Piecewise virus-immune dynamic model with HIV-1 RNA-guided therapy

• Published in: Journal of theoretical biology Vol. 377; pp. 36 - 46
• Main Authors: Tang, Biao, Xiao, Yanni, Cheke, Robert A., Wang, Ning
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 21.07.2015
• Subjects: Algorithms; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - therapeutic use; Antiretroviral Therapy, Highly Active - methods; CD4 Lymphocyte Count; Drug Administration Schedule; Filippov system; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - virology; HIV-1 - genetics; HIV-1 - isolation & purification; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Models, Immunological; Pseudo-equilibrium; RNA, Viral - blood; Sliding mode; Structured treatment interruptions; Viral Load; Pseudo-equilibrium; Filippov system; Sliding mode; Structured treatment interruptions
• ISSN: 0022-5193; 1095-8541
• DOI: 10.1016/j.jtbi.2015.03.040

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. •We develop a piecewise virus-immune dynamic model for HIV-1 RNA-guided therapy.•Analytical technique of Filippov system has been used to address global dynamics.•Proper combination of threshold and initial values can preclude HIV virus exceptionally growing.•HIV viral loads could either go to infinity or be maintained below a certain value.•The controllable region where HIV viral loads are maintained less a critical level can be maximized.