Journal of Applied Nonlinear Dynamics
Exploring the Dynamics of a Model for HIV Infection Featuring Dual Time Delays
Journal of Applied Nonlinear Dynamics 14(3) (2025) 575--604 | DOI:10.5890/JAND.2025.09.007
Sangeeta Kumari$^1$, Parimita Roy$^2$
$^1$ Department of Mathematics, School of Physical Sciences, Amrita Vishwa Vidyapeetham, Coimbatore-64112,
Tamilnadu, India
$^2$ Department of Mathematics, Thapar Institute of Engineering and Technology, Patiala, Punjab, India
Download Full Text PDF
Abstract
Mathematical models have significantly contributed by showing how virological synapses are created to enable cell-to-cell transmission. To replicate the crowding effect of Human Immunodeficiency Virus (HIV), this study, motivated by previous studies, attempts to develop a new compartmental epidemic model with two delays and nonlinear incidence rates. The first delay occurs between the time the virus enters the body and the beginning of HIV latency. The second delay occurs when infected cells must produce virions. We thoroughly investigated the local stability of the model's stable states using the delay differential equation stability theory and calculated the basic reproductive number ($R_0$). Numerical simulations were also conducted to assess the relative contributions of the two delayed viral transmission modes, investigate the effects of time delays and other factors on disease dynamics, and assess the effects of time delays on disease dynamics. We used the Partial Rank Correlation Coefficient (PRCC) to do a global sensitivity analysis and identify the most sensitive parameters affecting $R_0$, providing information on potential ways to slow down the progression of the HIV disease. We offered an extensive numerical analysis for our deterministic and delay models, including bifurcations and time series. Our simulation indicates that to keep the system predictable, we should control the time delay, $\tau_1$, which stands for the interval between viral entry into an uninfected target cell and the generation of an active target cell. In addition to outlining basic management measures, the current study demonstrates the complex dynamics of two delayed HIV models.
References
-
[1]  |
Pruett, S.B. (2003), Stress and the immune system, Pathophysiology, 9(3), 133-153.
|
-
[2]  |
Haynes, B.F., Putman, S.B., and Weinberg, J.B. (1996), Update on the issues of HIV vaccine development, Annals of Medicine, 28(1), 39-41.
|
-
[3]  |
Althaus, C.L. and De Boer, R.J. (2008), Dynamics of immune escape during HIV/SIV infection, PLoS Computational Biology, 4(7), e1000103.
|
-
[4]  |
Culshaw, R.V. and Ruan, S. (2000), A delay-differential equation model of HIV infection of CD4+ T-cells, Mathematical Biosciences, 165(1), 27-39.
|
-
[5]  |
De Boer, R.J. (2007), Understanding the failure of CD8+ T-cell vaccination against simian/human immunodeficiency virus, Journal of Virology, 81(6), 2838-2848.
|
-
[6]  |
Li, M.Y. and Shu, H. (2010), Global dynamics of an in-host viral model with intracellular delay, Bulletin of Mathematical Biology, 72, 1492-1505.
|
-
[7]  |
Nelson, P.W., Murray, J.D., and Perelson, A.S. (2000), A model of HIV-1 pathogenesis that includes an intracellular delay, Mathematical Biosciences, 163(2), 201-215.
|
-
[8]  |
Nowak, M.A. and May, R.M. (2000), Virus Dynamics: Mathematical Principles of Immunology and Virology, Oxford University Press.
|
-
[9]  |
O'Brien, T.R., Rosenberg, P.S., Yellin, F., and Goedert, J.J. (1998), Longitudinal HIV-1 RNA levels in a cohort of homosexual men, Journal of Acquired Immune Deficiency Syndromes, 18(2), 155-161.
|
-
[10]  |
Wolinsky, S.M., Korber, B.T., Neumann, A.U., Daniels, M., Kunstman, K.J., Whetsell, A.J., Furtado, M.R., Cao, Y., Ho, D.D., Safrit, J.T., and Koup, R.A. (1996), Adaptive evolution of human immunodeficiency virus-type 1 during the natural course of infection, Science, 272(5261), 537-542.
|
-
[11]  |
Perelson, A.S. and Nelson, P.W. (1999), Mathematical analysis of HIV-1 dynamics in vivo, SIAM Review, 41(1), 3-44.
