MODELLING AND ASSESSMENT OF THERAPEUTIC STRATEGIES FOR HIV INFECTION

AB Gumel¹, Xue-Wu Zhang¹, PN Shivakumar¹, ML Garba², Beni M Sahai^3,4
Departments of ¹Mathematics and ³Medical Microbiology, University of Manitoba; ²Center for HIV/STDs and Infectious Diseases, University of North Carolina; ⁴Cadham Provincial Laboratory, Winnipeg, Manitoba

Background and objective: Despite success of highly active antiretroviral therapy (HAART) in decreasing plasma viremia below detectable levels in many HIV-infected individuals, the long-term control or eradication of HIV remains problematic due to the persistence of latently-infected CD4⁺ T cells and other cells carrying replication-competent HIV. The objective of this study was to develop a mathematical model to assess therapeutic strategies including vaccines and to investigate the conditions necessary for eradication HIV in an individual.
Methods: Utilizing current understanding of HIV pathogenesis, a five-dimensional deterministic mathematical model was developed that monitors the temporal dynamics of uninfected CD4⁺ T cells, uninfected CD8⁺ T cells, productively-infected CD4⁺ T cells, latently-infected CD4⁺ T cells and HIV load. The solution of the model was obtained using Maple Software. The model was simulated with realistic parameter values and results depicted using Maple and GNUplot graphic softwares.
Results: Simulations of the model revealed the following: (i) HIV-specific CD8⁺ cytotoxic T cells (CTL) play an important role in suppressing viremia. (ii) In the absence of therapy, even the theoretically perfect anti-HIV CTL activity would fail to eliminate HIV regardless of the presence or absence of non-CD4⁺ T cell HIV reservoirs. (iii) Anti-HIV CTL action, even in the presence of 100% effective intermittent HAART and IL-2 therapy, is insufficient in eradicating HIV. (iv) Eradication of HIV in vivo is theoretically feasible provided a conventional anti-HIV vaccine and a new class of anti-HIV drugs that eliminate non-CD4⁺ T cell HIV reservoirs are used in conjunction with continuous HAART and IL-2 therapy.
Conclusions: Mathematical modelling is a very useful tool to gain deeper insight into pathogenesis and treatment of HIV disease. Model simulations reveal that (i) intermittent HAART and IL-2 therapy cannot eliminate HIV, and (ii) eradication of HIV in a patient is theoretically feasible with combination therapy involving a conventional anti-HIV vaccine.