Antiviral Agents in the Treatment of Herpes Virus Infections in Immunosuppressed Patients

  • Erik De Clercq

Abstract

Immunesuppressed patients, particularly patients with hematologic malignancies, are much more vulnerable to virus infections, i.e. herpes virus infections, than are healthy persons in the population at large. This is illustrated not only by such fatal diseases as AIDS (acquired immunodeficiency syndrome), CMV (cytomegalovirus) pneumonia and EBV (Epstein-Barr virus)-associated lymphoproliferative disorders, but also by those virus infections, i.e. HSV (herpes simplex virus) and VZV (varicella-zoster virus), that are usually mild and benign in healthy individuals but often serious and occasionally fatal in the immunosuppressed host.

Keywords

Oncol Interferon Purine Nucleoside Encephalitis 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    W. T. Ashton, J. D. Karkas, A. K. Field and R. L. Tolman, Activation by thymidine kinase and potent antiherpetic activity of 2’-nor-2’-deoxyguanosine (2’NDG), Biochem. Biophys. Res. Commun. 108:1716 (1982).PubMedCrossRefGoogle Scholar
  2. 2.
    H. H. Balfour, Jr., Intravenous acyclovir therapy for varicella in immunocompromised children, J. Pediatr. 104:134 (1984).PubMedCrossRefGoogle Scholar
  3. 3.
    H. H. Balfour, Jr., B. Bean, O. L. Laskin, R. F. Ambinder, J. D. Meyers, J. C. Wade, J. A. Zaia, D. Aeppli, L. E. Kirk, A. C. Segreti, R. E. Keeney and The Burroughs Wellcome Collaborative Acyclovir Study Group, Acyclovir halts progression of herpes zoster in immunocompromised patients, New Engl. J. Med. 308:1448 (1983).PubMedCrossRefGoogle Scholar
  4. 4.
    Y. Benoit, G. Laureys, M. -J. Delbeke and E. De Clercq, Oral BVDU treatment of varicella and zoster in children with cancer, Eur. J. Pediatr. 143:198 (1985).PubMedCrossRefGoogle Scholar
  5. 5.
    K. K. Biron and G. B. Elion, Effect of acyclovir combined with other antiherpetic agents on varicella zoster virus in vitro, Am. J. Med. 73(A):54 (1982).PubMedCrossRefGoogle Scholar
  6. 6.
    J. Boguslawska-Jaworska, E. Koscielniak and B. Rodziewicz, Acyclovir therapy for chickenpox in children with hematological malignancies, Eur. J. Pediatr. 142:130 (1984).PubMedCrossRefGoogle Scholar
  7. 7.
    W. H. Burns, R. Saral, G. W. Santos, 0. L. Laskin, P. S. Lietman, C. McLaren and D. W. Barry, Isolation and characterization of resistant herpes simplex virus after acyclovir therapy, Lancet i:421 (1982).CrossRefGoogle Scholar
  8. 8.
    J. J. Cassiman, E. De Clercq, A. S. Jones, R. T. Walker and H. Van den Berghe, Sister chromatid exchange induced by anti-herpes drugs, Brit. Med. J. 283:817 (1981).CrossRefGoogle Scholar
  9. 9.
    J. J. Cassiman, E. De Clercq and H. Van den Berghe, Induction of sister-chromatid exchange by 5-substituted 2’-deoxyuridines, Mutation Res. 117:317 (1983).PubMedCrossRefGoogle Scholar
  10. 10.
    Y. -C. Cheng, E. -S. Huang, J. -C. Lin, E. -C. Mar, J. S. Pagano, G. E. Dutschman and S. P. Grill, Unique spectrum of activity of 9-[(l,3-dihydroxy-2-propoxy)methyl]guanine against herpesviruses in vitro and its mode of action against herpes simplex virus type 1, Proc. Natl. Acad. Sci. USA 80:2767 (1983).PubMedCrossRefGoogle Scholar
  11. 11.
