Genital Herpes: Treatment Guidelines

, Withington Hospital and University of Manchester


Medscape General Medicine. 1997;1(2) 

In This Article

Managing First Episode of HSV Infection

During the first episode of HSV infection, most patients require analgesia, but opiate-containing analgesics are best avoided because they may cause constipation. Local treatment involves keeping the lesions clean and dry between periods of saline bathing, which may provide some symptomatic relief. Women who are experiencing painful micturition may gain some relief by passing urine while in a warm bath. Alternatively, local anesthetic gel may be applied 10 minutes prior to micturition, although care must be taken as this may sensitize the vulval skin. Women who develop urinary retention require catheterization either through a suprapubic route or via the urethra. The latter route is best achieved under suitable analgesia, but carries the risk of introducing the virus into the bladder; for that reason, the suprapubic route is the method of preference in the UK. It is important to stress the need for sexual partners to be screened for STDs and educated about genital herpes. The patient should be advised to avoid sexual intercourse until the lesions have completely healed.

Antiviral therapy. Although a number of agents have been used to treat primary episodes of genital herpes, the nucleoside analogue class of compounds has been shown to be the most effective and well tolerated in reducing the severity and duration of symptoms. Acyclovir is the most widely used antiviral agent for herpesvirus infections and has been used for more than a decade. It has been found to be safe when administered orally or topically, and development of drug resistance has not been a problem except in immunocompromised patients.

The mechanism of action is phosphorylation to acyclovir triphosphate, which inhibits HSV thymidine kinase and hence viral replication. The clinical benefit of acyclovir 200mg 5 times daily for 7 to 10 days (US) (Table I) and 5 days (UK) has been repeatedly confirmed in placebo-controlled studies.[1] However, studies have not shown a difference in the incidence of subsequent recurrence in treated versus untreated patients.[1]

A major limitation of acyclovir is its poor oral bioavailability (only 15% to 20%). Therefore, acyclovir must be taken 5 times daily about every 4 hours. This regimen may lead to poor patient compliance and thus decreased effectiveness of treatment. Despite the poor oral bioavailability of acyclovir, 3-times-a-day dosing is considered sufficient and endorsed by the US Centers for Disease Control and Prevention--though not FDA approved. The prodrug valacyclovir has much better oral bioavailability (54%)[2] and leads to higher serum concentrations of the active compound acyclovir. Valacyclovir 1g twice daily has been shown to be as effective as acyclovir 200mg 5 times daily.[2]

Famciclovir is a prodrug of the guanosine nucleoside analogue penciclovir. Famciclovir has better bioavailability (77%) than either acyclovir or valacyclovir. Penciclovir's mechanism of action is similar to that of acyclovir: it is converted into its triphosphate form by viral thymidine kinase. Although acyclovir and penciclovir have a similar activity against HSV in cell culture, replication of HSV begins much more quickly when acyclovir is discontinued than after termination of penciclovir.[3] The difference in replication rates is possibly due to varying drug half-lives. The tissue half-life of acyclovir is approximately 0.7 hours, compared with 10 hours (HSV-1) and 20 hours (HSV-2) for penciclovir. Famciclovir 250mg 3 times daily for 5 days (which can be extended to 10 days for severe infections) has been shown to be as effective as acyclovir.[3]

Do the in vitro differences between the active agents, acyclovir and penciclovir, matter therapeutically in humans? Recent studies using mice inoculated with HSV suggested that these in vitro differences may have therapeutic effects. Both valacyclovir and famciclovir were effective when given within 24 hours of inoculation. However, famciclovir proved to be superior to valacyclovir in disabling latency following the delayed administration of the drug.[4] A recent report based on clinical observations has shown that persons treated with famciclovir are less likely to return with a clinical recurrence of genital herpes within 1 to 6 months after first-episode infection than are persons treated with acyclovir.[5]

Superinfection. In severe first episodes or when there has been a delay in presentation for treatment, some women may present with a coexistent bacterial or fungal superinfection. This superinfection should be treated with an appropriate antibacterial or antifungal oral agent.

Counseling/patient education. Counseling at time of diagnosis should include patient education about the disease and emotional support in response to the typical initial patient reaction to the diagnosis: emotional distress, anxiety, and depression. A painful first episode can result in a severe grief reaction over the loss of health and personal image. The sequence of adaptation responses has been described as being remarkably similar to that for cancer.[6] A common response sequence observed by clinicians begins with initial shock and emotional numbing, followed by a frantic search for an immediate cure, and then a sense of isolation and loneliness as the person becomes aware of the potentially chronic nature of the condition. Individuals experience anger directed at the person thought to be the source of the infection, fear about the harmful consequences of the disease on sexuality and fertility, feelings of being contaminated, and depression. The negative connotations of having an STD may give rise to guilt and fear or to an irrational belief that the infection is a penalty for some real or imagined transgression. Patients should be offered a referral to a professional therapist, as needed.

Patients presenting with first-episode genital HSV infection must be told of the risks of transmission to sexual partners. They should be informed that although condoms have been shown to be effective in reducing the transmission of HSV,[7] the virus may be present symptomatically or asymptomatically in areas not covered by the condom. Patients should be advised to abstain from sexual intercourse until the acute episode has completely resolved and then to use condoms for at least 3 months after resolution because of the high likelihood of significant asymptomatic viral shedding following primary infection. Recommending the use of barrier methods to reduce the risk of HSV transmission may be acceptable to those having casual sexual partners or frequent partner change, but these methods are less likely to be acceptable to those in stable relationships or marriages.

A safe and effective vaccine for primary prevention of HSV infection would be useful to control transmission, and several vaccines are currently in development and undergoing evaluation.