Larry M. Baddour, MD
A novel antiviral reduced both genital HSV shedding and days with lesions in a dose-dependent manner.
Nucleoside analogues, which inhibit herpes simplex virus (HSV) DNA polymerase following phosphorylation by the viral thymidine kinase, have been a mainstay in the treatment and prevention of genital HSV-2 infections. These agents have limitations, however, including development of resistance and inability to reduce viral shedding.
Pritelivir, the first in a new class of antiviral agents, inhibits HSV replication by targeting the viral helicase–primase complex. It has shown potent in vitro activity, as well as efficacy in infection models; phase I studies have demonstrated no safety issues. Now, in an industry-sponsored, proof-of-concept study conducted at seven sites in the U.S., researchers have evaluated the effect of various doses of pritelivir in reducing the HSV-2 shedding rate.
The researchers enrolled 155 otherwise healthy adults who were seropositive for HSV-2 and had a history of genital herpes. Participants were randomly assigned in a 1:1:1:1:1 ratio to one of the following regimens for 28 days:
Participants obtained swabs from the genital area daily for HSV testing by polymerase chain reaction.
The relative risk for HSV-2 shedding was reduced with pritelivir, as compared to placebo, in a dose-dependent manner: 1.11 (95% confidence interval, 0.65–1.87) with the 5-mg daily dose; 0.57 (95% CI, 0.31–1.03) with the 25-mg daily dose; 0.13 (95% CI, 0.04–0.38) with the 75-mg daily dose; and 0.32 (95% CI, 0.17–0.59) for the 400-mg weekly dose. In addition, the proportion of days with genital lesions was significantly reduced for both the 75-mg daily and the 400-mg weekly groups compared to the placebo group (1.2% and 1.2% vs. 9.0%, respectively). Adverse-event rates were similar among the five groups.
Citation(s):
Wald A et al. Helicase–primase inhibitor pritelivir for HSV-2 infection. N Engl J Med 2014 Jan 16; 370:201.
