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Contact afpserv aafp. Want to use this article elsewhere? Get Permissions. Read the Issue. Sign Up Now. Next: Alcoholism in the Elderly. Mar 15, Issue. A typical genital herpes lesion. TABLE 5 Preventing Genital Herpes Infection Intervention Effect Abstention from sexual activity, limited lifetime number of sexual partners Prevention of exposure and transmission of disease 28 , 31 Use of condoms Protection against spread but not foolproof, because ulcers can occur on areas of the body not covered by condoms 14 Education about transmission and shedding Avoidance of high-risk situations 28 , 31 Education about autoinoculation to other parts of the body e.
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 , Persons receiving such therapy often report having experienced no symptomatic outbreaks. Suppressive therapy also is effective for patients with less frequent recurrences. Long-term safety and efficacy have been documented among patients receiving daily acyclovir, valacyclovir, and famciclovir Quality of life is improved for many patients with frequent recurrences who receive suppressive therapy rather than episodic treatment Providers should discuss with patients on an annual basis whether they want to continue suppressive therapy because frequency of genital HSV-2 recurrence diminishes over time for many persons.
However, neither treatment discontinuation nor laboratory monitoring is necessary because adverse events and development of HSV antiviral resistance related to long-term antiviral use are uncommon. Treatment with valacyclovir 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 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. 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.
Famciclovir appears somewhat less effective for suppression of viral shedding Ease of administration and cost also are key considerations for prolonged treatment.
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 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.
Episodic treatment of recurrent herpes is most effective if therapy is initiated within 1 day of lesion onset or during the prodrome that precedes some outbreaks. The patient should be provided with a supply of drug or a prescription for the medication with instructions to initiate treatment immediately when symptoms begin.
Acyclovir, famciclovir, and valacyclovir appear equally effective for episodic treatment of genital herpes — HSV-2 meningitis is a rare complication of HSV-2 genital herpes infection that affects women more than men Longer duration is recommended for CNS complications.
HSV-2 meningitis is characterized clinically by signs of headache, photophobia, fever, meningismus, and cerebrospinal fluid CSF lymphocytic pleocytosis, accompanied by mildly elevated protein and normal glucose For patients with previous episodes of documented HSV-2 meningitis, oral valacyclovir may be used for the entire course during episodes of recurrent HSV-2 meningitis. HSV meningitis should be distinguished from encephalitis, which requires a longer course 14—21 days of IV therapy. Impaired renal function warrants an adjustment in acyclovir dosage.
Hepatitis is a rare manifestation of disseminated HSV infection, often reported among pregnant women who acquire HSV during pregnancy Pregnant women in any trimester can present with fever and hepatitis markedly elevated transaminases but might not have any genital or skin lesions.
Among pregnant women with fever and unexplained severe hepatitis, disseminated HSV infection should be considered, and empiric IV acyclovir should be initiated pending confirmation Consistent and correct condom use has been reported in multiple studies to decrease, but not eliminate, the risk for HSV-2 transmission from men to women — Condoms are less effective for preventing transmission from women to men Results from a third trial conducted in Kenya did not demonstrate a substantial difference in HSV-2 acquisition among men who received MMC A systematic review indicated high consistency for decreased risk for HSV-2 acquisition among women with a male partner who underwent MMC These data indicate that MMC can be associated with decreased risk for HSV-2 acquisition among adult heterosexual men and with decreased risk for HSV-2 transmission from male to female partners.
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.
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 , , 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.
When counseling persons with symptomatic HSV-2 genital herpes infection, the provider should discuss the following:. When counseling persons with asymptomatic HSV-2 genital herpes infection, the provider should consider the following:. When counseling persons with HSV-1 genital herpes infection, the provider should consider the following:. 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 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.
Allergic and other adverse reactions to oral acyclovir, valacyclovir, and famciclovir are rare. Desensitization to acyclovir has been described Immunocompromised patients can have prolonged or severe episodes of genital, perianal, or oral herpes. Whereas ART reduces the severity and frequency of symptomatic genital herpes, frequent subclinical shedding still occurs , 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.
Recommended therapy for first-episode genital herpes is the same as for persons without HIV infection, although treatment courses might need to be extended for lesion resolution. The use of ganciclovir in the pediatric population warrants extreme caution due to this potential for long-term carcinogenicity and reproductive toxicity.
