INTRODUCTION
The human immune system is exceedingly complex in its response to viral pathogens. In the process of resolving an acute illness, some viruses, such as influenza, are eradicated by the immune system.
Other viruses, such as members of the Herpesviridae family, are controlled but not eradicated, resulting in chronic but typically clinically latent infection.Latency is defined as a state in which the viral genome is present within a cell without production of detectable virus.1 During this phase of the host-viral interaction, there is a delicate balance between viral persistence, pressure to replicate, and host immunity. The intricate framework of latency is established during early infection through mechanisms that modulate the immune response, which allows for containment of replication but not eradication of virus. These mechanisms include inhibition by natural killer cells, secretion of viral products that mimic chemokines and cytokines, inhibition of apoptosis, and interference with antigen presentation.1 After establishment of a latently infected reservoir in various sanctuary sites, these viruses alter their expression of genes, seemingly to a limited repertoire that allows the viral genome to exist undisturbed.1 Very low-level viral replication may occur, perhaps below the threshold of immune activation, preventing a full-blown immune response. Through a mechanism that is not well understood, these viruses may reactivate, often in the setting of waning immunity.1
Similar to the Herpesviridae family, infection with the human immunodeficiency virus (HIV) causes chronic infection; however, HIV replication is typically never fully controlled and is, at best, partially contained. The persistence of viremia inevitably results in a period of clinical latency that lasts between 8 and 10 years before progression to acquired immunodeficiency syndrome (AIDS).2 During this time, the infected host may have no symptoms referable to HIV infection, but virus continues to replicate, as evidenced by the presence of HIV-1 ribonucleic acid (RNA) detectable in plasma.3 Several studies demonstrate that individuals with high levels of viremia have more rapid progression of disease than those with lower viral loads.3-6 The level of viremia in this clinically quiescent phase of infection correlates with a decline in CD4+ count and progression to symptomatic disease.
Within 6 to 12 months after acute infection, viremia reaches an equilibrium commonly referred to as the viral load set point. For some individuals, the viral load set point may be very low and is associated with slow or nonprogressive disease. In some, the infection is controlled so efficiently that HIV remains undetectable in plasma without therapy. Many of these HIV controllers still harbor virus in their lymph nodes.7 The existence of these individuals raises the possibility that HIV viremia could be controlled as a latent infection without complete viral eradication.Several viral, host, and immunologic factors have been described that may influence the viral load set point and rate of progression to disease. The precise correlates of immune protection, however, are still unknown. In this chapter, we will review these factors and focus on potential mechanisms used by HIV to evade, delete, or attenuate HIV-specific host immunity.