A model of primary HIV-1 infection

We construct a model based on biological principles of the interaction of H IV-1 with the CD4(+) T cells at primary infection. Most of the parameters a re obtained from the literature, the remainder from fitting the output of t he model to data from seven patients. On the basis of the model we find tha t initial viral containment is due to an effective immune response. The vir al level after the initial peak, a surrogate marker of disease progression, was determined by the rate of reactivation of memory cells. Differences in this rate may occur because of inter- or intra-individual differences in t he capability of memory cells to recognise and dispose of variants of HIV, either due to immune escape mutations within the virus or because the virus directly inhibits reactivation. With no choice of parameters could direct and indirect killing produce the gradual loss in CD4(+) T cells with the ob served viral behaviour. The loss of CD4(+) T cells is perhaps due to defect ive expansion of activated cells of both HIV specific and nonspecific cells . As less memory cells are produced as a result then this compartment decre ases and hence so do naive numbers through less reversion of memory cells t o the naive phenotype. (C) 1998 Elsevier Science Inc. All rights reserved.