Modelling Two Different Therapy Strategies for Drug T-20 on HIV-1 Patients
-
摘要: 通过建立数学模型,描述了HIV-1感染者使用抗病毒治疗药物——融合酶抑制剂(T-20)的治疗效果.使用脉冲微分方程描述了T-20的使用过程,并考虑了两种不同的药物消除动力学:一级消除动力学与米-曼(Michaelis-Menten)消除动力学.此模型是个非自治微分方程系统,主要关注其无病平衡态,并研究当接受治疗者在服药完全依从的治疗过程中无病平衡态的稳定性.分别针对药物剂量与服药间隔得到了使得无病平衡态稳定的阈值条件.此外,还研究了间歇治疗的效果.研究表明,间歇治疗的效果甚至可以比完全不治疗还要糟糕.
-
关键词:
- enfuvirtide /
- HIV /
- 抗病毒治疗 /
- 数学模型 /
- 药物消除动力学
Abstract: A mathematical model that describes the antiretroviral therapy of the fusion inhibitor enfuvirtide on HIV-1 patients and the effect of enfuvirtide (formerly T-20) using impulsive differential equations were developed,taking into account two different drug elimination kinetics:first order and Michaelis-Menten.The model was a non-autonomous system of differential equations.For the time-dependent system,the disease-free equilibrium and its stability when therapy was taken with perfect adherence were focused on.Analytical thresholds for dosage and dosing intervals were determined to ensure that the disease-free equilibrium remains stable.The effects of supervised treatment interruption were also explored.It is shown that supervised treatment interruption may be worse than no therapy at all,thus strongly supporting no interruption strategies.-
Key words:
- enfuvirtide /
- HIV /
- antiretroviral therapy /
- mathematical model /
- drug elimination kinetic
-
[1] Moyle G. Stopping HIV fusion with enfuvirtide: the first step to extracellular HAART[J]. Journal of Antimicrobial Chemotherapy, 2003, 51(2): 213-217. doi: 10.1093/jac/dkg066 [2] Trottier B, Walmsley S. Safety of enfuvirtide in combination with an optimized background of antiretrovirals in treatment-experienced HIV-1-infected adults over 48 weeks[J]. Journal of Acquired Immune Deficiency Syndrome, 2005, 40(4): 413-421. doi: 10.1097/01.qai.0000185313.48933.2c [3] Liu S W, Wu S G, Jiang S B. Advancement in developing a new class of anti-AIDS drugs: HIV entry inhibitors[J]. Chinese Pharmacological Bulletin, 2005, 21(9): 1034-1040. [4] Castagna A, Biswas P, Beretta P, Lazzarin A. The appealing story of HIV entry inhibitors from discovery of biological mechanisms to drug development[J]. Drugs, 2005, 65(7): 879-904. doi: 10.2165/00003495-200565070-00001 [5] Clotet B, Raffi F, Cooper D, Delfraissy J F, Lazzarin A, Moyle G, Rockstroh J, Soriano V, Schapiro J. Clinical management of treatment-experienced, HIV-infected patients with the fusion inhibitor enfuvirtide: consensus recommendations[J]. AIDS, 2004, 18(8): 1137-1146. doi: 10.1097/00002030-200405210-00007 [6] Perelson A S, Kirschner D E, Boer R D. Dynamics of HIV infection of CD4+ T cells[J]. Mathe Bios, 1992, 114(1): 81-125. [7] Perelson A S. Modeling the Interaction of the Immue System With HIV. Mathematical and Statistical Approaches to AIDS Epidemiology[M]. Berlin: Springer, 1989: 350-370. [8] Perelson A S, Nelson P W. Mathematical analysis of HIV-1 dynamics in vivio[J]. SIAM Rev, 1999, 41(1): 3-44. doi: 10.1137/S0036144598335107 [9] Nowak M A, Bonhoeffer S, Shaw G M, May R M. Anti-viral drug treatment: dynamics of resistance in free virus and infected cell population[J]. J Theor Biol, 1997, 184(2): 203-221. doi: 10.1006/jtbi.1996.0307 [10] Smith R J, Wahl L M. Drug resistance in an immunological model of HIV-1 infection with impulsive drug effects[J]. Bulletin of Mathematical Biology, 2005, 67(4): 783-813. doi: 10.1016/j.bulm.2004.10.004 [11] Smith R J, Wahl L M. Distinct effects of protease and reverse transcriptase inhibition in an immunological model of HIV-1 infection with impulsive drug effects[J]. Bulletin of Mathematical Biology, 2004, 66(5): 1259-1283. doi: 10.1016/j.bulm.2003.12.004 [12] Smith R J. Adherence to antiretroviral HIV drugs: how many doses can you miss before resistance emerges? [J]. Proc R Soc B, 2006, 273(1586): 617-624. doi: 10.1098/rspb.2005.3352 [13] Wein L M, D’Amato R M, Perelson A S.Mathematical analysis of antiretroviral therapy aimed at HIV-1: eradication or maintenance of low viral loads[J]. J Theor Biol, 1988, 192(1): 81-98. [14] Nowak M A, May R M. Virus Dynamics[M]. Oxford:Oxford University Press, 2000. [15] Nelson P W, Murray J D, Perelson A S. A model of HIV-1 pathogenesis that includes an intracellular delay[J]. Math Biosci, 2000, 163(2): 201-215. doi: 10.1016/S0025-5564(99)00055-3 [16] Wolfgang H, McNerney G P, Chen P, Dale B M, Gordon R E, Chuang F Y S, Li X, Asmuth D M, Huser T, Chen B K. Quantitative 3D video microscopy of HIV transfer across T cell virological synapses[J]. Science, 2009, 323(5922): 1743-1747. doi: 10.1126/science.1167525 [17] Lifson J D, Feinberg M B, Reyes G R, Rabin L, Banapour B, Chakrabarti S, Moss B, Wong-Staal F, Steimer K S, Engleman E G. Induction of CD4-dependent cell fusion by the HTLV-III/LAV envelope glycoprotein[J].Nature, 1986, 323(6090): 725-728. doi: 10.1038/323725a0 [18] Sodroski J, Goh W C, Rosen C, Campbell K, Haseltine W A. Role of the HTLV-III/LAV envelope in syncytium formation and cytopathicity[J]. Nature, 1986, 322(6078): 470-474. doi: 10.1038/322470a0 [19] Levy J. HIV and the Pathogenesis of AIDS[M]. Washington DC: American Society for Microbiology, 2007. [20] Sato H, Orenstein J, Dimitrov D, Martin M. Cell-to-cell spread of HIV-1 occurs within minutes and may not involve the participation of virus particles[J]. Virology, 1992, 186(2): 712-724. doi: 10.1016/0042-6822(92)90038-Q [21] Csajka C, Verotta D. Pharmacokinetic-pharmacodynamic modelling: history and perspectives[J]. J Pharmacokin Biopharm, 2006, 33(3): 227-279. [22] Wagner J G. A modern view of pharmacokinetics[J]. J Pharmacokin Biopharm, 1973: 1(5): 363-401. [23] Wen Q, LOU Jie. The global dynamics of a model about HIV-1 infection in vivo[J]. Ricerche di Matematica, 2009, 58(1): 77-90. doi: 10.1007/s11587-009-0048-y [24] Ma Z, Song B, Hallam T G. The threshold of survival for systems in a fluctuating environment[J]. Bull Math Biol, 1989, 51(3): 311-323.
点击查看大图
计量
- 文章访问数: 1425
- HTML全文浏览量: 142
- PDF下载量: 832
- 被引次数: 0