Abstract
BackgroundHuman Immunodeficiency Virus (HIV) infection is a dynamic interaction of the pathogen and the host uniquely defined by the preference of the pathogen for a major component of the immune defense of the host. Simple mathematical models of these interactions show that one of the possible outcomes is a chronic infection and much of the modelling work has focused on this state.BifurcationHowever, the models also predict the existence of a virus-free equilibrium. Which one of the equilibrium states the system selects depends on its parameters. One of these is the net extinction rate of the preferred HIV target, the CD4+ lymphocyte. The theory predicts, somewhat counterintuitively, that above a critical extinction rate, the host could eliminate the virus. The question then is how to increase the extinction rate of lymphocytes over a period of several weeks to several months without affecting other parameters of the system.Testing the hypothesisProposed here is the use of drainage, or filtration, of the thoracic duct lymph, a well-established surgical technique developed as an alternative for drug immunosuppression for organ transplantation. The performance of clinically tested thoracic duct lymphocyte depletion schemes matches theoretically predicted requirements for HIV elimination.
Highlights
Human Immunodeficiency Virus (HIV) infection is a dynamic interaction of the pathogen and the host uniquely defined by the preference of the pathogen for a major component of the immune defense of the host
The prediction of the theoretical model calls for the removal of 5 to 10 percent of the total lymphocyte pool per day
The vaccination primes the system for a faster, stronger response, including proliferation of the responding lymphocytes
Summary
Theoretical predictions of system dynamics are not very encouraging for the prospects of HIV vaccines. Apoptosis of uninfected CD4+ lymphocytes in HIV infection is an appropriate response (for the host), albeit insufficient, since the cause of apoptosis is Tat protein produced by only the infected cells themselves. This prevents the system from eliminating the virus because the apoptotic signal weakens along with the infection. If vaccinations were to work, upon entry of the pathogen, they should provoke apoptosis of lymphocytes, not their proliferation Until such discoveries are made, and to test perhaps their ultimate potential, a simple surgical intervention to allow for removal of lymphocytes merits further investigation. An attractive aspect of using physical means of depletion is the possibility to terminate the treatment instantly and completely, as soon as any major deviations from the expected response would arise, indicating a failure of the model and alarming for unexpected risks
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