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An investigational drug with a novel mechanism of action reduced the rate of viral shedding in patients with genital herpes simplex virus-2 (HSV-2) infection, researchers reported.

In a small, double-blind, placebo-controlled study, the drug, dubbed pritelivir, also reduced the number of days patients had genital lesions, according to , of the University of Washington in Seattle, and colleagues.

The effect was dose-dependent, and the rate of adverse events was similar among treatment groups, Wald and colleagues reported in the Jan. 16 issue of the .

Although several drugs are licensed to treat HSV-2, they are all nucleoside analogs that block the action of the viral DNA polymerase, Wald and colleagues noted.

Also, while they "ameliorate" clinical disease, they do not reduce viral shedding and only partly block sexual transmission.

Pritelivir is the first in a new class of HSV drugs that blocks replication by targeting the viral helicase-primase enzyme complex, which works with the polymerase to direct HSV DNA synthesis.

In pre-clinical research, the drug was potent against HSV-1 and HSV-2 isolates and was efficacious in animals, while phase I trials in humans did not raise any safety concerns.

To test the efficacy of the drug and to find the best dose, Wall and colleagues studied outcomes in 156 people who took pritelivir either daily or weekly for 28 days.

The primary endpoint was comparison with placebo in the proportion of days in which viral shedding was seen, but the researchers also looked at the number of days in which lesions were observed as well as safety.

The bottom line, Wald and colleagues reported, was that a daily dose of 75 mg of the drug led to an 87% reduction in the relative risk of viral shedding.

That's important, commented of the University of California Los Angeles, because shedding is linked to transmission of the virus.

"How much a person sheds the virus is directly related to how much they spread the virus," he told 番茄社区.

The approved drugs "decrease lesions but not shedding," commented , of the University of California Davis.

If a drug can cut shedding it would reduce the risk of transmission, he added. "As in HIV, the concept of treatment as prevention can be considered," Pollard told 番茄社区.

Other findings, Wald and colleagues reported, include:

• Viral shedding was reduced 68%, compared with placebo, with a weekly dose of 400 mg.
• The percentage of days with genital lesions was 9% in the placebo group and 1.2% in both the 75-mg-a-day group and those getting 400 mg weekly. For both doses, the relative risk was 0.13 and was significantly different from placebo.
• The rate of adverse events was similar in all groups, including the placebo arm.

The findings are an important step toward better treatment for herpes infections, which can be life threatening, commented , and, both of the University of Alabama Birmingham.

In an accompanying editorial, they noted that the drug has the potential to be an alternative that will allow treatment in cases where resistance to approved drugs has developed.

And, they added, it opens the door to combination therapies, since pritelivir has a different target than the nucleoside analogs, such as acyclovir.

Other experts agreed that the potential for combining the drug with earlier medications is an exciting aspect of the research.

Combination therapy, commented UC Davis's Pollard, "is needed for severe illnesses caused by HSV, such as neonatal herpes and herpes encephalitis."

And, even though, like the earlier medications, the drug targets DNA replication, it "acts by a different mechanism," commented , of Albert Einstein College of Medicine in New York City.

Among other things, she told 番茄社区, that means it would be active against virus that is resistant to acyclovir and similar drugs.

On the other hand, combination treatment is not a slam-dunk, commented , of Scott & White Healthcare in Temple, Texas.

"More study is needed to understand how this drug interacts with the other anti-virals, along with how the drug works in the central nervous system," he told 番茄社区.

The next step for the research ought to be a trial comparing pritelivir with one or more of the approved drugs, several experts commented.

Indeed, Herold noted that such a study was started but has been placed on hold by the FDA because of unexplained dermal and hematologic toxicity in monkeys.

Wald and colleagues noted in the journal that the animals were given very high doses -- more than 70 times the 75-mg dose in the current study.

They added that there was no sign of the toxicity in participants in the study.

CORRECTION: This article, which was originally published Jan. 15, 2014, at 7:27 p.m., has been corrected (Jan. 16, 2014, at 12:245 p.m. ). Dr. Mutyala is at Scott & White Healthcare in Temple, Texas.

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