Skip to main navigation menu Skip to main content Skip to site footer

Systematic Review

Vol. 12 No. 1 (2009)

Suppressive valacyclovir therapy to reduce genital herpes transmission: Good public health policy?

  • Paul E Bonnar
DOI
https://doi.org/10.26443/mjm.v12i1.732
Submitted
November 12, 2020
Published
2020-12-01

Abstract

Genital herpes is a widespread sexually transmitted infection caused by the herpes simplex viruses (HSV). Suppressive valacyclovir therapy has been shown to significantly reduce HSV transmission. The benefits and costs of using valacyclovir to reduce transmission in couples discordant for genital herpes will be analyzed in order to better inform decision-making. By reducing transmission, the physical and psychological harms of living with symptomatic genital herpes will be prevented while saving on certain healthcare costs. However, the large number needed to treat and the low symptomatic rate among infected individuals may outweigh these benefits. The costs of trying to achieve a significant reduction in incidence include the psychological harms of identifying asymptomatic individuals through a large screening program and the economic costs of the antiviral agent and screening. When these issues are weighed, the high economic costs render a program to reduce incidence unfeasible. Nevertheless, it is clinically important to consider the consequences of transmission at an individual level. The specific circumstances that influence the decision to use suppressive therapy are identified.

References

  1. Cusini M, Ghislanzoni M. The importance of diagnosing genital herpes. J Antimicrob Chemother. 2001;47:9-16.
  2. Howard M, Sellors JW, Jang D, Robinson NJ, Fearon M, Kaczorowski J, et al. Regional distribution of antibodies to herpes simplex virus type 1 (HSV-1) and HSV-2 in men and women in Ontario, Canada. J Clin Microbiol. 2003;41(1):84-9.
  3. Fleming DT, McQuillan GM, Johnson RE, Nahmias AJ, AralSO, Lee FK, et al. Herpes simplex virus type 2 in the United States, 1976 to 1994. N Engl J Med. 1997;337:1105-11.
  4. Xu F, Sternberg MR, Kottiri BJ, McQuillan GM, Lee FK, Nahmias AJ, et al. Trends in herpes simplex virus type 1 and type 2 seroprevalence in the United States. JAMA. 2006;296:964-73.
  5. Stanberry LR, Jorgensen DM, Nahmias AJ. Herpes simplex viruses 1 and 2. In: Evans AS, Kaslow R, editors. Viral infections of humans: epidemiology and control. 4th ed. New York: Plenum Publishers; 1997. p. 419-54.
  6. Lafferty WE, Downey L, Celum C, Wald A. Herpes simplex virus type 1 as a cause of genital herpes: impact on surveillance and prevention. J Infect Dis. 2000;181:1454-7.
  7. Cherpes TL, Meyn LA, Hillier SL. Cunnilingus and vaginal intercourse are risk factors for herpes simplex virus type 1 acquisition in women. Sex Transm Dis. 2005;32:84-9.
  8. Gardella C, Brown Z, Wald A, Selke S, Zeh J, Morrow RA, et al. Risk factors for herpes simplex virus transmission to pregnant women: a couples study. Am J Obstet Gynecol. 2005;193:1891-9.
  9. Wald A, Zeh J, Selke S, Ashley RL, Corey L. Virologic characteristics of subclinical and symptomatic genital herpes infections. N Engl J Med. 1995;333:770-5.
  10. Lafferty WE, Coombs RW, Benedetti J, Critchlow C, Corey L. Recurrences after oral and genital herpes simplex virus infection. N Engl J Med. 1987;316:1444-9.
  11. Koelle DM, Benedetti J, Langenberg A, Corey L. Asymptomatic reactivation of herpes simplex virus in women after the first episode of genital herpes. Ann Intern Med. 1992;116:433-7.
