A comparison of elasticities of viral levels to specific immune response mechanisms in human immunodeficiency virus infection

Abstract

Background: The presence of an asymptomatic phase in an HIV infection indicates that the immune system can partially control the infection. Determining the immune mechanisms that contribute significantly to the partial control of the infection enhance the HIV infection intervention strategies and is important in vaccine development. Towards this goal, a discrete time HIV model, which incorporates the life cycle aspects of the virus, the antibody (humoral) response and the cell-mediated immune response is formulated to determine immune system components that are most efficient in controlling viral levels. Ecological relationships are used to model the interplay between the immune system components and the HIV pathogen. Model simulations and transient elasticity analysis of the viral levels to immune response parameters are used to compare the different immune mechanisms. Results: It is shown that cell-mediated immune response is more effective in controlling the viral levels than the antibody response. Killing of infected cells is shown to be crucial in controlling the viral levels. Our results show a negative correlation between the antibody response and the viral levels in the early stages of the infection, but we predicted this immune mechanism to be positively correlated with the viral levels in the late stage of the infection. A result that suggests lack of relevance of antibody response with infection progression. On the contrary, we predicted the cell-mediated immune response to be always negatively correlated with viral levels. Conclusion: Neutralizing antibodies can only control the viral levels in the early days of the HIV infection whereas cell-mediated immune response is beneficial during all the stages of the infection. This study predicts that vaccine design efforts should also focus on stimulating killer T cells that target infected cells.