Mitogen Immunotherapy for HIV Infections Exemplified by Phytohemagglutinin and Pokeweed Mitogen

The ideal treatment for HIV infections would supplement highly active antiretroviral therapy (HAART) started at the time of initial diagnosis with an agent that can facilitate cure in the briefest time possible to avoid adverse effects of extended HAART such as drug toxicity, noncompliance, and shortened telomere- inducedreplicative senescence of CD8 cells. As a crucial part of the regimen, the agent must be able to initiate killer reactions against the HIV, replenish CD4 cells, rejuvenate CD8 cells, block HIV invasion of CD4 cells, activate latent HIV-sequestering host cells, stimulate effective immune reactions against malignancies, generate effective immune responses against conventional and opportunistic infections, circumvent the treatment- and immune response-evading capacities of HIV mutations, and reconstitute immune and hematopoietic competences. Over the past decade, the L4 isolectin ofPHA has been presented as a mitogen capable of meeting these goals as they have become defined, but its potential has not been recognized sufficiently to expedite its evaluation. Pokeweed mitogen (PWM) offers the major advantage of being up to 500 times more potent than PHA and has much smaller molecular weight (22,500 to 38,000 daltons versus ̃125,000 daltons). Given by injection, it has demonstrated curative effects for metastatic malignancies in dogs and cats unassisted by ancillary therapy. Unlike PHA, PWM does not block the attachment of HIV gp l20 to CD4 membrane receptors, but it can obstruct CD4 cell invasion by binding with the CD4 receptors themselves. An expeditious manner of applying PWM would be to give minute doses of an ultra potent root extract capable of inducing a benign plasmacytoid lymphoblastic leukemoid reaction that reverses spontaneously after about 10 weeks. This might prove curative given in conjunction with HAART or possibly even without it. The preferred route of administration for the mitogens in humans would be intravenous although oral administration might prove more advantageous, particularly with PWM. These mitogens might be used singly or, if necessary, in combination after the toxicities have been carefully delineated in humans. Economic forces might restrict treatment availability solely to orally administered PWM therapy in poverty-stricken undeveloped countries if this were shown to be curative. These proposals originatingfrom the authors long concerned with mitogen management of various disorders including HIV infections but only peripherally involved with their clinical applications, are offered for consideration by investigators perceptive enough to see the wisdom of exploring the curative possibilities.