title: Immuno-modulatory strategies for reduction of HIV reservoir cells.
abstract: Antiretroviral therapy is able to suppress the viral load to below the detection limit, but it is not able to eradicate HIV reservoirs. Thus, there is a critical need for a novel treatment to eradicate (or reduce) the reservoir in order to eliminate the need for a lifelong adherence to antiretroviral therapy, which is expensive and potentially toxic. In this paper, we investigate the possible pharmacological strategies or combinations of strategies that may be beneficial to reduce or possibly eradicate the latent reservoir. We do this via studies with a validated mathematical model, where the parameter values are obtained with newly acquired clinical data for HIV patients. Our findings indicate that the strategy of reactivating the reservoir combined with enhancement of the killing rate of HIV-specific CD8+ T cells is able to eradicate the reservoir. In addition, our analysis shows that a targeted suppression of the immune system is also a possible strategy to eradicate the reservoir.
authors.affiliation: Center for Research in Scientific Computation, North Carolina State University, Raleigh, NC 27695-8212, USA. Electronic address: htbanks@ncsu.edu.
authors.forename: H T
authors.initials: HT
authors.lastname: Banks
authors.affiliation: Center for Research in Scientific Computation, North Carolina State University, Raleigh, NC 27695-8212, USA.
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Flores
authors.affiliation: Center for Research in Scientific Computation, North Carolina State University, Raleigh, NC 27695-8212, USA.
authors.forename: Shuhua
authors.initials: S
authors.lastname: Hu
authors.affiliation: Harvard Medical School and Mass General Hospital, Ragon Institute, Boston, MA, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Rosenberg
authors.affiliation: Harvard Medical School and Mass General Hospital, Ragon Institute, Boston, MA, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Buzon
authors.affiliation: Harvard Medical School and Mass General Hospital, Ragon Institute, Boston, MA, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Yu
authors.affiliation: Harvard Medical School and Mass General Hospital, Ragon Institute, Boston, MA, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Lichterfeld
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D049109:Cell Proliferation; D003198:Computer Simulation; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy*; D015497:HIV-1; D006706:Homeostasis; D006801:Humans; D008954:Models, Biological; D019562:Viral Load; D017735:Virus Latency
chemical_list: D019380:Anti-HIV Agents
keywords: Immune response; Inverse problem; Mathematical model; Stability analysis