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PD-1 blockade: A promising immunotherapy for HIV?

The progressive loss of effector function in the setting of chronic viral infections has been associated with the upregulation of programmed death 1 (PD-1), a negative regulator of activated T cells. In HIV infection, increased levels of PD-1 expression correlate with CD8(+) T cell exhaustion, which has been shown in vitro to be reversible with PD-1 blockade. Velu and colleagues recently reported the first in vivo study showing enhancement of a virus-specific immune response through PD-1 blockade using an anti-PD-1 antibody in an SIV-macaque model. Their results show an expansion of virus-specific, polyfunctional CD8(+) T cells. Anti-PD1 antagonists show promise as a novel immunotherapy for HIV. However, several issues including development of autoimmunity, regulatory T cells and multiple inhibitory receptors associated with CD8(+) T cell exhaustion should first be addressed to help ensure a successful response in chronic HIV infected patients.