Herpes Genitalis Treatment Guidelines

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Jun 30, 2024, 5:19:04 AM6/30/24

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The majority of persons infected with HSV-2 have not had the condition diagnosed, many of whom have mild or unrecognized infections but shed virus intermittently in the anogenital area. Consequently, most genital herpes infections are transmitted by persons unaware that they have the infection or who are asymptomatic when transmission occurs. Management of genital HSV should address the chronic nature of the infection rather than focusing solely on treating acute episodes of genital lesions.

Clinical diagnosis of genital herpes can be difficult because the self-limited, recurrent, painful, and vesicular or ulcerative lesions classically associated with HSV are absent in many infected persons at the time of clinical evaluation. If genital lesions are present, clinical diagnosis of genital herpes should be confirmed by type-specific virologic testing from the lesion by NAAT or culture (186). Recurrences and subclinical shedding are much more frequent for HSV-2 genital herpes infection than for HSV-1 genital herpes (439,440). Therefore, prognosis and counseling depend on which HSV type is present. Type-specific serologic tests can be used to aid in the diagnosis of HSV infection in the absence of genital lesions. Both type-specific virologic and type-specific serologic tests for HSV should be available in clinical settings that provide care to persons with or at risk for STIs. HSV-2 genital herpes infection increases the risk for acquiring HIV twofold to threefold; therefore, all persons with genital herpes should be tested for HIV (441).

herpes genitalis treatment guidelines

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Cytologic detection of cellular changes associated with HSV infection is an insensitive and nonspecific method of diagnosing genital lesions (i.e., Tzanck preparation) and therefore should not be relied on. Although a direct immunofluorescence assay using fluorescein-labeled monoclonal antibodies is also available for detecting HSV antigen from genital specimens, this assay lacks sensitivity and is not recommended (449).

Antiviral medication offers clinical benefits to symptomatic patients and is the mainstay of management. The goals for use of antiviral medications to treat genital herpes infection are to treat or prevent symptomatic genital herpes recurrences and improve quality of life and suppress the virus to prevent transmission to sexual partners. Counseling regarding the natural history of genital herpes, risks for sexual and perinatal transmission, and methods for reducing transmission is also integral to clinical management.

Newly acquired genital herpes can cause a prolonged clinical illness with severe genital ulcerations and neurologic involvement. Even persons with first-episode herpes who have mild clinical manifestations initially can experience severe or prolonged symptoms during recurrent infection. Therefore, all patients with first episodes of genital herpes should receive antiviral therapy.

Almost all persons with symptomatic first-episode HSV-2 genital herpes subsequently experience recurrent episodes of genital lesions. Intermittent asymptomatic shedding occurs among persons with HSV-2 genital herpes infection, even those with longstanding clinically silent infection. Antiviral therapy for recurrent genital herpes can be administered either as suppressive therapy to reduce the frequency of recurrences or episodically to ameliorate or shorten the duration of lesions. Certain persons, including those with mild or infrequent recurrent outbreaks, benefit from antiviral therapy; therefore, options for treatment should be discussed. Many persons prefer suppressive therapy, which has the additional advantage of decreasing the risk for transmitting HSV-2 genital herpes to susceptible partners (472,473).

Treatment with valacyclovir 500 mg daily decreases the rate of HSV-2 transmission for discordant heterosexual couples in which a partner has a history of genital HSV-2 infection (473). Such couples should be encouraged to consider suppressive antiviral therapy as part of a strategy for preventing transmission, in addition to consistent condom use and avoidance of sexual activity during recurrences. Suppressive antiviral therapy for persons with a history of symptomatic genital herpes also is likely to reduce transmission when used by those who have multiple partners. HSV-2 seropositive persons without a history of symptomatic genital herpes have a 50% decreased risk for genital shedding, compared with those with symptomatic genital herpes (476). No data are available regarding efficacy of suppressive therapy for preventing HSV-2 transmission among discordant couples in which a partner has a history of asymptomatic HSV-2 infection identified by a positive HSV-2 serologic test. Among HSV-2 seropositive persons without HIV infection, oral TDF/FTC and intravaginal tenofovir are ineffective at reducing the risk for HSV-2 shedding or recurrences (477).

