Skip to main content
SpringerLink
Log in

A Risk-Benefit Evaluation of Aciclovir for the Treatment and Prophylaxis of Herpes Simplex Virus Infections

  • Review Article
  • Published:
Drug Safety Aims and scope Submit manuscript

Abstract

The objective of this article is to review and evaluate risks and benefits associated with the use of aciclovir in the treatment and prophylaxis of common manifestations of herpes simplex virus (HSV) infections in immunocompetent and immunocompromised patients. Information was found through a MEDLINE search using keywords: herpes simplex virus, genital herpes, herpes labialis, aciclovir and acyclovir. Selected articles were randomised, double-blind, placebo-controlled, clinical trials. 30 such trials involving 3364 persons were evaluated. All articles were reviewed by the authors and the data were extracted and summarised. In both immunocompetent and immunocompromised hosts, aciclovir therapy demonstrated a high degree of clinical efficacy. None of the studies reported statistically significant differences between aciclovir and placebo for mild or major adverse events. This evaluation found that aciclovir is both effective and well tolerated for treatment and prophylaxis of genital, oral and mucocutaneous HSV infections in immunocompetent and immunocompromised patients. Inmost clinical scenarios, the benefit of aciclovir exceeded any risks by a comfortable margin. The availability of aciclovir as a generic preparation further improves the benefit to cost ratio.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Table III

Similar content being viewed by others

References

  1. Skoldenberg B. Genital herpes: past, present and future. Antiviral Chem Chemother 1997; 8(1 Suppl.): 43

    CAS  Google Scholar 

  2. Whitley RJ, Kimberlin DW, Roizman B. Herpes simplex viruses. Clin Infect Dis 1998; 26: 541–55

    Article  PubMed  CAS  Google Scholar 

  3. Rooney JF, Straus SE, Mannix ML, et al. Oral acyclovir to suppress frequently recurrent herpes labialis. Ann Intern Med 1993; 118(4): 268–72

    PubMed  CAS  Google Scholar 

  4. 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 Inf Dis 1994; 18: 570–8

    Article  CAS  Google Scholar 

  5. Montgomerie JZ, Becroft DM, Croxson MC, et al. Herpes simplex virus infection after renal transplantation. Lancet 1969; II: 867–71

    Article  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  7. Barton SE. All patients with recurrent genital herpes should be offered suppressive therapywith acyclovir. J Med Virol 1996; 6: 65–6

    Article  Google Scholar 

  8. 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 

  9. Scott LL, Sanchez PJ, Jackson GL, et al. Acyclovir suppression to prevent cesarean delivery after first-episode genital herpes. Obstetrics & Gynecology 1996; 87(1): 69–73

    Article  CAS  Google Scholar 

  10. Smith JR, Cowan FM, Munday P. The management of herpes simplex virus infection in pregnancy. Br J Obstet Gynaecol 1998; 105: 255–60

    Article  PubMed  CAS  Google Scholar 

  11. Corey L. Herpes simplex virus infections during the decade since the licensure of acyclovir. J Med Virol 1993; Suppl. 1: 7–12

    Article  PubMed  Google Scholar 

  12. Crooks RJ, Murray A. Valaciclovir-a review of a promising new antiherpes agent. Antiviral Chemistry & Chemotherapy 1994; 5Suppl. 1: 31–37

    Google Scholar 

  13. Sacks SL, Wilso BR. Genital herpes: management issues for the next century. Antiviral Chem Chemother 1997; 8Suppl. 1: 45–50

    CAS  Google Scholar 

  14. 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(1 Pt 1): 8–15

    PubMed  CAS  Google Scholar 

  15. McKenna D, Murphy G. Mucocutaneous herpes simplex infections. Irish Med J 1995; 88(6): 202–03

    CAS  Google Scholar 

  16. Momin F, Chandrasekar PH. Antimicrobial prophylaxis in bone marrow transplantation. Ann Intern Med 1995; 123: 205–15

    PubMed  CAS  Google Scholar 

  17. Schlech WF, Meagher N, Cohen AD, et al. A randomized double-blind placebo controlled trial of oral acyclovir in renal allograft recipients. Can J Infect Dis 1993; 4(2): 84–8

    PubMed  Google Scholar 

  18. Scoular A, Barton S. Therapy for genital herpes in immunocompromised patients: a national survey. GenitourinMed 1997; 73: 391–3

    CAS  Google Scholar 

  19. Wald A, Corey L, Cone R, et al. Frequent genital herpes simplex virus shedding in immunocompetent women. J Clin Invest 1997; 99(5): 1092–7

    Article  PubMed  CAS  Google Scholar 

  20. Balfour HH. Antiviral Drugs. N Engl J Med 1999; 340(16): 1255–67

    Article  PubMed  CAS  Google Scholar 

  21. 1998 Guidelines for treatment of sexually transmitted diseases. MMWR Morb Mortal Wkly Rep 1998; 47 (RR-1): 18–24

