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Predicting and preventing the emergence of antiviral drug resistance in HSV-2

Nature Medicine volume 4, pages 673–678 (1998)Cite this article

Abstract

Genital herpes, caused by herpes simplex virus, is the most prevalent sexually transmitted disease worldwide. In many developing countries genital herpes is untreated, and in the United States only 10% of cases are treated. We present a mathematical model that we use as a health policy tool to predict the levels of antiviral drug resistance that would emerge, if treatment rates were increased, and to identify the key factors in determining the emergence of drug resistance. We use our results to suggest control measures for herpes epidemics that would prevent the emergence of substantial levels of antiviral drug resistance.

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References

  1. Fleming, D.T. et al. Herpes Simplex Virus type 2 in the United States, 1976 to 1994. N. Engl. J. Med. 337, 1105–11 (1997).

    Article  CAS  Google Scholar 

  2. Nahmias, A.J., Lee, F.K. & Beckman-Nahmias, S. Sero-epidemiological and sociological patterns of herpes simplex virus infection in the world. Scand. J. Infect. Dis. 69, 19–36 (1990).

    CAS  Google Scholar 

  3. Oberle, M.W. et al. Herpes simplex virus type 2 antibodies: high prevalence in monogamous women in Costa Rica. Amer. J. Trop. Med. Hyg 41, 224–229 (1989).

    Article  CAS  Google Scholar 

  4. Marchant, J. & Roe, A. Genital herpes: recognizing and addressing patients's needs. Herpes Journal 4, 36–41 (1997).

    Google Scholar 

  5. Wildy, P., Field, H.J. & Nash, A.A. Classical herpes latency revisited. Soc. Gen. Microbiol. Symp. 33, 133–167 (1982).

    Google Scholar 

  6. Mertz, G.L., Schmidt, O. & Jourden, J.L. Frequency of acquisition of first episode genital infection with herpes simplex virus from symptomatic and asymptomatic source contacts. Sex. Tramm. Dis. 12, 33–39 (1985).

    Article  CAS  Google Scholar 

  7. Reichman, R.C. et al. Treatment of recurrent genital herpes simplex infections with oral acyclovir: a controlled trial. J. Am. Med. Assoc. 251, 2103–2107 (1984).

    Article  CAS  Google Scholar 

  8. Straus, S.E. et al. Suppression offrequently recurring genital herpes: a placebo-controlled double-blind trial of oralacyclovir. N. Engl. J. Med. 310, 1545–1550 (1984).

    Article  CAS  Google Scholar 

  9. Collins, P. & Darby, G. Laboratory studies of herpes simplex virus strains resistant to Acyclovir. Rev. Med. Virol. 1, 19–28 (1991).

    Article  CAS  Google Scholar 

  10. Larder, B.A. & Darby, G. Selection and characteristics of acyclovir-resistant herpes simplex virus type 1 mutants inducing altered DNA ploymerase activities. Virology 146, 262–271 (1985).

    Article  CAS  Google Scholar 

  11. Darby, G., Field, H.J. & Salisbury, S.A. Altered substrate specificity of herpes simplex virus thymidine kinase confers acyclovir-resistance. Nature 289, 81–83 (1981).

    Article  CAS  Google Scholar 

  12. Safrin, S. et al. A controlled trial comparing foscarnet with vidarabine for acyclovir-resistant mucocutaneous herpes simplex in the acquired immunodeficiency syndrome. N. Engl. J. Med. 325, 551–555 (1991).

    Article  CAS  Google Scholar 

  13. Hook, E.W. et al. Herpes simplex virus infection as a risk factor for human immunodeficiency virus infection in heterosexuals. J. Infect. Dis. 165, 251–255 (1992).

    Article  Google Scholar 

  14. Blower, S.M. & McLean, A.R. Prophylactic vaccines, risk behavior change and the probability of eradicating HIV in San Francisco. Science 265, 1451–1454 (1994).

    Article  CAS  Google Scholar 

  15. Blower, S.M., Small, P.M. & Hopewell, P. Control strategies for tuberculosis epidemics: new models for old problems. Science 273, 497–500 (1996).

    Article  CAS  Google Scholar 

  16. Blower, S.M. & Gerberding, J.L. The Dynamics of Drug Resistant Tuberculosis: A Theoretical Framework. J. Mol. Med. (In the press).

  17. Whitely, R.J. & Gnann, J.W. Acyclovir: a decade later. New Engl. J. Med. 327, 782–789 (1992).

    Article  Google Scholar 

  18. Kaplan, E.H. Economic evaluation and HIV prevention community planning - A policy analysts's perspective. in Handbook of HIV Prevention Policy Analysis (ed. Holtgrave,D.) (In the press).

  19. Wald, A., Zeh, J., Barnum, G., Davis, L.G. & Corey, L. Suppression of subclinical shedding of herpes simplex virus type 2 with acyclovir. Ann. Intern. Med. 124, 8–15 (1996).

