D-102 Immune-based interventions for HIV cure: lessons from NHP models

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Abstract

While the availability of potent anti-retroviral therapy, ART, has dramatically reduced the mortality and morbidity associated with HIV infection, no intervention that can functionally “cure” the infection is yet available. This is due to a persistent reservoir of latently infected cells that is resistant to both ART (which targets specific phases of the “productive” virus life cycle) and immune-based interventions (which require expression of viral proteins as target antigens). Over the past few years, the non-human primate model of SIV/SHIV infection of rhesus macaques has been developed and validated for studies of HIV eradication in the setting of fully suppressive ART. In this presentation, I will review: (i) the opportunities presented by the SIV/SHIV macaque models to conduct studies aimed at developing and testing novel interventions to achieve a functional cure for HIV infection; (ii) the main immune-based strategies that are currently explored to reduce or eliminate the virus reservoir in the NHP model (i.e., shock & kill, block & lock; soothe & schmooze; push & vanish; as well as transplant and gene therapy); and (iii) the published and ongoing preclinical trials of immune-based interventions that are conducted by our team in ART-treated SIV-infected rhesus macaques with the goal of inducing a functional cure. Among the used interventions I will discuss type I interferons, interleukin-21, FTY720, check-point blockade inhibition (i.e., inhibitors of PD-1, CTLA4, and LAG-3), CD8+ T cell depletion, CD4+ T cell depletion, and autologous stem cell transplantation.

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