Genital Herpes Simplex Virus (HSV)
Posted October 2007 — Currently Under Revision
Herpes simplex virus (HSV) is the etiologic agent of genital herpes. Infection with either of the two identified serotypes, HSV-1 or HSV-2, is lifelong. Most genital herpes is caused by HSV-2, whereas most orolabial herpes is caused by HSV-1. However, each serotype can cause disease in either location, and genital HSV-1 may often be acquired through contact with a partner’s mouth.1 Perinatal transmission can also occur, particularly when the mother experiences a primary infection during pregnancy. (For treatment of genital herpes in pregnant HIV-infected women, see Management of HIV-Infected Pregnant Women Including Prevention of Perinatal HIV Transmission.)
Serologic studies have documented HSV seropositivity in the overwhelming majority of HIV-infected patients (>95% in some series).2,3 Orolabial and anogenital disease caused by HSV in HIV-infected patients may vary from that in the non-HIV-infected populations in severity of initial infection or severity or frequency of recurrence. Another difference is that acyclovir resistance is rarely encountered in a non-HIV-infected host, but its frequency is increased in the HIV-infected population. Nevertheless, recommendations for treatment and prophylaxis are similar for the two patient groups.
The typical clinical course of genital herpes consists of small papules progressing to painful grouped 1- to 3-mm vesicles on an erythematous base that progress into shallow ulcerations. On mucosal surfaces, vesicles quickly rupture leaving moist erosions or superficial ulcers. Lesions are occasionally limited to small linear erosions or “slits.” In approximately 50% of patients, tingling, itching, or paraesthesia may precede primary or recurrent lesions by 24 to 48 hours. Of note, initial infection and reactivations may also be asymptomatic or minimally symptomatic despite active shedding of virus.
Most clinical episodes of genital herpes are recurrent disease. In primary HSV infection, lesions may be numerous, systemic symptoms may be present, and healing typically occurs over 2 to 3 weeks. In recurrent HSV, fewer lesions may appear, less or no systemic symptoms may be present, and healing usually occurs within 10 days. One study found that HSV recurrences in HIV-infected patients increased as CD4 counts decreased to <100 cells/mm3.4
Most genital herpes in HIV-infected patients present similarly to those in non-HIV-infected patients, although, as listed below, unusual presentations have been described in HIV-infected patients.
Clinicians should diagnose typical genital herpes through the presence of consistent clinical findings upon examination. Diagnosis of chronic nonhealing ulcerated herpes simplex or atypical lesions should be confirmed by culture or either histologic or pathologic examination. Recurrences do not require laboratory confirmation.
Clinicians should exclude coinfection with another pathogen, such as syphilis, when a recurring lesion is atypical.
Diagnostic methods for genital herpes in HIV-infected patients are the same as those for non-HIV-infected patients. Diagnosis of typical genital herpes is usually made through clinical examination. Confirmation of diagnosis through detection of HSV may be useful but is not necessary, and recurrences do not require laboratory confirmation. However, definitive diagnosis may be indicated in cases of unclear etiology and/or cases of suspected syphilis infection. The sensitivity of culture decreases with the duration of the lesion (i.e., less sensitive as lesion heals). HSV antigen detection tests are available, and PCR is available in some specialized laboratories.
Type-specific serologic assays measuring antibody to HSV-specific glycoprotein will reliably identify whether a patient has antibody, and therefore lifelong infection, to HSV-1 and/or HSV-2. Serologic tests do not determine whether a given lesion is due to HSV but may be useful for initial episodes. Serologic testing is of limited utility in HIV-infected patients because most series show that the overwhelming majority of HIV-infected patients have antibody to HSV-1 and -2.
Acyclovir, valacyclovir, or famciclovir should be used to treat HSV. Specific dosing recommendations and caveats are listed in Table 1.
Clinicians should consider the possibility of antiviral resistance if herpetic lesions fail to heal with standard antiviral therapy. Nonadherence and poor absorption should also be considered. The clinician should refer the patient to an HIV or Infectious Disease Specialist when acyclovir-resistant HSV is suspected.
In general, treatment is oral, well-tolerated, and effective. Systemic antiviral therapy has been shown to improve clinical symptoms and shorten the duration of symptoms and signs; however, treatment does not eliminate the virus. Topical antiviral therapy for genital herpes has minimal efficacy. Intravenous therapy is necessary for severe mucocutaneous progressive disease, visceral involvement (e.g., esophageal or hepatic), or antiviral resistance.
Persistent or recurrent lesions in patients receiving antiviral therapy should prompt an evaluation for poor absorption of the antiviral medication, nonadherence to the regimen, or the development of antiviral resistance.
Clinicians should obtain HSV drug-susceptibility tests, if available, when patients receiving antiviral treatment have persistent or recurrent HSV lesions.
Most resistant viral isolates are thymidine kinase (TK) deficient and are therefore resistant to acyclovir, valacyclovir, famciclovir, penciclovir, and ganciclovir. If available, drug susceptibility testing should be obtained when patients receiving antiviral treatment have persistent or recurrent HSV lesions.
Treatment options for resistant HSV are listed in Table 1. Following resolution of an episode of acyclovir-resistant HSV, recurrent outbreaks often demonstrate adequate susceptibility to medications used to treat acyclovir-resistant HSV (see Table 1).
