Herpes

Herpes Disorders Recurrence Transmission and prevention Diagnosis Epidemiology Treatment

Treatment

here is currently no cure that can eradicate herpes virus from the body, but antiviral medications can reduce the frequency, duration, and severity of outbreaks. Antiviral drugs also reduce asymptomatic shedding; it is believed asymptomatic HSV-2 viral shedding occurs on 10.8% of days per year in patients not undergoing antiviral treatment, versus 2.9% of days while on antiviral therapy. Non-prescription analgesics can reduce pain and fever during initial outbreaks. Topical anesthetic treatments such as prilocaine, lidocaine or tetracaine can also relieve itching and pain.

History

Herpes antiviral therapy began in the early 1960s with the experimental use of medication that interfered with viral replication called deoxyribonucleic acid (DNA) inhibitors. The original use was against normally fatal or disabilitating illness such as adult encephalitis, keratitis, in immunocompromised (transplant) patients, or disseminated herpes zoster. The original compounds used were 5-iodo-2'-deoxyuridine, AKA idoxuridine, IUdR, or(IDU) and1-ß-D-arabinofuranosylcytosine or ara-C, later marketed under the name cytosar or cytorabine. The usage expanded to include topical treatment of herpes simplex, zoster, and varicella. Some trials combined different antivirals with differing results.The introduction of 9-ß-D-arabinofuranosyladenine, AKA ara-A or vidarabine, considerably less toxic than Ara-C, in the mid 1970s, heralded the way for the beginning of regular neonatal antiviral treatment. Vidarabine was the first systemically administered antiviral medication with activity against HSV for which therapeutic efficacy outweighed toxicity for the management of life-threatening HSV disease. Intravenous vidarabine was licensed for use by the FDA in 1977. Other experimental antivirals of that period included: Heparin , trifluorothymidine (TFT), Ribivarin, interferon, Virazole, and 5-methoxymethyl-2'-deoxyuridine (MMUdR). The introduction of 9-(2-hydroxyethoxymethyl)guanine, AKA acyclovir, in the late 1970s[126] raised antiviral treatment another notch and led to vidarabine vs. acyclovir trials in the late 1980s. The lower toxicity and ease of administration over vidarabine has led to acyclovir becoming the drug of choice for herpes treatment after it was licensed By the FDA in 1998. Another advantage in the treatment of neonatal herpes included greater reductions in mortality and morbidity with increased dosages, something that did not occur when compared with increased dosages of vidarabine. On the other side of the equation, acyclovir seems to inhibit antibody response and newborns on acyclovir antiviral treatment experienced a slower rise in antibody titer than those on vidarabine.

Antiviral medication

Antiviral medications used against herpes viruses work by interfering with viral replication, effectively slowing the replication rate of the virus and providing a greater opportunity for the immune response to intervene. All drugs in this class depend on the activity of the viral enzyme thymidine kinase to convert the drug sequentially from its prodrug form to monophosphate (with one phosphate group), diphosphate (with two phosphate groups), and finally to the triphosphate (with three phosphate groups) form which interferes with viral DNA replication.

There are several prescription antiviral medications for controlling herpes simplex outbreaks, including aciclovir (Zovirax), valaciclovir (Valtrex), famciclovir (Famvir), and penciclovir. Aciclovir was the original, and prototypical, member of this drug class; it is now available in generic brands at a greatly reduced cost. Valaciclovir and famciclovir—prodrugs of aciclovir and penciclovir, respectively—have improved solubility in water and better bioavailability when taken orally. Aciclovir is the recommended antiviral for suppressive therapy for use during the last months of pregnancy to prevent transmission of herpes simplex to the neonate in cases of maternal recurrent herpes. The use of valaciclovir and famciclovir, while potentially improving treatment compliance and efficacy, are still undergoing safety evaluation in this context.

