Herpes simplex treatment

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:  Abdurahman Khalil, M.D. [2], Cafer Zorkun, M.D., Ph.D. [3], Lakshmi Gopalakrishnan, M.B.B.S.

## Overview[edit | edit source]

Antiviral therapy is the mainstay of management for genital herpes. Systemic antiviral drugs can partially control the signs and symptoms of herpes episodes when used to treat either first clinical and recurrent episodes, or when used as daily suppressive therapy. However, these drugs neither eradicate latent virus nor affect the risk, frequency, or severity of recurrences after the drug is discontinued. Randomized trials have indicated that three antiviral medications (Acyclovir, Valacyclovir, and Famciclovir) provide clinical benefit for genital herpes.[1][2][3][4][5][6][7][8][9] Topical therapy with antiviral drugs offers minimal clinical benefit; its use is discouraged.

Currently, there is no treatment that can eradicate any of the herpes viruses from the body. Supportive treatment includes non-prescription analgesics and topical anesthetic treatment (such as Prilocaine, Lidocaine, or Tetracaine) for itching and pain.[10][11] Counseling regarding the natural history of genital herpes, sexual and perinatal transmission, and methods to reduce transmission is an integral part of clinical management.

## Medical Therapy[edit | edit source]

### Antiviral Therapy[edit | edit source]

### Topical Treatments[edit | edit source]

#### Docosanol[edit | edit source]

* Docosanol prevents herpes simplex virus from fusing to cell membranes, thus barring the entry of the virus into the skin.
* It was approved for use after clinical trials by the FDA in July 2000.[12]
* It was the first over-the-counter antiviral drug approved for sale in the United States and Canada

#### Tromantadine[edit | edit source]

* Tromantadine is available as a gel that inhibits entry and spreading of the virus by altering the surface composition of skin cells and inhibiting release of viral genetic material.

#### Zilactin[edit | edit source]

* It is a topical analgesic barrier treatment, which forms a "shield" at the area of application to prevent a sore from increasing in size and decreases viral spreading during the healing process.

### Other Drugs[edit | edit source]

#### Cimetidine[edit | edit source]

Cimetidine commonly used in heartburn, has been shown to lessen the severity of herpes zoster outbreaks in several different instances, and offered some relief from herpes simplex.

#### Vaseline[edit | edit source]

* Vaseline or any other type of fat prevents water or saliva from reaching the cold sore. Since water helps in perpetuation of the cold sore, preventing water exposure will hasten the healing process.[13][14][15] This is an off-label use of the drug. It and Probenecid have been shown to reduce the renal clearance of aciclovir.[16] These compounds also reduce the rate, but not the extent, at which Valacyclovir is converted into Acyclovir.

#### Aspirin[edit | edit source]

* Low doses of Aspirin (125 mg daily) have shown to be beneficial in patients with recurrent HSV infections. However, there is a lack of sufficient supporting evidence.

* It reduces the level of the inflammatory mediators Prostaglandins [17]
* A recent study in animals showed inhibition of thermal (heat) stress-induced viral shedding of HSV-1 in the eye by Aspirin, and a possible benefit in reducing the frequency of recurrences.[18]

## Management of Sex Partner[edit | edit source]

* The sex partners of patients who have genital herpes can benefit from evaluation and counseling.
* Symptomatic sex partners should be evaluated and treated in the same manner as patients who have genital lesions.
* Asymptomatic sex partners of patients who have genital herpes should be questioned concerning histories of genital lesions and offered type-specific serologic testing for HSV infection.

## HIV Infection[edit | edit source]

* Immunocompromised patients can have prolonged or severe episodes of genital, perianal, or oral herpes. Lesions caused by HSV are common among HIV-infected patients and might be severe, painful, and atypical.
* HSV shedding is increased in HIV-infected persons. Whereas antiretroviral therapy reduces the severity and frequency of symptomatic genital herpes, frequent subclinical shedding still occurs.[19]
* Clinical manifestations of genital herpes might worsen during immune reconstitution after initiation of antiretroviral therapy.
* Suppressive or episodic therapy with oral antiviral agents is effective in decreasing the clinical manifestations of HSV among HIV-positive persons. [20][21]
* The extent to which suppressive antiviral therapy will decrease HSV transmission from this population is unknown. HSV type-specific serologies can be offered to HIV-positive persons during their initial evaluation if infection status is unknown, and suppressive antiviral therapy can be considered in those who have HSV-2 infection.

* Acyclovir, Valacyclovir, and Famciclovir are safe for use in immunocompromised patients in the doses recommended for treatment of genital herpes. For severe HSV disease, initiating therapy with acyclovir 5–10 mg/kg IV every 8 hours might be necessary.

* If lesions persist or recur in a patient receiving antiviral treatment, HSV resistance should be suspected and a viral isolate should be obtained for sensitivity testing (184). Such persons should be managed in consultation with an HIV specialist, and alternate therapy should be administered.

* All acyclovir-resistant strains are resistant to valacyclovir, and the majority are resistant to famciclovir. Foscarnet, 40 mg/kg IV every 8 hours until clinical resolution is attained, is frequently effective for treatment of acyclovir-resistant genital herpes. IntravenousCidofovir 5 mg/kg once weekly might also be effective. Imiquimod is a topical alternative, as is topical cidofovir gel 1%, which is not commercially available and must be compounded at a pharmacy. These topical preparations should be applied to the lesions once daily for 5 consecutive days.

* Clinical management of antiviral resistance remains challenging among HIV-infected patients, and other preventative approaches might be necessary. However, experience with another group of immunocompromised persons (hematopoietic stem-cell recipients) demonstrated that persons receiving daily suppressive antiviral therapy were less likely to develop acyclovir-resistant HSV compared with those who received episodic therapy with outbreaks.[22]

## Genital Herpes in Pregnancy[edit | edit source]

* Most mothers of infants who acquire neonatal herpes lack histories of clinically evident genital herpes.[23] *The risk for transmission to the neonate from an infected mother is high (30%–50%) among women who acquire genital herpes near the time of delivery and low (<1%) among women with histories of recurrent herpes at term or who acquire genital HSV during the first half of pregnancy.[24]

* However, because recurrent genital herpes is much more common than initial HSV infection during pregnancy, the proportion of neonatal HSV infections acquired from mothers with recurrent herpes is substantial. *Prevention of neonatal herpes depends both on preventing acquisition of genital HSV infection during late pregnancy and avoiding exposure of the infant to herpetic lesions during delivery. *Because the risk for herpes is high in infants of women who acquire genital HSV during late pregnancy, these women should be managed in consultation with an infectious disease specialist.

* Women without known genital herpes should be counseled to abstain from intercourse during the third trimester with partners known or suspected of having genital herpes. In addition, pregnant women without known orolabial herpes should be advised to abstain from receptive oral sex during the third trimester with partners known or suspected to have orolabial herpes.

* Some specialists believe that type-specific serologic tests are useful to identify pregnant women at risk for HSV infection and to guide counseling regarding the risk for acquiring genital herpes during pregnancy and that such testing should be offered to uninfected women whose sex partner has HSV infection.

* However, the effectiveness of antiviral therapy to decrease the risk for HSV transmission to pregnant women by infected partners has not been studied.

* All pregnant women should be asked whether they have a history of genital herpes. At the onset of labor, all women should be questioned carefully about symptoms of genital herpes, including prodromal symptoms, and all women should be examined carefully for herpetic lesions.* Women without symptoms or signs of genital herpes or its prodrome can deliver vaginally. Although cesarean section does not completely eliminate the risk for HSV transmission to the infant, women with recurrent genital herpetic lesions at the onset of labor should deliver by cesarean section to prevent neonatal HSV infection.

* The safety of systemic Acyclovir, Valacyclovir, and Famciclovir therapy in pregnant women has not been definitively established. Available data do not indicate an increased risk for major birth defects compared with the general population in women treated with acyclovir during the first trimester[25]findings that provide assurance to women who have had prenatal exposure to acyclovir. However, data regarding prenatal exposure to Valacyclovir and Famciclovir are too limited to provide useful information on pregnancy outcomes. *Acyclovir can be administered orally to pregnant women with first episode genital herpes or severe recurrent herpes and should be administered IV to pregnant women with severe HSV infection.

* Acyclovir treatment late in pregnancy reduces the frequency of cesarean sections among women who have recurrent genital herpes by diminishing the frequency of recurrences at term[26][27]); the effect of antiviral therapy late in pregnancy on the incidence of neonatal herpes is not known.

* No data support the use of antiviral therapy among HSV seropositive women without a history of genital herpes.

## Neonatal Herpes[edit | edit source]

* Infants exposed to HSV during birth, as documented by maternal virologic testing or presumed by observation of maternal lesions, should be followed carefully in consultation with a pediatric infectious disease specialist.
* Surveillance cultures of mucosal surfaces to detect HSV infection might be considered before the development of clinical signs of neonatal herpes. In addition, administration of acyclovir might be considered for infants born to women who acquired HSV near term because the risk for neonatal herpes is high for these infants. All infants who have neonatal herpes should be promptly evaluated and treated with systemic acyclovir.
* The recommended regimen for infants treated for known or suspected neonatal herpes is acyclovir 20 mg/kg IV every 8 hours for 21 days for disseminated and CNS disease or for 14 days for disease limited to the skin and mucous membranes.

## References[edit | edit source]

1. ↑ Leone PA, Trottier S, Miller JM (2002) Valacyclovir for episodic treatment of genital herpes: a shorter 3-day treatment course compared with 5-day treatment. Clin Infect Dis 34 (7):958-62. DOI:10.1086/339326 PMID: 11880962
2. ↑ Wald A, Carrell D, Remington M, Kexel E, Zeh J, Corey L (2002) Two-day regimen of acyclovir for treatment of recurrent genital herpes simplex virus type 2 infection. Clin Infect Dis 34 (7):944-8. DOI:10.1086/339325 PMID: 11880960
3. ↑ Aoki FY, Tyring S, Diaz-Mitoma F, Gross G, Gao J, Hamed K (2006) Single-day, patient-initiated famciclovir therapy for recurrent genital herpes: a randomized, double-blind, placebo-controlled trial. Clin Infect Dis 42 (1):8-13. DOI:10.1086/498521 PMID: 16323085
4. ↑ Chosidow O, Drouault Y, Leconte-Veyriac F, Aymard M, Ortonne JP, Pouget F et al. (2001) Famciclovir vs. aciclovir in immunocompetent patients with recurrent genital herpes infections: a parallel-groups, randomized, double-blind clinical trial. Br J Dermatol 144 (4):818-24. PMID: 11298543
5. ↑ Bodsworth NJ, Crooks RJ, Borelli S, Vejlsgaard G, Paavonen J, Worm AM et al. (1997) Valaciclovir versus aciclovir in patient initiated treatment of recurrent genital herpes: a randomised, double blind clinical trial. International Valaciclovir HSV Study Group. Genitourin Med 73 (2):110-6. PMID: 9215092
6. ↑ Fife KH, Barbarash RA, Rudolph T, Degregorio B, Roth R (1997) Valaciclovir versus acyclovir in the treatment of first-episode genital herpes infection. Results of an international, multicenter, double-blind, randomized clinical trial. The Valaciclovir International Herpes Simplex Virus Study Group. Sex Transm Dis 24 (8):481-6. PMID: 9293612
7. ↑ Diaz-Mitoma F, Sibbald RG, Shafran SD, Boon R, Saltzman RL (1998) Oral famciclovir for the suppression of recurrent genital herpes: a randomized controlled trial. Collaborative Famciclovir Genital Herpes Research Group. JAMA 280 (10):887-92. PMID: 9739972
8. ↑ Mertz GJ, Loveless MO, Levin MJ, Kraus SJ, Fowler SL, Goade D et al. (1997) Oral famciclovir for suppression of recurrent genital herpes simplex virus infection in women. A multicenter, double-blind, placebo-controlled trial. Collaborative Famciclovir Genital Herpes Research Group. Arch Intern Med 157 (3):343-9. PMID: 9040303
9. ↑ Reitano M, Tyring S, Lang W, Thoming C, Worm AM, Borelli S et al. (1998) Valaciclovir for the suppression of recurrent genital herpes simplex virus infection: a large-scale dose range-finding study. International Valaciclovir HSV Study Group. J Infect Dis 178 (3):603-10. PMID: 9728526
10. ↑ "Local anesthetic creams". BMJ. 297 (6661): 1468. 1988. PMID 3147021.
11. ↑ Kaminester LH, Pariser RJ, Pariser DM; et al. (1999). "A double-blind, placebo-controlled study of topical tetracaine in the treatment of herpes labialis". J. Am. Acad. Dermatol. 41 (6): 996–1001. PMID 10570387.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
12. ↑ "Drug Name: ABREVA (docosanol) - approval". centerwatch.com. July 2000. Retrieved 2007-10-17.
13. ↑ Kapińska-Mrowiecka M, Turowski G (1996) [Efficacy of cimetidine in treatment of Herpes zoster in the first 5 days from the moment of disease manifestation.] Pol Tyg Lek 51 (23-26):338-9. PMID: 9273526
14. ↑ Hayne ST, Mercer JB (1983) Herpes zoster: treatment with cimetidine. Can Med Assoc J 129 (12):1284-5. PMID: 6652595
15. ↑ Komlos L, Notmann J, Arieli J, Hart J, Levinsky H, Halbrecht I et al. (1994) IN vitro cell-mediated immune reactions in herpes zoster patients treated with cimetidine. Asian Pac J Allergy Immunol 12 (1):51-8. PMID: 7872992
16. ↑ De Bony F, Tod M, Bidault R, On NT, Posner J, Rolan P (2002) Multiple interactions of cimetidine and probenecid with valaciclovir and its metabolite acyclovir. Antimicrob Agents Chemother 46 (2):458-63. PMID: 11796358
17. ↑ Karadi I, Karpati S, Romics L. (1998). "Aspirin in the management of recurrent herpes simplex virus infection". Ann. Intern. Med. 128 (8): 696–697. PMID 9537952.CS1 maint: Multiple names: authors list (link)
18. ↑ Gebhardt BM, Varnell ED, Kaufman HE. (2004). "Acetylsalicylic acid reduces viral shedding induced by thermal stress". Curr. Eye Res. 29 (2–3): 119–125. PMID 15512958.CS1 maint: Multiple names: authors list (link)
19. ↑ Posavad, CM.; Wald, A.; Kuntz, S.; Huang, ML.; Selke, S.; Krantz, E.; Corey, L. (2004). "Frequent reactivation of herpes simplex virus among HIV-1-infected patients treated with highly active antiretroviral therapy". J Infect Dis. 190 (4): 693–6. doi:10.1086/422755. PMID 15272395. Unknown parameter `|month=` ignored (help)
20. ↑ Conant, MA.; Schacker, TW.; Murphy, RL.; Gold, J.; Crutchfield, LT.; Crooks, RJ. (2002). "Valaciclovir versus aciclovir for herpes simplex virus infection in HIV-infected individuals: two randomized trials". Int J STD AIDS. 13 (1): 12–21. PMID 11802924. Unknown parameter `|month=` ignored (help)
21. ↑ DeJesus, E.; Wald, A.; Warren, T.; Schacker, TW.; Trottier, S.; Shahmanesh, M.; Hill, JL.; Brennan, CA. (2003). "Valacyclovir for the suppression of recurrent genital herpes in human immunodeficiency virus-infected subjects". J Infect Dis. 188 (7): 1009–16. doi:10.1086/378416. PMID 14513421. Unknown parameter `|month=` ignored (help)
22. ↑ Erard, V.; Wald, A.; Corey, L.; Leisenring, WM.; Boeckh, M. (2007). "Use of long-term suppressive acyclovir after hematopoietic stem-cell transplantation: impact on herpes simplex virus (HSV) disease and drug-resistant HSV disease". J Infect Dis. 196 (2): 266–70. doi:10.1086/518938. PMID 17570114. Unknown parameter `|month=` ignored (help)
23. ↑ Brown, ZA.; Selke, S.; Zeh, J.; Kopelman, J.; Maslow, A.; Ashley, RL.; Watts, DH.; Berry, S.; Herd, M. (1997). "The acquisition of herpes simplex virus during pregnancy". N Engl J Med. 337 (8): 509–15. doi:10.1056/NEJM199708213370801. PMID 9262493. Unknown parameter `|month=` ignored (help)
24. ↑ Brown, ZA.; Wald, A.; Morrow, RA.; Selke, S.; Zeh, J.; Corey, L. (2003). "Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant". JAMA. 289 (2): 203–9. PMID 12517231. Unknown parameter `|month=` ignored (help)
25. ↑ Stone, KM.; Reiff-Eldridge, R.; White, AD.; Cordero, JF.; Brown, Z.; Alexander, ER.; Andrews, EB. (2004). "Pregnancy outcomes following systemic prenatal acyclovir exposure: Conclusions from the international acyclovir pregnancy registry, 1984-1999". Birth Defects Res A Clin Mol Teratol. 70 (4): 201–7. doi:10.1002/bdra.20013. PMID 15108247. Unknown parameter `|month=` ignored (help)
26. ↑ Scott, LL.; Hollier, LM.; McIntire, D.; Sanchez, PJ.; Jackson, GL.; Wendel, GD. (2002). "Acyclovir suppression to prevent recurrent genital herpes at delivery". Infect Dis Obstet Gynecol. 10 (2): 71–7. doi:10.1155/S1064744902000054. PMID 12530483.
27. ↑ Sheffield, JS.; Hollier, LM.; Hill, JB.; Stuart, GS.; Wendel, GD. (2003). "Acyclovir prophylaxis to prevent herpes simplex virus recurrence at delivery: a systematic review". Obstet Gynecol. 102 (6): 1396–403. PMID 14662233. Unknown parameter `|month=` ignored (help)

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