  12. Engelberg R, Carrell D, Krantz E, Corey L, Wald A. Natural history of genital herpes simplex virus type 1 infection. Sex Transm Dis. 2003;30:174-7.
  13. Ribes JA, Steele AD, Seabolt JP, Baker DJ. Six-year study of the incidence of herpes in genital and nongenital cultures in a central Kentucky medical center patient population. J Clin Microbiol. 2001;39:3321-5.
  14. Roberts CM, Pfister JR, Spear SJ. Increasing proportion of herpes simplex virus type 1 as a cause of genital herpes infection in college students. Sex Transm Dis. 2003;30:797-800.
  15. U.S. Food and Drug Administration [homepage on the Internet]. FDA Updates Labeling of Valtrex [updated 2003 Aug 29; cited 2008 Jul 10]. Available from: http://www.fda.gov/bbs/topics/ANSWERS/2003/ANS01250.ht ml.
  16. Notice of Compliance Listings [database on the Internet]. Health Canada. - [cited 2008 Jul 10]. Available from: http://www.hc- sc.gc.ca/dhp-mps/prodpharma/notices-avis/list/index-eng.php.
  17. Corey L, Wald A, Patel R, Sacks SL, Tyring SK, Warren T, et al. Once-daily valacyclovir to reduce the risk of transmission of genital herpes. N Engl J Med. 2004;350:11-20.
  18. Mertz GJ, Schmidt O, Jourden JL, Guinan ME, Remington ML, Fahnlander A, 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.
  19. Mertz GJ, Benedetti J, Ashley R, Selke SA, Corey L. Risk factors for the sexual transmission of genital herpes. Ann Intern Med. 1992;116:197-202.
  20. Carney O, Ross E, Bunker C, Ikkos G, Mindel A. A prospective study of the psychological impact on patients with a first episode of genital herpes. Genitourin Med. 1994;70:40-5.
  21. Patel R, Boselli F, Cairo I, Barnett G, Price M, Wulf HC. Patients’ perspectives on the burden of recurrent genital herpes. Int J STD AIDS. 2001;12:640-5.
  22. Romanowski B, Marina RB, Roberts JN. Patients' preference of valacyclovir once-daily suppressive therapy versus twice-dailyepisodic therapy for recurrent genital herpes: a randomized study. Sex Transm Dis. 2003;30:226-31.
  23. Luby ED, Klinge V. Genital herpes: a pervasive psychosocial disorder. Arch Dermatol. 1985;121:494-7.
  24. VanderPlate C, Aral S. Psychosocial aspects of genital herpes virus infection. Health Psychol. 1987;6:57-72.
  25. Miyai T, Turner KR, Kent CK, Klausner J. The psychosocial impact of testing individuals with no history of genital herpes for herpes simplex virus type 2. Sex Transm Dis. 2004;31:517- 21.
  26. Narouz N, Allan PS, Wade AH, Wagstaffe S. Genital herpes serotesting: a study of the epidemiology and patients’ knowledge and attitude among STD clinic attenders in Coventry, UK. Sex Transm Infect. 2003;79:35-41.
  27. Smith A, Denham I, Keogh L, Jacobs D, McHarg V, Marceglia A, et al. Psychosocial impact of type-specific herpes simplex serological testing on asymptomatic sexual health clinic attendees. Int J STD AIDS. 2000;11:15-20.
  28. Benedetti JK, Zeh J, Corey L. Clinical reactivation of genital herpes simplex virus infection decreases in frequency over time. Ann Intern Med. 1999;131:14-20.
  29. Benedetti J, Corey L, Ashley R. Recurrence rates in genital herpes after symptomatic first-episode infection. Ann Intern Med. 1994;121:847-54.
  30. Corey L, Adams HG, Brown ZA, Holmes KK. Genital herpes simplex virus infections: clinical manifestations, course, and complications. Ann Intern Med. 1983;98:958-72.
  31. Fisman DN, Lipsitch M, Hook EW 3rd, Goldie SJ. Projection of the future dimensions and costs of the genital herpes simplex type 2 epidemic in the United States. Sex Transm Dis. 2002;29:608-22.
