A study finds a new class of anti-viral drug significantly reduces both genital shedding and lesions related to HSV-2.

The only class of drugs currently available to treat HSV are nucleoside analogues (such as acyclovir) that work by a bit of genetic subterfuge: the drugs sneak into the viral DNA, masquerade as a building block HSV uses to make copies of itself, and ultimately cause the chain of viral replication to misfire.

Another anti-viral drug, helicase-primer inhibitors (HPI), also works by short-circuiting HSV replication. HPI’s crash the party at a different stage of the HSV replication cycle, though, and target an enzyme called helicase-primase that has a unique function in HSV replication that involves untwisting the famed DNA double helix. With microscopic brass knuckles firmly in place and an intimidating scowl on its face, the HPI stops replication by keeping the DNA strands tightly laced and giving the enzyme a black eye, to boot.

While both drugs do their jobs well enough, in vitro studies (think labs filled with test tubes and culture dishes) indicate HPI might ultimately prove to be more robust and active against HSV.

To assess how well a novel HPI, AIC316, works in preventing viral shedding of genital herpes, researchers led by the University of Washington’s Anna Wald, MD, MPH randomized subjects to receive a 28-day course of either placebo or one of four treatment regimens: daily AIC316 at 5mg, 25mg, or 75mg, or a weekly 400mg dose. Participants in this multi-center, phase II study were HSV-2 positive, healthy adults and collected daily samples of genital skin cells that were tested for HSV DNA.

The results with the 75mg group were most dramatic: subjects in this group experienced viral shedding on 2% of days, compared to 17% who received placebo. Those in the 75mg arm of the study also had subclinical shedding detected less often (on fewer than 2% of days versus 10% for those in the control group), genital lesions detected less frequently (on 1% of days versus 9%), and lower HSV DNA log copy numbers (2.8 compared to 5.1) or (2.8 log10 copies compared to 5.1 copies).

Much work remains before the value of HPI is fully understood, but the reduction in genital shedding of the virus is intriguing and HSV researchers can’t be blamed for day-dreaming about the potential of new drugs such as HPI as a tool to both manage symptoms and, possibly, reduce transmission.

Reference
Wald A, Stoelben S, Tyring S, Warren T, Johnston C, Haung M, Timmler B, Reubsamen-Schaeff H, Corey L, and Birkmann A. Effect of a novel antiviral helicase-primase inhibitor AIC316 on genital HSV shedding: randomized, double-blind, placebo-controlled trial. Sex Transm Infect 2011;87:A78-A79.