8. Modelling Coinfection Treatment
8.2. Model Simulations
Modelling Coinfection Treatment
Modelling Coinfection Treatment
agreement with what happens clinically in that during primary infection there is a dip in the T cell population and a spike in the infected T cell population. Thereafter the T cell population increases due to antigenic stimulation and the infected T cell population decreases due to specific immune responses and possible target cell limitation, whereupon they then settle down to their set-point values signalling the onset of the asymptomatic stage of infection.
Furthermore examining the model quantitatively we have noted previously that according to clinical records of viral load the spike should peak in the range 103 – 105 virons per mm3 and the set-point value should settle in the range 10 – 100 virons per mm3. Figure 25a shows that the simulation’s viral quantitative dynamics does also agree with these clinical observations.
8.2.2. Complete Course of HIV Infection
Since we have now established the model’s ability to simulate primary and asymptomatic stages of disease progression, one can test subsequent stages of disease progression.
Typically after a few years of the asymptomatic stage of infection the immune system inevitably starts to collapse resulting in the onset of AIDS. The reasons for the immune system collapsing are not fully understood by immunologists; however, there is much ongoing biological research to determine the cause. Using the present model one can simulate the immune system collapse by assuming that the virion production rates of infected T cells (gVT) and macrophages (gV) are increased over the period of a year [76]. This could be caused by mutations, increased efficiency in virion production or the immune system’s inability to contain virion production any longer due to, for example, large numbers of latently infected cells becoming active.
The complete course of HIV infection is shown in Figure 26. After an asymptomatic period of a few years, in this case five years into the infection, the viral production rate of both infected T cells and macrophages are simultaneously increased over the following year. This simulates the immune system collapsing, thereby signalling the onset of AIDS.
Modelling Coinfection Treatment
Figure 26 shows the immune system collapsing from the 1800th day (5th year) onward.
Towards the end of the 2160th day (6th year) both the T cell count and macrophage population are descending steeply while the viral load experiences a similarly dramatic ascent. These dynamics, as displayed by the model, are typical of the generalised clinical observations of the HIV disease progressing towards AIDS with the eventual collapse of the immune system.
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Figure 26: Simulations of the complete course of HIV infection. By the 5th year the immune system begins to display signs of collapsing, thus signaling the onset of AIDS. Towards the end of the 6th year the immune system is almost totally eroded resulting in full-blown AIDS and possibly even death.
Modelling Coinfection Treatment
8.2.3. HIV-TB Coinfection
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Figure 27: Simulations of the HIV-TB coinfection. The model is able to demonstrate that HIV- TB coinfection results in a higher set-point viral load when compared to HIV infection alone.
Modelling Coinfection Treatment
It has been noted earlier that an HIV-TB coinfected individual is more likely to progress rapidly toward AIDS than the person who has HIV alone. One of the factors that are indicative of rapid disease progression is the viral load. In general a higher viral load correlates with an increased likelihood of rapidly progressing towards AIDS. One way to test the model’s ability to display realistic clinical characteristics is to test whether TB infection in an HIV-positive individual does indeed increase the viral load which would thereby cause the immune system to collapse in a shorter amount of time.
Figure 27 simulates HIV-TB coinfection by introducing TB into the system on the 1000th day, about two and three quarter years, into HIV infection. Figures 27a and 27b show that coinfection results in an associated increase in viral load. The set-point viral load for HIV alone is about 282 virions per mm3. This is compared to 341 virions per mm3 for HIV-TB coinfection, which represents an increase of 25% in the viral load of the coinfected individual over the HIV-infected individual. The coinfected individual’s higher viral load would normally result in the immune system collapsing in a shorter amount of time. As has been discussed in Section 7.2.4, the higher viral load is due to the fact that there are more susceptible cells (macrophages and T cells) for HIV virions to infect. Figures 27c and 27d show that T cell and macrophage populations are slightly higher for HIV-TB coinfection than for HIV infection alone. This is as expected since the introduction of another pathogen, TB, into the system stimulates T cells and macrophages to increase their numbers in order to fight off the additional diseases. However, the already overworked immune system struggles to keep TB in check. From figure 27e one finds that the bacterial levels rapidly increase before settling to its set-point value establishing chronic TB infection.