  32. Szucs TD, Berger K, Fisman DN, Harbarth S. The estimated economic burden of genital herpes in the United States. An analysis using two costing approaches. BMC Infect Dis. 2001;1:5.
  33. Wald A, Langenberg AG, Link K, Izu AE, Ashley R, Warren T, et al. Effect of condoms on reducing the transmission of herpes simplex virus type 2 from men to women. JAMA. 2001;285:3100-6.
  34. Wald A, Langenberg AG, Krantz E, Douglas JM Jr, Handsfield HH, DiCarlo RP, et al. The relationship between condom use and herpes simplex virus acquisition. Ann Intern Med. 2005;143:707-13.
  35. Baker DA, Blythe JG, Miller JM. Once-daily valacyclovir hydrochloride for suppression of recurrent genital herpes. Obstet Gynecol. 1999;94:103-6.
  36. Patel R, Bodsworth NJ, Woolley P, Peters B, Vejlsgaard G, Saari S, 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.
  37. Reitano M, Tyring S, Lang W, Thoming C, Worm AM, Borelli S, et al. Valacyclovir for the suppression of recurrent genital herpes simplex virus infection: a large-scale dose range-finding study. J Infect Dis. 1998;178:603-10.
  38. Englund JA, Zimmerman ME, Swierkosz EM, Goodman JL, Scholl DR, Balfour HH Jr. Herpes simplex virus resistant to acyclovir. Ann Intern Med. 1990;112:416-22.
  39. Reyes M, Shaik NS, Graber JM, Nisenbaum R, Wetherall NT, Fukuda K, et al. Acyclovir-resistant genital herpes among persons attending sexually transmitted disease and human immunodeficiency virus clinics. Ann Intern Med. 2003;163:76- 80.
  40. DeJesus E, Wald A, Warren T, Schacker TW, Trottier S, Shahmanesh M, et al. Valacyclovir for the Suppression of Recurrent Genital Herpes in Human Immunodeficiency Virus–Infected Subjects. J Infect Dis. 2003;188:1009-16.
  41. Engel JP. Long-term suppression of genital herpes. JAMA. 1998;280:928-9.
  42. Corey L. The current trend in genital herpes. Sex Transm Dis. 1994;21 Suppl 2:S38-44.
  43. Koelle DM, Wald A. Herpes simplex virus: the importance of asymptomatic shedding. J Antimicrob Chemother. 2000;45 Suppl T3:1-8.
  44. Langenberg A, Benedetti J, Jenkins J, Ashley R, Winter C, Corey L. Development of clinically recognizable genital lesions among women previously identified as having “asymptomatic” herpes simplex virus type 2 infection. Ann Intern Med. 1989;110:882-7.
  45. Rein MF. Should sexually transmitted disease clinics routinely offer serologic testing for genital herpes? Curr Infect Dis Rep. 2006;8:1-2.
  46. Brugha R, Keersmaekers K, Renton A, Meheus A. Genital herpes infection: a review. Int J Epidemiol. 1997;26:698-709.
  47. Urato A, Caughey A. Universal herpes screening in pregnancy: not recommended and potentially harmful to patients. Am J Obstet Gynecol. 2007;196:e15-6.
  48. Guerry SL, Bauer HM, Klausner JD, Branagan B, Kerndt PR, Allen BG, et al. Recommendations for the selective use of herpes simplex virus type 2 serological tests. Clin Infect Dis. 2005;40:38-45.
  49. Wald A, Krantz E, Selke S, Lairson E, Morrow RA, Zeh J. Knowledge of partners’ genital herpes protects against herpes simplex virus type 2 acquisition. J Infect Dis. 2006;194:42-52.
  50. Williams JR, Jordan JC, Davis EA, Garnett GP. Suppressive Valacyclovir Therapy: Impact on the Population Spread of HSV- 2 Infection. Sex Transm Dis. 2007;34:123-31.
  51. Fisman DN, Lipsitch M, Hook EW 3rd, Goldie SJ. Projection of the future dimensions and costs of the genital herpes simplex type 2 epidemic in the United States. Sex Transm Dis. 2002;29:608-22.
  52. Fisman DN. Health related quality of life in genital herpes: a pilot comparison of measures. Sex Transm Infect. 2005;81:267–70.
