Role of cytokine agonists and immune checkpoint inhibitors toward HIV remission.

ABSTRACT

PURPOSE OF REVIEW The current article describes the current status of the use of cytokines and immune-checkpoint inhibitors as therapeutic strategies toward HIV remission. RECENT FINDINGS: Clinical trials using IL-2 and IL-7 showed increased levels of circulating T cells, although no reduction to the viral reservoir was observed. Studies in nonhuman primates (NHP) demonstrated that experimental IL-15 administration increased proliferation and cytotoxicity of simian immunodeficiency virus (SIV)-specific CD8 T cells, and promoted their localization to the lymph node (LN) B cell follicles. Immune checkpoint modulators targeting programed cell death-1 and cytotoxic T-lymphocyte associated protein 4, successfully used in oncologic diseases, have shown potential to restore HIV-specific function in early stage clinical trials, while also transiently increasing plasma and cell-associated viral RNA. Due to the complexity of the mechanisms regulating HIV persistence, it is very likely that combinatorial approaches, including cytokines with immune checkpoint blockades (ICBs), will be needed to achieve HIV remission. SUMMARY: The present review covers approaches based on cytokine agonists and immune checkpoint inhibitors that have shown promise toward therapeutic pathways for HIV remission. These strategies have been tested preclinically in animal models of HIV infection to determine their safety, activity, and mechanisms of action, with the goal to inform the design of the most synergistic combinatorial strategies. Several of these interventions are included in ongoing or planned clinical trials in HIV infection; these trials will elucidate the clinical efficacy of these innovative immunotherapy approaches toward HIV remission.