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Current Recommendations for the Treatment of Genital Herpes

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Abstract

The incidence of genital herpes continues to increase in epidemic-like fashion. Aciclovir (acyclovir) has been the original gold standard of therapy. The recent addition of famciclovir and valaciclovir as antiherpes drugs has improved convenience as well as the efficacy of treatment. Although aciclovir remains a widely prescribed and reliable drug, its administration schedule falls short of the ease of usage that the newer nucleoside analogues offer, for both episodic and suppressive therapy. Suppression of symptomatic disease and asymptomatic shedding from the genitalia have both become popular approaches, if not the primary targets of antiviral therapy. Knowing that asymptomatic disease leads to most cases of transmission strongly suggests that suppression with antiviral agents could reduce transmission risk in discordant couples. Unfortunately, the role for antivirals in reducing transmission remains to be proven in clinical trials. Neonatal herpes is now successfully treated using aciclovir. Current randomised clinical trials are examining aciclovir and valaciclovir administration, as well as safety and efficacy for post-acute suppressive therapy. Prevention of recurrences in pregnancy is also a topic under investigation, with a view to reducing the medical need for Cesarean section, or alternatively (and far less likely to be accomplished) to protect the neonate.

Although resistance is largely limited to the immunocompromised and a change in resistance patterns is not expected, several drugs are available for the treatment of aciclovir-resistant strains of herpes simplex. Foscarnet is the main alternative with proven efficacy in this setting. Unfortunately, administration of foscarnet requires intravenous therapy, although a single anecdote of topical foscarnet efficacy in this setting has been published. Alternatives include cidofovir gel, which is not commercially available but can be formulated locally from the intravenous preparation. Less effective alternatives include trifluridine and interferon. Future possibilities for treatment of genital herpes include a microparticle-based controlled-release formulation of aciclovir and resiquimod (VML-600; R-848). The search for an effective therapeutic vaccine for genital herpes has not been successful to date, although a live virus glycoprotein H-deficient (DISC) vaccine is currently in clinical trials. Recent data suggest that seronegative women are protected (albeit, not fully) by a glycoprotein D recombinant vaccine with adjuvant.

Despite the established safety and convenience of current treatment options, better suppressive options and topical treatment options are much needed. Studies using existing agents as potential tools to avoid Cesarean section, or transmission to neonate or partner are ongoing. Both vaccines and antivirals may eventually play a role in prevention of infection.

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References

  1. Sacks SL. Genital herpes simplex virus infection and treatment. In: Sacks SL, Straus SE, Whitley RA, et al., editors. Clinical management of herpes virus infections. Amsterdam: IOS Press, 1995: 55–74

    Google Scholar 

  2. Benedetti J, Corey L, Ashley R. Recurrence rates in genital herpes after symptomatic first-episode infection. Ann Intern Med 1994; 121: 847–54

    PubMed  CAS  Google Scholar 

  3. Schomogyi M, Wald A, Corey L. Herpes simplex virus-2 infection: an emerging disease? Infect Dis Clin North Am 1998; 12: 47–61

    Article  PubMed  CAS  Google Scholar 

  4. Fleming DT, McQuillan GM, Johnson RE, et al. Herpes simplex virus type 2 in the United States, 1976 to 1994. N Engl J Med 1997; 337: 1105–11

    Article  PubMed  CAS  Google Scholar 

  5. Johnson RE, Nahmias AT, Magder LS, et al. A seroepidemiologic survey of the prevalence of herpes simplex virus type 2 infection in the United States. N Engl J Med 1989; 321: 7–12

    Article  PubMed  CAS  Google Scholar 

  6. Mertz GJ, Benedetti J, Ashley R, et al. Risk factors for the sexual transmission of genital herpes. Ann Intern Med 1992; 116: 197–202

    PubMed  CAS  Google Scholar 

  7. Schaeffer HJ, Beauchamp L, de Miranda P, et al. 9-(2-hydroxyethoxymethyl)guanine activity against viruses of the herpes group. Nature 1978; 272: 583–5

    Article  PubMed  CAS  Google Scholar 

  8. Fyfe JA, Keller PM, Funnan PA, et al. Thymidine kinase from herpes simplex virus phosphorylates the new antiviral com-pound, 9-(2-hydroxyethoxymethyl)guanine. JBiol Chem 1978; 253: 8721–7

    CAS  Google Scholar 

  9. Derse D, Cheng Y-C, Funnan PA, et al. Inhibition of purified human and herpes simplex virus-induced DNA polymerases by 9-(2-hydroxyethoxyinethyl)guanine triphosphate: effects on primer-template function. JBiol Chem 1981;256: 11447–51

    CAS  Google Scholar 

  10. Funnan PA, St Clair MH, Spector T. Acyclovir triphosphate is a suicide inactivator of the herpes simplex virus DNA polymerase. J Biol Chem 1984; 259: 9575–9

    Google Scholar 

  11. Elion GB, Furman PA, Fyfe JA, et al. Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl)guanine. Proc Nat Acad Sci U S A 1977; 74: 5716–20

    Article  CAS  Google Scholar 

  12. de Miranda P, Blum MR. Pharmacokinetics of acyclovir after intravenous and oral administration. J Antimicrob Chemother 1983; 12 Suppl. B: 29–37

    Article  PubMed  Google Scholar 

  13. Burnette TC, de Miranda P. Metabolic disposition of the acyclovir prodrug valaciclovir in the rat. Drug Metab Dispos 1994; 22: 60–4

    PubMed  CAS  Google Scholar 

  14. Burnette TC, de Miranda P. Purification and characterization of an enzyme from rat liver that hydrolyzes 25 GU 87, the L-valyl ester prodrug of acyclovir [abstract]. Antiviral Res 1993; 20 Suppl. 1: 119

    Google Scholar 

  15. de Miranda P, Burnette TC. Metabolism and phannacokinetics of the acyclovir prodrug BW 256U 87 in cynomolgus monkeys [abstract]. Antiviral Res 1992; 17 Suppl. 1: 53

    Article  Google Scholar 

  16. Soul-Lawton J, Seaber E, On N, et al. Absolute bioavailability and metabolic disposition of valaciclovir, the L-valyl ester of acyclovir, following oral administration to humans. Antimicrob Agents Chemother 1995; 39: 2759–64

    Article  PubMed  CAS  Google Scholar 

  17. Weiler S, Blum MR, Doucette M, et al. Phannacokinetics of the acyclovir pro-drug valaciclovir after escalating single-dose and multiple-dose administration to normal volunteers. Clin Pharmacol Ther 1993; 54: 595–605

    Article  Google Scholar 

  18. Weller S, Blum MR, Smiley ML. Phase I phannacokinetics of the acyclovir prodrug, valaciclovir. Antiviral Res 1993; 20 Suppl. 1: 144

    Google Scholar 

  19. Wang LH, Schults M, Weiler S, et al. Phannacokinetics and safety of multiple-dose valaciclovir in geriatric volunteers with and without concomitant diuretic therapy. Antimicrob Agents Chemother 1996; 40: 80–5

    PubMed  CAS  Google Scholar 

  20. Spruance SL, Tyring SK, deGregorio B, et al. A large-scale, placebo-controlled, dose-ranging trial of peroral valaciclovir for episodic treatment of recurrent herpes genitalis. Arch Intern Med 1996; 156: 1729–35

    Article  PubMed  CAS  Google Scholar 

  21. Beutner KR, Friedman DJ, Forszpaniak C, et al. Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother 1995; 39: 1546–53

    Article  PubMed  CAS  Google Scholar 

  22. Patel R, Bodsworth NJ, Woolley P, et al. Valaciclovir for the suppression of recurrent genital HSV infection: a placebo-controlled study of once-daily therapy. Genitourin Med 1997; 73: 105–9