    J. M. Colacino and C. Lopez, Efficacy and selectivity of some nucleoside analogs as anti-human cytomegalovirus agents, Antimicrob. Agents Chemother. 24:505 (1983).PubMedGoogle Scholar
  12. 12.
    C. S. Crumpacker, L. E. Schnipper, S. I. Marlowe, P. N. Kowalsky, B. J. Hershey and M. J. Levin, Resistance to antiviral drugs of herpes simplex virus isolated from a patient treated with acyclovir, New Engl. J. Med. 306:343 (1982).PubMedCrossRefGoogle Scholar
  13. 13.
    E. De Clercq, The antiviral spectrum of (E)-5-(2-bromovinyl)-2’-deoxyuridine, J. Antimicrob. Chemother. 14, Suppl. A:85 (1984a).PubMedGoogle Scholar
  14. 14.
    E. De Clercq, Biochemical aspects of the selective antiherpes activity of nucleoside analogues, Biochem. Pharmacol. 33:2159 (1984b).PubMedCrossRefGoogle Scholar
  15. 15.
    E. De Clercq, Antiherpesvirus agents and the immune system, Zbl. Bakt. Suppl. 13:39 (1985a).Google Scholar
  16. 16.
    E. De Clercq, Antiviral agents and the immune system, in: “Antimicrobial Agents and Immunity,” J. Jeljaszewicz and G. Pulverer, eds., Academic Press Inc., London, in press (1985b).Google Scholar
  17. 17.
    E. De Clercq, Y. Benoit, G. Laureys and M. J. Delbeke, Clinical potentials of bromovinyldeoxyuridine (BVDU): in particular for oral treatment of varicella-zoster virus infections in children with cancer, in: “Proceedings of the International Symposium on Pharmacological and Clinical Approaches to Herpes Viruses and Virus Chemotherapy,” Oiso, Japan. Excerpta Medica International Congress Series (ICS 667), Elsevier Science Publishers, Amsterdam, in press (1985).Google Scholar
  18. 18.
    E. De Clercq and J. -J. Cassiman, Mutagenic potential of anti-herpes agents, Submitted for publication (1985).Google Scholar
  19. 19.
    E. De Clercq, J. Descamps, P. De Somer, P. J. Barr, A. S. Jones and R. T. Walker, (E)-5-(2-Bromovinyl)-2’-deoxyuridine: a potent and selective anti-herpes agent, Proc. Natl. Acad. Sci. USA 76:2947 (1979).PubMedCrossRefGoogle Scholar
  20. 20.
    E. De Clercq, J. Descamps, M. Ogata and S. Shigeta, In vitro susceptibility of varicella-zoster virus to E-5-(2-bromovinyl)-2’-deoxyuridine and related compounds, Antimicrob. Agents Chemother. 21:33 (1982).PubMedGoogle Scholar
  21. 21.
    E. De Clercq, J. Descamps, G. Verhelst, R. T. Walker, A. S. Jones, P. F. Torrence and D. Shugar, Comparative efficacy of antiherpes drugs against different strains of herpes simplex virus, J. Infect. Pis. 141:563 (1980).CrossRefGoogle Scholar
  22. 22.
    E. De Clercq and R. T. Walker, Synthesis and antiviral properties of 5-vinylpyrimidine nucleoside analogs, Pharmac. Ther. 26:1 (1984).CrossRefGoogle Scholar
  23. 23.
    E. De Clercq, Z. -X. Zhang, J. Descamps and K. Huygen, E-5-(2-Bromovinyl)-2’-deoxyuridine vs. interferon in the systemic treatment of infection with herpes simplex virus of athymic nude mice, J. Infect. Pis. 143:846 (1981).CrossRefGoogle Scholar
  24. 24.
    A. K. Field, M. E. Davies, C. Dewitt, H. C. Perry, R. Liou, J. Germershausen, J. D. Karkas, W. T. Ashton, D. B. R. Johnston and R. L. Tolman, 9-{[2-Hydroxy-l-(hydroxymethyl)ethoxy]methyl}guanine: a selective inhibitor of herpes group virus replication, Proc. Natl. Acad. Sci. USA 80:4139 (1983).PubMedCrossRefGoogle Scholar
  25. 25.