    Article  CAS  Google Scholar 

  20. Safrin, S. Cherrington, J. & Jaffe, H.S. Clinical use of cidofovir. Rev. Med. Virol. 7, 145–156(1997).

    Article  CAS  Google Scholar 

  21. Iman, R.L. & Helton, J.C. An investigation of uncertainty and sensitivity analysis techniques for computer models. Risk Analysis 8, 71–90 (1980).

    Article  Google Scholar 

  22. Mckay, M.D., Beckman, R.J. & Conover, W.J. A comparison of three methods for selecting values of input variables in the analysis of output from a computer code. Technometrics 21, 239–245 (1979).

    Google Scholar 

  23. Blower, S.M., Hartel, D., Dowlatabadi, H., May, R.M. & Anderson, R.M. Drugs, sex and HIV: a mathematical model for New York City. Phil.Trans. Roy Soc. Series B 321, 171–187(1991).

  24. Blower, S.M. & Dowlatabadi, H. Sensitivity and Uncertainty Analysis of complex models of disease transmission: an HIV model, as an example. Int. Statist. Rev. 62, 229–243 (1994).

    Article  Google Scholar 

  25. Blower, S.M. et al. The intrinsic transmission dynamics of tuberculosis epidemics. NatureMed. 1, 815–821 (1995).

    CAS  Google Scholar 

  26. Sanchez, M.A. & Blower, S.M. Uncertainty and sensitivity analysis of the basic reproductive rate: Tuberculosis as an example. Am. J. Epidemiol. 145, 1127–1138 (1997).

    Article  CAS  Google Scholar 

  27. Porco, T.C. & Blower, S.M. Quantifying the intrinsic transmission dynamics of tuberculosis. Theor. Popul. Biol. (in the press).

  28. Porco, T.C. A mathematical model of the ecology of Lyme disease. IMAJ. Math. Appl. Med. Biol. (in the press).

  29. Kost, R.G., Hill, E.L., Tigges, M. & Straus, S.E. Recurrent acyclovir-resistant genital herpes in an immunocompetent patient. N. Engl. J. Med. 329, 1777–1782 (1993).

    Article  CAS  Google Scholar 

  30. Englund, J.A. et al. Herpes simplex virus resistant to acyclovir. Ann. Intern. Med. 112, 416–422 (1990).

    Article  CAS  Google Scholar 

  31. Wade, J.C., McLaren, C. & Meyers, J.D. Frequency and significance of acyclovir-resistant herpes simplex virus isolated from marrow transplant patients receiving multiple courses of treatment with acyclovir. J. Infect. Dis. 148, 1077–1082 (1983).

    Article  CAS  Google Scholar 

  32. Barry, D.W., Nusinoff-Lehrman, S., Ellis, M.N., Biron, K.K. & Furman, P.A. Viral resistance, clinical experience. Scand. I. Infec. Dis. Suppl. 47, 155–164 (1985).

    CAS  Google Scholar 

  33. Mertz, G.J., Benedetti, J., Ashley, R., Selke, S. & Corey, L. Risk factors for the sexual transmission of genital herpes. Ann. Intern. Med. 116, 197–202 (1992).

    Article  CAS  Google Scholar 

  34. Mertz, G.J. et al. Transmission of genital herpes in couples with one asymptomatic and one asymptomatic partner: a prospective study. J. Infect. Dis. 157, 1169–77 (1988).

    Article  CAS  Google Scholar 

  35. Wald, A., Zeh, J., Selke, S., Ashley, R.L. & Corey, L. Virologic characteristics of sub-clinical and symptomatic genital herpes infections. N. Engl. J. Med. 333, 770–775 (1995).

    Article  CAS  Google Scholar 

  36. Benedetti, J., Corey, L. & Ashley, R. Recurrence rates of genital herpes after acquisition of symptomatic first episode infection. Ann. Intern. Med. 121, 847–54 (1994).

    Article  CAS  Google Scholar 

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Author notes

  1. G. Darby

    Present address: Department of Public Health, AIDS Office, 25 van Ness, Suite 500, San Francisco, California, 94102, USA

  2. S.M. Blower: Correspondence should be addressed to S.M.B.

Authors and Affiliations

  1. Department of Medicine and Department of Microbiology and Immunology, University of California San Francisco, 513, Parnassus, HSE, Room 401, San Francisco, California, 94143, USA

    S.M. Blower & T.C. Porco

  2. Glaxo Wellcome Research and Development, Medicines Research Center, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK

    G. Darby

Authors
  1. S.M. Blower
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  2. T.C. Porco
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  3. G. Darby
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Blower, S., Porco, T. & Darby, G. Predicting and preventing the emergence of antiviral drug resistance in HSV-2. Nat Med 4, 673–678 (1998). https://doi.org/10.1038/nm0698-673

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