Viral dynamics during primary simian immunodeficiency virus infection: effect of time-dependent virus infectivity

Abstract

A recent experiment involving simian immunodeficiency virus (SIV) infection of macaques revealed that the infectivity of this virus decreased over the first few months of infection. Based on this observation, we introduce a viral dynamic model in which viral infectivity varies over time. The model is fit to viral load data from eight (donor) monkeys infected by intravaginal inoculation of SIVmac251, three monkeys infected by intravenous inoculation of virus isolated from the donors during the ramp-up phase of acute infection, and three monkeys infected by intravenous inoculation of virus isolated at the viral set-point. Although we only analyze data from 14 monkeys, the new model with time-dependent infectivity seems to fit the data significantly better than a widely used model with constant infectivity (P = 2.44 x 10(-11)). Our results indicate that plasma virus infectivity on average decays approximately 8-fold (95% confidence interval [CI] = 5.1 to 10.3) over the course of acute infection, with the decay occurring exponentially with an average rate of 0.28 day(-1) (95% CI = 0.14 to 0.42 day(-1)). The decay rate in set point plasma virus recipient animals is approximately 16 times slower than in ramp-up plasma virus recipient animals and approximately 6 times slower than in donor animals. Throughout acute infection up to the set-point, the infection rate is higher in ramp-up plasma virus recipient animals than in set-point plasma virus recipient animals. These results show that the infectivity depends upon the source of viral infection.

FIG. 1.

Time-dependent infection rate β.

FIG. 2.

Fitted viral dynamics curves using the two models (solid line, model with time-varying infectivity; dashed line, model with constant infectivity) to the observed viral load data (•) for the eight donor animals in reference . Note how the fits with the varying infectivity model are systematically better, especially during the early part of viral growth, when the infectivity is varying faster.

FIG. 3.

Viral dynamics model curves using estimated parameters (solid line, model with time-varying infectivity; dashed line, model with constant infectivity) and observed viral load data (•) for three ramp-up plasma recipient animals (a) and three set-point plasma recipient animals in reference (b).

FIG. 4.

Average time-varying infection rate β(t) for donor animals (red), ramp-up plasma recipient animals (blue), set-point plasma recipient animals (green), and overall animals (black). Horizontal dashed lines represent the constant infection rate estimated by using model with constant infectivity.