    E. Gluckman, J. Lotsberg, A. Devergie, X. M. Zhao, R. Melo, M. Gomez Morales, T. Nebout, M. C. Mazeron and Y. Perol, Prophylaxis of herpes infections after bone-marrow transplantation by oral acyclovir, Lancet ii:706 (1983).CrossRefGoogle Scholar
  26. 26.
    I. M. Hann, H. G. Prentice, H. A. Blacklock, M. G. R. Ross, D. Brigden, A. E. Rosling, C. Burke, D. H. Crawford, W. Brumfitt and A. V. Hoffbrand, Acyclovir prophylaxis against herpes virus infections in severely immunocompromised patients: randomized double blind trial, Brit. Med. J. 287:384 (1983).CrossRefGoogle Scholar
  27. 27.
    J. -C. Lin, D. J. Nelson, C. U. Lambe and J. S. Pagano, Effects of nucleoside analogues in inhibition of Epstein-Barr virus, Presented at the International Symposium on Pharmacological and Clinical Approaches to Herpes Viruses and Virus Chemotherapy, Oiso, Japan, 10–13 September 1984 (1984a).Google Scholar
  28. 28.
    J. -C. Lin, M. C. Smith, Y. -C. Cheng and J. S. Pagano, Epstein-Barr virus: inhibition of replication by three new drugs, Science 221:578 (1983).PubMedCrossRefGoogle Scholar
  29. 29.
    J. -C. Lin, M. C. Smith and J. S. Pagano, Prolonged inhibitory effect of 9-(l,3-dihydroxy-2-propoxymethyl)guanine against replication of Epstein-Barr virus, J. Virol. 50:50 (1984b).PubMedGoogle Scholar
  30. 30.
    C. Lopez. K. A. Watanabe and J. J. Fox, 2’-Fluoro-5-iodo-aracytosine, a potent and selective anti-herpes agent, Antimicrob. Agents Chemother. 17:803 (1980).PubMedGoogle Scholar
  31. 31.
    E. -C. Mar, Y. -C. Cheng and E. -S. Huang, Effect of 9-(l,3-dihydroxy-2-propoxymethyl)guanine on human cytomegalovirus replication in vitro, Antimicrob. Agents Chemother. 24:518 (1983).PubMedGoogle Scholar
  32. 32.
    E. -C. Mar, P. C. Patel, Y. -C. Cheng, J. J. Fox, K. A. Watanabe and E. -S. Huang, Effects of certain nucleoside analogues on human cytomegalovirus replication in vitro, J. Gen. Virol. 65:47 (1984).PubMedCrossRefGoogle Scholar
  33. 33.
    P. C. Maudgal, E. De Clercq and L. Missotten, Efficacy of bromovinyldeoxyuridine in the treatment of herpes simplex virus and varicellazoster virus eye infections, Antiviral Res. 4:281 (1984).PubMedCrossRefGoogle Scholar
  34. 34.
    P. C. Maudgal, L. Dralands, L. Lamberts, E. De Clercq, J. Descamps and L. Missotten, Preliminary results of oral BVDU treatment of herpes zoster ophthalmicus, Bull. Soc. Beige Ophtalmol. 193:49 (1981a).Google Scholar
  35. 35.
    P. C. Maudgal, L. Missotten, E. De Clercq, J. Descamps and E. De Meuter, Efficacy of (E)-5-(2-bromovinyl)-2’-deoxyuridine in the topical treatment of herpes simplex keratitis, Albrecht von Graefes Arch. Klin. Exp. Ophthalmol. 216:261 (1981b).CrossRefGoogle Scholar
  36. 36.
