We propose to construct a mathematical model for evaluation of a potential therapy that uses genetically modified viruses to control HIV infection. Current anti-viral drug therapies may reduce HIV load below detection but do not cure the infection, due to a persistent, latent cellular reservoir. Moreover, drugs have significant drawbacks, such as cost, toxicity, and evolution of resistance. An alternative therapy is the use of engineered viruses designed to kill cells infected by HIV. These viruses considerably decrease the HIV-1 load in vitro (Schnell et al. 1997), but the potential effectiveness for reducing the viral load of AIDS patients is unknown. This therapeutic virus is expected to have two main effects in vivo. First, it will kill HIV-infected cells, thus compensating for the dysfunction of the immune system associated with AIDS. This will reduce the HIV-1 load, and aid in the recovery of the activated CD4+ T cells (Revilla & Garcia-Ramos 2003). These cells are the main target of HIV-1 and are essential to activate an immune response. Second, this recovery of cells will improve the immune system, thus providing further control on the HIV population. A mathematical model based on coupled ordinary differential equations will study the interactions among HIV-1, the CD4+ T cell, an immune response, and an engineered virus in an in vivo context. This model will examine the complex dynamics of the therapeutic infection. The main objective is to determine the efficiency of a therapeutic virus in concert with a strengthened immune response for controlling HIV load. In particular, our analysis will determine if the therapeutic virus will survive in a system with a depleted HIV load; establish the potential effect of the virus on the long-term reservoir of resting HIV-infected CD4+ T-cells; and evaluate the impact of attacking this reservoir on the control of HIV infection.
| Castillo-Guajardo, D; Garcia-Ramos, G (2010) Estimates of sexual partnership dynamics: extending negative and positive gaps to status lengths. J Epidemiol Community Health 64:672-7 |
| Garcia-Ramos, Gisela; Castillo, Derik; Crowley, Philip H (2010) Effectiveness of a 'hunter' virus in controlling human immunodeficiency virus type 1 infection. J Gen Virol 91:2513-23 |
