What Treatments are Available for Herpes?

Can herpes simplex be treated?

Many of us are accustomed to taking antibiotics or other medications that will rids us of infection quickly. There are antiviral drugs specific for herpes that will treat this infection. But unlike antibiotics for bacteria, they do not cure the infection. Herpes simplex virus has a complicated life cycle that enables it to persist within the body protected in neurons. The "target" to current anti-herpes drugs is made when the virus is on skin or mucosa but not in dormantly infected nerve cells.

Thus, the virus can be attacked and genital herpes treated; with medications called antiviral drugs. While these can't rid the body of HSV, they help people with herpes control the infection, keep symptoms to a minimum, and can even suppress the virus from reactivating in the genital region.

For many years, people diagnosed with genital herpes had to cope with recurrent symptoms without the benefit of any medications able to target herpes itself. Beginning in 1985, however, the advent of antiviral medication in pills, capsules, or liquid formulations gave patients new options for gaining a measure of control over the infection. Today, nearly 2 decades later, therapeutic options have expanded yet again, with a variety of antiviral agents reaching the market. Anyone whose quality of life is significantly affected by genital herpes should talk with a doctor about medication to control outbreaks and prevent transmission of genital herpes. Treatment choices and regimens for genital herpes vary greatly between individuals and physicians. This section provides some overviews of potential approaches and choices of drugs.

Treatment Regimens

Anti-herpes medication can help to control the infection in one of three ways:

Treating First episodes of Genital Herpes: : First episodes of genital herpes are generally the most severe. A 7 to 10-day course of medication can dramatically lessen the severity of a first episode. With medication, sores heal faster, other symptoms such as swollen glands and fever are reduced, and viral shedding is ended more quickly. Treatment also reduces the likelihood one might develop meningitis associated with genital herpes. We recommend everyone with a first episode infection be treated with an antiviral drug.

Episodic Therapy: Taken at the first warning sign of an outbreak, medication can help to shorten the duration of symptoms and speed healing of sores. People who have severe or prolonged recurrences and those who experience prodrome are most likely to benefit from episodic therapy. Gains are much greater if therapy is started before herpes lesions appear. In some cases, the prompt use of medication during prodrome will abort the episode before herpes lesions form. Episodic therapy is most effective when patients have medication on hand and can initiate treatment themselves.

Suppressive or Daily Therapy: In order to lessen the chance of recurrences or avert them altogether, patients can take antiviral medication every day for long periods of time. Patients on the suppressive regimen usually experience a dramatic reduction in the frequency of symptoms, and in one five-year study, 20 percent of patients had no recurrences at all. Overall in this study, the average number of outbreaks dropped from 13 to fewer than two per year by the end of the first year and one per year by the end of the fifth year. Daily therapy also reduces the frequency of subclinical HSV reactivation on mucosal surfaces. This is associated with a subsequent reduction in risk of transmission via sexual contact. It takes about 5 days of therapy to effectively suppress the virus to nearly undetectable levels. Thus, suppressive therapy needs to be initiated well before sexual activity to prevent transmission.

Combination of Suppression and Episode Therapy: Some patients benefit from a combination of suppressive therapy, e.g. 30-60 days, when they are going on vacation and the use of intermittent therapy or even no therapy for other time periods.

Who Should Use Antiviral Therapy?

There are benefits and costs to all 3 approaches: episodic therapy, daily therapy, or both episodic and daily therapy. Any individual may move from one category to another, e.g., persons with genital HSV-1 infection require treatment for their initial episodes, but rarely require daily suppressive therapy, as most do not recur. In contrast, over 90% of persons with first episode HSV-2 recur and the median number of recurrences yearly is 6 or 7. Thus, many persons with recurrent genital HSV-2 infection may prefer daily as opposed to episodic therapy. If transmission is a concern to a sexual partner, then daily therapy may be desired. Conversely, if both partners have genital herpes, treatment during outbreaks may be the most desirable approach. There is no one answer. Persons who have HIV or are immune compromised also do best with suppressive therapy (see section HIV and Herpes).

The Medications

There are 3 major medications used to treat genital herpes infections whether the infection is due to HSV-1 or HSV-2. The drugs differ somewhat in their chemical structure, how often you take them, price and FDA licensed indications. (Remember not every area where a drug is effective receives an FDA indication.) But, some doctors, health plans and insurance companies use FDA indications for how a drug is used or reimbursed.

All 3 drugs we will discuss: Acyclovir, Famciclovir and Valaciclovir work in a pretty similar fashion. They disrupt the process by which the virus makes copies of itself and spreads to new cells. They do this by inhibiting an enzyme that the virus has but human cells do not and then interrupting the viruses' ability to synthesize DNA. None of the therapies cures the viral infection. HSV-1 and HSV-2 will remain dormant in the body in the nerve ganglia. However, all 3 drugs can be used on a daily basis to inhibit large quantities of the virus to build up and cause lesions.

Some of the medications have been studied in greater detail and over longer time periods. Some doctors use the drugs interchangeably. Some use each drug in a specialized way/manner.

Acyclovir (Zovirax®)

Acyclovir was the first successful drug for genital herpes and was originally licensed in the early 1980s for the treatment and suppression of genital herpes. It is sold under the brand name Zovirax® but is now available as a generic from many manufacturers and is by far the cheapest of the available antivirals. It comes in intravenous, oral and topical formulations. This discussion will concentrate on its use as an oral medication. Most physicians do not feel topical acyclovir is very useful for genital herpes, and we agree.

