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Fighting a virus with a virus: a dynamic model for HIV-1 therapy.

  • Tomás Revilla
  • Gisela García-Ramos
Math Biosci 2003; 185 (2): 191-203
Abstract
A mathematical model examined a potential therapy for controlling viral infections using genetically modified viruses. The control of the infection is an indirect effect of the selective elimination by an engineered virus of infected cells that are the source of the pathogens. Therefore, this engineered virus could greatly compensate for a dysfunctional immune system compromised by AIDS. In vitro studies using engineered viruses have been shown to decrease the HIV-1 load about 1000-fold. However, the efficacy of this potential treatment for reducing the viral load in AIDS patients is unknown. The present model studied the interactions among the HIV-1 virus, its main host cell (activated CD4+ T cells), and a therapeutic engineered virus in an in vivo context; and it examined the conditions for controlling the pathogen. This model predicted a significant drop in the HIV-1 load, but the treatment does not eradicate HIV. A basic estimation using a currently engineered virus indicated an HIV-1 load reduction of 92% and a recovery of host cells to 17% of their normal level. Greater success (98% HIV reduction, 44% host cells recovery) is expected as more competent engineered viruses are designed. These results suggest that therapy using viruses could be an alternative to extend the survival of AIDS patients.

Unit definitions have no effect on the numerical analysis of the model. It remains the responsibility of the modeler to ensure the internal numerical consistency of the model. If units are provided, however, the consistency of the model units will be checked.

Name Definition
Id Name Spatial dimensions Size
default 1.0
Id Name Initial quantity Compartment Fixed
v 149.0 default
w 1.0 default
x 3.0 default
y 6.0 default
z 0.0 default

Initial assignments are expressions that are evaluated at time=0. It is not recommended to create initial assignments for all model entities. Restrict the use of initial assignments to cases where a value is expressed in terms of values or sizes of other model entities. Note that it is not permitted to have both an initial assignment and an assignment rule for a single model entity.

Definition
Id Name Objective coefficient Reaction Equation and Kinetic Law Flux bounds
v1 ∅ = x

lambda
v10 w = ∅

q*w
v2 x = ∅

d*x
v3 x = y

beta*v*x
v4 y = ∅

a*y
v5 y = z

alpha*w*y
v6 z = ∅

b*z
v7 ∅ = v

k*y
v8 v = ∅

u*v
v9 ∅ = w

c*z

Global parameters

Id Value
a 0.33
alpha 0.004
b 2.0
beta 0.004
c 2000.0
d 0.01
k 50.0
lambda 2.0
q 2.0
u 2.0

Local parameters

Id Value Reaction

Assignment rules

Definition

Rate rules

Definition

Algebraic rules

Definition
Trigger Assignments