    J. D. Meyers, J. C. Wade, C. D. Mitchell, R. Saral, P. S. Lietman, D. T. Durack, M. J. Levin, A. C. Segreti and H. H. Balfour, Jr., Multicenter collaborative trial of intravenous acyclovir for treatment of mucocutaneous herpes simplex virus infection in the immunocompromised host, Am. J. Med. 73(A):229 (1982).PubMedCrossRefGoogle Scholar
  37. 37.
    J. D. Meyers, J. C. Wade, D. H. Shepp and B. Newton, Acyclovir treatment of varicella-zoster virus infection in the compromised host, Transplantation 37:571 (1984).PubMedCrossRefGoogle Scholar
  38. 38.
    C. D. Mitchell, B. Bean, S. R. Gentry, K. E. Groth, J. R. Boen and H.H. Balfour, Jr., Acyclovir therapy for mucocutaneous herpes simplex infections in immunocompromised patients, Lancet i:1389 (1981).CrossRefGoogle Scholar
  39. 39.
    C. G. Prober, L. E. Kirk and R. E. Keeney, Acyclovir therapy of chickenpox in immunosuppressed children — A collaborative study, J. Pediatr. 101:622 (1982).PubMedCrossRefGoogle Scholar
  40. 40.
    R. Saral, R. F. Ambinder, W. H. Burns, C. M. Angelopulos, D. E. Griffin, P. J. Burke and P. S. Lietman, Acyclovir prophylaxis against herpes simplex virus infection in patients with leukemia, Ann. Intern. Med. 99:773 (1983).PubMedGoogle Scholar
  41. 41.
    R. Saral, W. H. Burns, 0. L. Laskin, G. W. Santos and P. S. Lietman, Acyclovir prophylaxis of herpes-simplex-virus infections. A randomized, double-blind, controlled trial in bone marrow transplant recipients, New Engl. J. Med. 305:63 (1981).PubMedCrossRefGoogle Scholar
  42. 42.
    P. Selby, R. L. Powles, S. Blake, K. Stolle, E. K. Mbidde, T. J. McElwain, E. Hickmott, P. D. Whiteman and A. P. Fiddian, Amino(hydroxyethoxymethyl)purine: a new well-absorbed prodrug of acyclovir, Lancet ii:1428 (1984).CrossRefGoogle Scholar
  43. 43.
    W. M. Shannon and F. M. Schabel, Jr., Antiviral agents as adjuncts in cancer chemotherapy, Pharmac. Ther. 11:263 (1980).CrossRefGoogle Scholar
  44. 44.
    S. Shigeta, T. Yokota, T. Iwabuchi, M. Baba, K. Konno, M. Ogata and E. De Clercq, Comparative efficacy of antiherpes drugs against various strains of varicella-zoster virus, J. Infect. Pis. 147:576 (1983).CrossRefGoogle Scholar
  45. 45.
    C. D. Sibrack, L. T. Gutman, C. M. Wilfert, C. McLaren, M. H. St. Clair, P. M. Keller and D. W. Barry, Pathogenicity of acyclovirresistant herpes simplex virus type 1 from an immunodeficient child, J. Infect. Pis. 146:673 (1982).CrossRefGoogle Scholar
  46. 46.
    D. F. Smee, J. C. Martin, J. P. H. Verheyden and T. R. Matthews, Antiherpes virus activity of the acyclic nucleoside 9-(l,3-dihydroxy-2-propoxymethyl)guanine, Antimicrob. Agents Chemother. 23:676 (1983).PubMedGoogle Scholar
  47. 47.
    C. A. Smith, B. Wigdahl and F. Rapp, Synergistic antiviral activity of acyclovir and interferon on human cytomegalovirus, Antimicrob. Agents Chemother. 24:325 (1983).PubMedGoogle Scholar
  48. 48.
    K. 0. Smith, K. S. Galloway, W. L. Kennell, K. K. Ogilvie and B. K. Radatus, A new nucleoside analog, 9-([2-hydroxy-l-(hydroxymethyl)-ethoxy]methyl)guanine, highly active in vitro against herpes simplex virus types 1 and 2, Antimicrob. Agents Chemother. 22:55 (1982).PubMedGoogle Scholar
  49. 49.
