title: Piecewise virus-immune dynamic model with HIV-1 RNA-guided therapy.
abstract: Clinical studies have used CD4 T cell counts to evaluate the safety or risk of plasma HIV-1 RNA-guided structured treatment interruptions (STIs), aimed at maintaining CD4 T cell counts above a safe level and plasma HIV-1 RNA below a certain level. However, quantifying and evaluating the impact of STIs on the control of HIV replication and on activation of the immune response remains challenging. Here we extend the virus-immune dynamic system by including a piecewise smooth function to describe the elimination of HIV viral loads and the activation of effector cells under plasma HIV-1 RNA-guided therapy, in order to quantitatively explore the STI strategies. We theoretically investigate the global dynamics of the proposed Filippov system. Our main results indicate that HIV viral loads could either go to infinity or be maintained below a certain level or stabilize at a previously given level, depending on the threshold level and initial HIV virus loads and effector cell counts. This suggests that proper combinations of threshold and initial HIV virus loads and effector cell counts, based on threshold policy, can successfully preclude exceptionally high growth of HIV virus and, in particular, maximize the controllable region.
authors.affiliation: School of Mathematics and Statistics, Xi׳an Jiaotong University, Xi׳an, 710049, PR China.
authors.forename: Biao
authors.initials: B
authors.lastname: Tang
authors.affiliation: School of Mathematics and Statistics, Xi׳an Jiaotong University, Xi׳an, 710049, PR China. Electronic address: yxiao@mail.xjtu.edu.cn.
authors.forename: Yanni
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Natural Resources Institute, University of Greenwich at Medway, Chatham Maritime, Chatham, Kent ME4 4TB, UK.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cheke
authors.affiliation: National Center for AIDS/STD Prevention and Control, Chinese Center for Disease Control and Prevention, 27 Nanwei Rd, Beijing 100050, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
mesh_terms: D000465:Algorithms; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D018448:Models, Immunological; D012367:RNA, Viral / Q000097:blood*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral
keywords: Filippov system; Pseudo-equilibrium; Sliding mode; Structured treatment interruptions