    PubMed  CAS  Google Scholar 

  23. Feinberg J, Hurwitz S, Cooper D, et al. A randomized, double-blind trial of valaciclovir prophylaxis for cytomegalovirus disease in patients with advanced human immunodeficiency virus infection. J Infect Dis 1998; 177: 48–56

    Article  PubMed  CAS  Google Scholar 

  24. Lowance D, Neumayer HH, Legendre CM, et al. Valacyclovir for the prevention of cytomegalovirus disease after renal transplantation. N Engl J Med 1999; 340: 1462–70

    Article  PubMed  CAS  Google Scholar 

  25. Vere Hodge RA, Cheng Y-C. The mode of action of penciclovir. Antiviral Chem Chemother 1993; 4 Suppl. 1: 13–24

    Google Scholar 

  26. Boyd MR, Bacon TH, Sutton D, et al. Antiherpesvirus activity of 9-(4-hydroxy-3-hydroxymethylbut-l-yl)guanine (BRL 39123) in cell culture. Antimicrob Agents Chemother 1987; 31: 1238–42

    Article  PubMed  CAS  Google Scholar 

  27. Vere Hodge RA. Famciclovir and penciclovir: the mode of action of famciclovir including its conversion to penciclovir. Antiviral Chem Chemother 1993; 4: 67–84

    CAS  Google Scholar 

  28. Pue MA, Benet LZ. Phannacokinetics of famciclovir in man. Antiviral Chem Chemother 1993; 4 Suppl. 1: 47–55

    CAS  Google Scholar 

  29. Earnshaw DL, Bacon TH, Darlison SJ, et al. Mode of anitivral action of penciclovir in MRC-5 cells infected cells with herpes simplex virus type-1 (HSV-1), HSV-2, and varicella-zoster virus. Antimicrob Agents Chemother 1992; 36: 2747–57

    Article  PubMed  CAS  Google Scholar 

  30. Vere Hodge RA, Sutton D, Boyd MR, et al. Selection of an oral prodrug (BRL42810; famciclovir) for the antiherpesvirus agent BRL 39123 [9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine; penciclovir]. Antimicrob Agents Chemother 1989; 33: 1765–73

    Article  PubMed  CAS  Google Scholar 

  31. Weinberg AA, Bate BJ, Masters HB. In vitro activities of penciclovir and acyclovir against herpes simplex virus types 1 and 2. Antimicrob Agents Chemother 1992; 36: 2037–8

    Article  PubMed  CAS  Google Scholar 

  32. Chatis PA, Crumpacker CS. Resistance of herpesvirus to antiviral drugs. Antimicrob Agents Chemother 1992; 36: 1589–95

    Article  PubMed  CAS  Google Scholar 

  33. Field HJ, Tewari D, Sutton D, et al. Comparison of efficacies of famciclovir and valaciclovir against herpes simplex virus type 1 in a murine immunosuppression model. Antimicrob Agents Chemother 1995; 39: 1114–9

    Article  PubMed  CAS  Google Scholar 

  34. Field HJ, Thackray AM. The effects of delayed-onset chemotherapy using famciclovir or valaciclovir in a murine immunosuppression model for HSV-1. Antiviral Chem Chemother 1995; 6: 210–6

    CAS  Google Scholar 

  35. Thackwray AM, Field HJ. Differential effects of famciclovir and valaciclovir on the pathogenesis of herpes simplex virus in a murine infection model including reactivation from latency. J Infect Dis 1996; 173: 291–9

    Article  Google Scholar 

  36. Saltzman R, Jurewicz R, Boon R. Safety of famciclovir in patients with herpes zoster and genital herpes. Antimicrob Agents Chemother 1994; 38: 2454–7

    Article  PubMed  CAS  Google Scholar 

  37. Daniels S, Schentag JJ. Drug interaction studies and safety of famciclovir in healthy volunteers: a review. Antiviral Chem Chemother 1993; 4 Suppl. 1: 57–64

    CAS  Google Scholar 

  38. Fowles SE, Pue MA, Pierce D, et al. Pharmacokinetics of penciclovir in healthy elderly subjects following a single oral administration of 750mg famciclovir [abstract]. Br J Clin Pharmacol 1992; 34: 450P

    Google Scholar 

  39. Fowles SE, Pierce DM, Prince WT, et al. Effect of food on bioavailability and pharmacokinetics of penciclovir, a novel antiherpes agent, following oral administration of the prodrug, famciclovir [abstract]. Br J Clin Pharmacol 1990; 29: 620P-1

    Google Scholar 

  40. Fowles SE, Fairless AJ, Pierce DM, et al. A further study of the effect of food on the bioavailability and pharmacokinetics of penciclovir after oral administration of famciclovir [abstract]. Br J Clin Pharmacol 1991; 32: 657P

    Google Scholar 

  41. Bryson YJ, Dillon M, Lovett M, et al. Treatment of first episodes of genital herpes simplex virus infection with oral acyclovir: a randomized double-blind controlled trial in normal subjects. N Engl J Med 1983; 308: 916–21

    Article  PubMed  CAS  Google Scholar 

  42. Mertz GJ, Critchlow, CW, Benedetti J, et al. Double-blind placebo-controlled trials of oral acyclovir in first-episode genital herpes simplex virus infection. JAMA 1984; 252: 1147–51

    Article  PubMed  CAS  Google Scholar 

  43. Mindel A, Adler MW, Sutherland S, et al. Intravenous acyclovir treatment for primary genital herpes. Lancet 1982; I: 697–700

    Article  Google Scholar 

  44. Corey L, Fife K, Benedetii JK, et al. Intravenous acyclovir for the treatment of primary genital herpes. Ann Intern Med 1983; 98: 914–21

    PubMed  CAS  Google Scholar 

  45. Wald A, Benedetti J, Davis G, et al. A randomized, double-blind, comparative trial comparing high-and standard-dose oral acyclovir for first-episode genital herpes infections. Antimicrob Agents Chemother 1994; 38: 174–6

    Article  PubMed  CAS  Google Scholar 

  46. Fife KH, Barabarash RA, Rudolph T, et al. Valaciclovir versus acyclovir in the treatment of first-episode genital herpes infection: results of an international, multicenter, double-blind, randomized clinical trial. Sex Transm Dis 1997; 24: 481–6

    Article  PubMed  CAS  Google Scholar 

  47. Murphy SM, Ruck F, Kitchin VS, et al. Oral famciclovir (FCV) a new antiherpes agent: comparative study with acyclovir in clinic initiated treatment of first episode genital herpes (FGH) [abstract]. The 2nd Congress of the European Acadamy of Dermatology and Venereology (EADV): 1991; Athens

  48. Loveless M, Sacks SL, Harris JRW. Famciclovir in the management of first-episode genital herpes. Infect Dis Clin Prac 1997; 6 (1 Suppl.): S12–16

    Article  Google Scholar 

  49. Reichman RC, Badger GJ, Mertz GJ, et al. Treatment of recurrent genital herpes simplex infections with oral acyclovir: a controlled trial. JAMA 1984; 251: 2103–7

    Article  PubMed  CAS  Google Scholar 

  50. Salo AP, Lassus A, Hovi T, et al. Double-blind placebo controlled trial of oral acyclovir in recurrent genital herpes. Eur J Sex Transm Dis 1983; 1: 95–8

    Google Scholar 

  51. Ruhnet-Forsbeck M, Sandstrom E, Andersson B, et al. Treatment of recurrent genital herpes simplex infections with oral acyclovir. J Antimicrob Chemother 1985; 16: 621–8