  53. Koutsky LA, Ashley RL, Holmes KK, Stevens CE, Critchlow CW, Kiviat N, et al. The frequency of unrecognized type 2 herpes simplex virus infection among women. Implications for the control of genital herpes. Sex Transm Dis. 1990;17:90-4.
  54. Langenberg AG, Corey L, Ashley RL, Leong WP, Straus SE. A prospective study of new infections with herpes simplex virus type 1 and type 2. N Engl J Med. 1999;341:1432-8.
  55. Xu F, Schillinger JA, Sternberg MR, Johnson RE, Lee FK, Nahmias AJ, et al. Seroprevalence and coinfection with herpes simplex virus type 1 and type 2 in the United States, 1988-1994. J Infect Dis. 2002;185:1019-24.
  56. Spruance SL. Pathogenesis of herpes simplex labialis: excretion of virus in the oral cavity. J Clin Microbiol. 1984;19:675-9.
  57. Brantley JS, Hicks L, Sra K, Tyring SK. Valacyclovir for the treatment of genital herpes. Expert Rev Anti Infect Ther. 2006;4:367-76.
  58. Miller CS, Avdiushko SA, Kryscio RJ, Danaher RJ, Jacob RJ. Effect of prophylactic valacyclovir on the presence of human herpesvirus DNA in saliva of healthy individuals after dental treatment. J Clin Microbiol. 2005;43:2173-80.
  59. Anderson BJ. Prophylactic valacyclovir to prevent outbreaks of primary herpes gladiatorum at a 28-day wrestling camp. Jpn J Infect Dis. 2006;59:6-9.
  60. Freeman EE, Weiss HA, Glynn JR, Cross PL, Whitworth JA, Hayes RJ. Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta- analysis of longitudinal studies. AIDS. 2006;20:73-83.
  61. Koelle DM, Abbo H, Peck A, Ziegweid K, Corey L. Direct recovery of herpes simplex virus (HSV) specific T lymphocyte clones from recurrent genital HSV-2 lesions. J Infect Dis. 1994;169:956-61.
  62. Mole L, Ripich S, Margolis D, Holodniy M. The impact of active herpes simplex virus infection on human immunodeficiency virus load. J Infect Dis. 1997;176:766-70.
  63. Schacker T, Zeh J, Hu H, Shaughnessy M, Corey L. Changes in plasma human immunodeficiency virus type 1 RNA associated with herpes simplex virus reactivation and suppression. J Infect Dis. 2002;186:1718-25.
  64. Schacker T. The role of HSV in the transmission and progression of HIV. Herpes. 2001;8:46-9.
  65. Kamali A, Nunn AJ, Mulder DW, Van Dyck E, Dobbins JG, Whitworth JA. Seroprevalence and incidence of genital ulcer infections in a rural Ugandan population. Sex Transm Infect. 1999;75:98-102.
  66. McFarland W, Gwanzura L, Bassett MT, Machekano R, Latif AS, Ley C, et al. Prevalence and incidence of herpes simplex virus type 2 infection among male Zimbabwean factory workers. J Infect Dis. 1999;180:1459-65.
  67. Strick LB, Wald A, Celum C. Management of herpes simplex virus type 2 infection in HIV type 1-infected persons. Clin Infect Dis. 2006;43:347-56.
  68. Kimberlin DW. Neonatal herpes simplex infection. Clin Microbiol Rev. 2004;17:1-13.
  69. Brown ZA, Selke S, Zeh J, Kopelman J, Maslow A, Ashley RL, et al. The acquisition of herpes simplex virus during pregnancy. N Engl J Med. 1997;337:509-15.
  70. Kulhanjian JA, Soroush V, Au DS, Bronzan RN, Yasukawa LL, Weylman LE, et al. Identification of women at unsuspected risk of primary infection with herpes simplex virus type 2 during pregnancy. N Engl J Med. 1992;326:916-20.
  71. Mindel A. Psychological and psychosexual implications of herpes simplex virus infections. Scand J Infect Dis Suppl. 1996;100:27-32.
  72. U.S. Census Bureau [homepage on the Internet]. United States Census 2000. [updated 2008 April 24; cited 2008 Jul 10]. Available from: http://www.census.gov/main/www/cen2000.html.

Downloads

Download data is not yet available.