PREDICTING THE PROBABILITY OF PERSISTENCE OF HIV INFECTION WITH THE STANDARD MODEL

Abstract

It is not well understood why the transmission of HIV may have a small probability of occurrence despite frequent high risk exposures or ongoing contact between members of a discordant couple. We explore the possible contributions made by distributions of system parameters beginning with the standard three-component differential equation model for the growth of a HIV virion population in an infected host in the absence of drug therapy. The overall dynamical behavior of the model is determined by the set of values of six parameters, some of which describe host immune system properties and others which describe virus properties. There may be one or two critical points whose natures play a key role in determining the outcome of infection and in particular whether the HIV population will persist or become extinct. There are two cases which may arise. In the first case, there is only one critical point P1at biological values and this is an asymptotically stable node. The system ends up with zero virions and so the host becomes HIV-free. In the second case, there are two critical points P1and P2at biological values. Here P1is an unstable saddle point and P2is an asymptotically stable spiral point with a non-zero virion level. In this case the HIV population persists unless parameters change. We let the parameter values take random values from distributions based on empirical data, but suitably truncated, and determine the probabilities of occurrence of the various combinations of critical points. From these simulations the probability that an HIV infection will persist, across a population, is estimated. It is found that with conservatively estimated distributions of parameters, within the framework of the standard 3-component model, the chances that a within-host HIV population will become extinct is between 0.6% and 6.9%. With less conservative parameter estimates, the probability is estimated to be as high as 24%. The many complicating factors related to the transmission and possible spontaneous elimination of the virus and the need for experimental data to clarify whether transient infections may occur are discussed. More realistic yet complicated higher dimensional models are likely to yield smaller probabilities of extinction.