    Article  Google Scholar 

  52. Tyring SK, Douglas JM, Corey, L, et al. Arandomized, placebo-controlled comparison of oral valacyclovir and acyclovir in immunocompetent patients with recurrent genital herpes infections. Arch Dermatol 1998; 134: 185–91

    Article  PubMed  CAS  Google Scholar 

  53. Centers for Disease Control and Prevention. Guidelines for treatment of sexually transmitted diseases: MMWR 47 (RR-1); 1–118 [online]. Available from: URL: http://aepo-xdv-www.epo.cdc.gov/wonder/prevguid/p0000480/entire.htm [Accessed 2000 Aug 22]

  54. Luby JP, Gnann Jr JW, Alexander WJ, et al. A collaborative study of patient-initiated treatment of recurrent genital herpes with topical acyclovir or placebo. J Infect Dis 1984; 150: 1–6

    Article  PubMed  CAS  Google Scholar 

  55. Corey L, Nahmias AJ, Guinan ME, et al. A trial of topical acyclovir in genital herpes simplex virus infections. N Engl J Med 1982; 306: 1313–9

    Article  PubMed  CAS  Google Scholar 

  56. Reichman RC, Badger GJ, Guinan ME, et al. Treatment of recurrent genital herpes simplex genitalis: a controlled trial. J Infect Dis 1983; 147: 336–40

    Article  PubMed  CAS  Google Scholar 

  57. Leone PA, Trottier S, Miller JM. A comparison of oral valaciclovir 500mg twice daily for three or five days in the treatment of recurrent genital herpes [abstract no. 22.012]. Abstracts from the 8th International Congress on Infectious Diseases: 1998 May 15–18; Boston (MA)

  58. Bodsworth NJ, Crooks RJ, Berell S, et al. Valaciclovir versus aciclovir in patient initiated treatment of recurrent genital herpes: a randomised, double-blind trial. Genitourin Med 1997; 73: 110–60

    PubMed  CAS  Google Scholar 

  59. Sacks SL, Aoki FY, Diaz-Mitoma F, et al. Patient-initiated, twice daily oral famciclovir for early recurrent genital herpes: a randomized, double-blind multicenter trial. JAMA 1996; 276: 44–9

    Article  PubMed  CAS  Google Scholar 

  60. Sacks SL, Martel A, Aoki F, et al. Early, clinic-initiated treatment of recurrent genital herpes using famciclovir: results of a Canadian, multicentre study [abstract]. ClinRes 1994; 42: 300A

    Google Scholar 

  61. Sacks SL, Aoki FY, Diaz-Mitoma F, et al. Reply to: Goldman BD. Famciclovir for genital herpes. JAMA 1997; 277: 210–1

    Google Scholar 

  62. Douglas JM, Critchlow C, Benedetti J, et al. A double-blind study of oral aciclovir for suppression of recurrences of genital herpes simplex virus infection. N Engl J Med 1984; 310: 1151–6

    Article  Google Scholar 

  63. Mindel A, Flaherty A, Carney O, et al. Dosage and safety of long-term suppressive aciclovir therapy for recurrent genital herpes. Lancet 1988; I: 926–8

    Article  Google Scholar 

  64. Mertz GJ, Jones CC, Mills J. Long-term aciclovir suppression of frequently recurring genital herpes simplex virus infection. JAMA 1988; 260: 201–6

    Article  PubMed  CAS  Google Scholar 

  65. Straus SE, Takiff HE, Seidlin M, et al. Suppression of frequently recurring genital herpes: a placebo-controlled double-blind trial of oral acyclovir. N Engl J Med 1984; 310: 1545–50

    Article  PubMed  CAS  Google Scholar 

  66. Mertz GJ, Eron L, Goldberg L, et al. Prolonged continuous versus intermittent oral aciclovir treatment in normal adults with frequently recurring genital herpes simplex virus infection. Am J Med 1988; 85: 14–9

    PubMed  CAS  Google Scholar 

  67. Goldberg LH, Kaufman R, Kurtz TO, et al. Long-term suppression of recurrent genital herpes with acyclovir: a 5-year benchmark. Arch Dermatol 1993; 129: 582–7

    Article  PubMed  CAS  Google Scholar 

  68. Perrin L, Hirscel B. Combination therapy in primary HIV infection. Antiviral Res 1996; 29: 87–9

    Article  PubMed  CAS  Google Scholar 

  69. Kaplowitz LG, Baker D, Gelb L, et al. Prolonged continuous acyclovir treatment of normal adults with frequently recurring genital herpes simplex virus infection. JAMA 1991; 265: 747–51

    Article  PubMed  CAS  Google Scholar 

  70. Straus SE, Croen KD, Sawyer MH, et al. Acyclovir suppression of frequently recurring genital herpes: efficacy and diminishing need during successive years of treatment. JAMA 1988; 260: 2227–30

    Article  PubMed  CAS  Google Scholar 

  71. Carney O, Ross E, Ikkos G, et al. The effect of suppressive acyclovir on the psychological morbidity associated with recurrent genital herpes. Genitourin Med 1993; 69: 457–9

    PubMed  CAS  Google Scholar 

  72. Reitano M, Tyring S, Lang W, et al. Valaciclovir for the suppression of recurrent genital herpes simplex virus infection: a large-scale dose range-finding study. J Infect Dis 1998; 178: 603–10

    Article  PubMed  CAS  Google Scholar 

  73. Mertz GJ, Loveless MO, Levin MJ, et al. Oral famciclovir for the suppression of recurrent genital herpes simplex virus infection in women: a multicenter, double-blind, placebo-controlled trial. Arch Intern Med 1997; 157: 343–9

    Article  PubMed  CAS  Google Scholar 

  74. Diaz-Mitoma F, Sibbald RG, Sharon SD, et al. Oral famciclovir for the suppression of recurrent genital herpes: a randomized controlled trial. JAMA 1998; 280: 887–92

    Article  PubMed  CAS  Google Scholar 

  75. Mertz GJ, Schmidt D, Jourden JL, et al. Frequency of acquisition of first-episode genital infection with herpes simplex virus from symptomatic and asymptomatic source contacts. Sex Transm Dis 1985; 12: 33–9

    Article  PubMed  CAS  Google Scholar 

  76. Wald A, Zeh J, Barnum G, et al. Suppression of subclinical shedding of herpes simplex virus type 2 with acyclovir. Ann Intern Med 1996; 124: 8–15

    PubMed  CAS  Google Scholar 

  77. Diaz-Mitoma F, Ruben M, Sacks S, et al. Detection of viral DNA to evaluate outcome of antiviral treatment of patients with recurrent genital herpes. J Clin Microbiol 1996; 34: 657–63

    PubMed  CAS  Google Scholar 

  78. Sacks SL, Hughes A, Rennie B, et al. Famciclovir for suppression of asymptomatic and symptomatic recurrent genital herpes shedding: a randomised, double-blind, double dummy, parallel group, placebo-controlled trial [abstract no. H-73]. Abstracts of the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy: 1997; 1997 Sep 28–Oct 1; Toronto

  79. Sacks SL, Shafran SD. BID Famciclovir suppression of asymptomatic genital herpes simplex virus shedding in men [abstract no. H-12]. Abstracts of the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy: 1998 Sep 24–27; San Diego (CA)

  80. Schacker T, Hu H, Koelle DM, et al. Famciclovir for the suppression of symptomatic and asymptomatic herpes simplex virus reactivation in HIV-infected persons. Ann Intern Med 1998; 128: 21–8

    PubMed  CAS  Google Scholar 

  81. Wald A, Warren T, Hu H, et al. Suppression of subclinical shedding of herpes simplex virus type 2 in the genital tract with valaciclovir [abstract no. H-82]. Abstracts of the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy: 1998 Sep 24–27; San Diego (CA)

