only be effective if the rescued T cells are targeted against nonescaped viral epitopes.