Herpes Simplex

Description

Alternative Names

Medications

No drug, to date, can actually cure herpes simplex virus. The infection may recur after treatment has been stopped, and during therapy, a patient can still transmit the virus to another person. Drugs are now available, however, that can reduce symptoms and improve healing times.

Acyclovir and Related Drugs

The major drugs developed to date against herpes simplex are antiviral agents called nucleosides and nucleotide analogues, which block viral reproduction. These drugs limit viral replication and its spread to other cells. They are not cures, however. They include acyclovir (Zovirax), valacyclovir (Valtrex), famciclovir (Famvir), and penciclovir. Acyclovir is the standard agent and available in oral, topical, and intravenous forms. Valacyclovir and famciclovir are available orally and topically. In their oral forms they are more convenient than acyclovir, although all are equally effective. Penciclovir is only available as an ointment.

Acyclovir. Acyclovir (Zovirax) is the standard nucleoside for treating many HSV infections. It penetrates most body tissues, including the cerebrospinal fluid that bathes the spinal cord and brain, but has little or no harmful effect on healthy cells. Although most effective against an active infection, acyclovir may also reduce the frequency of viral shedding.

Acyclovir is available in oral, injected, and topical forms. The form used depends on the site and location of the infection. The oral and intravenous forms speed healing of lesions and suppress viral shedding if taken within 24 hours of the first indication of a recurrent episode. Early treatment may even prevent the development of lesions in some patients. The primary downside of oral administration is the need for multiple doses, five or more, throughout the day.

The topical ointment version is the least effective form of acyclovir and may cause some pain, mostly because of other chemicals used in the preparation of the ointment.

Other Nucleosides and Nucleotide Analogues.

• Valacyclovir. Valacyclovir (Valtrex) is converted to acyclovir in the intestine and liver. It provides a higher concentration of acyclovir in the bloodstream without added toxicity and therefore requires less frequent dosing. It is available in a one-day regimen for oral herpes, a once-daily dose to suppress genital herpes, and a three-day treatment for recurrent herpes. Valacyclovir is most effective if taken within 24 hours of the first signs of an outbreak.
• Famciclovir. Famciclovir (Famvir) is converted into its active compound, penciclovir, within the infected cell by contact with an enzyme from the virus. It remains active in the body longer than acyclovir (half the dose is still active after 10 to 20 hours) and, like valacyclovir, requires less frequent dosing (usually two or three times a day). It is most effective if taken within six hours of symptoms' onset.
• Penciclovir. Penciclovir (Denavir) is active against herpes that affects the skin and is used in ointment or cream form. It may have the same benefits as an intravenous agent.
• Investigative Nucleosides. Brivudin (Helpin) is a nucleoside analogue and is proving to be every effective for varicella zoster virus (the cause of shingles). It may also have some effect against HSV in certain circumstances.

Side Effects. All these agents are well tolerated and have excellent safety records. Possible side effects from oral agents include nausea and vomiting, rash, headache, fatigue, tremor, and very rarely, seizures. They can effect the kidney, however, and people with kidney problems should use them with caution and at lower doses. Intravenous administration increases the risk for kidney problems and can cause blood clots at the injection site. In rare cases, it can cause central nervous system complications.

Although there is some evidence they may reduce shedding, they probably do not prevent it entirely. The use of condoms during asymptomatic periods is still essential, even when patients are taking these agents.

Risk for Resistant Viruses. As with antibiotics, physicians are concerned about signs of increasing viral resistance to acyclovir and similar drugs, particularly in immunocompromised patients (such as those with AIDS). Some experts believe, however, that the prevalence of drug-resistant viruses will be low for many years. They argue that widespread use of antiviral drugs will prevent many cases of herpes from developing and will slow the spread of the disease. Even patients on long-term suppressive drug therapy show few signs of drug resistance. In addition, research indicates that many people infected with strains that appear to be drug-resistant in laboratory tests still respond to these drugs.

Foscarnet

Foscarnet (Foscavir) is a powerful anti-viral agent known as a pyrophosphate analogue, and is the first choice for treatment for HSV strains that have become resistant to acyclovir and similar drugs. Administered intravenously, the drug can have toxic effects, including impaired kidney function (which is reversible) and seizures. Fever, nausea, and vomiting are common side effects. It can also cause ulcers on genital organs. As with other drugs, it does not cure herpes.

Cidofovir

Cidofovir (Vistide) is active against many viruses and may be useful in some cases of HSV. Intravenous cidofovir, for example, may be good choice for AIDS patients or bone marrow transplant recipients whose condition is resistant to acyclovir and foscarnet. Cidofovir shows promise as a topical treatment of recurrent genital herpes infections, although it can have severe side effects, including kidney damage.

Investigative Agents for Herpes

Resiquimod. Resiquimod is an immune response-modifier, which is an agent that uses the person's own immune system to fight disease. This agent applied as a gel is of particular interest for treating and preventing genital herpes. It is similar to, but far more potent than, imiquimod, an agent that is used to treat genital warts (which are caused by human papillomavirus). In one small study, as many as a third of treated patients had no recurrences over a six-month period (compared to 94% who were treated with a placebo). Furthermore, some resiquimod-treated patients did not experience a recurrence even after two years. In another case report, an HIV-infected man who developed a severe case of genital herpes that did not respond to acyclovir or other standard drugs responded well to imiquimod cream.

Helicase-Primase Inhibitors. A new class of drugs, called helicase-primase inhibitors, suppress an enzyme vital for HSV replication and growth. They have shown early promise in animal studies, but it will be some years before they are tested for safety and effectiveness in people.

Vaccines. Some experts believe that developing an effective HSV vaccine is the only practical way to control the disease and the spread of infection. Furthermore, if such a vaccine becomes available, then universal immunization may be the best approach. Vaccines also hold out the potential for eliminating latent, lifelong infections.

Various vaccines are in clinical trials or preclinical development, including mutated strains of herpes virus that cannot replicate, inactivated herpes viruses, and DNA vaccines that use genetic fragments of the virus to trigger an immune response. In a 2002 study, a vaccine, referred to as a glycoprotein-DalumMPL vaccine, was effective in preventing HSV-2 in many women without any herpes simplex infection. It was not useful, however, for men or for women already infected with HSV-1. This is a promising start.