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

Abstract

BackgroundThe 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.ResultsIt 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.ConclusionNeutralizing 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.Electronic supplementary materialThe online version of this article (doi:10.1186/1756-0500-7-737) contains supplementary material, which is available to authorized users.

On the efficiency of HIV transmission: Insights through discrete time HIV models

“…The stages in the HIV replication cycle are; receptor binding, cell entry, uncoating, reverse transcription of viral RNA into DNA, nuclear entry, integration of the viral DNA into the host DNA and transcription and translation of viral RNA, assembly of progeny virus particles and budding [47]. The life cycle stages of the virus are divided into three stages: the mature virus ( V ), the HIV Deoxyribonucleic Acid (DNA) ( D ) and the Provirus ( P ) as illustrated in our previous study [48]. A Negative Binomial distribution method is used to estimate the duration of the provirus stage.…”

“…A Negative Binomial distribution method is used to estimate the duration of the provirus stage. This resulted in two pseudo-provirus stages as illustrated in [48]. We let P represent the pseudo-provirus stage 1 and Q represent the pseudo-provirus stage 2.…”

“…Provirus particles progress from provirus stage to the mature virus stage over a variable time. To calculate the proportion that goes to the virus stage and the proportion that remains in the provirus stage we used the Negative Binomial Distribution method as illustrated in [48]. The approach resulted in two identical pseudo provirus stages which we denote by P and Q .…”

“…The stage specific survival in the provirus stage is the proportion of replication competent provirus and was determined as [52]. The provirus stage take a variable duration, we used the Negative Binomial Distribution method to estimate its duration as illustrated in one of our studies [48]. This resulted in two pseudo-provirus stages with transition probability θ 2 = 0.06315 and the probability of surviving and remaining in the same stage θ 3 = 0.43685.…”