Helicase-primase inhibitor pritelivir for HSV-2 infection

N Engl J Med. 2014 Jan 16;370(3):201-10. doi: 10.1056/NEJMoa1301150.

Abstract

Background: Pritelivir, an inhibitor of the viral helicase-primase complex, exhibits antiviral activity in vitro and in animal models of herpes simplex virus (HSV) infection. We tested the efficacy and safety of pritelivir in otherwise healthy persons with genital HSV-2 infection.

Methods: We randomly assigned 156 HSV-2-positive persons with a history of genital herpes to receive one of four doses of oral pritelivir (5, 25, or 75 mg daily, or 400 mg weekly) or placebo for 28 days. Participants obtained daily swabs from the genital area for HSV-2 testing, which was performed with a polymerase-chain-reaction assay. Participants also maintained a diary of genital signs and symptoms. The primary end point was the rate of genital HSV shedding.

Results: HSV shedding among placebo recipients was detected on 16.6% of days; shedding among pritelivir recipients was detected on 18.2% of days among those receiving 5 mg daily, 9.3% of days among those receiving 25 mg daily, 2.1% of days among those receiving 75 mg daily, and 5.3% of days among those receiving 400 mg weekly. The relative risk of viral shedding with pritelivir, as compared with placebo, was 1.11 (95% confidence interval [CI], 0.65 to 1.87) with the 5-mg daily dose, 0.57 (95% CI, 0.31 to 1.03) with the 25-mg daily dose, 0.13 (95% CI, 0.04 to 0.38) with the 75-mg daily dose, and 0.32 (95% CI, 0.17 to 0.59) with the 400-mg weekly dose. The percentage of days with genital lesions was also significantly reduced, from 9.0% in the placebo group to 1.2% in both the group receiving 75 mg of pritelivir daily (relative risk, 0.13; 95% CI, 0.02 to 0.70) and the group receiving 400 mg weekly (relative risk, 0.13; 95% CI, 0.03 to 0.52). The rate of adverse events was similar in all groups.

Conclusions: Pritelivir reduced the rates of genital HSV shedding and days with lesions in a dose-dependent manner in otherwise healthy men and women with genital herpes. (Funded by AiCuris; ClinicalTrials.gov number, NCT01047540.).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / adverse effects
  • Antiviral Agents / pharmacology
  • DNA, Viral / analysis
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Resistance, Viral
  • Female
  • Herpes Genitalis / drug therapy*
  • Herpes Genitalis / virology
  • Herpesvirus 2, Human* / genetics
  • Herpesvirus 2, Human* / isolation & purification
  • Humans
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Pyridines / administration & dosage*
  • Pyridines / adverse effects
  • Pyridines / pharmacology
  • Thiazoles / administration & dosage*
  • Thiazoles / adverse effects
  • Thiazoles / pharmacology
  • Viral Load / drug effects
  • Virus Shedding / drug effects*

Substances

  • Antiviral Agents
  • DNA, Viral
  • Pyridines
  • Thiazoles
  • pritelivir

Associated data

  • ClinicalTrials.gov/NCT01047540