DC CFAR investigator, Brad Jones, PhD, along with his colleague, John Huang, has published an article in The Journal of Clinical Investigation entitled, "Latent HIV reservoirs exhibit inherent resistance to elimination by CD8+ T cells".
In this article, the authors discuss the results of their study showing that treating CD4+ T cells from ART-treated individuals with combinations of potent latency-reversing agents and autologous CD8+ T cells consistently reduced cell-associated HIV DNA, but failed to deplete replication-competent virus. The study is in response to the idea that the presence of persistent, latent HIV reservoirs in CD4+ T cells has obstructed current efforts to cure infection. Additionally, the support of kick-and-kill paradigm has been largely based on success in latency models, which do not fully reflect the makeup of latent reservoirs in individuals on long-term antiretroviral therapy (ART). More recent studies have shown that CD8+ T cells have the potential to recognize defective proviruses, which comprise the vast majority of all infected cells, and that the proviral landscape can be shaped over time due to in vivo clonal expansion of infected CD4+ T cells. The new results discussed in this article suggest that cells harboring replication-competent HIV possess an inherent resistance to these CD8+ T cells that may need to be addressed to cure infection.
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