    K. F. Soike, A. D. Felsenfeld and P. J. Gerone, Acyclovir treatment of experimental simian varicella infection of monkeys, Antimicrob. Agents Chemother. 20:291 (1981a).PubMedGoogle Scholar
  50. 50.
    K. F. Soike, A. D. Felsenfeld, S. Gibson and P. J. Gerone, Ineffectiveness of adenine arabinoside and adenine arabinoside 5’-monophosphate in simian varicella infection, Antimicrob. Agents Chemother. 18:142 (1980).PubMedGoogle Scholar
  51. 51.
    K. F. Soike, S. Gibson and P. J. Gerone, Inhibition of simian varicella virus infection of African green monkeys by (E)-5-(2-bromovinyl)-2’-deoxyuridine (BVDU), Antiviral Res. 1:325 (1981b).CrossRefGoogle Scholar
  52. 52.
    D. A. Stevens, G. W. Jordan, T. F. Waddell and T. C. Merigan, Adverse effect of cytosine arabinoside on disseminated zoster in a controlled trial, New Engl. J. Med. 289:873 (1973).PubMedCrossRefGoogle Scholar
  53. 53.
    M. J. Tocci, T. J. Livelli, H. C. Perry, C. S. Crumpacker and A. K. Field, Effects of the nucleoside analog 2’-nor-2’deoxyguanosine on human cytomegalovirus replication, Antimicrob. Agents Chemother. 25:247 (1984).PubMedGoogle Scholar
  54. 54.
    G. Tricot, E. De Clercq, M. A. Boogaerts and R. L. Verwilghen, Oral bromovinyldeoxyuridine therapy for herpes simplex and varicellazoster virus infections in severely immunosuppressed patients, Submitted for publication (1985).Google Scholar
  55. 55.
    A. S. Tyms, J. M. Davis, D. J. Jeffries and J. D. Meyers, BWB759U, an analogue of acyclovir, inhibits human cytomegalovirus in vitro, Lancet ii:924 (1984).CrossRefGoogle Scholar
  56. 56.
    J. C. Wade, C. McLaren and J. D. Meyers, Frequency and significance of acyclovir-resistant herpes simplex virus isolated from marrow transplant patients receiving multiple courses of treatment with acyclovir, J. Infect. Pis. 148:1077 (1983).CrossRefGoogle Scholar
  57. 57.
    J. C. Wade, B. Newton, C. McLaren, N. Flournoy, R. E. Keeney and J. D.Meyers, Intravenous acyclovir to treat mucocutaneous herpes simplex virus infection after marrow transplantation, Ann. Intern. Med. 96:265 (1982).PubMedGoogle Scholar
  58. 58.
    K. A. Watanabe, U. Reichman, K. Hirota, C. Lopez and J. J. Fox,Nucleosides. 110. Synthesis and antiherpes virus activity of some 2’-fluoro-2’-deoxyarabinofuranosylpyrimidine nucleosides, J. Med. Chem. 22:21 (1979).PubMedCrossRefGoogle Scholar
  59. 59.
    P. D. Whiteman, A. Bye, A. S. E. Fowle, S. Jeal, G. Land and J. Posner, Tolerance and pharmacokinetics of A515U, an acyclovir analogue, in healthy volunteers, Eur. J. Clin. Pharmacol. 27:471 (1984).PubMedCrossRefGoogle Scholar
  60. 60.
    R. J. Whitley, M. Hilty, R. Haynes, Y. Bryson, J. D. Connor, S. -J. Soong, C. A. Alford and the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group, Vidarabine therapy of varicella in immunosuppressed patients, J. Pediatr. 101:125 (1982a).PubMedCrossRefGoogle Scholar
  61. 61.