|
-
[12]  |
Dubey, P., Dubey, U.S., and Dubey B. (2018), Modeling the role of acquired immune response and antiretroviral therapy in the dynamics of HIV infection, Mathematics and Computers in Simulation, 144, 120-137.
|
-
[13]  |
Naresh, R., Tripathi, A., and Sharma, D. (2009), Modelling and analysis of the spread of AIDS epidemic with immigration of HIV infectives, Mathematical and Computer Modelling, 49(5-6), 880-892.
|
-
[14]  |
Ngina, P., Mbogo, R.W., and Luboobi, L.S. (2019), HIV drug resistance: Insights from mathematical modelling, Applied Mathematical Modelling, 75, 141-161.
|
-
[15]  |
Molla, A., Korneyeva, M., Gao, Q., Vasavanonda, S., Schipper, P.J., Mo, H.M., Markowitz, M., Chernyavskiy, T., Niu, P., Lyons, N., Hsu, A., and Kempf, D.J. (1996), Ordered accumulation of mutations in HIV protease confers resistance to ritonavir, Nature Medicine, 2(7), 760-766.
|
-
[16]  |
Rong, L. and Perelson, A.S. (2009), Modeling HIV persistence, the latent reservoir, and viral blips, Journal of Theoretical Biology, 260(2), 308-331.
|
-
[17]  |
Shiri, T., Garira, W., and Musekwa, S.D. (2005), A two-strain HIV-1 mathematical model to assess the effects of chemotherapy on disease parameters, Mathematical Biosciences $\&$ Engineering, 2(4), 811-832.
|
-
[18]  |
Wodarz, D. and Lloyd, A.L. (2004), Immune responses and the emergence of drug-resistant virus strains in vivo, Proceedings of the Royal Society B: Biological Sciences, 271(1544), 1101-1109.
|
-
[19]  |
Huang, Y. and Lu, T. (2008), Modeling long-term longitudinal HIV dynamics with application to an AIDS clinical study, Journal of Mathematical Biology, 56(6), 1384-1408.
|
-
[20]  |
Smith, R.J. (2006), Adherence to antiretroviral HIV drugs: How many doses can you miss before resistance emerges?, Proceedings of the Royal Society B: Biological Sciences, 273(1586), 617-624.
|
-
[21]  |
Wu, H., Huang, Y., Acosta, E.P., Rosenkranz, S.L., Kuritzkes, D.R., Eron J.J., Perelson A.S., and Gerber J.G. (2005), Modeling long-term HIV dynamics and antiretroviral response: Effects of drug potency, pharmacokinetics, adherence, and drug resistance, Journal of Acquired Immune Deficiency Syndromes, 39(3), 272-283.
|
-
[22]  |
Ghosh D., Krishnan A., Gibson B., Brown S.E., Latkin C.A., and Altice F.L. (2017), Social network strategies to address HIV prevention and treatment continuum of care among at-risk and HIV-infected substance users: A systematic scoping review, AIDS and Behavior, 21, 1183-1207.
|
-
[23]  |
Latkin C.A., Davey-Rothwell M.A., Knowlton A.R., Alexander K.A., Williams C.T., and Boodram B. (2013), Social network approaches to recruitment, HIV prevention, medical care, and medication adherence, Journal of Acquired Immune Deficiency Syndromes, 63(01), S54-S61.
|
-
[24]  |
Twumasi, C., Asiedu, L., and Nortey, E.N. (2019), Markov chain modeling of HIV, tuberculosis, and Hepatitis B transmission in Ghana, Interdisciplinary Perspectives on Infectious Diseases, 2019, 1-9.
|
-
[25]  |
Wang, J., Lang, J., and Zou, X. (2017), Analysis of an age-structured HIV infection model with virus-to-cell infection and cell-to-cell transmission, Nonlinear Analysis: Real World Applications, 34, 75-96.
|
-
[26]  |
Kirschner, D.E. and Webb, G.F. (1997), Understanding drug resistance for monotherapy treatment of HIV infection, Bulletin of Mathematical Biology, 59(4), 763-785.