  82. Straus SE, Seidlin M, Takiff HE, et al. Effect of oral acyclovir treatment on symptomatic and asymptomatic virus shedding in recurrent genital herpes. Sex Transm Dis 1989; 16: 107–13

    Article  PubMed  CAS  Google Scholar 

  83. Whitley RJ, Nahmias AJ, Vinistine AM, et al. The natural history of herpes simplex virus infection of mother and newborn. Pediatrics 1980; 66: 489–94

    PubMed  CAS  Google Scholar 

  84. Stone KM, Brooks CA, Guinan ME, et al. National surveillance for neonatal herpes simplex virus infections. Sex Transm Dis 1989; 16: 152–6

    Article  PubMed  CAS  Google Scholar 

  85. Brown ZA, Benedetti J, Ashley RL, et al. Neonatal herpes simplex virus infection in relation to asymptomatic maternal infection at the time of labor. N Engl J Med 1991; 324: 1247–52

    Article  PubMed  CAS  Google Scholar 

  86. Whitley RJ, Arvin A, Prober C, et al. A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex virus infection. N Engl J Med 1991; 324: 444–9

    Article  PubMed  CAS  Google Scholar 

  87. Koutsky LA, Ashely RL, Holmes KK, et al. The frequency of unrecognised type 2 herpes simplex virus infection among women: implications for the control of genital herpes. Sex Transm Dis 1990; 17: 90–4

    Article  PubMed  CAS  Google Scholar 

  88. Brown ZA, Benedetti JK, Watts DH, et al. A comparison between detailed and simple histories in the diagnosis of genital herpes complicating pregnancy. Am J Obstet Gynecol 1995; 172: 1299–303

    Article  PubMed  CAS  Google Scholar 

  89. Brown ZA, Vontver LA, Benedetti J, et al. Genital herpes during pregnancy: risk factors associated with recurrences and asymptomatic shedding. Am J Obstet Gynecol 1985; 153: 24–30

    PubMed  CAS  Google Scholar 

  90. Brown ZA, Selke S, Zeh J, et al. The acquisition of herpes simplex virus during pregnancy. N Engl J Med 1997; 337: 509–15

    Article  PubMed  CAS  Google Scholar 

  91. Prober CG, Sullender WM, Yasukawa LL, et al. Low risk of herpes simplex virus infections in neonates exposed to the virus at the time of vaginal delivery to mothers with recurrent genital herpes simplex virus infections. N Engl J Med 1987; 316: 240–4

    Article  PubMed  CAS  Google Scholar 

  92. Prober CG, Corey L, Brown ZA, et al. The management of pregnancies complicated by genital infections with herpes simplex virus. Clin Infect Dis 1992; 15: 1031–8

    Article  PubMed  CAS  Google Scholar 

  93. American College of Obstetricians and Gynecologists (ACOG). Perinatal herpes simplex virus infections. Washington (DC): ACOG Technical Bulletin, 1988: 122

    Google Scholar 

  94. Roberts SW, Cox SM, Dax J, et al. Genital herpes during pregnancy: no lesions, no cesarean. Obstet Gynecol 1995; 85: 261–4

    Article  PubMed  CAS  Google Scholar 

  95. Haddad J, Langer B, Astruc D, et al. Oral acyclovir and recurrent genital herpes during late pregnancy. Obstet Gynecol 1993; 82: 102–4

    PubMed  CAS  Google Scholar 

  96. Scott LL, Sanchez PJ, Jackson GL, et al. Acyclovir suppression to prevent cesarean delivery after first-episode genital herpes. Obstet Gynecol 1996; 87: 69–73

    Article  PubMed  CAS  Google Scholar 

  97. Brocklehurst P, Kinghorn G, Carney O, et al. A randomised placebo controlled trial of suppressive acyclovir in late pregnancy in women with recurrent genital herpes infection. Br J Obstet Gynaecol 1998; 105: 275–80

    Article  PubMed  CAS  Google Scholar 

  98. Stray-Pedersen B. Acyclovir in late pregnancy to prevent neonatal herpes simplex [letter]. Lancet 1990; 336: 756

    Article  PubMed  CAS  Google Scholar 

  99. Andrews EB, Yankaskas BC, Cordero JF, et al. Acyclovir in pregnancy registry: six years experience. N Engl J Med 1992; 79: 7–13

    CAS  Google Scholar 

  100. Kimberlin D, Powell D, Gruber W, et al. Administration of oral acyclovir suppressive therapy after neonatal herpes simplex virus disease limited to the skin, eyes, and mouth: results of a Phase I/II trial. Pediatr Infect Dis J 1996; 15: 247–54

    Article  PubMed  CAS  Google Scholar 

  101. Kimberlin DF, Weiler S, Whitiey RJ, et al. Pharmacokinetics of oral valacyclovir and acyclovir in late pregnancy. Am J Obstet Gynecol 1998; 179: 846–51

    Article  PubMed  CAS  Google Scholar 

  102. Parris D, Harrington JE. Herpes simplex virus variants resistant to high concentrations of acyclovir exist in clinical isolates. Antimicrob Agents Chemother 1982; 22: 71–7

    Article  PubMed  CAS  Google Scholar 

  103. Crumpacker CS, Schnipper LE, Marlowe SI, et al. Resistance to antiviral drugs of herpes simplex virus isolated from a patient treated with acyclovir. N Engl J Med 1982; 306: 343–6

    Article  PubMed  CAS  Google Scholar 

  104. Burns WH, Saral R, Santos GW, et al. Isolation and characterisation of resistant herpes simplex virus after acyclovir therapy. Lancet 1982; I: 421–3

    Article  Google Scholar 

  105. Wade JC, McLaren C, Meyers JD. Frequency and significance of acyclovir-resistant herpes simplex virus isolated from marrow transplant patients receiving multiple courses of treatment with acyclovir. J Infect Dis 1983; 148: 1077–82

    Article  PubMed  CAS  Google Scholar 

  106. Erlich KS, Mills J, Chatis P, et al. Acyclovir-resistant herpes simplex virus infections in patients with the acquired immunodeficiency syndrome. N Engl J Med 1989; 320: 293–6

    Article  PubMed  CAS  Google Scholar 

  107. Englund JA, Zimmerman ME, Swierkosz EM, et al. Herpes simplex virus resistant to acyclovir: a study in a tertiary care centre. Ann Intern Med 1990; 112: 416–22

    PubMed  CAS  Google Scholar 

  108. Christophers J, Clayton J, Craske J, et al. Survey of resistance of herpes simplex virus to acyclovir in northwest England. Antimicrob Agents Chemother 1998; 42: 868–72

    PubMed  CAS  Google Scholar 

  109. Nugier F, Colin JN, Aymard M, et al. Occurrence and characterization of acyclovir-resistant herpes simplex virus isolates: report on a two-year sensitivity screening survey. J Med Virol 1992; 36: 1–12

    Article  PubMed  CAS  Google Scholar 

  110. Reusser P, Cordonnier C, Einsele H, et al. European survey of herpesvirus resistance to antiviral drugs in bone marrow transplant recipients. Bone Marrow Transplant 1996; 17: 813–7

    PubMed  CAS  Google Scholar 

  111. Darville JM, Ley BE, Roome APCH, et al. Acyclovir-resistant herpes simplex virus infections in a bone marrow transplant population. Bone Marrow Transplant 1998; 22: 587–9

    Article  PubMed  CAS  Google Scholar 

  112. Kost RG, Hill EL, Tigges M, et al. Brief report: recurrent acyclovir-resistant genital herpes in an immunocompetentpatient. N Engl J Med 1993; 329: 1777–82

    Article  PubMed  CAS  Google Scholar 

  113. Pottage Jr JC, Kessler KA. Herpes simplex virus resistance to acyclovir: clinical relevance. Infect Agents Dis 1995; 4: 115–24

