Purpose of review: To discuss the recent major advances in the understanding of how host immune defenses contribute to HIV reservoir control.
Recent findings: Immune control of HIV-1 reservoirs is a two-step process: viral replication activation from latent reservoirs followed by elimination of virus-expressing cells by the host. Environmental factors, such as pro-inflammatory type-I interferon, chemokines or cytokines, can facilitate HIV-1 replication, confer dormancy in CD4+ cells or confer resistance to cytopathogenic effects of cytotoxic CD8 T cells. Therefore, they constitute a double-edged sword for immune control of HIV reservoirs. Concomitantly, adaptive immunity takes advantage of CD4 T-cell homeostatic mechanisms and can expose HIV-1 antigen-expressing cells to HIV-specific cytotoxic CD8 T cells, and limit virus spreading. These highly interconnected phenomena can lead to quasi-equilibrium between the HIV-1 reservoirs and host immune control that can serve as a model for the ‘shock and kill’ immune-based therapeutic strategies in play in the course of finding an HIV cure.
Summary: Immune control of HIV reservoirs in CD4 T cells involves modulation of both HIV-1 latency and the continuous reseeding of the reservoir offering conceptual models that may advance HIV cure strategies.