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A model for treatment strategy in the chemotherapy of AIDS

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Abstract

Mathematical models are developed for the chemotherapy of AIDS. The models are systems of differential equations describing the interaction of the HIV infected immune system with AZT chemotherapy. The models produce the three types of qualitative clinical behavior: anuninfected steady state, aninfected steady state (latency) and aprogression to AIDS state. The effect of treatment is to perturb the system from progression to AIDS back to latency. Simulation of treatment schedules is provided for the consideration of treatment regimes. The following issues of chemotherapy are addressed: (i) daily frequency of treatment, (ii) early versus late initiation of treatment and (iii) intermittent treatment with intervals of no treatment. The simulations suggest the following properties of AZT chemotherapy: (i) the daily period of treatment does not affect the outcome of the treatment, (ii) treatment should not begin until after the final decline of T cells begins (not until the T cell population falls below approximately 300 mm−3) and then, it should be administered immediately and (iii) a possible strategy for treatment which may cope with side effects and/or resistance, is to treat intermittently with chemotherapy followed by interruptions in the treatment during which either a different drug or no treatment is administered. These properties are revealed in the simulations, as the model equations incorporate AZT chemotherapy as a weakly effective treatment process. We incorporate into the model the fact that AZT treatment does not eliminate HIV, but only restrains its progress. The mathematical model, although greatly simplified as a description of an extremely complex process, offers a means to pose hypotheses concerning treatment protocols, simulate alternative strategies and guide the qualitative understanding of AIDS chemotherapy.

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Literature

  • Agur, Z. 1989. A new method for reducing cytotoxicity of the anti-AIDS drug AZT. InBiomedical Modeling and Simulation, D. S. Levine, (Ed), pp. 59–61. J. C. Baltzer AG, Scientific Publishing.

  • Anderson, D. J.,et al.. 1992. Effects of disease stage and AZT therapy on the detection of HIV-1 in semen.J. Amer. Med. Assoc. 267, 2769–2774.

    Article  Google Scholar 

  • Chow, Y. K.,et al. 1993. Use of evolutionary limitations of HIV-1 multidrug resistance to optimize therapy.Nature 361, 650–655.

    Article  Google Scholar 

  • Cojocaru, L. and Z. Agur. 1992. A theoretical analysis of interval drug dosing for cell-cycle-phase-specific drugs.Math. Biosci. 109, 85–97.

    Article  MATH  Google Scholar 

  • Cojocaru, L. and Z. Agur. 1993. New mathematical methods for evaluating toxicity of anti-cancer drugs and AZT. Preprint.

  • Concorde Coordinating Committee. 1994. MRC/ANRS randomized double-blind controlled trial of immediate and deferred AZT in symptom-free HIV infection.Lancet 343, 871–881.

    Article  Google Scholar 

  • Cooper, D. A.,et al. 1991. The efficacy and safety of AZT with or without acyclovir in the treatment of patients with AIDS related complex.AIDS 5, 933–943.

    Google Scholar 

  • Cox, H. P.,et al. 1990. Outcomes of treatment with AZT of patients with AIDS and symptomatic HIV infection.Nurse Practitioner 15, 36–43.

    Article  Google Scholar 

  • Dimitrov, D. S.et al. 1993. Quantitation of HIV-type 1 infection kinetics.J. Virology 67, 2182–2190.

    MathSciNet  Google Scholar 

  • Fischl, M. A.,et al. 1990. The safety and efficacy of AZT in the treatment of subjects with mildly symptomatic HIV type 1.Ann. Int. Med. 112, 727–737.

    Google Scholar 

  • Graham, N. M. H.,et al. 1992. The effects on survival of early treatment of HIV infection.New Engl. J. Med. 326, 1037–1042.

    Article  Google Scholar 

  • Hamilton, J. D.,et al. 1992. A controlled trial of early vs. late treatment with AZT in symptomatic HIV infection.New Engl. J. Med. 326, 437–443.

    Article  Google Scholar 

  • Harnevo, L. E. 1993. Simple models for interactions of the HIV and the immune system: can we point to a specific threshold for the onset of AIDS? InProceedings of the World Congress for Non-linear Analysts. To appear.

  • Haseltine, W. A. and F. Wong-Staal. 1988. The molecular biology of the AIDS virus.Scientific American October, 53–62.

    Google Scholar 

  • Hirsch, M. S. 1990. Chemotherapy of HIV infections: Current practice and future prospects.J. Infectious Diseases 161, 845–857.

    Google Scholar 

  • Ho, D. D.,et al. 1995. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection.Nature 373, 123–126.

    Article  Google Scholar 

  • Kaiser, J. D. 1993.Immune Power. New York: St. Martin's Press.

    Google Scholar 

  • Kirschner, D., R. Mehr and A. Perelson. 1995. The role of the thymus in HIV infection. Preprint.