  22. Amir J, Harel L, Smetana Z, et al. Treatment of herpes simplex gingivostomatitis with aciclovir in children: a randomised double blind placebo controlled study. BMJ 1997; 314: 1800–3

    Article  PubMed  CAS  Google Scholar 

  23. Spruance SL, Hamill ML, Hoge WS, et al. Acyclovir prevents reactivation of herpes simplex labialis in skiers. JAMA 1988; 260(11): 1597–9

    Article  PubMed  CAS  Google Scholar 

  24. Raborn GW, Martel AY, Grace MGA, et al. Oral acyclovir in prevention of herpes labialis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998; 85: 55–9

    Article  PubMed  CAS  Google Scholar 

  25. Shaw M, King M, Best JM, et al. Failure of acyclovir cream in treatment of recurrent herpes labialis. BMJ 1985; 291: 7–9

    Article  PubMed  CAS  Google Scholar 

  26. Fiddian AP, Ludmilaivanyi. Topical acyclovir in the management of recurrent herpes labialis. Br J Dermatol 1983; 109: 321–6

    Article  PubMed  CAS  Google Scholar 

  27. Mindel A, Adler MW, Sutherland S, et al. Intravenous acyclovir treatment for primary genital herpes. Lancet 1982; I(8274): 697–700

    Article  Google Scholar 

  28. Thin RN, Nabarro JM, Parker JD, et al. Topical acyclovir in the treatment of initial genital herpes. Br J Vener Dis 1983; 59: 116–9

    PubMed  CAS  Google Scholar 

  29. Corey L, Nahmias AJ, Guinan M, et al. Trial of topical acyclovir in genital herpes simplex virus infections. N Engl J Med 1982; 306(220): 1313–9

    Article  PubMed  CAS  Google Scholar 

  30. Mertz GJ, Critchlow CW, Benedetti J. et al. Double-blind placebo-controlled trial of oral acyclovir in first-episode genital herpes simplex virus infection. JAMA 1984; 252(9): 1147–51

    Article  PubMed  CAS  Google Scholar 

  31. Bryson YJ, Dillion M, Lovett M, et al. Treatment of first episodes of genital herpes simplex virus infection with oral acyclovir. N Engl J Med 1983; 308(16): 916–21

    Article  PubMed  CAS  Google Scholar 

  32. Reichman RC, Badger GJ, Guinan ME, et al. Topically administered acyclovir in the treatment of recurrent herpes simplex genitalis: a controlled trial. J Inf Dis 1983; 147(2): 336–40

    Article  CAS  Google Scholar 

  33. Reichman RC, Badger GJ, Mertz GJ, et al. Treatment of recurrent genital herpes simplex infections with oral acyclovir. JAMA 1984; 251(16): 2103–07

    Article  PubMed  CAS  Google Scholar 

  34. Nilsen AE, Aasen T, Halsos AM, et al. Efficacy of oral acyclovir in the treatment of initial and recurrent genital herpes. Lancet 1982; II(8298): 571–3

    Article  Google Scholar 

  35. 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 

  36. Thin RN, Jeffries DJ, Taylor PK, et al. Recurrent genital herpes suppressed by oral acyclovir: a multicentre double blind trial. J Antimicrob Chemother 1985; 16: 219–26

    Article  PubMed  CAS  Google Scholar 

  37. Mertz GJ, Jones CC, Mills J, et al. Long-term acyclovir suppression of frequently recurring genital herpes simplex virus infection. JAMA 1988; 260(2): 201–6

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  39. Douglas JM, Critchlow C, Benedetti J, et al. A double-blind study of oral acyclovir for suppression of recurrences of genital herpes simplex virus infection. N Engl J Med 1984; 310(24): 1551–6

    Article  PubMed  CAS  Google Scholar 

  40. 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(24): 1545–50

    Article  PubMed  CAS  Google Scholar 

  41. Shepp DH, Newton BA, Dandliker PS, et al. Oral acyclovir therapy for mucocutaneous herpes simplex virus infections in immunocompromised marrow transplant recipients. Ann of Intern Med 1985; 102: 783–5

    CAS  Google Scholar 

  42. Meyers JD, Wade JC, Mitchell CD, et al. Multicenter collaborative trial of intravenous acyclovir for treatment of mucocutaneous herpes simplex virus infection in the immunocompromised host. Am J Med 1982; 73:vnSuppl 1A: 229–35

    Article  PubMed  CAS  Google Scholar 

  43. Wade JC, Newton B, McLaren C, et al. Intravenous acyclovir to treat mucocutaneous herpes simplex virus infection after marrow transplantation. Ann Intern Med 1982; 96(3): 265–9

