Latent HIV reservoirs are the greatest challenge facing an HIV cure. Here, we review recent evidence supporting an important role for the host immune response, in particular HLA class I-restricted CD8+ T lymphocytes, in modulating HIV reservoirs during natural infection. These observations indicate that factors governing immune-mediated control of HIV may also contribute to the clearance of viral reservoirs. As such, critical gaps in our understanding of HIV immunology hinder efforts to develop both an effective HIV vaccine as well as novel therapies that may lead to a cure. The importance of elucidating correlates of protective cellular immunity should be recognized during research to develop and test potential HIV elimination strategies.
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