    R. J. Whitley, S. -J. Soong, R. Dolin, R. Betts, C. Linnemann, Jr., C. A. Alford, Jr. and The NIAID Collaborative Antiviral Study Group, Early vidarabine therapy to control the complications of herpes zoster in immunosuppressed patients, New Engl. J. Med. 307:971 (1982b).PubMedCrossRefGoogle Scholar
  62. 62.
    R. J. Whitley, S. Spruance, F. G. Hayden, J. Overall, C. A. Alford, Jr., J. M. Gwaltney, S. -J. Soong and The NIAID Collaborative Antiviral Study Group, Vidarabine therapy for mucocutaneous herpes simplex virus infections in the immunocompromised host, J. Infect. Pis. 149:1 (1984).CrossRefGoogle Scholar
  63. 63.
    J. Wildiers and E. De Clercq, Oral (E)-5-(2-bromovinyl)-2’-deoxyuridine treatment of severe herpes zoster in cancer patients, Eur. J. Cancer. Clin. Oncol. 20:471 (1984).PubMedCrossRefGoogle Scholar
  64. 64.
    C. W. Young, R. Schneider, B. Leyland-Jones, D. Armstrong, C. T. C. Tan, C. Lopez, K. A. Watanabe, J. J. Fox and F. S. Philips, Phase I evaluation of 2’-fluoro-5-iodo-l-$-D-arabinofuranosylcytosine in immunosuppressed patients with herpesvirus infection, Cancer Res. 43:5006 (1983).PubMedGoogle Scholar
  65. 33.
    P. C. Maudgal, E. De Clercq and L. Missotten, Efficacy of bromovinyldeoxyuridine in the treatment of herpes simplex virus and varicella-zoster virus eye infections, Antiviral Res. 4:281 (1984).PubMedCrossRefGoogle Scholar
  66. 34.
    P. C. Maudgal, L. Dralands, L. Lamberts, E. De Clercq, J. Descamps and L. Missotten, Preliminary results of oral BVDU treatment of herpes zoster ophthalmicus, Bull. Soc. Beige Ophtalmol. 193:49 (1981a).Google Scholar
  67. 35.
    P. C. Maudgal, L. Missotten, E. De Clercq, J. Descamps and E. De Meuter, Efficacy of (E)-5-(2-bromovinyl)-2’-deoxyuridine in the topical treatment of herpes simplex keratitis, Albrecht von Graefes Arch. Klin. Exp. Ophthalmol. 216:261 (1981b).CrossRefGoogle Scholar
  68. 36.
    J. D. Meyers, J. C. Wade, C. D. Mitchell, R. Saral, P. S. Lietman, D. T. Durack, M. J. Levin, A. C. Segreti and H. H. Balfour, Jr., Multicenter collaborative trial of intravenous acyclovir for treatment of mucocutaneous herpes simplex virus infection in the immunocompromised host, Am. J. Med. 73(A):229 (1982).PubMedCrossRefGoogle Scholar
  69. 37.
    J. D. Meyers, J. C. Wade, D. H. Shepp and B. Newton, Acyclovir treatment of varicella-zoster virus infection in the compromised host, Transplantation 37:571 (1984).PubMedCrossRefGoogle Scholar
  70. 38.
    C. D. Mitchell, B. Bean, S. R. Gentry, K. E. Groth, J. R. Boen and H.H. Balfour, Jr., Acyclovir therapy for mucocutaneous herpes simplex infections in immunocompromised patients, Lancet i:1389 (1981).CrossRefGoogle Scholar
  71. 39.
    C. G. Prober, L. E. Kirk and R. E. Keeney, Acyclovir therapy of chickenpox in immunosuppressed children — A collaborative study, J. Pediatr. 101:622 (1982).PubMedCrossRefGoogle Scholar
  72. 40.
    R. Saral, R. F. Ambinder, W. H. Burns, C. M. Angelopulos, D. E. Griffin, P. J. Burke and P. S. Lietman, Acyclovir prophylaxis against herpes simplex virus infection in patients with leukemia, Ann. Intern. Med. 99:773 (1983).PubMedGoogle Scholar
  73. 41.