|
-
[27]  |
Rong, L., Feng, Z., and Perelson, A.S. (2007), Emergence of HIV-1 drug resistance during antiretroviral treatment, Bulletin of Mathematical Biology, 69, 2027-2060.
|
-
[28]  |
Iwami, S., Holder, B.P., Beauchemin, C.A., Morita, S., Tada, T., Sato, K., Igarashi, T., and Miura, T. (2012), Quantification system for the viral dynamics of a highly pathogenic simian/human immunodeficiency virus based on an in vitro experiment and a mathematical model, Retrovirology, 9, 1-12.
|
-
[29]  |
Iwami, S., Takeuchi, J.S., Nakaoka, S., Mammano, F., Clavel, F., Inaba, H., Kobayashi, T., Misawa, N., Aihara K., Koyanagi Y., and Sato K. (2015), Cell-to-cell infection by HIV contributes over half of virus infection, eLife, 4, e08150.
|
-
[30]  |
Komarova, N.L., Anghelina, D., Voznesensky I., Trinité B., Levy D.N., and Wodarz D. (2013), Relative contribution of free-virus and synaptic transmission to the spread of HIV-1 through target cell populations, Biology Letters, 9(1), 20121049.
|
-
[31]  |
Komarova, N.L., Levy, D.N., and Wodarz, D. (2013), Synaptic transmission and the susceptibility of HIV infection to anti-viral drugs, Scientific Reports, 3(1), 2103.
|
-
[32]  |
Dumrongpokaphan, T., Lenbury, Y., Ouncharoen, R., and Xu, Y. (2007), An intracellular delay-differential equation model of the HIV infection and immune control, Mathematical Modelling of Natural Phenomena, 2(1), 84-112.
|
-
[33]  |
Hu, Q., Hu, Z., and Liao, F. (2016), Stability and Hopf bifurcation in an HIV-1 infection model with delays and logistic growth, Mathematics and Computers in Simulation, 128, 26-41.
|
-
[34]  |
Lai, X., and Zou, X. (2015), Modeling cell-to-cell spread of HIV-1 with logistic target cell growth, Journal of Mathematical Analysis and Applications, 426(1), 563-584.
|
-
[35]  |
Pawelek, K.A., Liu, S., Pahlevani, F., and Rong, L. (2012), A model of HIV-1 infection with two time delays: Mathematical analysis and comparison with patient data, Mathematical Biosciences, 235(1), 98-109.
|
-
[36]  |
Alshorman, A., Wang, X., Meyer, M.J., and Rong, L. (2017), Analysis of HIV models with two time delays, Journal of Biological Dynamics, 11(sup1), 40-64.
|
-
[37]  |
Song, X., Zhou, X., and Zhao, X. (2010), Properties of stability and Hopf bifurcation for an HIV infection model with time delay, Applied Mathematical Modelling, 34(6), 1511-1523.
|
-
[38]  |
Mallick, U.K., Rahman, A., Biswas, M.H.A., Samsuzzoha, M. and Roy, S.K. (2023), An optimal immunotherapeutic treatment of HIV infections to regain the targeted CD4+ T cell count: A boundary value problem approach, Journal of Applied Nonlinear Dynamics, 12(01), 39-51.
|
-
[39]  |
Capasso, V. and Serio, G. (1978), A generalization of the Kermack-McKendrick deterministic epidemic model, Mathematical Biosciences, 42(1-2), 43-61.
|
-
[40]  |
Tipsri, S. and Chinviriyasit, W. (2015), The effect of time delay on the dynamics of an SEIR model with nonlinear incidence, Chaos Solitons \& Fractals, 75, 153-172.
|
-
[41]  |
Ngo, H.A., Nguyen, H.D., and Dik, M. (2021), Stability analysis of a novel delay differential equation of HIV infection of CD4+ T-cells, arXiv preprint arXiv:2101.00758.
|
-
[42]  |
Van den Driessche, P. and Watmough, J. (2002), Reproduction numbers and sub-threshold endemic equilibria for compartmental models of disease transmission, Mathematical Biosciences, 180(1-2), 29-48.
|
-
[43]  |
Hassard, B.D., Kazarinoff, N.D., and Wan, Y.H. (1981), Theory and applications of Hopf bifurcation (Vol. 41), CUP Archive.
|