Modelling the interaction between human immunodeficiency virus, mycobacterium tuberculosis and the human immune system, including the effects of drug therapy.

Abstract

Tuberculosis (TB) is the leading cause of death in individuals infected with human immunodeficiency virus (HIV) in several African countries, including South Africa. HIV-positive individuals do not have the immune system resources to keep TB in check and are as much as 30 times more likely to develop active TB than people who are HIV-negative. Many people infected with HIV develop TB as the first manifestation of AIDS and TB accelerates disease progression in HIV-positive individuals. HIV and TB pathogenesis are thus inextricably intertwined so that it is necessary for medical practitioners to have an understanding of the dynamics and treatment of HIV-TB coinfection. At present the question remains as to whether the best time for coinfected individuals to start antiretroviral treatment for HIV is at the beginning, the peak, or after the completion of the TB treatment phase. This dissertation was undertaken with the aim of obtaining some clarity on this question by creating a mathematical model of HIV-TB coinfection and its treatment. This needs an understanding of the biological interactions; therefore the dissertation begins with a discussion of the biological mechanisms of HIV, the human immune system, TB and the drug therapies for each disease. Thereafter a brief introduction to mathematical modelling reviews basic HIV models, which are then modified to include HIV drug therapy. Analyses and simulations of these models were carried out, which yielded some insights into the dynamics of HIV and HIV therapy. Finally HIV-TB coinfection is introduced by reviewing a previously developed model. Based on all the models reviewed, a model for coinfection is developed which includes treatment for HIV and TB. Numerical simulations suggest that, if HIV disease progression is at an advanced stage of the immune system collapsing towards AIDS, with low T-cell count and high viral load, it is necessary to treat for both diseases simultaneously to ensure a positive survival prognosis for the coinfected individual. However, if disease progression is in the early stages of AIDS, with T-cell count and viral load beginning to display signs of the immune system collapse but still at reasonable levels relative to advanced stages, it need not be necessary to treat both diseases simultaneously. TB can be treated first, and upon completion HIV treatment can be initiated thus sparing the coinfected individual from the compounded side-effects and drug-drug interactions which usually result from simultaneous treatment.