    R. Saral, W. H. Burns, 0. L. Laskin, G. W. Santos and P. S. Lietman, Acyclovir prophylaxis of herpes-simplex-virus infections. A randomized, double-blind, controlled trial in bone marrow transplant recipients, New Engl. J. Med. 305:63 (1981).PubMedCrossRefGoogle Scholar
  74. 42.
    P. Selby, R. L. Powles, S. Blake, K. Stolle, E. K. Mbidde, T. J. McElwain, E. Hickmott, P. D. Whiteman and A. P. Fiddian, Amino(hydroxyethoxymethyl)purine: a new well-absorbed prodrug of acyclovir, Lancet ii:1428 (1984).CrossRefGoogle Scholar
  75. 43.
    W. M. Shannon and F. M. Schabel, Jr., Antiviral agents as adjuncts in cancer chemotherapy, Pharmac. Ther. 11:263 (1980).CrossRefGoogle Scholar
  76. 44.
    S. Shigeta, T. Yokota, T. Iwabuchi, M. Baba, K. Konno, M. Ogata and E. De Clercq, Comparative efficacy of antiherpes drugs against various strains of varicella-zoster virus, J. Infect. Pis. 147:576 (1983).CrossRefGoogle Scholar
  77. 45.
    C. D. Sibrack, L. T. Gutman, C. M. Wilfert, C. McLaren, M. H. St. Clair, P. M. Keller and D. W. Barry, Pathogenicity of acyclovirresistant herpes simplex virus type 1 from an immunodeficient child, J. Infect. Pis. 146:673 (1982).CrossRefGoogle Scholar
  78. 46.
    D. F. Smee, J. C. Martin, J. P. H. Verheyden and T. R. Matthews, Antiherpes virus activity of the acyclic nucleoside 9-(l,3-dihydroxy-2-propoxymethyl)guanine, Antimicrob. Agents Chemother. 23:676 (1983).PubMedGoogle Scholar
  79. 47.
    C. A. Smith, B. Wigdahl and F. Rapp, Synergistic antiviral activity of acyclovir and interferon on human cytomegalovirus, Antimicrob. Agents Chemother. 24:325 (1983).PubMedGoogle Scholar
  80. 48.
    K. 0. Smith, K. S. Galloway, W. L. Kennell, K. K. Ogilvie and B. K. Radatus, A new nucleoside analog, 9-([2-hydroxy-l-(hydroxymethyl)-ethoxy]methyl)guanine, highly active in vitro against herpes simplex virus types 1 and 2, Antimicrob. Agents Chemother. 22:55 (1982).PubMedGoogle Scholar
  81. 49.
    K. F. Soike, A. D. Felsenfeld and P. J. Gerone, Acyclovir treatment of experimental simian varicella infection of monkeys, Antimicrob. Agents Chemother. 20:291 (1981a).PubMedGoogle Scholar
  82. 50.
    K. F. Soike, A. D. Felsenfeld, S. Gibson and P. J. Gerone, Ineffectiveness of adenine arabinoside and adenine arabinoside 5’-monophosphate in simian varicella infection, Antimicrob. Agents Chemother. 18:142 (1980).PubMedGoogle Scholar
  83. 51.
    K. F. Soike, S. Gibson and P. J. Gerone, Inhibition of simian varicella virus infection of African green monkeys by (E)-5-(2-bromovinyl)-2’-deoxyuridine (BVDU), Antiviral Res. 1:325 (1981b).CrossRefGoogle Scholar
  84. 52.
    D. A. Stevens, G. W. Jordan, T. F. Waddell and T. C. Merigan, Adverse effect of cytosine arabinoside on disseminated zoster in a controlled trial, New Engl. J. Med. 289:873 (1973).PubMedCrossRefGoogle Scholar
  85. 53.
    M. J. Tocci, T. J. Livelli, H. C. Perry, C. S. Crumpacker and A. K. Field, Effects of the nucleoside analog 2’-nor-2’deoxyguanosine on human cytomegalovirus replication, Antimicrob. Agents Chemother. 25:247 (1984).PubMedGoogle Scholar
  86. 54.