    PubMed  CAS  Google Scholar 

  114. Jones TJ, Paul P. Disseminated acyclovir-resistant herpes simplex virus type 2 treated successfully with foscarnet. J Infect Dis 1995; 171: 508–9

    Article  PubMed  CAS  Google Scholar 

  115. Darby G, Field HJ. Altered substrate specificity of herpes simplex virus thymidine kinase confers acyclovir-resistance. Nature 1981; 289: 81–3

    Article  PubMed  CAS  Google Scholar 

  116. Field HJ. Persistent herpes simplex virus infections and mechanisms of virus drug resistance. Eur J Clin Microbiol Infect Dis 1989; 8: 671–80

    Article  PubMed  CAS  Google Scholar 

  117. Hill EL, Hunter GA, Ellis MN. In vitro and in vivo characterization of herpes simplex virus clinical isolates recovered from patients infected with human immunodeficiency virus. Antimicrob Agents Chemother 1991; 35: 2322–8

    Article  PubMed  CAS  Google Scholar 

  118. Chatis PA, Crumpacker CS. Analysis of the thymidine kinase gene from clinically isolated acyclovir-resistant herpes simplex viruses. Virology 1991; 180: 793–7

    Article  PubMed  CAS  Google Scholar 

  119. Sasadeusz JJ, Sacks SL. Spontaneous reactivation of thymidine kinase-deficient, acyclovir-resistant type 2 herpes simplex virus: masked heterogeneity or reversion? J Infect Dis 1996; 174: 476–82

    Article  PubMed  CAS  Google Scholar 

  120. Parker AC, Craig JIO, Collins P, et al. Acyclovir-resistant herpes simplex virus infection due to altered DNA polymerase [letter]. Lancet 1987; II: 1461

    Article  Google Scholar 

  121. Sacks SL, Wanklin RJ, Reece DE, et al. Progressive esophagitis from acyclovir-resistant herpes simplex: clinical roles for DNA polymerase mutants and viral heterogeneity. Ann Intern Med 1989; 111: 893–9

    PubMed  CAS  Google Scholar 

  122. Blower SM, Porco TC, Darby G. Predicting and preventing the emergence of antiviral drug resistance in HSV-2. Nat Med 1998; 4: 673–8

    Article  PubMed  CAS  Google Scholar 

  123. Helgstrand E, Eriksson B, Johansson NG, et al. Trisodium phosphonoformate, a new antiviral compound. Science 1978; 201: 819–21

    Article  PubMed  CAS  Google Scholar 

  124. Wagstaff AJ, Bryson HM. Foscarnet: a reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic use in immunocompromised patients with viral infections. Drugs 1994; 48: 199–226

    Article  PubMed  CAS  Google Scholar 

  125. Balfour H, Benson C, Braun J, et al. Management of acyclovir-resistant herpes simplex and varicella-zoster virus infections. J AIDS 1994; 7: 254–60

    Google Scholar 

  126. Chatis M, Schrager LE, Crumpacker CS. Successful treatment with foscarnet of an acyclovir-resistant mucocutaneous infection with herpes simplex virus in a patient with acquired immune deficiency syndrome. N Engl J Med 1989; 320: 297–300

    Article  PubMed  CAS  Google Scholar 

  127. Jacobson MA. Review of the toxicities of foscarnet. J AIDS 1992; 5 Suppl. 1: S11–17

    Google Scholar 

  128. Wallin J, Lernestedt J, Ogenstad S, et al. Topical treatment of recurrent genital herpes infections with foscarnet. Scand J Infect Dis 1985; 17: 165–72

    PubMed  CAS  Google Scholar 

  129. Barton S, Munday P, Kinghorn G, et al. Topical treatment of recurrent genital herpes simplex virus infections with trisodium phosphonoformate (foscarnet): double blind, placebo controlled, multicentre study. Genitourin Med 1986; 62: 247–50

    PubMed  CAS  Google Scholar 

  130. Swetter SM, Hill EL, Kern ER, et al. Chronic vulvar ulceration in an immunocompetent woman due to acyclovir-resistant, thymidine kinase-deficient herpes simplex virus. J Infect Dis 1998; 177: 543–50

    Article  PubMed  CAS  Google Scholar 

  131. Sacks SL, Reece DE, Galloway P, et al. Acyclovir (ACV) resistance in herpes simplex virus (HSV) isolates from a patient with esophagitis: a thymadine kinase (TK) positive, foscarnet (PFA) resistant strain with response to intravenous PFA. 27th Interscience Conference on Antimicrobial Agents and Chemotherapy: 1987 Oct 4–7; New York (NY)

  132. Chatis PA, Miller CH, Schrager LE, et al. Successful treatment with foscarnet of an acyclovir-resistant mucocutaneous infection with herpes simplex virus in a patient with acquired immunodeficiency syndrome. N Engl J Med 1989; 320: 297–300

    Article  PubMed  CAS  Google Scholar 

  133. Vinckier F, Boogaerts M, De Clerck D, et al. Chronic herpetic infection in an immunocompromised patient: report of a case. J Oral Maxillofac Surg 1987; 45: 723–8

    Article  PubMed  CAS  Google Scholar 

  134. Youle MM, Hawkins DA, Collins P, et al. Acyclovir-resistant herpes in AIDS treated with foscarnet. Lancet 1988; II: 341–2

    Article  Google Scholar 

  135. Safrin S. Treatment of acyclovir-resistant herpes simplex virus infections in patients with AIDS. J AIDS 1992; 5 Suppl. 1: S29–32

    Google Scholar 

  136. Safrin S, Assaydeen T, Follansbee S, et al. Foscarnet therapy for acyclovir-resistant mucocutaneous herpes simplex virus infection in 26 AIDS patients: preliminary data. J Infect Dis 1990; 161: 1078–84

    Article  PubMed  CAS  Google Scholar 

  137. Safrin S, Crumpacker C, Chatis P, et al. A controlled trial comparing foscarnet with vidarabine for acyclovir-resistant mucocutaneous herpes simplex in the acquired immunodeficiency syndrome. N Engl J Med 1991; 325: 551–5

    Article  PubMed  CAS  Google Scholar 

  138. Birch CJ, Tachedjian G, Doherty RR, et al. Altered sensitivity to antiviral drugs of herpes simplex virus isolates from a patient with the acquired immunodeficiency syndrome. J Infect Dis 1990; 161: 731–4

    Article  Google Scholar 

  139. Safrin S, Kemmerly S, Plotkin B, et al. Foscarnet-resistant herpes simplex virus infection in patients with AIDS. J Infect Dis 1994; 169: 193–6

    Article  PubMed  CAS  Google Scholar 

  140. Snoeck R, Andrei G, Gerard M, et al. Successful treatment of progressive mucocutaneous infection due to acyclovir-and foscarnet-resistant herpes simplex virus with (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC). Clin Infect Dis 1994; 18: 570–8

    Article  PubMed  CAS  Google Scholar 

  141. Safrin S, Elbeik T, Phan L, et al. Correlation between response to acyclovir and foscarnet therapy and in vitro susceptibility results for isolates of herpes simplex virus from human immunodeficiency virus-infected patients. Antimicrob Agents Chemother 1994; 38: 1246–50

    Article  PubMed  CAS  Google Scholar 

  142. Ho HT, Woods KL, Bronson JJ, et al. Intracellular metabolism of the antiherpes agent 1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine. Mol Pharmacol 1992; 41: 197–202

    PubMed  CAS  Google Scholar 

  143. Cihlar T, Votruba I, Hoska K, et al. Metabolism of (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]-cytosine (HPMPC) in human embryonic lung cells. Collect Czech Chem Commun 1992; 57: 661–72

