The model we present includes naive, memory, and effector CD4+ and CD8+ T cells specific for either HIV or a generic set of nonHIV antigens. It tracks and measures thymic production of naive T cells, different forms of HIV-infected CD4+ T cells (pre- and post-integration), cytokine cross-regulation, and concentrations of free HIV particles in the lymph nodes and the peripheral blood. We explicitly address the concept that HIV dynamics are embedded within the context of an immune system that is constantly responding to other antigenic challenges. Thus, exposure to environmental antigens drives the homeostatic balance in the nonHIV-specific part of the model, and when HIV is present, exposure also drives the infection rate. Inoculation with HIV virus activates the HIV-specific part of the model, which in turn affects the nonHIV-specific T cell dynamics in the model.
The model can reproduce the T cell and viral dynamics of a prototypical patient at different stages: uninfected and healthy, experiencing the acute and latent phases of HIV infection, and undergoing antiviral therapy. In particular, this model captures the biphasic decline of viremia following antiretroviral therapy by simulating the interaction of virus-producing CD4+ T cells and HIV-specific CD8+ T cells. The comprehensive representation of the nonHIV-specific T cell dynamics makes this model particularly suitable for studying the restoration of the immune system using different combinations of antiretroviral and immune therapies.