Famciclovir (Famvir®)

This was the second drug licensed for the treatment of genital herpes. Famciclovir has also been shown to be effective for both episodic and suppressive therapy of genital herpes. Difference dosages are used for different treatment goals.

Valaciclovir (Valtrex®)

This is the third antiviral drug for genital herpes. Valaciclovir is a derivative of acyclovir that provides much better absorption and hence blood levels of acyclovir. Some people have called it intravenous acyclovir in pill form. The active ingredient is acyclovir. The better absorption allows less frequent dosing.

First Episode Infections

All three medications work well in the therapy of first episode infections and even comparative trials have shown no clinical differences. The critical issue is that people with first episode genital herpes get treated early, so that the virus does not disseminate or cause excessive disease. None of the medications prevent the virus from reaching the ganglia and reactivating (see Complications of Genital Herpes). Most authorities treat first episode infection for 7-10 days. Improvement clinically usually starts about 36-72 hours post initiation of medication. Dosages vary, but common doses are famciclovir 250mg po BID, valaciclovir 500 mg po BID, and Acyclovir 400mg po TID.

Treatment of Recurrent Disease

The major issue facing persons with recurrent genital herpes is whether to use what physicians call episodic therapy, that is taking pills when there is an outbreak versus taking pills on a daily basis to prevent recurrences from occurring or to prevent transmission to another sexual partner. This decision will vary between individuals and is likely to vary over time in any one individual. Adherence and timing of medication is important in both approaches.

For episodic therapy to work best, one needs to initiate therapy as early as possible at the beginning the outbreak, preferably due to ealy "itching" prodromal stage. For suppressive or daily therapy, compliance to daily medication is important, especially if one is using suppression to reduce transmission of infection to others (see Transmission).

Episodic Therapy

There are many dosages and approaches to using the medication for the treatment of recurrent episodes of genital herpes. Some are listed here

Acyclovir: The FDA licensed dosages of acyclovir are 200mg capsules 5 times a day for 5 days. A commonly utilized dosage by many doctors is a 400 mg tablet 3 times a day for 5 days. A recent study showed that 3 800mg tablets for 2 days also worked well.

Famciclovir: The dosage of famciclovir for episodic therapy is 125mg twice daily for 5 days. Famciclovir therapy is quite effective in reducing symptoms and speeding healing of lesions of episodes of genital herpes.

Valaciclovir: Valaciclovir is also effective in reducing the symptoms and signs of recurrent genital herpes. The most commonly utilized dosage for valaciclovir is 500mg twice daily for 5 days. A recent study showed that 1000mg a day for 2 days worked as well.

Suppression of Clinical Recurrences

Daily Therapy: Daily therapy is utilized for two major reasons: 1) For people who develop recent genital herpes frequently, e.g., once every month or two, or 2) For people who are in a sexual relationship with a person who does not have genital herpes and who want to reduce their risk of transmitting genital herpes to others (This should be done in the context of condom use.). All three medications are well tolerated and well studied for suppressing reactivations of genital herpes in a person. Only valaciclovir has been shown to reduce transmission to others.

Acyclovir: 400mg tablets twice daily is the recommended initial starting dose

Famciclovir: Famvir® 250mg twice a day is the FDA licensed dose

Valaciclovir (Valtrex®): For persons with <10 recurrences yearly 500mg once daily, for persons with> 10 recurrences per year 1000mg once daily or 500mg twice daily.

Reduction in Transmission: The dose for reduction in transmission is 500 mg po once daily. Some authorities would recommend 500mg twice daily, albeit this doubles the cost.

Safety Issues

All 3 medications have outstanding safety records.

Acyclovir has been used by more than 30 million individuals in 96 countries and has an outstanding safety record. Large numbers of people have taken it continuously for at least ten years, also without serious adverse effects.

Acyclovir has been studied in pregnant women, although the trials are small. All three antivirals mentioned earlier are Pregnancy Category B. This means that animal studies have not shown teratogenic effects, but adequate studies have not been done in humans. Therefore, the benefit must outweigh the risk. It is important to note that many drugs used in pregnant women are classified as Pregnancy Category B.

Drug-resistant strains of herpes have been identified in people with weakened immune systems, such as people with AIDS, those who receive prolonged cancer chemotherapy, or have bone marrow, or organ transplants. The prolonged use of acyclovir or famciclovir or valaciclovir in these persons can select out strains of HSV-1 or HSV-2 that are less likely to respond to therapy with acyclovir, valaciclovir or famciclovir. On the other hand, there has been no increase in drug-resistant strains of herpes in the general population since acyclovir was introduced in 1985, and sensitivity to acyclovir remains high in those taking the drug even for several years. A recent Centers for Disease Control survey that measured acyclovir resistance in STD clinics in the United States showed less than 0.5% of strains display any loss in sensitivity to the drugs. Most strains of virus that are resistant to one of these drugs are resistant to the other. In immunocompetent persons, most authorities feel that resistance is not a major consideration in determining whether to initiate therapy for genital herpes or for determining the type or duration of therapy.

Vaccines

In addition to the new antiviral therapies listed here, researchers are hard at work on vaccines for herpes. The initial goal of such research is a preventive vaccine that would protect the vaccine recipient from infection if he or she were later exposed to herpes. The same type of vaccines might also provide therapeutic benefit to those already infected by reducing their number of herpes outbreaks. While there are some glimmers of hope in this area. There is no licensed effective vaccine. In some research centers: studies of candidate HSV vaccines are underway.