  • Kirschner, D. and A. Perelson. 1995. A model for the immune system response to HIV: AZT treatment studies. InMathematical Populations Dynamics III. Theory of Epidemics, O. Arino, D. Axelrod and M. Kimmel (Eds), Vol. 1, pp. 295–310. Winnepeg, Manitoba: Wuerz Publishing.

    Google Scholar 

  • Kirschner, D. E. and G. F. Webb, 1995. Effects of drug resistance on chemotherapy strategies in the treatment of HIV infection. Preprint.

  • Lagakos, S., C. Pettinelli, D. Stein and P. A. Volderding. 1993. The Concorde Trial.Lancet 341, 1276.

    Article  Google Scholar 

  • Landonio, G.et al. 1993. Comparison of two dose regimes of AZT in an open, randomized, multicetre study for severe HIV-related thromocytopenia.AIDS 7, 209–212.

    Google Scholar 

  • Lenderking, W. R.,et al. 1994. Evaluation of the quality of life associated with Zidovudine treatment in asymptomatic human immunodeficiency virus infection.New. Engl. J. Med. 330, 738–743.

    Article  Google Scholar 

  • Lundgren, J. D.,et al. 1994. Comparison of long-term prognosis of patients with AIDS treated and not treated with Zidovudine.J. Amer. Med. Assoc. 271, 1088–1092.

    Article  Google Scholar 

  • McKallip, R. J., M. Nagarkatti and P. S. Nagarkatti. 1995. Immunotoxicity of AZT: inhibitory effect on thymocyte differentiation and peripheral T cell response to gp120 of HIV.Tox. Appl. Pharm. 131, 53–63.

    Article  Google Scholar 

  • McLean, A. and M. Nowak, 1991. Interactions between HIV and other pathogens.J. Theoret. Biol. 155, 69–86.

    Article  Google Scholar 

  • McLean, A. and M. Nowak. 1992. Competition between AZT sensitive and AZT resistant strains of HIV.AIDS 6, 71–79.

    Google Scholar 

  • McLeod, G. X. and S. M. Hammer. 1992. Zidovudine: 5 years later.Ann. Int. Med. 117, 487–501.

    Google Scholar 

  • Meng, T. C.,et al. 1992. Combination therapy with AZT and DDC in patients with advanced HIV infection.Ann. Int. Med. 116, 13–19.

    Google Scholar 

  • Montaner, J.,et al. 1993. Clinical correlates ofin vitro HIV-1 resistance to AZT.AIDS 7, 189–196.

    Google Scholar 

  • Mulder, J. W.,et al. 1994. AZT twice daily in asymptomatic subjects with HIV infection and a high risk of progression to AIDS: a randomized, double-blind placebo-controlled study.AIDS 8, 313–321.

    Article  Google Scholar 

  • Nozyce, M.,et al. 1994. A 12-month study of the effects of oral AZT on neurodevelopmental functioning in a cohort of vertically HIV-infected inner-city children.AIDS 8, 635–639.

    Google Scholar 

  • Perelson, A. S. 1989. Modeling the interaction of the immune system with HIV. InMathematical and Statistical Approaches to AIDS Epidermiology. Lecture Notes in Biomath., C. Castillo-Chavez (Ed), Vol. 83, pp. 350–370. New York: Springer-Verlag.

    Google Scholar 

  • Perelson, A., D. Kirschner and R. DeBoer. 1993. The dynamics of HIV infection of CD4+ T cells.Math. Biosci. 114, 81–125.

    Article  MATH  Google Scholar 

  • Redfield, R. and D. Burke. 1988. HIV infection: The clinical picture.Scientific American October, 90–98.

    Article  Google Scholar 

  • Ruedy, J., M. Schechter and J. S. G. Montaner. 1990. Zidovudine for early HIV infection: who, when and how?Ann. Int. Med. 112, 721–722.

    Google Scholar 

  • Volberding, P. A. 1994. Intermittent therapy.AIDS 7, 454–456.

    Google Scholar 

  • Volberding, P. A.,et al. 1990. Zidovudine in asymptomatic human immunodeficiency virus infection.New Engl. J. Med. 322, 941–949.

    Article  Google Scholar 

  • Volderding, P. A.,et al., 1994. The duration of Zidovudine benefit in persons with asymptomatic HIV infection.J. Amer. Med. Assoc. 272, 437–442.

    Article  Google Scholar 

  • Wolfram, S. A. 1988.Mathematica: A System for Doing Mathematics by Computer. Reading, MA: Addison-Wesley.

    MATH  Google Scholar 

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Correspondence to Denise Kirschner.

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Kirschner, D., Webb, G.F. A model for treatment strategy in the chemotherapy of AIDS. Bltn Mathcal Biology 58, 367–390 (1996). https://doi.org/10.1007/BF02458312

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