Several studies with mice provide evidence that treatment with famciclovir soon after initial infection can help lower the incidence of future outbreaks, by reducing the amount of latent virus in the neural ganglia. A review of human subjects treated with famciclovir during their first herpes episode supports these findings, with only 4.2 percent of famciclovir-treated patients experiencing a recurrence within one to six months after the first outbreak, compared to 19 percent of acyclovir-treated patients. Despite these promising results, early famciclovir treatment for herpes has yet to find mainstream adoption. However, the potential effect on latency drops to zero a few months post-infection.

Antiviral medications are also available as topical creams for treating recurrent outbreaks on the lips, although their effectiveness is disputed. Penciclovir cream has a 7-17 hour longer cellular half-life than aciclovir cream, increasing its effectiveness relative to aciclovir when topically applied.

Topical treatments

Docosanol is available as a cream for direct application to the affected area of skin. It prevents HSV from fusing to cell membranes, thus barring the entry of the virus into the skin. Docosanol was approved for use after clinical trials by the FDA in July 2000. Docosanol is marketed by Avanir Pharmaceuticals under the name Abreva. It was the first over-the-counter antiviral drug approved for sale in the United States and Canada. Avanir Pharmaceuticals and GlaxoSmithKline Consumer Healthcare were the subject of a U.S. nationwide class-action suit in March, 2007 due to the misleading claim that it cut recovery times in half.

Tromantadine is available as a gel that inhibits the entry and spread of the virus by altering the surface composition of skin cells and inhibiting release of viral genetic material. Zilactin is a topical analgesic barrier treatment, which forms a "shield" at the area of application to prevent a sore from increasing in size, and decrease viral spreading during the healing process.

Lipactin by Novartis is another over-the-counter topical gel which has been clinically shown to reduce sympotms and healing duration of a Herpes Simplex infection.

There is some limited research that has shown that tea tree oil may have topical anti-viral activity, especially with the Herpes virus

Other drugs

Cimetidine, a common component of heartburn medication, has been shown to lessen the severity of herpes zoster outbreaks in several different instances. This is an off-label use of the drug. It and probenecid have been shown to reduce the renal clearance of aciclovir. These compounds also reduce the rate, but not the extent, at which valaciclovir is converted into aciclovir.

Limited evidence suggests that low dose aspirin (125 mg daily) might be beneficial in patients with recurrent HSV infections. Aspirin (acetylsalicylic acid) is an non-steroidal anti-inflammatory drug which reduces the level of prostaglandins—naturally occurring lipid compounds—that are essential in creating inflammation. A recent study in animals showed inhibition of thermal (heat) stress induced viral shedding of HSV-1 in the eye by aspirin, and a possible benefit in reducing the frequency of recurrences.

Another treatment is the use of petroleum jelly. Healing of cold sores is sped by barring water or saliva from reaching the sore.

Vaccines

Zostavax is a live vaccine developed by Merck & Co. (September, 2008) which has been shown to reduce the incidence of herpes zoster (known as Shingles) by 51.3% in a pivotal phase III study of 38,000 adults aged 60 and older who received the vaccine.

The National Institutes of Health (NIH) in the United States is currently conducting phase III trials of Herpevac, a vaccine against HSV-2. The vaccine has only been shown to be effective for women who have never been exposed to HSV-1. Overall, the vaccine is approximately 48% effective in preventing HSV-2 seropositivity and about 78% effective in preventing symptomatic HSV-2. During initial trials, the vaccine did not exhibit any evidence of preventing HSV-2 in males. Additionally, the vaccine only reduced the acquisition of HSV-2 and symptoms due to newly acquired HSV-2 among women who did not have HSV-2 infection at the time they got the vaccine. Because about 20% of persons in the United States have HSV-2 infection, this further reduces the population for whom this vaccine might be appropriate.

Researchers at the University of Florida have made a hammerhead ribozyme that targets and cleaves the mRNA of essential genes in HSV-1. The hammerhead which targets the mRNA of the UL20 gene greatly reduced the level of HSV-1 ocular infection in rabbits and reduced the viral yield in vivo.