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HIV-1 dynamics revisited: biphasic decay by cytotoxic T lymphocyte killing?

  • RA Arnaout
  • MA Nowak
  • Dominik Wodarz
Proc. Biol. Sci. 2000; 267 (1450): 1347-1354
Abstract
The biphasic decay of blood viraemia in patients being treated for human immunodeficiency virus type 1 (HIV-1) infection has been explained as the decay of two distinct populations of cells: the rapid death of productively infected cells followed by the much slower elimination of a second population the identity of which remains unknown. Here we advance an alternative explanation based on the immune response against a single population of infected cells. We show that the biphasic decay can be explained simply, without invoking multiple compartments: viral load falls quickly while cytotoxic T lymphocytes (CTL) are still abundant, and more slowly as CTL disappear. We propose a method to test this idea, and develop a framework that is readily applicable to treatment of other infections.

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
x 2.5 default
y 0.07 default
z 0.5 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
v2 x = ∅

d*x
v3 x = y

beta*s*x*y
v4 y = ∅

a*y
v5 y = ∅

p*y*z
v6 ∅ = z

c*y
v7 z = ∅

b*z

Global parameters

Id Value
a 0.02
b 0.15
beta 0.5
c 1.0
d 0.02
lambda 0.05
p 1.0
s 0.0
v 0.0

Local parameters

Id Value Reaction

Assignment rules

Definition
v = 1000000.0*y

Rate rules

Definition

Algebraic rules

Definition
Trigger Assignments