The role of antigenic stimulation and cytotoxic T cell activity in regulating the long-term immunopathogenesis of HIV: mechanisms and clinical implications

This paper develops a predictive mathematical model of cell infection, host immune response and viral replication that reproduces observed long-term t rends in human immunodeficiency virus (HIV) pathogenesis. Cell activation i nduced by repeated exposure to many different antigens is proposed as the p rincipal mechanism of providing target cells for HIV infection and, hence, of CD4 + T cell depletion, with regulation of the overall T cell pool size causing concomitant CD8 pool increases. The model correctly predicts the cr oss-patient variability in disease progression, the rate of which is found to depend on the efficacy of anti-HIV cytotoxic T lymphocyte responses, ove rall viral pathogenicity and random effects. The model also predicts a vari ety of responses to anti-viral therapy, including episodic residual viral r eplication and discordant responses and we find that such effects can be su ppressed by increasing the potency of treatment.