    Article  CAS  Google Scholar 

  144. Jones RJ, Bischofberger NJ. Minireview: nucleotide prodrugs. Antiviral Res 1995; 27: 1–17

    Article  PubMed  CAS  Google Scholar 

  145. Andrei G, Snoeck R, Goubau P, et al. Comparative activity of various compounds against clinical strains of herpes simplex virus. Eur J Clin Microbiol Infect Dis 1992; 11: 143–51

    Article  PubMed  CAS  Google Scholar 

  146. De Clerq E, Holy A. Efficacy of (S)-2-(3-hydroxy-2-phosphonyl-methoxy propyl)cytosine in various models of herpes simplex virus infection in mice. Antimicrob Agents Chemother, 1991; 35: 701–6

    Article  Google Scholar 

  147. Lalezari JP, Drew WL, Glutzer E, et al. Treatment with intravenous (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine of acyclovir-resistant mucocutaneous infection with herpes simplex virus inapatient with AIDS. J Infect Dis 1994; 170: 570–2

    Article  PubMed  CAS  Google Scholar 

  148. Snoeck R, Andrei G, de Clerq E, et al. A new topical treatment for resistant herpes simplex infections. N Engl J Med 1993; 329: 968–9

    Article  PubMed  CAS  Google Scholar 

  149. Mendel DB, Barkhimer DB, Chen MS. Biochemical basis for increased susceptibility to cidofovir of herpes simplex viruses with altered or deficient thymidine kinase activity. Antimicrob Agents Chemother 1995; 39: 2120–2

    Article  PubMed  CAS  Google Scholar 

  150. Talarico C, Stanet S, Lambe C, et al. Mode of action studies on the anti-cytomegalovirus nucleoside analog [l-(2-hydroxy-1-hydroxymethyl)ethyoxy-methyl)cytosine] (abstract no. 92). Antiviral Res 1990; S1: 87

    Google Scholar 

  151. Merta A, Votruba I, Rosenberg I, et al. Inhibition of herpes simplex virus DNA polymerase by diphosphates of acyclic phosphonylmethyoxalkyl nucleotide analogues. Antiviral Res 1990; 13: 209–18

    Article  PubMed  CAS  Google Scholar 

  152. Neyts J, Snoeck R, Schols D, et al. Selective inhibition of human cytomegalovirus DNA synthesis by (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine [(S)-HPMPC] and 9-(1,3-dihydorxy-2-propoxymethyl)guanine (DHPG)). Virology 1990; 179: 41–50

    Article  PubMed  CAS  Google Scholar 

  153. Naesens L, Snoeck R, Andrei G, et al. HPMPC (cidofovir), PMEA (adefovir) and related acyclic nucleoside phosphonate analogues: a review of their pharmacology and clinical potential in the treatment of viral infections. Antiviral Chem Chemother 1997; 8: 1–23

    CAS  Google Scholar 

  154. Bravo FJ, Stanberry LR, Kier AB, et al. Evaluation of HPMPC therapy for primary and recurrent genital herpes in mice and guinea pigs. Antiviral Res 1993; 21: 59–72

    Article  PubMed  CAS  Google Scholar 

  155. Palmer J, Vogt PE, Kern ER. Prevention and treatment of experimental genital herpes simplex virus type 2 (HSV-2) infections with topical HPMPC [abstract no. 205]. Antiviral Res 1995; 26: A334

    Google Scholar 

  156. Aduma PP, Connelly MC, Srinivas RV, et al. Metabolic diversity and antiviral activities of acyclic nucleoside phosphonates. Mol Pharmacol 1995; 47: 816–22

    PubMed  CAS  Google Scholar 

  157. Cundy KC, Petty BG, Flaherty J, et al. Clinical pharmacokinetics of cidofovir in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother 1995; 39: 1247–52

    Article  PubMed  CAS  Google Scholar 

  158. Wachsman M, Petty BG, Cundy KC, et al. Pharmacokinetics, safety and bioavailability of HPMPC (cidofovir) in human immunodeficiency virus-infected subjects. Antiviral Res 1996; 29: 153–61

    Article  PubMed  CAS  Google Scholar 

  159. Lalezari J, Schacker T, Feinberg J, et al. A randomized, doubleblind, placebo-controlled trial of cidofovir gel for the treatment of acyclovir-unresponsive mucocutaneous herpes simplex virus infection in patients with AIDS. J Infect Dis 1997; 176: 892–8

    Article  PubMed  CAS  Google Scholar 

  160. Sacks SL, Shafran SD, Diaz-Mitoma F, et al. A multicenter phase I/II dose escalation study of single-dose cidofovir gel for treatment of recurrent genital herpes. Antimicrob Agents Chemother 1998; 42: 2996–9

    PubMed  CAS  Google Scholar 

  161. Colin J, Malet F, Chastel C, et al. Use of collagen shields in the treatment of herpetickeratitis. Curr Eye Res 1991; 10: 189–91

    Article  PubMed  Google Scholar 

  162. Murphy M, Morley A, Eglin RP, et al. Topical trifluridine for mucocutaneous acyclovir-resistant herpes simplex II in AIDS patient [letter]. Lancet 1992; 340: 1040

    Article  PubMed  CAS  Google Scholar 

  163. Weaver D, Weissbach N, Kapell K, et al. Topical trifluridine treatment of acyclovir-resistant herpes simplex disease [abstract no. 507]. 31st Interscience Conference on Antimicrobial Agents and Chemotherapy: 1991 Sep 29–Oct 2; Chicago (IL)

  164. Birch CJ, Tyssen DP, Tachedjian G, et al. Clinical effects and in vitro studies of trifluorothymidine combined with interferon-alpha for treatment of drug-resistant and -sensitive herpes simplex virus infections. J Infect Dis 1992; 166: 108–12

    Article  PubMed  CAS  Google Scholar 

  165. Chatterjee S, Hunter E, Whitley R. Effect of cloned human interferons on protein synthesis and morphogenesis of herpes simplex virus. J Virol 1985; 56: 419–25

    PubMed  CAS  Google Scholar 

  166. Overall JC, Yeh TJ, Kern ER. Sensitivity of herpes simplex virus 1 and 2 to three preparations of human interferon. J Infect Dis 1980; 142: 943

    Article  PubMed  Google Scholar 

  167. Lebwohl M, Gordon M, Conant M, et al. Recombinant α-2 interferon in the treatment of recurrent herpes genitalis [abstract]. J Invest Dermatol 1987; 88: 505

    Google Scholar 

  168. Shupack J, Stiller M, Knobler E, et al. Topical alpha-interferon in recurrent genital herpes simplex infection: a double-blind, placebo-controlled clinical trial. Dermatologica 1990; 181: 134–8

    Article  PubMed  CAS  Google Scholar 

  169. Shupack J, Stiller M, Davis I, et al. Topical alpha-interferon ointment with dimethyl sulfoxide in the treatment of recurrent genital herpes simplex. Dermatology 1992; 184: 40–4

    Article  PubMed  CAS  Google Scholar 

  170. Vonka V, Petrovska P, Borecky L, et al. Increased effects of topically applied interferon in herpes simplex virus-induced lesions by caffeine. Acta Virol 1995; 39: 125–30

    PubMed  CAS  Google Scholar 

  171. Eron LJ, Toy C, Salsitz B, et al. Therapy of genital herpes with topically applied interferon. Antimicrob Agents Chemother 1987; 31: 1137–9

    Article  PubMed  CAS  Google Scholar 

  172. Friedman-Kien AE, Klein RJ, Glaser RD, et al. Treatment of recurrent genital herpes with topical alpha interferon gel combined with nonoxynol 9. J Am Acad Dermatol 1986; 15: 989–94