    PubMed  CAS  Google Scholar 

  44. Whitley RJ, Levin M, Barton N, et al. Infections caused by herpes simplex virus in the immunocompromised host: natural history and topical acyclovir therapy. J Inf Dis 1984; 150(3): 323–9

    Article  CAS  Google Scholar 

  45. Saral R, Ambinder RF, Burns WH, et al. Acyclovir prophylaxis against herpes simplex virus infection in patients with leukemia. Ann Intern Med 1983; 99: 773–6

    PubMed  CAS  Google Scholar 

  46. Prentice HG, Hann IM. Prophylatic studies against herpes infections in severely immunocompromised patients with acyclovir. J Infect 1983; 6Suppl. I: 17–21

    Article  PubMed  CAS  Google Scholar 

  47. Pettersson E, Hovi T, Ahonen J, et al. Prophylactic oral acyclovir after renal transplantation. Transplantation 1985; 39(3): 279–81

    Article  PubMed  CAS  Google Scholar 

  48. Anderson H, Scarffe JH, Sutton RNP, et al. Oral acyclovir prophylaxis against herpes simplex virus in non-Hodgkin lymphoma and acute lymphoblastic leukaemia patients receiving remission induction chemotherapy. Br J Cancer 1984; 50: 45–49

    Article  PubMed  CAS  Google Scholar 

  49. Saral R, Burns WH, Laskin OL, et al. Acyclovir prophylaxis of herpes-simplex virus infections. N Engl J Med 1981; 305(2): 63–7

    Article  PubMed  CAS  Google Scholar 

  50. Seale L, Jones CJ, Kathpalia S, et al. Prevention of herpesvirus infections in renal allograft recipients by low-dose acyclovir. JAMA 1985; 254(24): 3435–3438

    Article  PubMed  CAS  Google Scholar 

  51. Straus SE, Smith HA, Brickman C, et al. Acyclovir for chronic mucocutaneous herpes simplex virus infection in immunosuppressed patients. Ann Intern Med 1982; 96: 270–7

    PubMed  CAS  Google Scholar 

  52. Stein DS, Graham NMH, Park LP, et al. The effect of the interaction of acyclovir with zidovudine on progression to AIDS and survival: analysis of data in the multicenter AIDS cohort study. Ann Intern Med 1994; 121: 100–8

    PubMed  CAS  Google Scholar 

  53. Sawyer MH, Webb DE, Balow JE, et al. Acyclovir-induced renal failure. Am J Med 1988; 84: 1067–71

    Article  PubMed  CAS  Google Scholar 

  54. Becker BN, Fall P, Hall C, et al. Rapidly progressive acute renal failure due to acyclovir. Am J Kidney Dis 1993; 22(4): 611–5

    PubMed  CAS  Google Scholar 

  55. Spiegal DM, Lau K. Acute renal failure and coma secondary to acyclovir therapy. JAMA 1986; 255(14): 1882–3

    Article  PubMed  CAS  Google Scholar 

  56. Tomson CR, Goodship THJ, Rodger RSC. Psychiatric side-effects of acyclovir in patients with chronic renal failure. Lancet 1985; II(8451): 385–6

    Article  Google Scholar 

  57. Bataille P, Devos P, Noel JL, et al. Psychiatric side-effects with acyclovir [letter]. Lancet 1985; II(8457): 724

    Article  Google Scholar 

  58. Grella M, Ofosu JR, Klein BL. Prolonged oral acyclovir administration associated with neutropenia and thrombocytopenia. Am J Emer Med 1998; 16(4): 396–8

    Article  CAS  Google Scholar 

  59. 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 

  60. GlaxoWellcome. Acyclovir pregnancy registry and valacyclovir pregnancy registry interim report. GlaxoWellcome Inc. Worldwide Epidemiology; 1984 Jun 1-1988 Jul 31.

  61. Englund JA, Zimmerman ME, Swierkosz EM, et al. Herpes simplex virus resistant to acyclovir. Ann Intern Med 1990; 112: 416–22

    PubMed  CAS  Google Scholar 

  62. Field HJ, Thackray AM. Can herpes simplex virus latency be prevented using conventional nucleoside analogue chemotherapy? Antiviral Chem Chemother 1997; 8Suppl. 1: 59–66

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Experimental and Clinical Pharmacology, University of Minnesota, 7-151 WDH, 308 Harvard St. S.E., Minneapolis, Minnesota, MN 55455, USA

    Stephani Leflore, Peter L. Anderson &  Courtney V. Fletcher

Authors
  1. Stephani Leflore
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter L. Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Courtney V. Fletcher
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Courtney V. Fletcher.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Leflore, S., Anderson, P.L. & Fletcher, C.V. A Risk-Benefit Evaluation of Aciclovir for the Treatment and Prophylaxis of Herpes Simplex Virus Infections. Drug-Safety 23, 131–142 (2000). https://doi.org/10.2165/00002018-200023020-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-200023020-00004

Keywords

Search

Navigation