Therapeutic vaccines and immunological intervention in HIV infection: a paradigm change

The purpose is to review current knowledge of immunological interventions in HIV infection and discuss strategies for the establishment of functional cure and/or HIV eradication.

Therapeutic vaccines and cytokines have been historically the immunological interventions developed with the objective to enhance the HIV-specific cell-mediated immune responses and to suppress virus replication. Both these interventions have shown only partial antiviral effects. The recent identification and generation of human broad neutralizing antibodies provides potent immunological intervention associated with effective suppression of virus replication in the absence of antiretroviral therapy. Furthermore, the identification that the major HIV cell reservoir containing replication competent and infectious virus is composed by programed cell death protein 1 (PD-1) positive memory CD4 T cells offers the opportunity to target directly the HIV cell reservoir with anti-PD-1 antibodies. Anti-PD-1 antibody therapy may be also critical to prevent exhaustion of CD8 T cells.

The availability of a diverse armamentarium of immunological intervention offers the opportunity to investigate the efficacy of the combined use of different immunological interventions in inducing prolonged virus suppression in the absence of antiretroviral therapy and functional cure HIV or HIV eradication.