    Article  PubMed  CAS  Google Scholar 

  173. Sacks SL, Varner TL, Davies KS, et al. Randomized, double-blind, placebo-controlled, patient-initiated study of topical high-and low-dose interferon-α with nonoxynol-9 in the treatment of recurrent genital herpes. J Infect Dis 1990; 161: 692–8

    Article  PubMed  CAS  Google Scholar 

  174. Lebwohl M, Sacks S, Conant M, et al. Recombinant alpha-2 interferon gel treatment of recurrent herpes genitalis. Antiviral Res 1992; 17: 235–43

    Article  PubMed  CAS  Google Scholar 

  175. Glezerman M, Cohen V, Movshovitz M, et al. Placebo-controlled trial of topical interferon in labial and genital herpes. Lancet 1988; I: 150–2

    Article  Google Scholar 

  176. Field AK, Tuomari AV, McGeever-Rubin B, et al. (+)-(lα,2b,3a)-9-[2,3-Bis (hydroxymethyl) cyclobutyl] guanine [(±)BHCG]: a potent and selective inhibitor of herpesviruses. Antiviral Res 1990; 13: 41–52

    Article  PubMed  CAS  Google Scholar 

  177. Kohlbrenner WE, Carter CD, Fesik SW, et al. Efficiency of phosphorylation of the Cyclobut-G (A-69992) enantiomers by HSV-1 thymidine kinase dose not correlate with their anti-herpesvirus activity. Biochem Pharmacol 1990; 40: R5–10

    Article  PubMed  CAS  Google Scholar 

  178. Koyano S, Suzutani T, Yoshida I, et al. Analysis of phosphorylation pathways of antiherpesvirus nucleosides by varicella-zoster virus-specific enzymes. Antimicrob Agents Chemother 1996; 40: 920–3

    PubMed  CAS  Google Scholar 

  179. Terry BJ, Cianci CW, Hagen ME. Inhibition of herpes simplex virus type 1 DNA polymerase by [1R(1α,2β,3α)-9-[2,3-bis(hydroxymethyl)cyclobutyl]guanine. Mol Pharmacol 1991; 40: 591–6

    PubMed  CAS  Google Scholar 

  180. Bisacchi GS, Braitman A, Cianci CW, et al. Synthesis and antiviral activity of enantiomeric forms of cyclobutyl nucleoside analogues. J Med Chem 1991; 34: 1415–21

    Article  PubMed  CAS  Google Scholar 

  181. Izuta S, Shimada N, Kitagawa M, et al. Inhibitory effects of triphosphate derivatives of oxetanocin G and related compounds on eukaryotic and viral DNA polymerases and human immunodeficiency virus reverse transcriptase. J Biochem 1992; 112: 81–7

    PubMed  CAS  Google Scholar 

  182. Yamanaka G, Tuomari AV, Hagen M, et al. Selective activity and cellular pharmacology of [1R-1α,2β,3α)-9-[2,3-bis-(hydroxymethyl)cyclobutyl]guanine in herpesvirus-infected cells. Mol Pharmacol 1991; 40: 446–53

    PubMed  CAS  Google Scholar 

  183. Braitman A, Swerdel MR, Olsen SJ, et al. Evaluation of SQ 34,514: pharmacokinetics and efficacy in experimental herpesvirus infections in mice. Antimicrob Agents Chemother 1991; 35: 1464–8

    Article  PubMed  CAS  Google Scholar 

  184. Tenney DJ, Yamanaka G, Voss SM, et al. Lobucavir is phosphorylated in human cytomegalovirus-infected and -uninfected cells and inhibits the viral DNA polymerase. Antimicrob Agents Chemother 1997; 41: 2680–5

    PubMed  CAS  Google Scholar 

  185. Yang H, Drain RL, Franco CA, et al. Efficacy of BMS-180194 against experimental cytomegalovirus infections in immunocompromised mice. Antiviral Res 1996; 29: 233–41

    Article  PubMed  CAS  Google Scholar 

  186. Yang H, Dalton J, Drain R, et al. Lobucavir (BMS-180194): a new herpesvirus topical agent effective against cutaneous infection in guinea pigs [abstract no. H117]. Abstracts of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy: 1996 Oct 17–20; New Orleans (LA)

  187. Petty BG, Saito H, Summerill RS, et al. Pharmacokinetics and bioavailability of cygalovir (BMS-180194) in asymptomatic HIV-and CMV-seropositive volunteers [abstract]. Antiviral Res 1994; 23 Suppl. 1: 18

    Google Scholar 

  188. Hellman N, DeHertogh D, Stewart M, et al. Sequential ascending multiple-dose safety and pharmacokinetic study of oral lobucavir (BMS-180194) in asymptomatic volunteers seropositive for HIV and CMV [abstract no. 133]. Antiviral Res 1995; 26: A296

    Google Scholar 

  189. Flaherty J, Lalezari J, Petty B, et al. Pharmacokinetics and safety of oral lobucavir in cytomegalovirus-infected HIV patients [abstract 302-S31]. 4th Conference on Retroviruses and Opportunistic Infections: 1997 Jan 22–26; Washington (DC)

  190. Safrin S, McKinley G, McKeough M, et al. Treatment of acyclovir-unresponsive cutaneous herpes simplex virus infection with topically applied SP-303. Antiviral Res 1994; 25: 185–92

    Article  PubMed  CAS  Google Scholar 

  191. Orozco-Topete R, Sierra-Madero J, Cano-Dominguez C, et al. Safety and efficacy of Virend for topical treatment of genital and anal herpes simplex lesions in patients with AIDS. Antiviral Res 1997; 37: 91–103

    Article  Google Scholar 

  192. De Clercq E, descamps J, Verhelst G, et al. Comparative efficacy of antiherpes drugs against different strains of herpes simplex virus. J Infect Dis 1980; 141: 563–74

    Article  PubMed  Google Scholar 

  193. Teh CZ, Sacks SL. Susceptibility of recent clinical isolates of herpes simplex virus to 5-ethyl-2’-deoxyuridine: preferential inhibition of herpes simplex virus type 2. Antimicrob Agents Chemother 1983; 23: 637–40

    Article  PubMed  CAS  Google Scholar 

  194. Schinazi RF, Scott RT, Peters J, et al. Antiviral activity of 5-ethyl-2’-deoxyuridine against herpes simplex viruses in cell culture, mice, and guinea pigs. Antimicrob Agents Chemother 1985; 28: 552–60

    Article  PubMed  CAS  Google Scholar 

  195. Spruance SL, Freeman DJ, Sheth NV. Comparison of topically applied 5-ethyl-2’-deoxyuridine and acyclovir in the treatment of cutaneous herpes simplex virus infection in guinea pigs. Antimicrob Agents Chemother 1985; 10: 103–6

    Article  Google Scholar 

  196. Sacks SL, Tyrrell LD, Lawee D, et al. Randomized, double-blind, placebo-controlled, clinic-initiated, Canadian multicenter trial of topical edoxudine 3.0% cream in the treatment of recurrent genital herpes. J Infect Dis 1991; 164: 665–72

    Article  PubMed  CAS  Google Scholar 

  197. Flamel Technologies. Viropump investigator’s brochure. Vénissieux: Flamel Technologies, 1998

  198. Tomai M, Gisbon S, Imbertson L, et al. Immunomodulating and antiviral activities of the imidazoquinoline S-28463. Antiviral Res 1995; 28: 253–64

    Article  PubMed  CAS  Google Scholar 

  199. Bernstein DI, Miller RL, Tepe E, et al. Effect of S-28463 in reducing recurrent genital HSV-2 in guinea pigs [abstract no. 209]. 8th International Conference on Antiviral Research: 1995 Apr 23–28; Santa Fe (NM)

