Immune reconstitution in HIV infection

The course of the human immunodeficiency virus (HIV) infection has dramatically changed since the immune reconstitution induced by new antiretroviral therapeutic regimens, or highly active antiretroviral therapy (HAART) combining inhibitors of the HIV reverse transcriptase (RTI) and protease (PI). Indeed, by blocking virus production these agents allow the immune system to reconstitute the CD4 cell pools and to restore the host’s protection against pathogens [1, 2, 3, 4, 5]. The success of antiviral therapies illustrates the key role played by HIV in the pleiomorphic immune alterations observed during the infection, i.e., the severe CD4 cell depletion and the profound immune defects leading to loss of immune control of opportunistic pathogens. The fast and efficient immune reconstitution obtained at any stage of the disease also demonstrates that these major immune deficiencies are not definitively altering the immune system allowing reconstitution due to its enormous plasticity. The mechanisms underlying these immune alterations as well as their correction under therapy are still heavily debated. Nevertheless, such immune reconstitution represents a real breakthrough for HIV-infected patients but also allows better understanding of the pathophysiology of the HIV disease as well as the homeostasis of the immune system. This chapter will briefly review the various mechanisms and aspects of the immune alterations induced by HIV and describe the kinetics and mechanisms, the current successes and limitations of the immune reconstitution.