부산대학교 도서관

A key challenge for the development of a cure to HIV-1 infection is the persistent viral reservoir established during early infection. Previous studies using Toll-like receptor 7 (TLR7) agonists and broadly neutralizing antibodies (bNAbs) have shown delay or prevention of viral rebound following antiretroviral therapy (ART) discontinuation in simian-human immunodeficiency virus (SHIV)-infected rhesus macaques. In these prior studies, ART was initiated early during acute infection, which limited the size and diversity of the viral reservoir. Here we evaluated in SHIV-infected rhesus macaques that did not initiate ART until 1 year into chronic infection whether the TLR7 agonist vesatolimod in combination with the bNAb PGT121, formatted either as a human IgG1, an effector enhanced IgG1, or an anti-CD3 bispecific antibody, would delay or prevent viral rebound following ART discontinuation. We found that all 3 antibody formats in combination with vesatolimod were able to prevent viral rebound following ART discontinuation in a subset of animals. These data indicate that a TLR7 agonist combined with antibodies may be a promising strategy to achieve long-term ART-free HIV remission in humans. Author summary: In a rhesus macaque model for chronic HIV infection where ART was not initiated before 1 year of infection, we demonstrate that the HIV bNAb PGT121 (formatted in three immune cell engager formats) together with the TLR7 agonist vesatolimod can partially prevent viral rebound following discontinuation of ART. Importantly, in most of the animals that did not rebound following the ART discontinuation, CD8+ cell depletion did not result in viral rebound, suggesting that the lack of rebound was not dependent on CD8+ T or NK cells. To the best of our knowledge, no similar study has been performed in the nonhuman primate model with animals that started ART deep into chronic infection. This proof-of-concept study in chronically infected rhesus macaques supports that this treatment regimen may represent a strategy to achieve long-term ART-free HIV remission in humans. [ABSTRACT FROM AUTHOR]