Administration of ganciclovir to pediatric patients should be undertaken only after careful evaluation and only if the potential benefits of treatment outweigh the potential risks. Ganciclovir is indicated for the treatment and prevention of CMV infections in immunocompromised patients. Despite the absence of data, utilization of intravenous ganciclovir is largely being supplanted by oral valganciclovir in clinical practice. Dose reduction, roughly proportional to the degree of reduction in creatinine clearance, is necessary in persons with impaired renal function Spector et al.
Because ganciclovir is efficiently removed by hemodialysis, a supplemental dose is recommended after dialysis Swan et al. Strains of HSV that are resistant to acyclovir because of TK deficiency also are much less sensitive to ganciclovir. DNA polymerase HSV mutants that are ganciclovir-resistant have been generated in vitro but are not yet a clinical problem.
Valganciclovir was approved by the FDA in March, Because it is well absorbed after oral administration, it may represent a favorable option to intravenously-administered ganciclovir for the treatment and suppression of CMV infections in immunocompromised hosts.
Valganciclovir is an L-valine ester prodrug of ganciclovir and as such has the same mechanism of action, antiviral spectrum, and potential for development of resistance as ganciclovir Cocohoba and McNicholl, Valganciclovir is rapidly converted to ganciclovir, with a mean plasma half-life of about 30 minutes Jung and Dorr, The area under the curve of ganciclovir after oral administration of valganciclovir is one-third to one-half of that attained after intravenous administration of ganciclovir.
Patients with impaired renal function require dosage reduction that is roughly proportional to their reduction in creatinine clearance Cocohoba and McNicholl, Valganciclovir provides a more tolerable means by which ganciclovir can be delivered to the body than does intravenous ganciclovir.
Studies of this drug to date have not included investigations of use for HSV infections. Valganciclovir has similar indications to ganciclovir. However, based upon limited controlled trials published to date, it currently is approved for the induction and maintenance therapy of CMV retinitis Martin et al. The recommended dose of valganciclovir for induction therapy is mg twice daily for 2 weeks.
The recommended dose for maintenance therapy is mg once daily. Resistance mechanisms are identical between ganciclovir and valganciclovir. Since selective pressure resulting from exposure to lower concentrations of drug appears to increase the likelihood of resistance developing among CMV isolates Drew et al.
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Author Information Authors David W. Introduction The discovery of effective antiviral agents has been facilitated by advances in the fields of molecular biology and virology. Antiviral therapy Clinical efficacy in HSV-1 and HSV-2 infections Genital herpes For the treatment of first episode genital herpes, the dose of oral acyclovir is mg orally five times per day, or mg orally three times per day Table Table HSV disease in the immunocompromised host Acyclovir also is indicated for the treatment of disseminated HSV infections in otherwise normal hosts, including pregnant women, and mucocutaneous HSV infections in immunocompromised hosts Kimberlin and Prober, HSV keratitis or keratoconjunctivitis Topical therapy with acyclovir for HSV ocular infections is effective, but probably not superior to trifluridine Hovding, Challenges for achieving clinical benefit, including adverse drug effects Perhaps the most prominent challenge impacting clinical benefit of acyclovir therapy relates to the timing of drug initiation following onset of disease symptoms.
Clinical indications Acyclovir is licensed in the United States for the treatment of initial episodes and management of recurrent episodes of genital herpes, for the treatment of chickenpox, and for the treatment of acute herpes zoster infections.
Antiviral resistance Resistance of HSV to acyclovir has become an important clinical problem, especially among immunocompromised patients exposed to long-term therapy Englund et al. Mechanism of action and pharmacokinetics In cells which are infected with HSV, the viral thymidine kinase TK phosphorylates penciclovir to its monophosphate derivative, which in turn is converted to the active penciclovir triphosphate by cellular kinases.
Clinical efficacy in HSV-1 and HSV-2 infections Genital herpes In the episodic treatment of genital herpes, famciclovir reduces time to healing, time to cessation of viral shedding, and durations of lesion edema, vesicles, ulcers, and crusts when compared with placebo Sacks et al. Recurrent herpes labialis Topical penciclovir Denavir for the treatment of recurrent herpes labialis reduces time to healing and duration of pain by about half a day Boon et al. Challenges for achieving clinical benefit, including adverse drug effects Famciclovir is as well tolerated as acyclovir.
