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

摘要

Steady-state levels of HIV-1 viraemia in the plasma vary more than a 1000-fold between HIV-positiveudpatients and are thought to be influenced by several di¡erent host and viral factors such as host target celludavailability, host anti-HIV immune response and the virulence of the virus. Previous mathematicaludmodels have taken the form of classical ecological food-chain models and are unable to account for thisudmultifactorial nature of the disease. These models suggest that the steady-state viral load (i.e. the setpoint)udis determined by immune response parameters only. We have devised a generalized consensusudmodel in which the conventional parameters are replaced by so-called `process functions'. This veryudgeneral approach yields results that are insensitive to the precise form of the mathematical model. Hereudwe applied the approach to HIV-1 infections by estimating the steady-state values of several processudfunctions from published patient data. Importantly, these estimates are generic because they areudindependent of the precise form of the underlying processes. We recorded the variation in the estimatedudsteady- state values of the process functions in a group of HIV-1 patients.We developed a novel model byudproviding explicit expressions for the process functions having the highest patient-to-patient variation inudtheir estimated values. Small variations from patient to patient for several parameters of the new modeludcollectively accounted for the large variations observed in the steady-state viral burden. The novel modeludremains in full agreement with previous models and data.