title: Modeling the Slow CD4+ T Cell Decline in HIV-Infected Individuals.
abstract: The progressive loss of CD4+ T cell population is the hallmark of HIV-1 infection but the mechanism underlying the slow T cell decline remains unclear. Some recent studies suggested that pyroptosis, a form of programmed cell death triggered during abortive HIV infection, is associated with the release of inflammatory cytokines, which can attract more CD4+ T cells to be infected. In this paper, we developed mathematical models to study whether this mechanism can explain the time scale of CD4+ T cell decline during HIV infection. Simulations of the models showed that cytokine induced T cell movement can explain the very slow decline of CD4+ T cells within untreated patients. The long-term CD4+ T cell dynamics predicted by the models were shown to be consistent with available data from patients in Rio de Janeiro, Brazil. Highly active antiretroviral therapy has the potential to restore the CD4+ T cell population but CD4+ response depends on the effectiveness of the therapy, when the therapy is initiated, and whether there are drug sanctuary sites. The model also showed that chronic inflammation induced by pyroptosis may facilitate persistence of the HIV latent reservoir by promoting homeostatic proliferation of memory CD4+ cells. These results improve our understanding of the long-term T cell dynamics in HIV-1 infection, and support that new treatment strategies, such as the use of caspase-1 inhibitors that inhibit pyroptosis, may maintain the CD4+ T cell population and reduce the latent reservoir size.
authors.affiliation: Department of Biology, New York University, New York, New York, United States of America.
authors.forename: Sunpeng
authors.initials: S
authors.lastname: Wang
authors.affiliation: Departamento de Medicina Preventiva, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Patricia
authors.initials: P
authors.lastname: Hottz
authors.affiliation: Departamento de Medicina Preventiva, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.|Projeto Praça Onze, Hospital Escola São Francisco de Assis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Mauro
authors.initials: M
authors.lastname: Schechter
authors.affiliation: Department of Mathematics and Statistics, and Center for Biomedical Research, Oakland University, Rochester, Michigan, United States of America.
authors.forename: Libin
authors.initials: L
authors.lastname: Rong
mesh_terms: D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D049109:Cell Proliferation; D003198:Computer Simulation; D016207:Cytokines / Q000276:immunology; D018450:Disease Progression; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D018448:Models, Immunological
chemical_list: D016207:Cytokines