    G. Tricot, E. De Clercq, M. A. Boogaerts and R. L. Verwilghen, Oral bromovinyldeoxyuridine therapy for herpes simplex and varicellazoster virus infections in severely immunosuppressed patients, Submitted for publication (1985).Google Scholar
  87. 55.
    A. S. Tyms, J. M. Davis, D. J. Jeffries and J. D. Meyers, BWB759U, an analogue of acyclovir, inhibits human cytomegalovirus in vitro, Lancet ii:924 (1984).CrossRefGoogle Scholar
  88. 56.
    J. C. Wade, C. McLaren and J. D. Meyers, Frequency and significance of acyclovir-resistant herpes simplex virus isolated from marrow transplant patients receiving multiple courses of treatment with acyclovir, J. Infect. Pis. 148:1077 (1983).CrossRefGoogle Scholar
  89. 57.
    J. C. Wade, B. Newton, C. McLaren, N. Flournoy, R. E. Keeney and J. D.Meyers, Intravenous acyclovir to treat mucocutaneous herpes simplex virus infection after marrow transplantation, Ann. Intern. Med. 96:265 (1982).PubMedGoogle Scholar
  90. 58.
    K. A. Watanabe, U. Reichman, K. Hirota, C. Lopez and J. J. Fox,Nucleosides. 110. Synthesis and antiherpes virus activity of some 2’-fluoro-2’-deoxyarabinofuranosylpyrimidine nucleosides, J. Med. Chem. 22:21 (1979).PubMedCrossRefGoogle Scholar
  91. 59.
    P. D. Whiteman, A. Bye, A. S. E. Fowle, S. Jeal, G. Land and J. Posner, Tolerance and pharmacokinetics of A515U, an acyclovir analogue, in healthy volunteers, Eur. J. Clin. Pharmacol. 27:471 (1984).PubMedCrossRefGoogle Scholar
  92. 60.
    R. J. Whitley, M. Hilty, R. Haynes, Y. Bryson, J. D. Connor, S. -J. Soong, C. A. Alford and the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group, Vidarabine therapy of varicella in immunosuppressed patients, J. Pediatr. 101:125 (1982a).PubMedCrossRefGoogle Scholar
  93. 61.
    R. J. Whitley, S. -J. Soong, R. Dolin, R. Betts, C. Linnemann, Jr., C. A. Alford, Jr. and The NIAID Collaborative Antiviral Study Group, Early vidarabine therapy to control the complications of herpes zoster in immunosuppressed patients, New Engl. J. Med. 307:971 (1982b).PubMedCrossRefGoogle Scholar
  94. 62.
    R. J. Whitley, S. Spruance, F. G. Hayden, J. Overall, C. A. Alford, Jr., J. M. Gwaltney, S. -J. Soong and The NIAID Collaborative Antiviral Study Group, Vidarabine therapy for mucocutaneous herpes simplex virus infections in the immunocompromised host, J. Infect. Pis. 149:1 (1984).CrossRefGoogle Scholar
  95. 63.
    J. Wildiers and E. De Clercq, Oral (E)-5-(2-bromovinyl)-2’-deoxyuridine treatment of severe herpes zoster in cancer patients, Eur. J. Cancer. Clin. Oncol. 20:471 (1984).PubMedCrossRefGoogle Scholar
  96. 64.
    C. W. Young, R. Schneider, B. Leyland-Jones, D. Armstrong, C. T. C. Tan, C. Lopez, K. A. Watanabe, J. J. Fox and F. S. Philips, Phase I evaluation of 2’-fluoro-5-iodo-l-$-D-arabinofuranosylcytosine in immunosuppressed patients with herpesvirus infection, Cancer Res. 43:5006 (1983).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Erik De Clercq
    • 1
  1. 1.Rega Institute for Medical ResearchKatholieke Universiteit LeuvenLeuvenBelgium

Personalised recommendations