PD-1 Blockade and TLR7 Activation Lack Therapeutic Benefit in Chronic Simian Immunodeficiency Virus-Infected Macaques on Antiretroviral Therapy.
Antimicrob Agents Chemother
; 63(11)2019 11.
Article
em En
| MEDLINE
| ID: mdl-31501143
ABSTRACT
Antiretroviral therapy (ART) limits human immunodeficiency virus 1 (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. Programmed death-1 (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, Toll-like receptor 7 (TLR7) activation with the agonist vesatolimod, or a combination of the two agents in chronically simian immunodeficiency virus (SIV)-infected macaques suppressed with ART for more than 2 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Imunodeficiência Adquirida dos Símios
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Antirretrovirais
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Receptor 7 Toll-Like
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Receptor de Morte Celular Programada 1
Limite:
Animals
Idioma:
En
Revista:
Antimicrob Agents Chemother
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos