Clinical Manual for Management of the HIV-Infected Adult
2006 Edition

Section 6: Disease-Specific Treatment

Herpes Simplex, Mucocutaneous

July 2006

Background

Herpes simplex virus (HSV) types 1 and 2 cause both primary and recurrent oral and genital disease. HSV usually appears as a vesicular eruption of the mucous membranes of the oral or perioral area, vulva, perianal skin, rectum, and occasionally the inguinal or buttock areas. The eruption develops into tender or painful ulcerated lesions that are frequently covered with a clear yellow crust. In some patients, however, the typical painful vesicular or ulcerative lesions may be absent. Persons with HIV disease and low CD4 counts have more frequent recurrences of HSV and more extensive ulcerations than HIV-uninfected people. Persistent HSV eruption (>1 month) is an AIDS-indicator diagnosis.

S: Subjective

The patient may complain of eruption of red, painful vesicles or ulcers ("fever blisters") with or without an exudate in the mouth, on the genitals, or in the perianal area. The patient may complain of burning, tingling, or itching before eruption of the lesions.

The vesicles will rupture and ulcerate, generally crusting over and healing in approximately 7-14 days. The lesions may be pruritic and are often painful. As immunosuppression progresses, the lesions may recur more frequently, grow larger or coalesce, and become chronic and nonhealing.

Perform a history, asking the patient about the symptoms above, duration, associated symptoms, and history of HSV or similar symptoms.

O: Objective

Look for punctate, grouped vesicular or ulcerative lesions on an erythematous base on the mouth, anus, or external genitals, or ones that are visible on speculum or anoscopic examination. When immunosuppression is severe, lesions may coalesce into large painful ulcerations that spread to the skin of the thighs, lips, face, or perirectal region. Recurrent lesions may start atypically, first appearing as a fissure, pustule, or abrasion.

A: Assessment

A partial differential diagnosis includes:

• Oral aphthous ulcers
• Chancroid
• Syphilis
• Cytomegalovirus
• Candidiasis
• Drug-related eruption

P: Plan

Diagnostic Evaluation

The diagnosis of HSV is usually based on the clinical appearance and symptoms, without laboratory testing.

If the diagnosis is uncertain, obtain a specimen from a freshly opened vesicle or the base of an ulcer for culture confirmation. Note that lesions that are >72 hours old or are beginning to resolve may not show HSV in culture.

Polymerase chain reaction (PCR) is also a sensitive diagnostic test for detection of herpes DNA in ulcerative lesions, but is more expensive and less widely available than viral culture.

If culture is not available, perform a Tzanck smear by staining scrapings from the base of the lesion with Giemsa or methylene blue to reveal multinucleated giant cells. Note that this test is fairly insensitive.

If cultures are negative and there is a high suspicion of HSV infection, skin may be taken from the edge of the ulcer for biopsy. Biopsy material may also be cultured.

Single serologic tests that detect HSV-1 or HSV-2 antibodies can determine whether a patient has ever been infected with herpes, and a 4-fold or greater rise in antibody titer between acute and convalescent serum specimens may diagnose primary HSV. However, only about 5% of persons with recurrences will develop a 4-fold rise in titer.

Strongly consider checking for syphilis with a rapid plasma reagin (RPR) or Venereal Disease Research Laboratory (VDRL) test in any patient who presents with genital, anal, or oral ulceration.

Treatment

Empiric treatment for suspicious lesions is often initiated in the absence of laboratory confirmation. In some instances, treatment can be started empirically and, if no response is seen within 7-10 days, laboratory studies could be undertaken.

Episodic outbreak

• Acyclovir (Zovirax) can be given 400 mg orally 3 times daily or 200 mg orally 5 times daily until ulcers heal, usually within 7-14 days. This treatment helps the healing of lesions but does not prevent recurrences. Large, extensive ulcers may need to be treated for a longer period of time.
• Famciclovir (Famvir) 500 mg orally for 7-14 days is another option but is more expensive than acyclovir.
• Valacyclovir (Valtrex) 1,000 mg orally twice daily for 7-14 days is also more expensive than acyclovir.

Adjust the dosage for renal impairment.

Severe disease

• Treat initially with intravenous acyclovir.

Acyclovir-resistant HSV

• The diagnosis of acyclovir-resistant HSV should be confirmed with culture and sensitivities. Cross-resistance to famciclovir, valacyclovir, and ganciclovir will be present as well. The usual alternative is foscarnet (40 mg/kg every 8 hours intravenously); other possibilities include topical trifluridine and topical cidofovir.

Chronic suppressive therapy

• Consider suppressive therapy with acyclovir (200-400 mg orally twice daily), famciclovir (250 mg orally twice daily), or valacyclovir (500 mg orally twice daily) for patients with frequent or severe recurrences. Treatment should be continued indefinitely. Note that suppressive therapy also reduces the risk of transmission of HSV.

Patient Education

• Patients should be told that HSV has no cure, and outbreaks may occur at intervals for the rest of their lives.
• HSV is easily spread through kissing (if mouth or lips are infected) and sexual contact (oral, anal, or vaginal). HSV is often is transmitted when no lesions are present, so it is important that patients inform their sex partners of their herpes infection before sex. Patients must avoid all sexual contact while lesions are visible, because a lot of virus is present at those times. Condom use at each sexual encounter offers the best chance of preventing HSV transmission. If HSV is transmitted, sexual partners also will have it for life.
• Instruct patients to avoid use of occlusive dressings or ointments, which can prevent healing of sores.
• Acyclovir is most effective when taken early in the outbreak, so patients not taking suppressive therapy should keep medication on hand and start treatment at the first signs of eruption.
• HSV in a pregnant woman can cause severe illness in the newborn, so women must inform their obstetricians and pediatricians if they are exposed to or infected with HSV during pregnancy. Pregnant women should avoid having sex with partners who have HSV. Men who have HSV should avoid having sex with pregnant women who do not have HSV, because new HSV infection during pregnancy is much riskier to the baby than HSV infection acquired before the pregnancy.

References

• Centers for Disease Control and Prevention, National Institutes of Health, HIV Medicine Association/Infectious Diseases Society of America. Treating Opportunistic Infections Among HIV-Infected Adults and Adolescents. MMWR Recomm Rep. 2004 Dec 17; 53(RR15);1-112. Available online at aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?GuidelineID=14. Accessed May 19, 2006.
• Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2002. MMWR Recomm Rep. 2002 May 10;51(RR-6):1-78.
• Corey L. Herpes Simplex Virus. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases, 6th ed. Philadelphia: Elsevier; 2005:1762-80.
• Corey L, Wald A, Patel R, et al. Once-daily valacyclovir to reduce the risk of transmission of genital herpes. N Engl J Med. 2004 Jan 1;350(1):11-20.
• Sande MA, Eliopoulos GM, Moellering RC, et al. The Sanford Guide to HIV/AIDS Therapy, 14th ed. Hyde Park, VT: Antimicrobial Therapy, Inc.; 2005.