Mitogens for curative therapy of HIV-1 infections; an update

The curative objectives of administering mitogens in conjunction with HAART have been to initiate killer reactions against HIV-1, replenish CD4 cells, rejuvenate CD8 cells, stimulate effective immune reactions against malignancies, generate tolerated immune responses against conventional and opportunistic infections, resist treatment-evading tactics of HIV mutations, and reconstitute both immune and hematopoietic competences. With recent observations that these aims might be thwarted by sequestration of HIV-1 infection in memory cells residing in the circulation, lymph nodes, and spleen as well as in various other sites not readily accessible to eradication, stronger emphasis should be focused primarily on mitogen-induced blockage of HIV-1 entry into CD4 cells. Equally important would be the mitogen panactivation of any cells sequestering virions and proviruses, thereby forcing them out of the latent G0 phase and exposing them to destruction by HAART and the immune responses. While the currently best established mitogens for HIV-1 therapy, PHA-L4 and PWM, might be successfully applied independently or in tandem, other mitogens may be found suitable for evaluation.