title: Computational study to determine when to initiate and alternate therapy in HIV infection.
abstract: HIV is a widespread viral infection without cure. Drug treatment has transformed HIV disease into a treatable long-term infection. However, the appearance of mutations within the viral genome reduces the susceptibility of HIV to drugs. Therefore, a key goal is to extend the time until patients exhibit resistance to all existing drugs. Current HIV treatment guidelines seem poorly supported as practitioners have not achieved a consensus on the optimal time to initiate and to switch antiretroviral treatments. We contribute to this discussion with predictions derived from a mathematical model of HIV dynamics. Our results indicate that early therapy initiation (within 2 years postinfection) is critical to delay AIDS progression. For patients who have not received any therapy during the first 3 years postinfection, switch in response to virological failure may outperform proactive switching strategies. In case that proactive switching is opted, the switching time between therapies should not be larger than 100 days. Further clinical trials are needed to either confirm or falsify these predictions.
authors.affiliation: Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Inhoffenstraße 7, 38124 Braunschweig, Germany.
authors.forename: Matthias
authors.identifier: 0000-0003-1496-0566
authors.initials: M
authors.lastname: Haering
authors.affiliation: Institut für Geophysik und extraterrestrische Physik, Technische Universität Braunschweig, Mendelssohnstraße 3, 38106 Braunschweig, Germany.
authors.forename: Andreas
authors.identifier: 0000-0003-0334-6712
authors.initials: A
authors.lastname: Hördt
authors.affiliation: Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Inhoffenstraße 7, 38124 Braunschweig, Germany ; Institute for Biochemistry, Biotechnology and Bioinformatics, Braunschweig University of Technology, Braunschweig, 38106 Braunschweig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Meyer-Hermann
authors.affiliation: Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Inhoffenstraße 7, 38124 Braunschweig, Germany.
authors.forename: Esteban A
authors.initials: EA
authors.lastname: Hernandez-Vargas
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018791:CD4 Lymphocyte Count / Q000379:methods; D019295:Computational Biology; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008962:Models, Theoretical; D019562:Viral Load / Q000379:methods
chemical_list: D019380:Anti-HIV Agents