On the Intra-Host Dynamics of HIV-1 Infections

A theory for the pathogenesis of human immunodeficiency virus type 1 (HIV-1) infection is presented and analyzed using a mathematical modelling approach. The objective is the investigation of some essential mechanisms underlying such a process. The theory is based on the observation that predominantly infects and replicates in CD4+-T cells, and that the infection process within an infected individual is characterized by ongoing generation and selection of HIV variants with increasing reproductive capacity. This evolutionary process is considered to be the cause of the gradual loss of immunocompetence and the final destruction of the immune system observed in most patients. The basic mathematical model of the theory describes the population dynamics of the susceptible and infected cells as well as those of the virus. The immune response has been explicitly considered in the model in a rather simple form. To allow for a more realistic description of the HIV infection process an extension of the model has been developed. The extended model explicitly incorporates the effect of the permanently increasing susceptibility of CD4+-T cell clones, as a result of the evolutionary process. The modified model reproduces and possibly explains a wide variety of findings about the HIV infection process. Numerical results indicate that the effect of the initial dose is minimal and restricted to primary infection. According to the model predictions the impact of the HIV evolutionary speed is crucial for the progression to disease. An important progression determinant is the initial infection rate, being a component of the viral reproductive capacity. An influential role in disease progression seems to be played by the initial CD4+-T cell count.

STILIANAKIS Nikolaos;  SCHENZLE Dieter; 

2006-09-18

ELSEVIER

JRC30818