Recurrences are less frequent after the first episode of HSV-1 genital herpes, compared with genital HSV-2 genital herpes, and genital shedding rapidly decreases during the first year of infection (479). No data are available regarding the efficacy of suppressive therapy for preventing transmission among persons with HSV-1 genital herpes infection. Because of the decreased risk for recurrences and shedding, suppressive therapy for HSV-1 genital herpes should be reserved for those with frequent recurrences through shared clinical decision-making between the patient and the provider.

Hepatitis is a rare manifestation of disseminated HSV infection, often reported among pregnant women who acquire HSV during pregnancy (484). Pregnant women in any trimester can present with fever and hepatitis (markedly elevated transaminases) but might not have any genital or skin lesions. HSV hepatitis is associated with fulminant liver failure and high mortality (25%). Therefore, a high index of suspicion for HSV is necessary, with a confirmatory diagnosis by HSV PCR from blood (485). Among pregnant women with fever and unexplained severe hepatitis, disseminated HSV infection should be considered, and empiric IV acyclovir should be initiated pending confirmation (484).

Randomized clinical trials have demonstrated that PrEP with daily oral TDF/FTC decreases the risk for HSV-2 acquisition by 30% in heterosexual partnerships (492). Pericoital intravaginal tenofovir 1% gel also decreases the risk for HSV-2 acquisition among heterosexual women (493). Among MSM and transgender women, daily oral TDF/FTC decreases the risk for severe ulcers with symptomatic genital HSV-2 infection but not for HSV-2 acquisition (494). Insufficient evidence exists that TDF/FTC use among those who are not at risk for HIV acquisition will prevent HSV-2 infection, and it should not be used for that sole purpose. Oral TDF does not prevent HSV-2 acquisition among persons with HIV infection who are taking TDF as part of their ART regimen (495). No data indicate that antivirals (acyclovir, valacyclovir, or famciclovir) can be taken as PrEP by persons without HSV-2 to prevent its acquisition.

Counseling of persons with genital herpes and their sex partners is crucial for management. The goals of counseling include helping patients cope with the infection and preventing sexual and perinatal transmission. Although initial counseling can be provided at the first visit, patients often benefit from learning about the chronic aspects of the disease after the acute illness subsides. Multiple resources, including Internet sites and printed materials, are available to assist patients, their partners, and clinicians who provide counseling (496,497) ( and ).

Although the psychological effect of a serologic diagnosis of HSV-2 infection in a person with asymptomatic or unrecognized genital herpes appears minimal and transient (498,499), certain persons with HSV infection might express anxiety concerning genital herpes that does not reflect the actual clinical severity of their disease; the psychological effect of HSV infection can be substantial. Common concerns about genital herpes include the severity of initial clinical manifestations, recurrent episodes, sexual relationships and transmission to sex partners, and ability to bear healthy children.

For persons with symptomatic HSV-1 genital herpes or asymptomatic HSV-2 genital herpes, suppressive therapy can be considered for those who have substantial psychosocial distress caused by the diagnosis of genital herpes. For women who have genital herpes, the providers who care for them during pregnancy and those who will care for their newborn infant should be informed of their infection (see Genital Herpes During Pregnancy).

The sex partners of persons who have symptomatic genital herpes can benefit from evaluation and counseling. Symptomatic sex partners should be evaluated and treated in the same manner as patients who have symptomatic genital herpes. Asymptomatic sex partners of patients who have symptomatic genital herpes should be asked about a history of genital symptoms and offered type-specific serologic testing for HSV-2. For partners without genital herpes, no data are available on which to base a recommendation for PEP or PrEP with antiviral medications or that they would prevent acquisition, and this should not be offered to patients as a prevention strategy.

Immunocompromised patients can have prolonged or severe episodes of genital, perianal, or oral herpes. Lesions caused by HSV are common among persons with HIV infection and might be severe, painful, and atypical (501). HSV shedding is increased among persons with HIV infection (502). Whereas ART reduces the severity and frequency of symptomatic genital herpes, frequent subclinical shedding still occurs (503,504). Clinical manifestations of genital herpes might worsen during immune reconstitution early after initiation of ART. HSV-2 type-specific serologic testing can be considered for persons with HIV infection during their initial evaluation, particularly among those with a history of genital symptoms indicative of HSV infection.