Herpes simplex virus infection is increasingly common in the United States. New antiviral medications have expanded treatment options for the two most common cutaneous manifestations, orolabial and genital herpes. Acyclovir therapy remains an effective and often less expensive option. Famciclovir and valacyclovir offer improved oral bioavailability and convenient oral dosing schedules but are more expensive than acyclovir. Patients who have six or more recurrences of genital herpes per year can be treated with one of the following regimens: acyclovir, 400 mg twice daily; valacyclovir, 1 g daily; or famciclovir, 250 mg twice daily. These regimens are effective in suppressing 70 to 80 percent of symptomatic recurrences. Episodic treatment of recurrent genital herpes is of questionable benefit, but it may be helpful in appropriately selected patients. There is little evidence indicating benefit from treatment of recurrent orolabial herpes, which tends to be mild and infrequent.

Herpes simplex virus (HSV) affects more than one third of the world's population1 and is responsible for a wide array of human disease, with effects ranging from discomfort to death. Before the 1970s, when acyclovir (Zovirax) was introduced as an antiviral drug, cutaneous HSV infection was managed with drying agents and other local care. Newer antiviral drugs with once-daily dosage benefits have emerged during the past several years. Famciclovir (Famvir) and valacyclovir (Valtrex) offer effective and convenient therapeutic choices but are often more expensive than acyclovir.

The Virus and Pathogenesis
HSV is a double-stranded DNA virus that may enter the host through abraded skin or intact mucous membranes.1 Epithelial cells are the initial targets. Once infected, these cells die, releasing clear fluid intradermally to form vesicles and merging with other cells to create multinucleated giant cells.

Retrograde transport through adjacent neural tissue to sensory ganglia leads to lifelong latent infection.1 Reactivation of the virus is triggered by local or systemic stimuli such as immunodeficiency, trauma, fever, menstruation, ultraviolet (UV) light and sexual intercourse.1–3 Although emotional stress is assumed to trigger HSV recurrence, recent research fails to show a definite causative role.4 Once reactivated, the virus is transported by the neuron back to the epithelium, where more replication occurs, and another outbreak ensues.

HSV exists as two separate types, labeled 1 and 2, which have affinities for different body sites.2 Ninety percent of infections caused by HSV-2 are genital, and 90 percent of those caused by HSV-1 are oral; the reason for this division is unknown.5 In addition, oral HSV-1 infection recurs more frequently than oral HSV-2, and genital HSV-2 recurs more often than genital HSV-1.

Diagnosis
The diagnosis of genital HSV infection may be made clinically, but laboratory confirmation is recommended in patients presenting with primary or suspected recurrent infection. The gold standard of diagnosis is viral isolation by tissue culture,1 although this process can take as long as four to five days, and the sensitivity rate is only 70 to 80 percent. Despite these limitations, viral culture is still the diagnostic test of choice for HSV skin infections.

Tzanck preparations and antigen claritin 10 mg usa detection tests have lower sensitivity rates (50 to 70 percent) bactrim 400/80 mg cost than viral culture.3 Serologic testing is extremely sensitive but is not helpful during primary infection because of the delay in antibody development.2 Polymerase chain reaction enzyme-linked immunosorbent assay (PCR-ELISA) is extremely sensitive (96 percent) and specific (99 percent) but expensive.1 For this reason, it is not used for the diagnosis of skin lesions but is the laboratory test of choice for diagnosing HSV encephalitis.

Antiviral Medications
Acyclovir, an acyclic guanosine analog, binds viral DNA polymerase, acting as a chain terminator and ending replication. Its mechanism of action necessitates early administration, because replication may end as soon as 48 hours into a recurrence.3

Oral bioavailability is only 15 to 30 percent; concentrations 10-fold higher can be achieved with intravenous administration.6 The half-life of acyclovir is about 2.5 hours, and the dosage must be adjusted in patients with renal failure. The drug penetrates well into most body tissues, including the brain, and crosses the placenta.

Acyclovir is a safe and extremely well-tolerated drug. Data from more than 35 million patients have been consistent and reassuring.6 Some authorities have proposed making acyclovir available as a nonprescription drug. Toxicity is rare, but in patients who are dehydrated or who have poor renal function, the drug can crystallize in the renal tubules, leading to a reversible creatinine elevation or, rarely, acute tubular necrosis. Adverse effects, usually mild, include nausea, vomiting, rash and headache. Lethargy, tremulousness, seizures and delirium have been reported rarely in studies of renally impaired patients.2,3

The Acyclovir in Pregnancy Registry has documented prenatal exposures in more than 850 women (with 578 first-trimester exposures) without any adverse outcomes.7 However, the total number of pregnancies monitored to-date may not be enough to detect defects that occur only infrequently.6 Therefore, the drug is labeled pregnancy category C by the U.S. Food and Drug Administration.

Valacyclovir, a new antiviral agent, is the l-valine ester prodrug of acyclovir; it is easily absorbed and converted to acyclovir. It has an oral bioavailability three to five times greater than that of acyclovir,8 and several large trials have shown that it is safe bactrim 800/160mg usa and well tolerated.8–10

Famciclovir, another new antiviral medication, is the oral form of penciclovir, a purine analog similar to acyclovir. Oral bioavailability is 77 percent, and the drug is quickly converted to its active form.11 Mechanism and efficacy are similar to those of acyclovir.12 Famciclovir's intracellular half-life is 10 times longer than acyclovir's; despite this, dosing less frequently than twice daily is not recommended.13

Genital Herpes
Genital HSV infection is usually transmitted through sexual contact; therefore, it generally does not occur before adolescence. When genital herpes occurs in a preadolescent, the possibility of abuse must be considered, as with all sexually transmitted diseases in children.

Recent evidence indicates that 21.9 percent of all persons in the United States 12 years of age or older have serologic evidence of HSV-2 infection14; this figure has increased by 30 percent since the late 1970s. Independent risk factors include multiple sexual partners, increasing age, female gender, low socioeconomic status and human immunodeficiency virus (HIV) infection.1,2,14,15


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