Figure 2

Effect of increased burst size in coinfected cells on the growth dynamics of the virus population. (a) Two growth curves are plotted. If no increased burst size is assumed in coinfected cells, then a straight exponential phase of virus growth is observed. In the presence of an increased burst size in coinfected cells, however, the exponential rate of virus growth increases as virus load rises over time. Hence increased viral output in coinfected cells speeds up virus growth significantly. The graph also shows that an increased burst size in coinfected cells leads to a higher equilibrium virus load. (b) This graph shows that for the case of an increased burst size in coinfected cells, different measures of virus load do not necessarily correlate with each other as virus load grows, especially at higher virus loads. This is because the rate of virus production per infected cell increases with higher virus loads. Free virus is given by v in the model, the number of infected cells by ΣI _i , and provirus is given by the total number of integrated genomes. (c) Increased burst size in coinfected cells and treatment dynamics. Treatment is assumed to reduce the overall viral replication rate to a certain degree. Two curves are shown, where treatment is started at different times. The parameters and the treatment strength are identical for the two curves. If treatment is started earlier when virus load is relatively low, the virus population is suppressed by the drug because the overall rate of viral replication is relatively low. On the other hand, when treatment is started later when virus load is higher, a larger number of coinfected cells with increased viral output leads to faster viral replication kinetics such that the drug is not potent enough anymore to control the virus population. (d) Same principle, but demonstrated in an equilibrium setting. If equilibrium virus load is relatively low, treatment is successful. If equilibrium virus load is higher, treatment can be unsuccessful due to the larger burst size of multiply infected cells. Parameters were chosen as follows. (a,b) λ = 10; d = 0.1; β = 0.027; a = 0.2; k = 4; u = 1; ϵ = 1; g = 0.75; η = 0.5; n = 200. (c,d) λ = 10; d = 0.1; β = 0.03; a = 0.2; k = 4; u = 1; ϵ = 1; g = 0.75; η = 0.5; n = 200. . During treatment, the viral infection rate was reduced to β = 0.015.