Clinical indications Famciclovir was approved by the FDA for the treatment of acute herpes zoster in , and subsequently was approved for the treatment and suppression of genital HSV disease in immunocompetent patients. Dosage regimens For the episodic treatment of recurrent genital HSV disease, the dosage of famciclovir is mg twice daily, administered for 5 days Table Antiviral resistance Because penciclovir, like acyclovir, must be activated by the viral encoded TK enzyme, TK-deficient viral strains are resistant to both acyclovir and penciclovir.
Valaciclovir Valaciclovir is the L-valyl ester of acyclovir that is rapidly converted to acyclovir after oral administration by first-pass metabolism in the liver Jacobson, Mechanism of action and pharmacokinetics As a prodrug of acyclovir, valaciclovir has the same mechanism of action, antiviral spectrum, and resistance profiles as those of its parent drug, acyclovir.
Clinical efficacy in HSV-1 and HSV-2 infections Genital herpes Valaciclovir treatment of first-episode genital HSV is as effective as acyclovir therapy, while at the same time providing a more favorable dosing schedule compared with acyclovir Fife et al. Herpes simplex encephalitis Herpes simplex encephalitis is managed acutely with intravenous acyclovir, as discussed above. Challenges for achieving clinical benefit, including adverse drug effects The profiles of adverse effects and potential drug interactions observed with valaciclovir therapy are the same as those observed with acyclovir treatment.
Clinical indications Valaciclovir is indicated for the treatment of herpes zoster, and for the treatment or suppression of genital herpes. Dosage regimens Adult treatment doses for HSV-1 and HSV-2 infections are: 1 1 gram orally twice daily for 7—10 days for first episode genital herpes Table Mechanism of action and pharmacokinetics Cidofovir is a novel acyclic phosphonate nucleotide analogue.
Challenges for achieving clinical benefit, including adverse drug effects The principle adverse event associated with systemic administration of cidofovir is nephrotoxicity. Foscarnet Foscarnet is an organic analogue of inorganic pyrophosphate, with the chemical name of phosphonoformic acid PFA.
Mechanism of action and pharmacokinetics Foscarnet directly inhibits DNA polymerase by blocking the pyrophosphate binding site and preventing cleavage of pyrophosphate from deoxynucleotide triphosphates Wagstaff and Bryson, Challenges for achieving clinical benefit, including adverse drug effects The most common adverse effects of foscarnet are nephrotoxicity and metabolic derangements. Clinical indications Foscarnet is indicated for the treatment of acyclovir-resistant mucocutaneous HSV infections in immunocompromised patients, and is the drug of choice for both HSV and VZV infections caused by acyclovir-resistant strains.
Antiviral resistance Foscarnet does not require activation by viral kinases, including thymidine kinase, and therefore is active in vitro against HSV TK-deficient mutants. Ganciclovir Ganciclovir is a nucleoside analogue that differs from acyclovir by having an extra hydroxymethyl group on the acyclic side chain. Mechanism of action and pharmacokinetics As with acyclovir and penciclovir, the first step in ganciclovir phosphorylation is carried out by a virus-encoded enzyme, and the final steps by cellular enzymes.
Clinical indications Ganciclovir is indicated for the treatment and prevention of CMV infections in immunocompromised patients. Antiviral resistance Strains of HSV that are resistant to acyclovir because of TK deficiency also are much less sensitive to ganciclovir. Mechanism of action and pharmacokinetics Valganciclovir is an L-valine ester prodrug of ganciclovir and as such has the same mechanism of action, antiviral spectrum, and potential for development of resistance as ganciclovir Cocohoba and McNicholl, Antiviral therapy Valganciclovir provides a more tolerable means by which ganciclovir can be delivered to the body than does intravenous ganciclovir.
Clinical indications Valganciclovir has similar indications to ganciclovir. Dosage regimens The recommended dose of valganciclovir for induction therapy is mg twice daily for 2 weeks.
Antiviral resistance Resistance mechanisms are identical between ganciclovir and valganciclovir. References Alexander L. Patient and physician partnerships in managing genital herpes. Pickering L. American Academy of Pediatrics Herpes simplex. Anonymous Sexually transmitted diseases treatment guidelines Morb. Wkly Rep. Aoki, F. New Orleans, LA, p. Baker D. Valacyclovir for prevention of recurrent herpes labialis: 2 double-blind, placebo-controlled studies.
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