A-103 Combined immune-based strategies targeting viral persistence in ART-suppressed SIV-infected rhesus macaques

Abstract

Antiretroviral therapy (ART) suppresses viral replication in HIV-infected individuals, but does not eliminate an extremely durable reservoir of latently infected cells that is established early after infection. Understanding the phenotype and location of latently infected cells represents a critical challenge in designing a cure for HIV; furthermore, many HIV-infected individuals given ART exhibit residual inflammation, which may contribute to virus persistence. This presentation will discuss immune based strategies targeting HIV persistence developed over the past several years using the model of SIV infection in rhesus macaques. Recent work identified PD-1+ follicular helper CD4+ T-cells as an important cellular compartment for viral persistence. We have described that CTLA-4+PD-1-memory CD4+ T-cells, which share phenotypic markers with regulatory T-cells and localize outside the B-cell follicle of the lymph nodes, are significantly enriched in SIV-DNA; contain robust levels of replication-competent virus; and increase their contribution to the SIV reservoir with prolonged ART. Finally, we showed that Interleukin-21 and IFN-alpha administration in ART-treated, SIV-infected RMs reduces residual immune activation during ART and temporally delay viral rebound after ART treatment interruption. These recent advancements highlight the complexity and diversity of the mechanisms and T-cell populations that can contribute to the residual reservoirs of virally infected cells. Developing a range of different interventions to target individual components of viral reservoirs represent both a formidable challenge and an exciting opportunity for the years to come.