Small variations in multiple parameters account for wide variations in HIV-1 set-points: a novel modelling approach

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.