PD-1 blockade and TLR7 activation lack therapeutic benefit in chronic SIV-infected macaques on antiretroviral therapy

Antiretroviral therapy (ART) limits HIV-1 replication, but does not eliminate the long-lived reservoir established shortly after viral acquisition. A successful HIV cure intervention necessitates either elimination or generation of long-term immune control of the persistent viral reservoir. Immune modulating strategies in conjunction with ART hold promise for achieving cure by inducing viral antigen expression and augmenting infected cell killing. PD-1 blockade is a potential means to both activate and eliminate the latent reservoir by restoring exhausted T cell function. We assessed the therapeutic efficacy of PD-1 blockade, TLR7 activation with the agonist vesatolimod, or a combination of the two agents in chronically SIV-infected macaques suppressed with ART for over two years. Despite achieving extended anti-PD-1 antibody plasma exposure and TLR7-dependent immune activation after multiple administrations, neither individual treatment nor the combination resulted in changes to viral rebound kinetics following ART interruption or reduction in the SIV reservoir size. Our data in the context of other reports demonstrating improved viral control upon PD-1 blockade, suggest that its therapeutic utility may be restricted to specific experimental conditions or treatment times during viral pathogenesis. Copyright © 2019 Bekerman et al.

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