(A) Model of the cellular immune response against HIV. In the absence of immune activation, pools of resting T

_{H} (CD4) cells, CTLs (CD8), and pAPCs divide at rates,

*ρ*_{4},

*ρ*_{8},

*ρ*_{D} and die at rates

,

, and

, reaching homeostatic concentrations

,

, and

, respectively. Activated T

_{H} cells become infected through contact with free virions at a rate constant

*σ*, whereas resting cells are assumed to be non-susceptible to the virus. T

_{H} cells are activated at a rate constant

*a*_{4} after contacting a pAPC with an HIV epitope or by other antigens at rate constant

*b* (background activation). T

_{H} cells establishing synapses with pAPCs have a probability

*d* of being concomitantly infected with the same viral type. Infected cells release virions at a rate constant

*α* and die at a rate constant

. CTL pre-activation occurs after contacting infected cells (

*a*_{8}) or pAPCs (

*a*_{8D}). A co-stimulatory signal from activated T

_{H} cells is necessary for completing CTL activation (

*a*_{8′}). Infected cells are lysed by CTLs at a rate constant

*k*. Death rate constants for activated T

_{H} cells

, CTLs

, and pAPCs

and virion inactivation rates (

*Γ*_{V}) are not shown for simplicity. The full list of variables and parameters is available in Appendix S1, which also provides references to empirical work justifying the parameter values used (see also main text). A fraction

*μ* of the virions released in each cell infection become escape mutants. Avoidance of CTL activation or CTL-mediated killing leads to CTL escape (red bars), whereas avoidance of T

_{H} cell activation leads to T

_{H} escape (blue bars). The model allows full T-cell (purple), T

_{H}-only (blue), and CTL-only (red) escape mutants. (B) Control model in which the virus targets a nonimmune cell type C (e.g., hepatocytes, epithelial cells, etc.) instead of T

_{H} cells. Two key differences with the HIV model are that viral replication is not dependent upon immune activation and that transinfection does not take place. Variables, parameters, and equations for this model are also shown in Appendix S1.

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