V. Muller et al., Small variations in multiple parameters account for wide variations in HIV-1 set-points: a novel modelling approach, P ROY SOC B, 268(1464), 2001, pp. 235-242
Citations number
48
Categorie Soggetti
Experimental Biology
Journal title
PROCEEDINGS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES
Steady-slate levels of HIV-1 viraemia in the plasma vary more than a 1000-f
old between HIV-positive patients and are thought to be influenced by sever
al different host and viral factors such as host target cell availability,
host anti-HIV immune response and the virulence of the virus. Previous math
ematical models have taken the form of classical ecological food-chain mode
ls and are unable to account for this multifactorial nature of the disease.
These models suggest that the steady-state viral load (i.e. the set-point)
is determined by immune response parameters only. We have devised a genera
lized consensus model in which the conventional parameters are replaced by
so-called 'process functions'. This very general approach yields results th
at are insensitive to the precise form of the mathematical model. Here we a
pplied the approach to HIV-1 infections by estimating the steady-state valu
es of several process functions from published patient data. Importantly, t
hese estimates are generic because they are independent of the precise form
of the underlying processes. We recorded the variation in the estimated st
eady-state values of the process functions in a group of HIV-1 patients. We
developed a novel model by providing explicit expressions for the process
functions having the highest patient-to-patient variation in their estimate
d values. Small variations from patient to patient for several parameters o
f the new model collectively accounted for the large variations observed in
the steady-state viral burden. The novel model remains in full agreement w
ith previous models and data.