Engaging innate immunity in HIV-1 cure strategies

Abstract

Combination antiretroviral therapy (ART) can block multiple stages of the HIV-1 life cycle to prevent progression to AIDS in people living with HIV-1. However, owing to the persistence of a reservoir of latently infected CD4⁺ T cells, life-long ART is necessary to prevent viral rebound. One strategy currently under consideration for curing HIV-1 infection is known as 'shock and kill'. This strategy uses latency-reversing agents to induce expression of HIV-1 genes, allowing for infected cells to be cleared by cytolytic immune cells. The role of innate immunity in HIV-1 pathogenesis is best understood in the context of acute infection. Here, we suggest that innate immunity can also be used to improve the efficacy of HIV-1 cure strategies, with a particular focus on dendritic cells (DCs) and natural killer cells. We discuss novel latency-reversing agents targeting DCs as well as DC-based strategies to enhance the clearance of infected cells by CD8⁺ T cells and strategies to improve the killing activity of natural killer cells.