V. REACTIVATION AND CHRONIC SUPPRESSIVE THERAPY
Soon after resolution of primary symptoms, HSV becomes latent in the patient’s cranial nerve or dorsal root sensory ganglia. In most cases, genital herpes establishes latency in the sacral plexus. Unlike HIV, HSV assumes both a clinical and cellular latency because the virus is believed to replicate at a lower rate during this period. The immune response seems to play an important role in driving HSV into its initial latent state and in maintaining HSV latency.9 The chronic immunodeficiency brought about by HIV places patients at increased risk for HSV reactivation. HSV replication is believed to be stimulated by a number of factors, including fever (thus the term fever blister), sun exposure, concurrent viral infection, and possibly localized trauma, hormonal changes, or stress.10
Subclinical reactivation, or viral shedding (detection of virus on mucosal surface without clinical signs/symptoms), of HSV infection is common in HIV-infected and non-HIV-infected patients. HSV-2 reactivation is more frequent in HIV-infected patients.11 HAART has little impact on subclinical HSV reactivation.12 Chronic suppressive therapy may be warranted for patients with frequent symptomatic recurrences. Suppressive antiviral therapy has been shown to decrease the frequency of recurrences, to decrease but not eliminate HSV shedding, and to decrease transmission of HSV to non-HSV-infected partners in immunocompetent hosts.13,14 There is evidence that HSV reactivation is associated with increased HIV RNA levels15 and that chronic daily HSV antiviral therapy decreases HIV RNA levels to baseline in patients not receiving HAART.15,16 This has led some authorities to suggest that HSV suppressive therapy be considered in HIV-infected patients who are not receiving effective ARV therapy.17 Discontinuation of chronic HSV suppression may be indicated when patients have achieved sustained immunologic response from HAART and have not experienced recent HSV reactivation.
VI. PREVENTION OF TRANSMISSION
Clinicians should educate HIV/HSV coinfected patients with genital herpes about the following:
- the use of latex condoms to decrease the risk of transmission, including the risk of superinfection if the partner has one or both viruses
- the significance of the role of genital HSV infection in potentiating the spread of HIV even in the absence of clinically apparent ulcers and during chronic suppressive therapy
- the frequency of potentially infectious viral HSV reactivation even in the absence of clinically apparent ulcers
- viral HSV shedding and infectivity are decreased but not eradicated with chronic suppressive therapy
A. Prevention of HIV Transmission
An increasing number of studies are addressing the role of HSV in promoting local HIV replication and potentiating HIV transmission. Genital ulcers from HSV,18,19 as well as from syphilis and chancroid,19 increase the likelihood that genital secretions will contain an infectious amount of HIV. This increases the potential for contact between HIV in genital secretions and genital mucosal cells receptive to HIV infection.19 As such, clinicians should stress the importance of using effective barrier methods to HIV/HSV coinfected patients.
B. Prevention of HSV Transmission
Viral HSV shedding has been shown to be higher in HIV coinfected patients than in those who are seropositive for HSV alone,23,24 indicating the increased risk of HSV transmission by HIV/HSV coinfected patients. Latex condoms have demonstrated efficacy in reducing transmission of genital HSV infection, and clinically effective chronic suppressive therapy decreases, but does not eliminate, viral HSV shedding and infectivity. The combination of both methods may help further reduce the risk of HSV transmission.
VII. MANAGEMENT OF PARTNERS
Clinicians should consider both HIV and STI exposures to partners when HIV-infected patients present with a new STI. Clinicians should also assess for the presence of other STIs (see Management of STIs in HIV-Infected Patients). (AIII)
A. Management of HIV Exposure in Partners
Updated March 2012
When HIV-infected patients present with a new STI, clinicians should offer assistance with notifying partners of both the potential HIV and STI exposures or should refer patients to other sources for partner notification assistance ( Partner Services in New York State or CNAP in New York City). Partners without confirmed HIV infection should undergo HIV testing at baseline, 1, 3, and 6 months. Confirmatory testing according to New York State regulations must be performed to confirm HIV diagnoses.
Clinicians must report confirmed cases of HIV according to New York State Public Health Law (for more information about required reporting, see www.health.ny.gov/diseases/aids/regulations/index.htm).
Clinicians should educate patients with non-HIV-infected partners or partners of unknown HIV status to be vigilant for any post-exposure acute HIV symptoms in their partners, such as febrile illness accompanied by rash, lymphadenopathy, myalgias, and/or sore throat (see Diagnosis and Management of Acute HIV Infection). (AIII)
Partners who present within 36 hours of an HIV exposure should be evaluated as soon as possible for initiation of post-exposure prophylaxis therapy (see HIV Prophylaxis Following Non-Occupational Exposure). (AII)
Presentation of a new STI in HIV-infected patients suggests exposure of both HIV and the STI to their partners. In this case, offering HIV non-occupational post-exposure prophylaxis (nPEP) to partners is usually not an option because the period prior to STI symptom onset is usually longer than the 36-hour window for initiating HIV nPEP. Therefore, sequential HIV testing of partners without confirmed HIV infection should be performed for early identification of potential HIV acquisition. However, if a patient with an HIV exposure does present within 36 hours, evaluation for nPEP should occur (see HIV Prophylaxis Following Non-Occupational Exposure).
B. Management of HSV Exposure
Clinicians should counsel patients to inform all sex partners of their HSV exposure and should educate HSV-infected patients about the risk of transmission to their sex partner(s), including the risk of superinfection if both partners are infected with HSV or HIV.
Sex partners who are symptomatic for genital herpes should be treated or referred for treatment.
HSV-infected patients and, when possible, their sex partners should receive counseling about informing all sex partners of their HSV exposure. Education of sex partners of HSV-infected patients and treatment or referral for treatment of partners who are symptomatic for HSV can further reduce the risk of transmission.
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