During the HIV infection several quasispecies of the virus arise, which are
able to use different coreceptors, in particular the CCR5 and CXCR4 coreceptors
(R5 and X4 phenotypes, respectively). The switch in coreceptor usage has been
correlated with a faster progression of the disease to the AIDS phase. As
several pharmaceutical companies are starting large phase III trials for R5 and
X4 drugs, models are needed to predict the co-evolutionary and competitive
dynamics of virus strains. We present a model of HIV early infection which
describes the dynamics of R5 quasispecies and a model of HIV late infection
which describes the R5 to X4 switch. We report the following findings: after
superinfection or coinfection, quasispecies dynamics has time scales of several
months and becomes even slower at low number of CD4+ T cells. The curve of CD4+
T cells decreases, during AIDS late stage, and can be described taking into
account the X4 related Tumor Necrosis Factor dynamics. Phylogenetic inference
of chemokine receptors suggests that viral mutational pathway may generate R5
variants able to interact with chemokine receptors different from CXCR4. This
may explain the massive signaling disruptions in the immune system observed
during AIDS late stages and may have relevance for vaccination and therapy.Comment: 21 pages, 14 figure