title: Helicase-primase inhibitor pritelivir for HSV-2 infection.
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.).
authors.affiliation: From the University of Washington and Fred Hutchinson Cancer Research Center, Seattle (A.W., L.C., A.M., C.J., M.-L.H., S. Selke); AiCuris, Wuppertal, Germany (B.T., S. Stoelben, H.-P.S., H.R.-S., A.B.); Westover Heights Clinic, Portland, OR (T.W.); University of Texas, Houston (S.T.); University of Utah, Salt Lake City (J.K.); Indiana University School of Medicine, Indianapolis (K.F.); and Cetero Research, Miami (L.G.).
authors.forename: Anna
authors.initials: A
authors.lastname: Wald
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
authors.forename: Burkhard
authors.initials: B
authors.lastname: Timmler
authors.forename: Amalia
authors.initials: A
authors.lastname: Magaret
authors.forename: Terri
authors.initials: T
authors.lastname: Warren
authors.forename: Stephen
authors.initials: S
authors.lastname: Tyring
authors.forename: Christine
authors.initials: C
authors.lastname: Johnston
authors.forename: John
authors.initials: J
authors.lastname: Kriesel
authors.forename: Kenneth
authors.initials: K
authors.lastname: Fife
authors.forename: Lawrence
authors.initials: L
authors.lastname: Galitz
authors.forename: Susanne
authors.initials: S
authors.lastname: Stoelben
authors.forename: Meei-Li
authors.initials: ML
authors.lastname: Huang
authors.forename: Stacy
authors.initials: S
authors.lastname: Selke
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Stobernack
authors.forename: Helga
authors.initials: H
authors.lastname: Ruebsamen-Schaeff
authors.forename: Alexander
authors.initials: A
authors.lastname: Birkmann
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D004279:DNA, Viral / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D005260:Female; D006558:Herpes Genitalis / Q000188:drug therapy* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D013449:Sulfonamides; D013844:Thiazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D019562:Viral Load / Q000187:drug effects; D017201:Virus Shedding / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D011725:Pyridines; D013449:Sulfonamides; D013844:Thiazoles; C453221:pritelivir