  200. Sauder D, Tomai M, McDermott D, et al. Systemic and cutaneous pharmacodynamics of topical R-848 gel in humans [abstract]. The 38th Interscience Conference on Antimicrobial Agents and Chemotherapy: 1998 Sep 24–27; San Diego (CA): A-90

  201. Spruance SL, Tyring S, Bleazard C, et al. Immunomodulation to decrease recurrences of herpes genitalis: a double-blind, dose ranging study of topical R-848 [abstract]. The 40th Interscience Conference on Antimicrobial Agents and Chemotherapy: 2000 Sep 17–20; Toronto: A466

  202. Stanberry LR. The concept of immune-based therapies in chronic viral infections. J AIDS 1994; 7 Suppl. 1: S1–5

    Google Scholar 

  203. Milligan GN, Bernstein DI, Bourne N. T lymphocytes are required for protection of the vaginal mucosae and sensory ganglia of immune mice against reinfection with herpes simplex virus type 2. J Immunol 1998; 160: 6093–100

    PubMed  CAS  Google Scholar 

  204. Kuklin NA, Daheshia M, Chun S, et al. Role of mucosal immunity in herpes simplex virus infection. J Immunol 1998; 160: 5998–6003

    PubMed  CAS  Google Scholar 

  205. Burke RL. Development of a herpes simplex virus subunit vaccine for prophylactic and therapeutic use. Rev Infect Dis 1991; 13 Suppl. 11: S906–11

    Article  PubMed  CAS  Google Scholar 

  206. Ashley R, Mertz G, Clark H, et al. Humoral immune response to herpes simplex virus type 2 glycoproteins in patients receiving a glycoprotein subunit vaccine. J Virol 1985; 56: 475–81

    PubMed  CAS  Google Scholar 

  207. Stanberry LR, Berstein DI, Burke RL, et al. Vaccination with recombinant herpes simplex virus glycoproteins: protection against initial and recurrent genital herpes. J Infect Dis 1987; 155: 914–20

    Article  PubMed  CAS  Google Scholar 

  208. Heineman TC, Connelly BL, Bourne N, et al. Immunization with recombinant varicella-zoster virus expressing herpes simplex virus type 2 glycoprotein D reduces the severity of genital herpes in guinea pigs. J Virol 1995; 69: 8109–13

    PubMed  CAS  Google Scholar 

  209. Mertz GJ, Hasley R, Burke RL, et al. Double-blind, placebo-controlled trial of a herpes simplex virus type 2 glycoprotein vaccine in persons at high risk for genital herpes infection. J Infect Dis 1990; 161: 653–60

    Article  PubMed  CAS  Google Scholar 

  210. Straus SE, Corey L, Burke RL, et al. Placebo-controlled trial of vaccination with recombinant glycoprotein D of herpes simplex virus type 2 for immunotherapy of genital herpes. Lancet 1994; 343: 1460–5

    Article  PubMed  CAS  Google Scholar 

  211. Langenberg AG, Burke RL, Adair SF, et al. A recombinant glycoprotein vaccine for herpes simplex virus type 2: safety and immunogenicity. Ann Intern Med 1995; 122: 889–98

    PubMed  CAS  Google Scholar 

  212. Corey L, Langenberg AG, Ashley R, et al. Recombinant glycoprotein vaccine for the prevention of genital HSV-2 infection: two randomized controlled trials. Chiron HSV Vaccine Study Group. JAMA 1999; 282: 331–40

    CAS  Google Scholar 

  213. Ashley RL, Crisostomo F, Doss M, et al. Cervical antibody responses to a herpes simplex virus type 2 glycoprotein subunit vaccine. J Infect Dis 1998; 178: 1–7

    Article  PubMed  CAS  Google Scholar 

  214. Straus SE, Wald A, Kost RG, et al. Immunotherapy of recurrent genital herpes with recombinant herpes simplex virus type 2 glycoproteins D and B: results of a placebo-controlled vaccine trial. J Infect Dis 1997; 176: 1129–34

    Article  PubMed  CAS  Google Scholar 

  215. Mastrolorenzo A, Tiradritti L, Salimbeni L, et al. Multicentre clinical trial with herpes simplex virus vaccine in recurrent herpes infection. Int J STD AIDS 1995; 6: 431–5

    PubMed  CAS  Google Scholar 

  216. Spruance S. Gender-specific efficacy of a prophylactic SBAS4-adjuvanted gD2 subunit vaccine against genital herpes disease (GHD): results of two clinical efficacy trials [abstract]. The 40th Interscience Conference on Antimicrobial Agents and Chemotherapy: 2000 Sep 17–20; Toronto: L-6

  217. Ulmer JB, Donnelly JJ, Parker SE, et al. Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 1993; 259: 1745–9

    Article  PubMed  CAS  Google Scholar 

  218. Webster RG, Fynan EF, Santoro JC, et al. Protection of ferrets against influenza challenge with a DNA vaccine to the hemagglutinin. Vaccine 1994; 12: 1495–504

    Article  PubMed  CAS  Google Scholar 

  219. Donnelly JJ, Friedman A, Martinez D, et al. Preclinical efficacy of a prototype DNA vaccine: enhanced protection against antigenic drift in influenza virus. Nat Med 1995; 1: 583–7

    Article  PubMed  CAS  Google Scholar 

  220. Robinson HL, Hunt LA, Webster RG. Protection against a lethal influenza virus challenge by immunization with a hemaglutinin-expressing plasmid DNA. Vaccine 1993; 11: 957–60

    Article  PubMed  CAS  Google Scholar 

  221. Fynan EF, Webster RG, Fuller DH, et al. DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations. Proc Natl Acad Sci U S A 1993; 90: 11478–82

    Article  PubMed  CAS  Google Scholar 

  222. Xiang ZQ, Spitalnik S, Tran M, et al. Vaccination with a plasmid vector carrying the rabies glycoprotein gene induces protective immunity against rabies virus. Virology 1994; 199: 132–40

    Article  PubMed  CAS  Google Scholar 

  223. Cox GJM, Zamb TJ, Babiuk LA. Bovine herpesvirus 1: immune responses in mice and cattle injected with plasmid DNA. J Virol 1993; 67: 5664–7

    PubMed  CAS  Google Scholar 

  224. Xu D, Liew FY. Genetic vaccination against leishmaniasis. Vaccine 1994; 12: 1534–6

    Article  PubMed  CAS  Google Scholar 

  225. Sedegah M, Hedstrom RC, Hobart P, et al. Protection against malaria by immunization with plasmid DNA encoding circumsporozoite protein. Proc Natl Acad Sci U S A 1994; 91: 9866–70

    Article  PubMed  CAS  Google Scholar 

  226. Manickan E, Rouse RJD, Yu Z, et al. Genetic immunization against herpes simplex virus: protection is mediated by CD4+ T lymphocytes. J Immunol 1995; 155: 259–65

    PubMed  CAS  Google Scholar 

  227. Bourne N, Stanberry LR, Bernstein DI, et al. DNA immunization against experimental genital herpes simplex virus infection. J Infect Dis 1996; 173: 800–7

    Article  PubMed  CAS  Google Scholar 

  228. Hickling JK, Chisholm SE, Duncan IA, et al. Immunogenicity of a disabled infectious single cycle HSV-2 vaccine in phase 1 clinical trials in HSV-2 seropositive and seronegative volunteers [abstract no. 22.008]. Abstracts of the 8th International Congress on Infectious Diseases: 1998 May 15–18; Boston

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Leung, D.T., Sacks, S.L. Current Recommendations for the Treatment of Genital Herpes. Drugs 60, 1329–1352 (2000). https://doi.org/10.2165/00003495-200060060-00007

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